Search PubMed⌕ Search

Biomedical subjects

B M Wolfe

Publications and source records attributed to B M Wolfe.

At least 91 records · Page 5Linked to original sources
PubMed1989

Accumulation of an apoE-poor subfraction of very low density lipoprotein in hypertriglyceridemic men.

Studies were undertaken to investigate the mechanism of the marked accumulation of an apoE-poor very low density lipoprotein (VLDL) subfraction in untreated Type IV and IIb hypertriglyceridemic subjects. Heparin-Sepharose chromatography was used to separate large VLDL (Sf 60-400) from fasted subjects, into an apoE-poor, unbound fraction and an apoE-rich, bound fraction. As a percent of total VLDL protein, the apoE-poor fraction comprised 40 +/- 4% of total VLDL in hypertriglyceridemic subjects versus 25% in normal subjects. Compared to the apoE-rich, bound fraction, this apoE-poor material was found to have a 5-fold lower ratio of apoE to apoC (0.20 +/- 0.06 vs 0.91 +/- 0.18, P less than 0.005), but a 1.5-fold higher ratio of triglyceride to protein (11.41 +/- 0.85 vs 7.97 +/- 0.77, P less than 0.01). In addition, the apoE-poor fraction was found to be enriched 2-fold in apoB-48 (10.30 +/- 2.41% vs 5.73 +/- 1.59% of total apoB, P less than 0.005) compared to the apoE-rich fraction, suggesting that the apoE-poor fraction contains more chylomicron remnants. The amount of this apoE-poor VLDL was markedly reduced following a reduction in VLDL triglyceride levels (a decrease from 40 +/- 4% to 21 +/- 2% of VLDL protein following a 50% reduction in VLDL triglyceride levels). The large VLDL from Type I, III, and V hyperlipoproteinemic subjects subfractionated using heparin-Sepharose showed an equal distribution of apoE between the two fractions in contrast with the Type IV and IIb subjects. The separation of VLDL from Type I, III, and V subjects using heparin-Sepharose involves a mechanism other than apoE binding. Separation in the latter likely results from apoB-100 binding to heparin, as opposed to apoE binding of VLDL from Type IV and IIb subjects.

Apolipoproteins E↗
PubMed1988

Effect of total parenteral nutrition on hepatic histology.

We evaluated the effect of total parenteral nutrition (TPN) on abnormalities of hepatic histology. Liver biopsies of 93 patients who were concurrently receiving TPN were compared with a control group of 35 patients. The control patients were matched for extent of preexisting liver disease and degree of illness. The liver biopsy specimens were blindly graded on 19 histopathologic findings, including fatty change, portal inflammation, and cholestasis. Twenty-seven clinical variables, such as preexisting liver disease, the presence or absence of sepsis or shock, and number of days receiving TPN before biopsy, were recorded. Individual and partial correlations were established between the clinical variables and histopathologic findings. The control and TPN groups proved to have been closely matched regarding the extent of risk factors for hepatic histopathologic features. Positive correlations were repeatedly found between abnormal hepatic histologic features and preexisting liver disease, abdominal sepsis, renal failure, and blood transfusion but not with the administration of TPN. We conclude that clinical phenomena, such as existing liver disease, renal failure, and abdominal sepsis, rather than administration of TPN, had a predominant effect on histopathologic features in this group of patients.

Humans↗
PubMed1988

Effect of elevated free fatty acids on glucose oxidation in normal humans.

In vitro studies indicating an inverse relationship between free fatty acid (FFA) availability and glucose oxidation led to proposal of the glucose-fatty acid cycle. In vivo studies have yielded conflicting results regarding the effect of FFA on glucose oxidation. In the present study the effect of FFA on glucose oxidation was determined in six normal volunteer subjects. The rate of glucose uptake was fixed by using a constant glucose infusion to suppress endogenous glucose production. Glucose was infused continuously overnight and during the four hour study at 8 mg/kg X min to ensure use of glucose as an energy substrate by virtually all tissues. Following a two-hour baseline glucose infusion, infusion of 20% IV fat emulsion at 1.0 mL/min plus heparin was added to the constant glucose infusion for two additional hours. Total carbohydrate oxidation was determined by indirect calorimetry, and the direct oxidation of the infused (plasma) glucose was measured by the use of U-13C-glucose. Glycogen oxidation was calculated as the difference between total carbohydrate oxidation and the oxidation of plasma glucose. Glucose uptake was calculated from the infusion rate, corrected for any changes in plasma and/or urine glucose concentration. Glucose uptake closely approximated the rate of IV glucose infusion and was unchanged by fat infusion. The percent of CO2 production from U-13C-glucose oxidation (74.5 +/- 12.3, mean +/- SD) was not affected by FFA, nor was the percent of glucose uptake oxidized (37.5 +/- 4.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Neurotoxicity of amphotericin B methyl ester in dogs.

