Biomedical subjects
Publications and source records attributed to K J Ho.
A forty-one year old man with a three year history of malignant hypertension developed massive rectal bleeding. A mesenteric arteriogram showed vascular changes compatible with necrotizing angitis. Histologic examination of the resected right hemicolon confirmed malignant hypertension as the cause of angitis.
Compartmental analysis of the disappearance curve of serum cholesterol specific activity after an intravenous administration of a tracer does of cholesterol-4-14C was carried out in five patients with resection of the distal small intestine, cecum, and proximal colon. The data fit best a two compartment model in all five cases with the rapidly exchangeable pool of 16.6+/-3.2 g (mean +/- SD, 60% of the mean of 15 normal subjects) and the slowly exchangeable pool of 31.5 +/- 10.9 g (65%). The reduction of the pool sizes was associated with a shorter mean transit time of cholesterol, 22.15 +/- 8.07 days (40%) and increased turnover rate, 2.42 +/- 0.72g/ day (172%). Direct fecal analysis for the neutral sterols and bile acids derived from the exchangeable pool confirmed the turnover rate obtained from the compartmental analysis. The increased fecal excretion was mainly in the bile acid fraction. The study suggests that the ileal and proximal colon resection results in bile acid malabsorption which, in turn, increases hepatic cholesterol and bile acid synthesis. The synthetic rates, however, could not compensate totally for the excretory rate. Therefore, the pool size decreased to a new low steady state of equilibrium.
The serum cholesterol level in man is predominantly dependent on the rate of endogenous synthesis. The liver is the main site of cholesterol synthesis and this activity is in turn intimately related to the ingestion of food. When no food is present in the intestine, as during periods of total parenteral nutrition, both normal individuals and patients with familiar hypercholesterolemia show a pronounced lowering of their serum cholesterol. The establishment of a portacaval shunt makes this a permanent change. This and other evidence lead us to postulate the existence of an intestinal factor capable of stimulating hepatic cholesterogenesis. The function of this factor would be to increase the synthesis of chol
A 36-year-old white man with gastric cancer manifested his disease clinically by respiratory distress and roentgenographically by Kerley's B lines. The pathogenesis of these lines and the importance of their recognition are emphasized.
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A total of 194 gallbladder biles from various ethnic groups were analyzed for their composition. The solubility of cholesterol in bile was determined mainly by its relative amounts of phospholipid and bile salt present. Bile from patients with gallstones was usually supersaturated with cholesterol above the boundary of the metastable state. Biles from normal white subjects of Finland, New Zealand, and the United States were already in the metastable state of supersaturation with cholesterol. The Masai of East Africa and black subjects of the Unites States had a bile level below the limit of maximum cholesterol solubility. This study indicates that the difference in the prevalence of cholesterol cholelithiasis in various ethnic groups was related to the difference in their bile compontified factors.
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A patient is described who developed the full-blown picture of hemochromatosis 24 months after a side-to-side portacaval shunt. No clear-cut explanation for this rapid development of hemochromatosis is apparent and a possible mechanism for this phenomenon is discussed.
Cholesterol contents of 16 different tissues were determined in 12 normal roosters, 12 roosters with diet-induced, exogenous hypercholesteremia, 10 actively laying hens with minimal endogenous hypercholesteremia, and 12 nonlaying hens with hereditable extreme hyperlipidemia. The tissue cholesterol contents of the normal roosters were strikingly similar to that of the corresponding tissues of the mammals except for a low cholesterol content of the brain in chickens. The hypercholesteremia in the roosters fed a 2% cholesterol diet for 2 months was associated with an increase of cholesterol content in all tissues except the brain, muscle, and adipose tissue. The actively laying hens, on the other hand, had a decreased cholesterol content in most tissues, despite the persistence of a minimal hypercholesteremia for 18 months and significant aortic cholesterol accumulation with mild atherosclerosis. The nonlaying hens developed extreme hypercholesteremia and severe atherosclerosis but only a moderately expanded cholesterol pool in most tissues. The results indicated a remarkable difference in tissue response to diet-induced exogenous hypercholesteremia and endogenous hyperlipidemia associated with laying activity in chickens and the propensity of their aortas to accumulate excessive cholesterol in the presence of either endogenous or exogenous hyperlipidemia.
