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ROBERT KHO-SENG LIM October 15, 1897-July 8, 1969 BY HORACE W. DAVENPORT ROBERT K. S. LIM lived two lives. In the first, he was a physiologist with research interests in the control of gastric secretion and the neurophysiology of pain. He estab- lishecl Western physiology in China while teaching at the Peking Union Medical College. In his second life, Robert K. S. Lim organized medical relief corps and trainee! doctors, nurses and technicians to meet the needs of China at war. He supervised meclical ser- vices on the field] of battle from the Great Wall to the retreat with Stilwell through the Burmese jungle. He built hospitals and meclical schools on MainIanc! China and on Taiwan, and after the war he rebuilt his country's meclical education and medical research. He was "one of the great men of China,"* the abundantly clecoratec] Lieutenant General in the Army ant! Surgeon General of the Republic of China. In both lives, Robert K. S. Lim was the vivacious, gen- erous, charming, energetic, athletic and artistic man who spoke with a Scottish burr and was universally known as Bobby. Robert Lim's ancestors came to Singapore from Fukien Province in southwestern China. The surname means a small * B. Tuchman, Stilwell and Me American Experience in China, 1911-45 (New York: Macmillan, 1970). 281

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282 BIOGRAPHICAL MEMOIRS forest represented by two trees, ant! the present official trans- literation of the charcter is Lin. Although the Lim family, like many from their province, retained the old spelling, R. K. S. Lim sometimes appears in the indexes of books about war in China and in library catalogs as R. K. S. Lin. Robert Lim's father, Lim Boon Keng, dic3 so well as a poor boy at the Raffles Institution in Singapore that he won the Queen's Scholarship to Edinburgh University where he grad- uated in medicine. He worker! briefly with W. B. Harcly in Cambridge, and together they published a paper in the Journal of Physiology* on the origin and function of leucocytes in the frog. On returning to Singapore, I.im Boon Keng practiced medicine, but he was also active in public affairs in China as well as in Singapore. He was a Legislative Council- lor, and in 1911 he was appointed Medical Advisor to the Chinese Ministry of the Interior. The next year he became physician and confidential secretary to Sun Yat-sen. He rep- resented his country at meetings in Paris and Rome, ant! in 1923, with the help of a millionaire friend, he established the University of Amoy. Lim Boon Keng married Margaret Tuan-Keng Wong, one of the first Chinese women to be eclucated in the United States, and they had four sons, the oldest being Robert Kho-seng. Lim Boon Keng (lied at the vernerable age of eighty-eight in Singapore. Bobby Lim was born in Singapore on October 15, IS97. His father sent Bobby to ScotIancl when he was eight years old. The boy was in the charge of his father's apothecary, who was also an itinerant lay preacher, and in moving from parish to parish, Bobby's education was more peripatetic than substantial. Later, Bobby attended Watson's School in Ectin- burgh where he prepared for the University. At the outbreak of the First World War, Lim volunteered! and was assigned to *journal of Physiology, 15(1894):361-74.

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ROBERT KHO-SENG LIM 283 the Indian Army in France as a warrant officer. His job was to drill recruits, and the young sons of Maharajas who had joined the colors objected to being ordered arounc! by a young "Chinaman." In 1916, Lim was allowed to return to Edinburgh for medical studies, ant! he receiver! the M.B. and Ch.B. degrees in 1919. In the Medical School of Edinburgh University, Lim quickly established himself as a protege of Sir Edward Sharpey-Schafer, the Professor of Physiology, and as an undergraduate he worked in the Physiology Laboratory on problems suggested by Sharpey-Schafer. Immediately upon graduation, he was appointed Lecturer in Physiology with responsibility for teaching histology. The next year Lim pre- sented the results of his research to earn the Ph.D. In the tradition of British physiology, microscopic anat- omy came within the purview of the Physiology Department, and Lim cleveloped skill in histological techniques and obser- vations. His first major publication was a study of the his- tology of tadpoles whose development had been accelerated by being fed thyroid. This paper is notable for Limes draw- ings. Lim had considerable skill as a draughtsman, and he tract transiently wanted to be an artist before his father per- suaclecl him to try medicine first. He continued to illustrate his papers with clelicate drawings. The best example is Lim's paper, published in 1922,* on the microscopic anatomy of the gastric mucosa. The paper is distinguished by its smooth style, by its thoroughness baser! on wide observation and meticulous attention to detail, and by its correlation of struc- ture with function. him carried the microscopic anatomy of the gastric mu- cosa almost as far as it could be carried until the advent of electronmicroscopy. In fact, he carried it a little further than *Quarterly Journal of Microscopical Science, 66(1922): IS7-2 12.