Clinical and neuropathologic effects of chronically administered intravenous (iv) amphotericin B methyl ester (AME) were observed in 3 male dogs (2 German shorthaired pointers and 1 pit bull). Each dog received 6.2-7.3 g of AME (299-327 mg/kg body weight) over a period of 11-12 weeks. One dog developed neurologic signs of severe diffuse brain dysfunction and at necropsy all 3 dogs had a marked leukoencephalopathy, most severe in centrum ovale and subcortical white matter of frontal lobes. Brain histopathology included diffuse myelin loss, oligodendrocyte depletion, accumulation of macrophages filled with sudanophilic lipid, fibrillary astrogliosis, and swelling or fragmentation of many axons. Two control dogs administered iv glucose showed no neuropathologic abnormalities. These findings closely resemble the clinical and neuropathologic abnormalities that developed in patients during the first human trial of AME for treatment of fungal infections, but differ from those of animal studies that did not closely simulate the long-term drug administration required for antifungal therapy in humans. It was concluded that before human clinical trial is authorized, experimental protocols for animal studies of drug toxicity should reflect the anticipated human use of the drug, both in dose and duration.

Amphotericin B↗
PubMed1987

Substitution of mixed amino acids resembling soy protein for mixed amino acids resembling casein in the diet reduces plasma cholesterol in slowly, but not rapidly fed nor fasted baboons.

Studies of cholesterol and triglyceride metabolism were conducted under steady-state conditions in conscious restrained female baboons to ascertain whether the cholesterol- and triglyceride-lowering effects of soy protein v casein in nonrodents can be explained by differences in amino acid composition between the two proteins and whether the lipid-lowering effects of soy protein are influenced by fasting or the rate of feeding, ie, the nutritional state. The metabolic changes underlying the changes in serum cholesterol and triglyceride concentration were also investigated. Isocaloric diets consisting of 45% mixed amino acids (soy or casein type), 50% glucose and 5% corn oil, including all nutritional requirements, were infused intraduodenally for five days. There were no differences in lipid levels between the soy and casein diets in fasting baboons (days 4 or 5) or when the daily diet (calculated to equal 24 hours of energy utilization) was given rapidly by constant intraduodenal infusion over seven hours (day 4). During rapid feeding there was, unexpectedly, no significant change in plasma cholesterol concentration, but the estimated rate of cholesterol oxidation to bile acids fell significantly by 38 +/- 6% (from 39 +/- 4 to 24 +/- 3 mg/d). Significant differences between the soy and casein diets were observed only in the fed state produced by the slow constant isocaloric intraduodenal infusions of the diets [5.8 mg mixed amino acids (soy or casein type) plus 7.2 mg glucose/min/kg body wt0.75] on day 5. These diets were calculated to equal the simultaneous rate of energy utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1987

Effects of cyclosporine in recent-onset juvenile type 1 diabetes: impact of age and duration of disease.

Administration of cyclosporine resulted in reduced insulin requirements and improved glycemic control in patients with insulin-dependent diabetes mellitus of recent onset, but the drug was less effective in young children. Renal toxic effects and other problems related to therapy resolved after discontinuation of the drug. Sustained remission seemed dependent on continued administration of cyclosporine. Although short-term control of diabetes may be achieved in some patients, more studies are needed to determine whether cyclosporine can be given safely as maintenance therapy to maintain glycemic control and prevent the long-term consequences of the disease.

Adolescent↗
PubMed1986

Complications of parenteral nutrition.

All hospitalized patients except infants (a total of 1,647 patients) who received central venous TPN solutions at UCDMC from 1981 through 1985 were studied to determine the incidence of complications from the use of TPN. A complication was considered to have occurred if the patient experienced obvious morbidity, mortality, or both; an event known to be deleterious, despite a lack of demonstrable morbidity; or premature loss of the central venous catheter. Complications related to catheter placement occurred in 5.7 percent of patients, sepsis in 6.5 percent, mechanical complications in 9 percent, and metabolic complications in 7.7 percent. The incidence of induction of sepsis increased during 1984 to 1985 due to the introduction of multilumen central venous catheters. The most frequent catheter placement complications were hemorrhage and pneumothorax. Major venous thrombosis and nursing mishaps were the most common mechanical complications. Metabolic complications were infrequent and were generally not severe after adjustment of the protocol in late 1981. Four patients (0.2 percent) died from TPN-associated complications: a child on home TPN who underwent a catheter change and in whom hyperosmolar hyperglycemic coma developed, a patient with end-stage chronic obstructive pulmonary disease in whom tension pneumothorax occurred, a patient who died from complications of subclavian artery laceration, and a patient who died from Candida septicemia. Complications of TPN are frequent and may be severe. Quality assurance mechanisms for identification of these complications are necessary and should form the basis for the establishment of appropriate protocols.

