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Biomedical subjects

J Zimmerman

Publications and source records attributed to J Zimmerman.

At least 109 records · Page 6Linked to original sources

Source origin of a 50-msec latency auditory evoked field component in young schizophrenic men.

We recorded auditory evoked magnetic fields in response to 128 15-msec duration 1-KHz tone pips from both hemispheres of 6 young schizophrenic men. Auditory evoked potentials were recorded conventionally from a vertex lead. The approximately 50-msec latency component was identified in both the magnetic (M50) and electroencephalographic (EEG) (P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. Magnetic resonance imaging was used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the planum temporale in both left and right hemispheres in all subjects. Normal inter-hemispheric asymmetry (with respect to external bony landmarks) of the M50 source was not found in this patient group. Additionally, left (but not right) hemisphere source anatomy differed in several respects from data previously reported in normals.

Adult↗

Source location of a 50 msec latency auditory evoked field component.

We recorded auditory evoked magnetic fields in response to 128 15 msec duration 1 kHz tone pips from both hemispheres of 6 normal adult males. Auditory evoked potentials were recorded conventionally from a vertex lead. An approximately 50 msec latency component was identified in both the magnetic (called the M50) and EEG (called the P50) recordings. Isofield topographical contour maps were used to estimate M50 source location and depth. With respect to extracranial bony landmarks, M50 source locations were significantly higher and tended to be more posterior, over the left hemisphere. M50 and P50 latencies were not significantly different in 5 of 6 subjects; in one, M50 latencies were significantly longer than P50 latencies over the left hemisphere. Magnetic resonance images in 5 subjects were used to identify the neuroanatomical structure(s) present at the estimated source location. M50 sources appeared to reside in the cortex of the planum temporale in both left and right hemispheres in all 5 subjects.

Adult↗

Seasonal variations in the frequency of endoscopically diagnosed duodenal ulcer in Israel.

The seasonal pattern of endoscopically diagnosed duodenal ulcer disease in a representative Israeli medical center was evaluated retrospectively for the period 1980-1986. We reviewed all 9861 endoscopy records and found 1692 duodenal ulcers. We calculated the percentage of duodenal ulcers of the total examinations performed each month. In Israel, the frequency of duodenal ulcers was significantly increased during January and February and was significantly lower during the months May-June and July-August when compared to the rest of the year.

Duodenal Ulcer↗

Efficient expression of the yeast metallothionein gene in Escherichia coli.

The yeast metallothionein gene CUP1 was cloned into a bacterial expression system to achieve efficient, controlled expression of the stable, unprocessed protein product. The Escherichia coli-synthesized yeast metallothionein bound copper, cadmium, and zinc, indicating that the protein was functional. Furthermore, E. coli cells expressing CUP1 acquired a new, inducible ability to selectively sequester heavy metal ions from the growth medium.

Amino Acid Sequence↗

Regulation of cellular and humoral immune responses to collagen type I or collagen type II.

We have investigated the characteristics of antigen-specific reductions in murine immune responses to rat collagen type I (R-CI), chick collagen type II (C-CII) or bovine collagen type II (B-CII). Intravenous pretreatment with the appropriate soluble collagen or collagen-coupled spleen cells led to the development of antigen-specific reduced immune responses, the former treatment being more effective than the latter. In the case of CII, pretreatment with R-CI or non-related antigens was ineffective. However, pretreatment with denatured bovine-CII, native bovine-CII or chick-CII led to immune hyporesponsiveness for either the homologous or heterologous CII molecule. A delayed development of the diminished immune responses was observed for the cell-mediated immune response (CMI), as measured by in vivo delayed-type hypersensitivity (DTH), in that no reduction was evident at Day 7 but a significantly decreased response was observed at Day 14. Collagen-specific IgG and IgM antibody responses were consistently reduced by the pretreatment and remained reduced during the study period. The antigen-specific hyporesponsive state was not sensitive to cyclophosphamide treatment and was not transferable with hyporesponsive spleen cells. Additionally, we have induced unresponsiveness to CII by treating mice with an antibody directed to T helper cells (GK1.5). This treatment led to profound reductions in CII CMI responses as well as CII antibody levels. However, this unresponsive state is not permanent and not transferable with spleen cells from treated mice. These two types of procedures, soluble B-CII i.v. or GK1.5 treatment, not only resulted in CII hyporesponsive states, but also produced delayed onset and decreased incidence of arthritis in the appropriate strains.

Animals↗

Comparison of misoprostol and ranitidine in the treatment of duodenal ulcer.