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284 BIOGRAPHICAL MEMOIRS the resolution possible in light microscopy warranted, for in papers publishes] later from China he described how mito- chondria dissociate cluring secretion into a free lipid which condenses to form the Golgi apparatus and a remainder which either catalyzes or enters into the secretion. Lim described the structure of the stomach, because he was aIreacly studying its function. The results were reported in a flood of papers in 1923. At this time research in gastrointestinal physiology was in the doldrums. In Russia, Pavlov had turned to the study of conditioner] reflexes, and in the United States, Walter B. Cannon had stopped work on the mechanical factors of digestion when he discovered he had been burned by X-rays. Cannon's observation on the supposes! relation between gas- tric motility and the sensation of hunger had been taken up, without any notable results, by A. J. CarIson, whose reputa- tion rests more on his picturesque behavior than on his scientific accomplishments. CarIson's industrious pupil, Andrew C. Ivy, was just beginning his long career. In 1902 William Bayliss ant! Ernest H. Starling had estab- lishec! the fact that a hormone from the upper intestinal mucosa, secretin, could stimulate pancreatic secretion, but no progress had been maple in purifying the hormone or in delineating its role in the course of digestion. Ec~kins had shown, by methods very similar to those of Bayliss ant! Starling, that extracts of the gastric antral mucosa stimulate secretion of acid by the oxyntic mucosa, and he had postu- latec! that his extracts contained a hormone which he called gastrzn. Unfortunately for E6kins, the two subsequent discoveriesthat crude tissue extracts always contain his- tamine ant! that histamine stimulates acid secretion were generally interpreted to mean that E6kins had made a luclicrous mistake. This conclusion, which was to trouble gastroenterology

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ROBERT KHO-SENG LIM 285 for another fifty years, was not accepted by Robert Lim. He repeated E6kins's experiments with no significant improve- ment, and he found that extracts of the pyloric mucosa, but not extracts of other tissues, stimulate acid! secretion. Rec- ognizing that the crucial test of a gastric hormone wouIc! be demonstration of it in gastric venous blooct, Lim unsuccess- fully tried to finct acid-stimulating properties in blooc! drawn from clogs digesting a meal. Lim became interested] in the properties of pyloric secre- tion. With his colleague, N. M. Dott, Lim prepared, in a two-stage operation, a pouch of the gastric antrum devoid of oxyntic mucosa. Dott probably contributed much of the surgical skill, for he published separately on operative tech- niques. The pouch was found to secrete a viscid, alkaline secretion containing a proteolytic enzyme active in acid but not in alkaline solution. A dog with such a pouch was reacly for the next step: the demonstration that stimulation of the pouch causes acid secretion by the remote oxyntic mucosa, but Lim did not do the experiment. In the autumn of 1922, lLim applied to the China Medical Board of New York for a fellowship to enable him to study in European and American universities. His application was im- mediately welcomed by Roger S. Greene, the Board's Secre- tary. Greene knew Lain Boon Keng by reputation, and the day before he received Lim's letter he had been toIcl about Lim by the Chinese Minister to the United States. Greene asked Lim whether, if he received a fellowship, he wouIct be willing to take a year's appointment at the Peking Union Medical College. The Peking Union Medical College had been developed by the China Medical Board with an endowment from the Rockefeller Foundation. In 1915 the Board, with the advice of W. H. Welch and Simon FIexner, tract bought the mis- sionary-foundecI Union Medical College in Peking anct had