Acidosis↗
PubMed1986

Clinical studies of intestinal folate conjugases.

Clinical differences between the two human intestinal mucosal folate conjugases were assessed by measurement of their activities in normal individuals and in patients with chronic diarrhea of differing causes. Intracellular folate conjugase (ICFC) was 15-fold more active than brush border folate conjugase (BBFC) in jejunal mucosa from seven obese patients undergoing elective gastric bypass surgery. The activity of ICFC was similar among normal volunteers and patients with diarrhea of unknown origin (DUO), gluten-sensitive enteropathy (GSE), inflammatory bowel disease (IBD), and the short bowel syndrome (IBD-SBS). By contrast, BBFC, sucrase, and lactase were decreased significantly in GSE, and BBFC was increased in IBD-SBS. The activity of BBFC correlated with lactase and with sucrase in the normal subjects and in patients with DUO, whereas no correlations were found with the activity of ICFC in any group. Our clinical studies confirm that ICFC and BBFC are different enzymes. ICFC is not affected by intestinal disease, whereas the activity of jejunal BBFC, like that of other brush border enzymes, is decreased by mucosal injury and is also capable of adapting to distal small intestinal disease or surgical resection.

Adult↗
PubMed1986

Divergent effects of d-norgestrel on the metabolism of rat very low density and low density apolipoprotein B.

Rats treated with the contraceptive steroid d-norgestrel have lower plasma very low density lipoprotein (VLDL)-triglycerides and higher low density lipoprotein (LDL)-cholesterol than controls. To explain these results, the kinetics of VLDL and LDL turnover were studied by injecting 125I-labeled rat-VLDL and 131I-labeled rat-LDL simultaneously into rats treated with a small dose of d-norgestrel (4 micrograms per day per kg body weight0.75 for 18 days, n = 22) and their untreated controls (n = 22). VLDL- and LDL-apoB specific activity-time curves obtained over 50 hr best conformed to a three-pool model. VLDL-apoB clearance expressed as irreversible catabolic rate (k01) was markedly enhanced in the treated versus control rats (0.57 vs. 0.34 pools hr-1), leading to a marked reduction in VLDL-apoB pool size (270 vs. 420 micrograms). However, VLDL-apoB production rates were similar in the two groups (160 vs. 140 micrograms/hr, respectively). The 125I-labeled apoB specific activity-time curve derived from the catabolism of 125I-labeled VLDL-apoB also showed enhanced clearance in d-norgestrel-treated rats. 125I-Labeled IDL-apoB and 125I-labeled LDL-apoB specific activity-time curves failed to intersect the VLDL-apoB curve at maximal heights, suggesting input of intermediate density lipoprotein (IDL) and LDL independent of VLDL catabolism in both groups. However, the extent of independent LDL-apoB production was similar in both groups. Clearance of 131I-labeled LDL-apoB following injection of 131I-labeled rat-LDL was delayed in the d-norgestrel-treated versus control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs.

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.

Alanine Transaminase↗
PubMed1985

Limited efficacy of early postoperative jejunal feeding.

Twenty patients underwent placement of a jejunal catheter for early postoperative feeding at the time of upper abdominal operations, and a control group of 11 patients underwent operative procedures of similar magnitude without jejunostomy. Advancement of the rate of feeding to target intake over 6 to 7 days was attempted. Complications from the feeding led to cessation or curtailment of intake in 65 percent of the patients. Specific complications included abdominal pain and distention, diarrhea, and retrograde reflux of the feeding into the stomach. No statistically significant difference in nitrogen balance was demonstrated between the fed and unfed groups, presumably due to the limitations of nutrient delivery or absorption in the fed groups or elevated breath hydrogen excretion in patients with abdominal pain and distention suggests that the nature of the nutrients, particularly complex carbohydrates, is a factor in the development of feeding complications. Caution must be exercised in advancing the rate of postoperative jejunal feeding.

Breath Tests↗
PubMed1985

Toxicity of amphotericins on chronic administration to mongrel dogs.