The efficacy of misoprostol (a synthetic analogue of prostaglandin E1) and ranitidine in the treatment of duodenal ulcer was evaluated. Seventy-one patients with endoscopically proven duodenal ulcer were randomized in a double-blind manner in one of two groups that received two daily doses of 400 micrograms misoprostol or 150 mg ranitidine. Ulcer healing was assessed endoscopically after 4 weeks of treatment; in subjects who had not healed treatment was continued and endoscopy was repeated after another 4 weeks. The mean age, sex distribution and tobacco, alcohol and caffein consumption were similar in both groups. In the misoprostol-treated group, healing of the ulcer was observed in 74.8% of patients at 4 weeks and in 86.5% at 8 weeks; in the ranitidine group (n = 34), the healing rate was 91.2 and 100%, respectively. The differences between healing rates in the two groups were not statistically significant. In the misoprostol group (n = 37), 27% of patients experienced diarrhea; of these, two were withdrawn from the trial due to this side effect. These results, which are part of a multicenter international study, suggest that misoprostol at a daily dose of 800 micrograms is as effective as 300 mg/day ranitidine in the treatment of duodenal ulcer.

Adult↗

Competitive inhibition of folate absorption by dihydrofolate reductase inhibitors, trimethoprim and pyrimethamine.

Trimethoprim and pyrimethamine, inhibitors of dihydrofolate reductase (DHFR), cause folate deficiency in some patients. We investigated impairment of intestinal folate absorption by these drugs. By use of the in vivo intestinal-loop methods in rats, absorption of [3H] folic acid was significantly decreased in the presence of either drug. Kinetic studies using the influx chamber method demonstrated a pattern of competitive inhibition of folate transport. [3H] folic acid absorption from jejunal loops was determined 3-16 h after IV administration of methotrexate; this treatment abolished DHFR activity in the small intestine. In rats pretreated with methotrexate, luminal disappearance and systemic absorption of folic acid were significantly enhanced with respect to controls. Trimethoprim and pyrimethamine are weak competitive inhibitors of intestinal folate transport and folate absorption inhibition occurs at the site of membrane transport and appears to be unrelated to concurrent inhibition of DHFR activity in enterocytes.

Animals↗

Role of sodium ion in transport of folic acid in the small intestine.

The effect of sodium on folate transport across the intestinal luminal membrane was analyzed using two techniques: the "influx" chamber and isolated brush-border membrane vesicles. Preincubation of tissue in Na+-free medium did not have a consistent effect on folic acid influx provided that Na+ was present in the test solution. Replacement of Na+ in the test solution by choline+ resulted in a significant reduction of folic acid influx. However, when intestinal sheets that had been equilibrated in Na+-free solution were exposed to test solution containing either Na+, Li+, K+, Rb+, Cs+, Tris+, or guanidinium+ as main cations, folic acid influx was not significantly decreased. Concentration-dependence studies showed that replacement of Na+ by Rb+ did not affect the saturable mechanism of folate transport. Rather, a decrease in nonsaturable folic acid uptake accounted for the slightly reduced influx observed in the presence of Rb+. Experiments with brush-border membrane vesicles revealed that methotrexate uptake was significantly higher in the presence of external Na+ than in the presence of K+, but was not different from uptake in the presence of K+ plus valinomycin. These data suggest that the saturable component of folate transport is not Na+ dependent, and nonsaturable transport of folic acid across the luminal membrane occurs in part through a conductive pathway that involves a negatively charged species of folate and a cation whose membrane permeability affects the rate of folate transport. The importance of Na+ in this process in vivo derives from the fact that Na+ is the most permeant cation available at the absorptive site in the small intestine.

Animals↗

Dietary fat, adipose tissue composition, and the development of carcinoma of the colon.

Dietary fat and plasma lipids have been implicated in the development of carcinoma of the colon. Because of the difficulties in obtaining accurate dietary histories, subcutaneous adipose tissue fatty acids were analyzed to compare fat intake in 3 groups of patients undergoing colonoscopy: patients with carcinoma of the colon (n = 53; average age, 64 yr; 47% male), patients with neoplastic polyps (n = 34; age 63 yr; 71% male), and patients with normal findings (controls; n = 68; age 58 yr; 40% male). The groups were similar with regard to body mass index and coffee and egg consumption. One-way analysis of variance of the plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, 9 adipose fatty acids, groups of polyunsaturated fatty acids (vegetable origin), saturated fatty acids (animal origin), or the ratio of polyunsaturated to saturated fatty acids did not show any significant differences across the 3 groups. The quality of dietary fat does not appear to be associated with the development of carcinoma of the colon or of neoplastic polyps in this population.