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286 BIOGRAPHICAL MEMOIRS begun to build a medical school along Western lines.* 'rhe aims of the school were "to give medical education compara- ble with that provident by the best mectical schools in the United States and Europe, through..."! an undergraduate curriculum and through graduate training in research and practice. Emphasis was always on quality, and pressure from the Chinese government for quantity was firmly resisted. The stated goal of those responsible for the College was to have Western medical science taken over by the Chinese people so that it became part of their national life. The suggestion that Lim consider an appointment at P.U.M.C. was an example of the Boards continued search for competent Orientals. Lim replied that the chief object in his life was to return to China to teach physiology and to clo research there as efficiently as it was being done in the West. However, he cautiously refused to commit himself completely to P.U.M.C. without assurances of an acloquate salary and a senior appointment. Him received the fellowship, and he came to the United States in the autumn of 1924. Although the China Medical Board tract suggested that I,im study in two departments, those of Joseph ErIanger in St. Louis and A. J. CarIson in Chicago, Lim worked only in the Department of Physiology of the University of Chicago. That laboratory was the only one in the country with a current reputation in gastro- intestinal physiology. Most of the work was being clone by a *The administrative history of P.U.M.C. is fully described in M. E. Ferguson, China Medical Board and Peking Union Medical College (New York: China Medical Board of New York, Inc., 1970). The records of the China Medical Board and of P.U.M.C. are now in the Rockefeller Archive Center, North Tarrytown, New York. Copies of letters relating to Lim have been made available to me through the courtesy of the Center's Director and Associate Director, I. W. Ernst and I. W. Hess. The educational and scientific program of P.U.M.C. is described in J. Z. Bowers, Western Medicine in a Chinese Palace (New York: The Josiah Macy, Jr. Foundation, 1972). Bowers is wrong in identifying Lim's first wife as Sharpey-Schafer's daughter. tFerguson, p. 44.

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ROBERT KHO-SENG LIM 287 team uncier A. C. Ivy, and Lim was put to work as a member of the team. Research was on the control of gastrointestinal secretion and motility, and dogs with chronically prepared pouches and fistulas were usecI. In one stucly in which Lim participated, the entire stomach was separated from the esophagus and duodenum, and macle into a pouch draining to the body surface. The vagus nerves hac! been cut, ant! cephalic stimuli could not affect the pouch through them. The pouch's secretion could be collected, and thereby the efficacy of stimuli could be cleterminecI. Because the distal end of the esophagus had been anastomosed to the proximal end of the cluodenum, the clog could eat naturally. With such a preparation, Ivy, Lim and McCarthy found that mixed meals, meat extracts and milk stimulated gastric secretion after a latent period of one or more hours. Fats fee! inhibited basal or continuous secretion. This team, and indeec! all such teams for many years, was dominated by Ivy; Lim, as a visiting fellow, cannot be held responsible for the conclusions of papers bearing his name. He can only be juciged by the use to which he later put what he had Earned in Chicago. The paper just cited lamely con- cludec! that stimulation of gastric secretion by foocI in the intestine must result from some vascular response. More- over, ". . . our work proves that E6kins' pyloric hormone theory is utterly inadequate; that there is either no hormone mechanism, or, if one, that the whole gastro-intestinal tract is involved."* What Lim thought when he eventually saw this paper in print is unknown, but it seems unlikely that he, who tract only recently published several papers of his own af- firming the existence of gastrin, hacl abruptly changed his mincI. * A. C. Ivy, R. K. S. Lim, and J. E. McCarthy, "Contributions to the Physiology of Gastric Secretion. II. Intestinal Phase of Gastric Secretion," Journal of Experimental Physiology, 15(1925):55-68.

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288 BIOGRAPHICAL MEMOIRS Having received a satisfactory appraisal of Lim from A. J. Carison, a recommendation which said that Lim made an excellent impression even on those prejudiced against the Chinese, the China Medical Board recommenclec! that Lim be made an Associate Professor in physiology at P.U.M.C. In the meantime, Lim's father hac! begun to organize the University of Amoy, and he asked his son to build a mectical school from scratch. In contrast with the superb school, hospital, and staff being completecl in Peking, Amoy had no buildings and no faculty, but young Lim conic! have at least the title of Profes- sor. To get him for Peking, the P.U.M.C. made him a Visiting Professor with no increase in salary over that previously offered. In September of 1925 the trustees of the school made him Head of the Department of Physiology. By the time Lim arrived in Peking in 1924, the builclings of P.U.M.C. had been completed. The preclinical and clinical clepartments, a hospital, and faculty residences occupied the site of a Prince's palace. The Prince's name of Wu sounder! much like the Chinese word for oil, anct P.U.M.C. was known to the Chinese as the Oil Prince's Palace. Lim occupied a fully equipped Physiology Department, and during his tenure from 1924 to 1938 he hacl a staff of seven professionals, five of them Oriental. The China Medical Board sent visiting pro- fessors to P.U.M.C., and the list is an honor roll of American meclical science. In ~ 935 both Anton I. Carison ant] Walter B. Cannon were Visiting Professors of Physiology. him establishecl a vigorous research program in collabora- tion with many colleagues and students. He foun~lec! the Chinese Physiological Society, and the Society began publica- tion of the Chinese Journal of Physiology. I.im was managing editor, and he published many papers in the journal. He also organized a Peking branch of the Society for Experimental Biology and Medicine which gave him the opportunity of