Conditioned mongrel dogs were given 30 i.v. injections of either AMB (amphotericin B, 0.75 mg/kg body weight), AME (amphotericin B methyl ester, 10 mg/kg body weight), or 5% glucose solution without antimicrobic. Severe loss of body weight and nephrotoxicity occurred with AMB; hepatic dysfunction resulted with AME; astrogliosis and pallor of the myelin were found in dogs given AME and 5% glucose solution.

Amphotericin B↗
PubMed1985

Human intestinal folate conjugase: adaptation after jejunoileal bypass.

During intestinal absorption, dietary polyglutamyl folates are hydrolyzed to monoglutamyl folates by pteroylpolyglutamate hydrolase (folate conjugase). This enzyme is present in the brush border and intracellular fractions of human jejunal mucosa. We compared the activities of brush border and intracellular folate conjugase (BBFC and ICFC), and other mucosal enzymes in the jejunum in continuity and bypassed loop in nine patients who underwent intestinal reconstitution operations 3 to 9 yr after jejunoileal bypass. Control jejunum was obtained from seven obese patients undergoing gastric bypass surgery. Jejunal morphometry showed mucosal hyperplasia with taller villi, larger crypts, and no change in cell size in the jejunum in continuity as compared to control or bypass jejunum. In brush border fractions, specific activities of sucrase and BBFC were significantly greater in the jejunum in continuity than in the control or bypass jejunum. In contrast, the specific activities of the other brush border and intracellular enzymes, including ICFC, were similar in all three segments. This is the first evidence that BBFC, like sucrase, adapts to luminal nutrition. The difference in response of BBFC and ICFC to diet and/or pancreato-biliary secretions provides evidence that these are distinct enzymes which are regulated by different mechanisms.

Adaptation, Physiological↗
PubMed1984

Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset.

Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.

Adolescent↗
PubMed1984

Preliminary observations of a form of coherence therapy for osteoporosis.

Five patients suffering from osteoporosis were subjected to from three to eight cycles of a form of Coherence Therapy for Osteoporosis (1) used at this center. Assessment of the patients' trabecular bone remodeling activity as measured by histomorphometric analyses of trans-iliac crest bone biopsies showed a marked improvement.

Aged↗
PubMed1984

Hypotriglyceridemic effects of levonorgestrel in rats.

The progestin, levonorgestrel administered orally to fed female rats significantly lowers both plasma total and very low density lipoprotein triglycerides. In contrast, plasma total cholesterol and low density lipoprotein cholesterol rose significantly. Suspensions of isolated hepatocytes were used to study the effects of levonorgestrel on triglyceride synthesis by examining the incorporation of labelled precursors [( 9,10- 3H]palmitate and [U-14C]glycerol) into triglycerides. Levonorgestrel (10(-4) M) significantly inhibited the incorporation of both precursors into hepatocyte triglycerides and also reduced their incorporation into the triglycerides (nearly all in d less than 1.006) released into the medium. These results suggest that inhibition of hepatic triglyceride synthesis and release can account at least for part of the lowering of plasma VLDL which occurs during administration of levonorgestrel.

Animals↗
PubMed1984

Turnover of very low-density lipoprotein-apoprotein B is increased by substitution of soybean protein for meat and dairy protein in the diets of hypercholesterolemic men.

The effect of dietary protein source on the kinetics of plasma very low-density lipoprotein (VLDL) (Sf 60 to 400) in hypercholesterolemic men was investigated. Using a crossover design, five subjects received sequentially either 1) a high polyunsaturated fat, low cholesterol control diet containing mixed protein from meat, dairy products, and plant sources or 2) an all-plant protein experimental diet in which the meat and dairy protein of the former diet was replaced by soybean protein and soy milk. There was no significant change in the mean values for fasting serum cholesterol and triglycerides over the 6-wk period of administration of the control versus experimental diets. The kinetics of VLDL (Sf 60 to 400) apolipoprotein B were studied at the end of each dietary period after reinjection of 125I-labeled autologous VLDL (Sf 60 to 400). The VLDL apolipoprotein B pool size was similar during the experimental and control protocols; however, the fractional catabolic rate was consistently higher during the experimental protocol (8.5 +/- 1.3 versus 6.5 +/- 1.2 day-1, p less than 0.01) and the production rate of apoprotein B was higher than control in four of five subjects (mean values 18.6 +/- 3 versus 12.6 +/- 1 mg/day/kg, respectively). Administration of an all-plant protein diet significantly increased the fractional turnover rate of VLDL apolipoprotein B, even when no changes in VLDL ago B pool size or VLDL lipid concentrations were observed.

Adult↗