The gallbaldder or hepatic bile from six species of animals had a uniformly low cholesterol content far below its maximum solubility. Cholesterol feeding for more than 1 month had little effect on the biliary composition in chickens, rabbits, and rats, but selectively doubled the absolute and relative concentration of cholesterol in the biles of hamsters, and increased the cholesterol concentration to a level of its maximum solubility in gallbladder bile of ground squirrels and hepatic bile of prairie dogs. The gallbladder bile of prairie dogs reached the boundary of metastable supersaturation of cholesterol and subsequently developed cholesterol crystals and gallstones. A circadian change of the relative concentration of bile acid, cholesterol, and phospholipid in the hepatic bile of the rats with chronic biliary drainage was also observed as a consequence of cholesterol feeding.
The bile acid pool was first determined in six adult male rats to be 12.8 +/- 0.7 mg/100 g by comparing the total radioactivity of tritiated bile acid drained through the bile fistula and the initial bile acid specific activity. The distribution of bile acids in the enterohepatic circulatory system at various times of the day was then studied in 24 additional rats, each received a single dose of tritiated taurocholate intraperitoneally and was sacrificed 24 h later. The nearly complete recovery of the administered radioactivity from the serum, liver intestinal wall and content, and 24-h feces indicated the confinement of bile acids to the enterohepatic circulation. A remarkable circadian fluctuation of the bile acid content was observed in serum, liver, and intestinal contents. The patterns of such rhythmic change varied from each other in various segments of the intestinal tract but seemed to correlate with the time sequence of movement of bowel content and absorption of bile acids. The circadian rhythm of hepatic synthesis of bile acids but not cholesterol observed by others might be, in part, directly related to the circadian fluctuation of the amount of bile acids in the liver.
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A 69-year-old white male with autoimmune hyperlipidemia for 19 years characterized by high serum levels (1,5000 to 3,400 mg. per deciliter) of IgA firmly bound to very-low- and low-density lipoproteins (serum total cholesterol 852 +/- 51 mg./dl., free cholesterol 340 +/- 52, triglyceride 1638 +/- 411, phospholipid 934 +/- 84) received intravenously a tracer dose of cholesterol-4-14C. Serum cholesterol specific activity was followed for 337 days and analyzed by two methods: (1) compartmental analysis which revealed the best fit of a two-compartment model with rapidly exchangeable pool 710 gm. (2,563 per cent of the mean of 15 normal subjects), slowly exchangeable pool 317 gm. (651 per cent), mean transit time 92.5 days (167 per cent), turnover rate 9.23 gm. per day (654 per cent), and excretory coefficient 0.013 (25 per cent); (2) a simulated five-compartment model involving serum free, esterified, red blood cell, and rapidly and slowly exchangeable tissue cholesterols for which pool sizes of 17, 25, 2.4, 674, and 350 gm., respectively, were calculated and a turnover rate of 9.44 gm./day agreed well with that of the two-compartment model. The extreme hyperlipoproteinemia and expanded body cholesterol pools were primarily due to the impairment of feedback control of cholesterol synthesis as a consequence of the complexing of lipoprotein and IgA.
The distribution of bile acid in the enterohepatic circulatory system at different times of the day was determined in 48 hamsters exposed to a rigid light schedule (6 AM to 6 PM) and fed, ad libitum, for 4 weeks. In each portion of the enterohepatic circulatory system, the relative amount of bile acid was determined 24 hours after an intraperitoneal administration of [3H]taurocholic acid by comparing the radioactivity recovered from that portion with the total radioactivity remaining in the entire system. A circadian fluctuation of the relative bile acid content (percent of total) was observed in serum, liver, gallbladder, and intestinal contents. The patterns of such rhythmic change varied in various segments of the intestinal tract but correlated well with the time sequence of the movement of bowel content. Rhythms in the serum and liver were intimately related to the intestinal absorption of bile acid. Due to its small capacity, the gallbladder played only a minor role in the regulation of such a rhythm.
Rats with chronic biliary drainage under a rigid lighting schedule (light on at 6 A.M. and off at 6 P.M.) exhibited a remarkable circadian rhythm of bile flow, biliary concentrations and excretory rates of bile salts, cholesterol, and phospholipid. The peak was attained at midnight and nadir at noon except for the peak concentrations of cholesterol and phospholipid occurring at 8 P.M. Cholesterol feeding abolished the circadian rhythm of biliary cholesterol and phospholipid concentrations but not their excretory rates because the daily fluctuation of the bile flow remained unchanged. Bilateral vagotomy enhanced the bile flow rate and shifted the peak of circadian rhythm of all parameters except bile salt 4 h earlier. Bilateral adrenalectomy abolished the circadian variation of the concentration of cholesterol and phospholipid and minimized that of bile salt, but the daily fluctuation of their excretory rates persisted in a lower amplitude. The studies suggested that such circadian rhythm might be controlled simultaneously by multiple factors and could not be entirely abolished by any single special treatment.