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ROBERT KHO-SENG LIM 289 publishing summaries of his work in a journal more easily accessible to Western physiologists. By means of transplanted ant! perfused stomachs, Lim stuclied gastric metabolism and the control of secretion. His most important result was the demonstration that feeding olive oil inhibits secretion by a transplanter! pouch of the stomach. In the process of preparation, the gastric tissue forming the pouch was totally separated from the donor dog, and it was therefore completely extrinsically clenervated. The inhibitory influence of fat feeding must have been carried by the blood, and Lim showed that fat absorbed into the lymph was not responsible. Lim coined the word enterogastrone for the putative hormone, and he shower! that it is probably different from the hormone cholecystokinin which had recently been identiBlecl by Ivy. Lim attempted to purify enterogastrone, but he succeeded no better than many after him. Today, it appears that the inhibitory property of entero- gastrone is only one of the properties of a number of poly- peptides extractable from the intestinal mucosa. Although the hormonal mechanism clescribed by Lim indubitably exists' his name for it is being discarded. Working with pupils ant! colleagues from other depart- ments, Lim clid three other substantial pieces of physiological research at P.U.M.C. He found a presser center in the lateral parts of the floor of the IVth ventricle between the levels of the acoustic strict and the inferior fovea. Stimulation of the center electrically or by iontophoresis of acetylcholine elicits typical and complete sympathetic responses. The efferent pathway goes unilaterally clown the ventrolateral columns of the spinal cord, and through it both sympathetic neurones and the adrenal medulla are excited. Stimulation of the central end of the cut sciatic nerve has its familiar presser effects mediated by the center Lim described. In a thorough

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290 BIOGRAPHICAL MEMOIRS comparative study, Lim demonstrates! that a similar presser response follows stimulation of corresponding parts of the medulla in fish, amphibians, reptiles, birds, and eight species of mammals. Lim's efforts to identify circulating hormones released from the gastrointestinal mucosa made him a master of the techniques of cross circulation and vivi-perfusion. In vivi- perfusion, an organ removed from a donor animal, usually a dog, is perfused by way of the carotid arteries anc! jugular veins of another animal. The perfusing animal is frequently unanesthetized, its vessels being isolated uncler local anes- thetic. Lim used this method to study humoral transmission in the central nervous system. In this case, the organ per- fused was the severed head of a donor dog. Stimulation of the central ens! of the vagus nerves of the perfused heat! is fol- lowed by a small and brief fall in the blooct pressure of the perfusing dog and then by a large and prolonged rise in its blooc! pressure. Lim showed, using standarct pharmacologi- cal and physiological methods, that the response is me(li- ated by acety~choline liberates! by the perfused head. The transient fall in blood pressure is the direct effect of acetyI- choline on the cardiovascular system, and the rise is caused by epinephrine liberatecl from the adrenal medulla under the stimulus of acety~choline. Using the same vivi-perfused preparation, but one in which the life of acety~choline was not prolonge(1 by eserine, Lim found that when afferent fibers of the vagus nerve are stimulated there is also a pressor response, but one which is abolished by extirpation of the donor's pituitary glancI. Fur- thermore, bloocl draining the perfused head also contains an oxytocic and an anticliuretic principle. Lim, returning to his histological methods, found that exhaustion of the reflex is correlate(1 with disappearance of secretory granules from the posterior pituitary gland, and that the reflex returns when

