The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and of two enzymes involved in mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease.

Regulation of the mevalonate pathway.

Background. Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case–control study, we explored whether H. pylori infection increases the risk of gastric carcinoma. Methods. From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results. Results. The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patient...

https://www.nejm.org/doi/pdf/10.1056/NEJM199110173251603

Helicobacter pylori infection and the risk of gastric carcinoma.

Methods for assessment, e.g., anthropometric indicators and imaging techniques, of several phenotypes of human obesity, with special reference to abdominal fat content, have been evaluated. The correlation of fat distribution with age, gender, total body fat, energy balance, adipose tissue lipoprotein lipase and lipolytic activity, adipose tissue receptors, and genetic characteristics are discussed. Several secreted or expressed factors in the adipocyte are evaluated in the context of fat tissue localization. The body fat distribution and the metabolic profile in nonobese and obese individuals is discussed relative to lipolysis, antilypolysis and lipogenesis, insulin sensitivity, and glucose, lipid, and protein metabolism. Finally, the endocrine regulation of abdominal visceral fat in comparison with the adipose tissue localized in other areas is presented.

/pdf/subcutaneous-and-visceral-adipose-tissue-their-relation-to-5crse4rslq.pdf

Subcutaneous and visceral adipose tissue : Their relation to the metabolic syndrome

Plasma-high-density-lipoprotein concentration and development of ischæmic heart-disease

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

/pdf/hepatic-stellate-cells-protean-multifunctional-and-enigmatic-1ctrvjmfhn.pdf

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

A radioimmunoassay for human plasma retinol-binding protein (RBP) has been developed utilizing a double antibody precipitation technique. RBP was purified 1500- to 2000-fold by procedures described previously. A specific anti-human RBP antiserum was prepared in rabbits by three once-weekly injections of purified RBP emulsified with Freund's adjuvant. RBP was iodinated with (131)I and the RBP-(131)I was purified by gel filtration on Sephadex G-100 after complex formation with human plasma prealbumin. The RBP-(131)I was completely (> 95%) immunoprecipitable in the presence of an excess of specific antiserum, it was not (< 5%) immunoprecipitable in the absence of specific antiserum, and it could be completely displaced from antibody by excess unlabeled RBP. The standard curve obtained in the immunoassay with normal plasma was identical to that with pure RBP. Duplicate samples differed from their mean by 5 +/-5% (+/-SD). There was a quantitative recovery of pure RBP added in varying amounts to normal plasma. The immunoassay accurately measured RBP in amounts of 10-100 ng per assay tube. There was no significant difference in the immunoreactivity of apo-RBP as compared to holo-RBP. The mean plasma values (+/-SEM) for a group of 76 normal subjects were 47.2 +/-1.6 mug/ml for males and 41.6 +/-1.6 mug/ml for females. Plasma RBP levels were markedly depressed (15 +/-2.3 mug/ml) in 14 patients with acute viral hepatitis. There was a highly significant correlation between the plasma levels of RBP and of vitamin A in both normal subjects and patients with hepatitis. In all subjects plasma RBP was generally saturated with retinol. The data suggest that under normal circumstances RBP circulates almost exclusively as the holoprotein.

/pdf/radioimmunoassay-of-human-plasma-retinol-binding-protein-3t006aohiu.pdf

Radioimmunoassay of human plasma retinol-binding protein

The immunohistochemical localizationof cellularretinol-bindingprotein (CRBP) was studied in rat testis and epididymis. Parallel studies were also carried out on the localization of plasma retinolbinding protein (RBP) and transthyretin (TTR) in testis. The studies employed antibodies purified by immunosorbent affinity chromatography, permitting the specific staining and localization of each antigen by the unlabeled peroxidase-antiperoxidase method. For RBP and TTR, specific immune staining was found in the interstitial spaces between the seminiferous tubules, and not in the tubules themselves. In contrast, strong specific immune staining for CRBP was found in the seminiferous tubules, with a striking localization within Sertoli cells. Moreover, a distinct cyclic variation of specific staining for CRBP within Sertoli cells was observed during the spermatogenic cycle. This cyclic variation was seen with regard to both the intensity of stainingand to the anatomic distribution of CRBP within the Sertoli cells. Within the epididymis CRBP was selectively localized to the proximal portion of the caput epididymidis, with variations in intensity of the staining of the epithelium of the ducts in different histological zones. Specific immune staining for CRBP was very weak or absent in the other portions of the epididymis. These results were confirmed by radioimmunoassay. Vitamin A-deficient rats showed markedly reduced specific immune staining for CRBP in both testes and epididymides, and greatly reduced levels of CR3? in these tissues on radioimmunoassay. These studies on the localization of CRBP provide information concerning the specificcells and anatomic loci within the testis and epididymis where retinol may be playing an important role in sperm formation and maturation.

/pdf/immunohistochemical-studies-on-the-localization-of-cellular-36qrmrsg20.pdf

DeWitt S. Goodman

Papers

Radioimmunoassay of human plasma retinol-binding protein

Immunohistochemical studies on the localization of cellular retinol-binding protein in rat testis and epididymis.

Retinyl palmitate hydrolase activity in normal rat liver.

Plasma transthyretin. Tissue sites of degradation and turnover in the rat.

Pathways of absorption of retinal and retinoic acid in the rat