Adipose Tissue↗

Ethanol inhibits triglyceride synthesis and secretion by human small intestinal mucosa.

We studied the effect of ethanol on human intestinal lipid absorption and on triglyceride synthesis and secretion. Human duodenojejunal biopsy specimens were incubated in a micellar lipid solution containing carbon 14-labeled oleate in the presence of ethanol 0.1%, 1.0%, and 5.0% (vol/vol). Tissue triglyceride synthesis was significantly decreased by 52.0% +/- 7.7%, 57.0% +/- 9.0%, and 81.3% +/- 4.0% (mean +/- SEM), respectively, when compared with triglyceride synthesis by control biopsy specimens incubated in the absence of ethanol. Tissue levels of oleate were increased in biopsy specimens incubated in the presence of ethanol by 90% +/- 30% and 115% +/- 5% for ethanol concentrations of 1.0% and 5.0% (vol/vol), respectively (P less than 0.02). At ethanol concentration of 0.01%, no change in tissue oleate or triglyceride levels was noted. The effect of 1.0% and 5.0% ethanol on triglyceride synthesis may reflect in large part their significant increase of the medium osmolarity. However, the osmolarity of the medium containing 0.1% ethanol was similar to that of the ethanol-free medium, and its effect is therefore probably specific. Duodenojejunal biopsy specimens were also preincubated for 30 minutes in a micellar lipid solution containing 14C-oleate, and subsequently were organ cultured in micellar-free medium in the presence or absence of ethanol 1.0% (vol/vol). During organ culture, the decrease in tissue oleate levels was similar in biopsy tissue cultured in the presence or absence of ethanol. However, in the presence of ethanol, triglyceride secretion to the organ culture medium was reduced by 49.9% +/- 11.1% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenum↗

Competitive inhibition of folic acid absorption in rat jejunum by triamterene.

Triamterene, a diuretic agent, has been reported to cause megaloblastic anemia in some patients. Because this drug is a pteridine derivative, we investigated its effect on folic acid absorption in the rat jejunum. In an in vivo intestinal loop method, triamterene inhibited the intestinal absorption of folic acid in a dose-dependent fashion, with 50% inhibition of systemic absorption occurring at a luminal concentration of 0.01 mmol/L of triamterene. Kinetic analysis using the influx chamber method demonstrated that triamterene is a competitive inhibitor of intestinal folate transport, with a Ki of 0.125 mmol/L. Because therapeutic doses can result in luminal concentration of the drug approximating or exceeding the Ki, the interaction between triamterene and folate absorption is potentially of clinical interest.

Animals↗

Effect of moderate isocaloric modification of dietary carbohydrate on high-density lipoprotein composition and apolipoprotein A-1 turnover in humans.

Plasma lipid and apolipoprotein (apo) levels were determined in five normolipidemic subjects and five patients with Type IV hypertriglyceridemia (HTG) who were fed for greater than or equal to 6 weeks on two isocaloric diets. The first diet contained carbohydrates (CHO) as 55% of total calories, 29% as fat and 16% as protein. The second diet contained 40% CHO, 45% fat and 15% protein in normolipidemic subjects and 40% CHO, 41% fat and 19% protein in patients with HTG. All diets had a cholesterol content of approximately 400 mg/day and a polyunsaturated/saturated fatty acid ratio of approximately 1:0. Apo A-1 kinetics were measured during the last 2 weeks of each dietary period. The composition and distribution of high-density lipoproteins (HDL), subclasses HDL2 and HDL3, were determined at the end of each dietary term. In the HTG patients, administration of a 40% compared with 55% CHO diet caused a significant decrease of plasma triglyceride levels and an increase of HDL-cholesterol; low-density lipoprotein (LDL) levels increased and very low-density lipoprotein (VLDL) levels decreased (P less than 0.01 and less than 0.07, respectively). Similar quantitative changes of VLDL and HDL levels were found in the normolipidemic subjects. No significant change in plasma levels of apo A-I, A-II and E occurred. Apo A-I kinetic studies revealed decreased synthetic rates and fractional catabolic rates on the low CHO diet. Separation of HDL subfractions by zonal ultracentrifugation in both groups revealed an increase in HDL3-cholesterol ester and protein, and a decrease in HDL2 protein, phospholipid and cholesterol. Our findings indicate that moderate changes in dietary CHO and fat content affect HDL levels, composition and apo A-I metabolism.

Adult↗