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ROBERT KHO-SENG LIM 297 Corresponding Member, Royal Academy of Sciences, Bologna, 1932 Member, Permanent Commission for Biological Standardization, League of Nations, 1935 Counsellor, Academia Sinica, 1936 Foreign Associate, National Academy of Sciences, Washington, 1942; Member, 1955 Honorary Member, American Gastroenterological Association, 1946 Honorary Fellow, American College of Surgeons, 1947 Member, Permanent Committee of the International Congress of Physiology, 1947 Honorary Member, Association of Military Surgeons of the United States, 1948 American Society for Pharmacology and Experimental Therapeu- tics, 1952 Society of Toxicology, 1963 Fellow, American College of Clinical Pharmacology and Chemo- therapy, 1964 MILITARY RECORD Warrant Of firer, Indian Army, 1914- 1916 Lieutenant, RAMC,1919 Field Director, Chinese Red Cross Medical Relief Commission, North China, 1933 Director, Chinese Red Cross Medical Relief Corps, 1937-1943 Inspector General of Medical Service, Chinese Army, 1942,1944 Deputy Surgeon General, Chinese Army, 1944~1945 Surgeon General and Lieutenant General, Chinese Army, 1945- 1949 D E C O. RA T. I O N S Great Britain: 1914-1915 Star; General Service Medal, Victory Medal, 1918 United States: Legion of Merit, Officer Grade, 1943; Medal of Freedom with Silver Palms, 1946 Republic of China: Kan Ching Medal; Chung Ching Medal; Sheng Li Medal; Yun Hui Order, 1st Class; Victory Medal, 1945

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298 BIOGRAPHICAL MEMOIRS BIBLIOGRAPHY 1918 Period of survival of the shore-crab (Carcinus maenas) in distilled water. Proc. R. Soc. Edinburgh, 38:1~22 Experiments on the respiratory mechanism of the shore-crab. Proc. R. Soc. Edinburgh, 38:48-56. 1919 With E. Sharpey-Schafer. The effects of adrenaline on the pulmo- nary circulation. Q. j. Exp. Physiol., 12: 157-97. Staining methods with alcoholic eosin and methylene blue. Q. 3. Microsc. Sci., 63:541~4. 1920 A parasitic spiral organism in the stomach of the cat. Parasitology, 12: 108-12. The histology of tadpoles fed with thyroid. Q. j. Exp. Physiol., 12:30~16. 1922 With B. B. Sarkar and I. P. H. Graham Brown. Effect of thyroid feeding on bone marrow of rabbits. I. Pathol. Bacteriol. 25:228~6. The gastric mucosa. Q.~. Microsc. Sci., 66:187-212. 1923 With S. E. Ammon. The "gastrin" content of the human pyloric mucous membrane. Brit. J. Exp. Pathol., 4:27-29. With N. M. Dott. Observations on the isolated pyloric segment and on its secretion. Q. 5. Exp. Physiol., 13: 159-75. With A. R. Matheson and W. Schlapp. A new gastro-duodenal technique. Edinburgh Med. I., 30:265-75. A method for recording gastric secretion in acute experiments on normal animals. Q. 3. Exp. Physiol., 13:71-78. The question of a gastric hormone. Q. 3. Exp. Physiol., 13:7~103. With S. E. Ammon. The effect of portal and jugular injections of pyloric extracts on gastric secretion. Q. j. Exp. Physiol., 13:115-29.

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ROBERT KHO-SENG LIM 299 The source of the proteolytic enzyme in extracts of the pyloric mucous membrane. Q. 3. Exp. Physiol., 13: 139 44. With A. R. Matheson and W. Schlapp. An improved method for investigating the secretory function of the stomach and duode- num in the human subject. Q. j. Exp. Physiol., 13:33~5. With A. R. Matheson and W. Schlapp. Observations on the human gastro-duodenal secretions with special reference to the action of histamine. Q. j. Exp. Physiol., 13:361-91. With W. Schlapp. The effect of histamine, gastrin and secretin on the gastro-duodenal secretions in animals. Q. j. Exp. Physiol., 13:393-404. 1924 On the relationship between the gastric acid response and basal secretion of the stomach. Am. I. Physiol., 69:31~33. 1925 With A. C. Ivy and I. E. McCarthy. Contributions to the physiology of gastric secretion. III. An attempt to prove that a humoral mechanism is concerned in gastric secretion by blood transfu- sion and cross-circulation. Am. l. Physiol., 74:606-38. With A. C. Ivy and J. E. McCarthy. Contributions to the physiology of gastric secretion. I. Gastric secretion by local (mechanical and chemical) stimulation. Q. l. Exp. Physiol., 15:13-53. With A. C. Ivy and J. E. McCarthy. Contributions to the physiology of gastric secretion. II. The intestinal phase of gastric secretion. Q. J. Exp. Physiol., 15:55-68. 1926 With T. G. Ni. Changes in the blood constituents accompanying gastric secretion. I. Chloride. Am. l. Physiol., 75:475-86. With W. C. Ma. Mitochondrial changes in the cells of the gastric glands in relation to activity. Q. J. Exp. Physiol., 16:87-110. With C. Chao. Observations on the "reversed" uterine horn of the rabbit. Proc. Soc. Exp. Biol. Med., 23:66~69. With H. Necheles. Demonstration of a gastric excitant in circulating blood by vivi-dialysis. Proc. Soc. Exp. Biol. Med., 24: 197-98.

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300 BIOGRAPHICAL MEMOIRS 1927 A method of vessel-anastomosis for vivi-perfusion, cross circulation and transplantation. Chin. I. Physiol., 1:37-50. With C. T. Loo and A. C. Liu. Observations on the secretion of the transplanted stomach. Chin. if. Physiol., 1:51-62. With C. Chao. On the mechanism of the transportation of ova. I. Rabbit uterus. Chin. I. Physiol., 1:17~98. With H. Necheles and H. C. Hou. The influence of meals on the acutely denervated (vivi-perfused) stomach. Chin. I. Physiol., 1 :26~70. With W. C. Ma and A. C. Liu. Changes in the Golgi apparatus of the gastric gland cells in relation to activity. Chin. J. Physiol., 1 :30~30. With T. C. Shen and C. L. Hou. Observations on the conduction of the nerve impulse in the cooled phrenic nerve. Chin. I. Physiol., 1 :367-89. 1928 With T. G. Ni. The gas and sugar metabolism of the vivi-perfused stomach. Chin. I. Physiol., 2:4~86. With C. T. Loo and H. C. Chang. The basal secretion of the stomach. I. The influence of residues in the small and large intestine. Chin. I. Physiol., 2:259~78. With C. L. Hou and T. G. Ni. The chloride metabolism of the vivi-perfused stomach. Chin. I. Physiol., 2:29~304. With S. M. Ling and A. C. Liu. The lipid metabolism of the stomach and its relation to the mitochondria-Golgi complex. Chin. J. Physiol., 2:305-28. With Y. P. Kuo. On the mechanism of the transportation of ova. II. Rabbit and pig oviduct. Chin. J. Physiol., 2:38~98. With H. Necheles. Isolation of the gastric and pancreatic secretory excitants from the circulation by vivi-dialysis. Chin. I. Physiol., 2:415-34. 1929 With H. C. Hou. The basal secretion of the stomach. II. The influ- ence of nerves and the question of secretory "tone" and reac- tivity. Chin. J. Physiol., 3:41-56. With T. G. Ni, H. Necheles, and H. C. Chang. The carbohydrate

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ROBERT KHO-SENG LIM 301 metabolism of the normal, phlorizinized and diabetic vivi- perfused stomach. Chin. }. Physiol., 3:123-56. With T. P. Feng and H. C. Hou. On the mechanism of inhibition of gastric secretion by fat. Chin. I. Physiol., 3:371-80. With H. C. Hou. Factors regulating splenic contraction during exercise. Lingnan Sci. J., 8:301-27. With H. C. Hou. Influence of mechanical factors on "basal" gastric secretion. Proc. Soc. Exp. Biol. Med., 26:27~71. With H. C. Chang. Behaviour of denervated spleen in adrenal- ectomized animal. Proc. Soc. Exp. Biol. Med., 26:271-72. 1930 With H. C. Hou, H. C. Chang, and T. P. Feng. The basal secretion of the stomach. III. The influence of feeding bone and other hard objects. Chin. I. Physiol., 4: 1-20. With T. Kosaka. On the mechanism of the inhibition of gastric secretion by fat. The role of bile and cystokinin. Chin. I. Physiol., 4:213-20. With T. Kosaka. Demonstration of the humoral agent in fat inhibi- tion of gastric secretion. Proc. Soc. Exp. Biol. Med., 27:89~91. 1931 With F. Y. Hsu. The depressor or vasostatic reflex. Chin. I. Physiol., 5:29-52. With T. C. Shen, T. G. Ni, and C. T. Loo. The gas metabolism of the mechanically perfused stomach. Chin. l. Physiol.,5: 103-41. With H. C. Chang. The basal secretion of the stomach. IV. The influence of mechanical irritation of the pyloric region. Chin. J. Physiol., 5:233-50. 1932 With T. Kosaka, S. M. Ling, and A. C. Liu. On the mechanism of the inhibition of gastric secretion by fat. A gastric-inhibitory agent obtained from the intestinal mucosa. Chin. I. Physiol., 6:107-28. 1933 With T. Kosaka. On the mechanism of the inhibition of gastric motility by fat. An inhibitory agent from the intestinal mucosa. Chin. J. Physiol., 7:5-12.

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302 BIOGRAPHICAL MEMOIRS Observations on the mechanism of the inhibition of gastric function by fat. Q. l. Exp. Physiol., 23:263-68. 1934 With A. C. Liu and l. C. Yuan. Quantitative relationships between the oxyntic and other gastric component secretions. Chin. I. Physiol., 8:1-36. With S. M. Ling and A. C. Liu. Depressor substances in extracts of the intestinal mucosa. Purification of enterogastrone. Chin. }. Physiol., 8:219-36. 1935 With H. C. Chang, T. P. Feng, S. M. Ling, A. C. Liu, T. C. Loo, and T. C. Shen. Outline of Physiology. Peking: P.U.M.C. Publications. 1936 With H. C. Chang. A simple method of mechanically stimulating the carotid sinus receptors. Chin. I. Physiol., 10:29-32. With T. H. Sub and C. H. Wang. The effect of intracisternal appli- cations of acetylcholine and the localization of the presser centre. Chin. I. Physiol., 10:61-78. With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a myelencephalic sympathetic centre. I. The effect of stimulation of the presser area on visceral function. Chin. l. Physiol., 10:445-70. With S. M. Ling, A. C. Liu, and I. C. Yuan. Quantitative relation- ships between the basic and other components of pancreatic secretion. Chin. I. Physiol., 10:475-92. 1937 With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a myelencephalic sympathetic centre. II. Experimental evidence for a reflex sympathetic centre in the medulla. Chin. }. Physiol., 11 :355-66. With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a myelencephalic sympathetic centre. III. Experimental localiza- tion of the centre. Chin. J. Physiol., 11:367-84. With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a myelencephalic sympathetic centre. IV. Experimental localiza- tion of its descending pathway. Chin. J. Physiol., 11:385-408.

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ROBERT KHO-SENG LIM 303 With H. C. Chang, K. F. Chia, and C. H. Hsu. Humoral transmis- sion of nerve impulses at central synapses. I. Sinus and vagus afferent nerves. Chin. l. Physiol., 12: 1-36. With Y. M. Lu. On the question of a myelencephalic sympathetic centre. V. Comparative study of location of myelencephalic presser (sympathetic?) centre in vertebrates. Chin. J. Physiol., 12: 197-222. With H. C. Chang, K. F. Chia, and C. H. Hsu. A vagus-post- pituitary reflex. I. Pressor component. Chin. I. Physiol., 12: 309-26. 1938 With H. C. Chang, K. E. Chia, and C. H. Hsu. Humoral transmis- sion of nerve impulses at central synapses. II. Central vagus transmission after hypophysectomy in the dog. Chin. J. Physiol., 13: 13-32. With H. C. Chang and Y. M. Lu. Humoral transmission of nerve impulses at central synapses. III. Central vagus transmission after hypophysectomy in the cat. Chin. I. Physiol., 13:3~48. With M. P. Chen, S. C. Wang, and C. L. Yi. On the question of a myelencephalic sympathetic centre. VI. Syndrome of lesions of the myelencephalo-spinal sympathetic neurons. Chin. I. Phys- iol., 13:49~60. With S. C. Wang and C. L. Yi. On the question of a myelencephalic sympathetic centre. VII. The depressor area a sympatho- inhibitory centre. Chin. J. Physiol., 13:61-78. With H. C. Chang, W. M. Hsieh, and T. H. Li. Humoral transmis- sion of nerve impulses at central synapses. IV. Liberation of acetylcholine into the cerebrospinal fluid by afferent vague. Chin. J. Physiol., 13: 153-66. With H. C. Chang, Y. M. Lu, C. C. Wang, and K. G. Wang. A vague-post-pituitary reflex. III. Oxytocic component. Chin. I. Physiol., 13:269-84. 1939 With H. C. Chang, J. J. Huang, and K. J. Wang. A vagus-post- pituitary reflex. VI. Phenomena of exhaustion and recupera- tion. Chin. J. Physiol., 14:1-8. With H. C. Chang, W. M. Hsieh, and T. H. Li. Studies on tissue

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304 BIOGRAPHICAL MEMOIRS acetylcholine. VI. The liberation of acetylcholine from nerve trunks during stimulation. Chin. I. Physiol., 14:19~26. With H. C. Chang, W. M. Hsieh, L. Y. Lee, and T. H. Li. Studies on tissue acetylcholine. VII. Acetylcholine content of various nerve trunks and its synthesis in vitro. Chin. }. Physiol., 14:27-38. With H. C. Chang, K. F. Chia, and J. J. Huang. A vagus-post- pituitary reflex. VIII. Anti-diuretic effect. Chin. I. Physiol., 14: 161-74. 1956 With M. H. Pindell, H. G. Glass, and K. Rink. The experimental evaluation of sedative agents in animals. Ann. N. Y. Acad. Sci., 64:667-78. 1958 With O. E. Fancher. The sedative and contrasedative activity of the two geometric isomers of 2-ethylcrotonylurea. Arch. Int. Pharmacodyn. Ther., 115:418-25. 1960 With M. N. Carroll. Observations on the neuropharmacology of morphine and morphinelike analgesia. Arch. Int. Pharmaco- dyn. Ther., 125:383-403. Visceral receptors and visceral pain. Ann. N. Y. Acad. Sci., 86:73-89. With C. N. Liu and R. L. Moffitt.A StereotaxicAtlas of the Dog's Brain. Springfield, Ill.: Charles C Thomas. 1961 With K. G. Rink, H. G. Glass, and E. Soaje-Echague. The evaluation of cumulation and tolerance by the determination of A-ED50s and C-ED50s. Arch. Int. Pharmacodyn. Ther., 130:336-53. 1962 With F. Guzman and C. Braun. Visceral pain and pseudoaffective response to intra-arterial injection of bradykinin and other algesic agents. Arch. Int. Pharmacodyn. Ther., 136:353-84. With Soaje-Echague. Anticonvulsant activity of some carbinylureas. J. Pharmacol. Exp. Ther., 138:224-28.

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ROBERT KHO-SENG LIM 305 With C. N. Liu, F. Guzman, and C. Braun. The visceral receptors concerned in visceral pain and the pseudoaffective response to intra-arterial injection of bradykinin and other algesic agents. I. Comp. Neurol., 1 18:269~93. With G. D. Potter and F. Guzman. Visceral pain evoked by intra- arterial injection of Substance P. Nature, 193:983-84. 1964 With F. Guzman, C. Braun, G. D. Potter, and D. W. Rodgers. Narcotic and non-narcotic analgesics which block visceral pain evoked by intra-arterial injection of bradykinin and other algesic agents. Arch. Int. Pharmacodyn. Ther., 149:571-88. With F. Guzman, D. W. Rodgers, K. Goto, C. Braun, G. D. Dickerson, and R. I. Engle. Site of action of narcotic and non- narcotic analgesics determined by blocking bradykinin-evoked visceral pain. Arch. Int. Pharmacodyn. Ther., 152:25-58. Animal techniques for evaluating hypnotics. In: Animal and Clinical Pharmacologic Techniques in Drug Evaluation, ed. J. H. Nodine and P. E. Siegler, vol. 1, pp. 291-97. Chicago: Year Book Medical Publishers. 1965 With G. D. Dickerson, R. i. Engle, F. Guzman, and D. W. Rodgers. The intraperitoneal bradykinin-evoked pain test for analgesia. Life Sci., 4: 2063-69. 1966 A revised concept of the mechanism of analgesia and pain. In: Pain, ed. R. S. Knighton and P. R. Dumke, pp. 117-54. Boston: Little, Brown. Salicylate analgesia. In: The Salicylates, ed. M. l. H. Smith and P. K. Smith, pp. 155-202. New York: Interscience Publishers, Wiley. 1967 With D. G. Miller, F. Guzman, D. W. Rodgers, R. W. Rodgers, S. K. Wang, P. W. Chao, and T. W. Shih. Pain and analgesia eval- uated by the intraperitoneal bradykinin-evoked pain method in man. Clin. Pharmacol. then, 8:521~2. Pain mechanisms. Anesthesiology, 28:106-10.

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306 BIOGRAPHICAL MEMOIRS 1968 With F. Guzman. Manifestations of pain in algesia evaluation in animals and man. In: Pain, ed. A. Soulairac, }. Cahn, and I. Charpentier, pp. 119~52. London: Academic Press. 1969 With G. Krauthamer, F. Guzman, and R. R. Fulp. Central nervous system activity associated with the pain evoked by bradykinin and its alteration by morphine and aspirin. Proc. Natl. Acad. Sci. USA, 63 :70~12. 1970 Pain. Annul Rev. Physiol., 32:269-88.

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