Permanent abnormal response to a glucose load after prenatal ethanol exposure in rats

Postnatal development of the glucose and insulin balance in offspring of ethanol-treated and control rats has been studied. Newborn rats were separated from their mothers and placed with normal lactating, nonethanol-treated dams. Prenatal exposure to ethanol led to hypoglycemia on the first day of extrauterine life and a general tendency to hyperinsulinemia during the entire postnatal period studied. The glucose-tolerance test in weaned rats (30 days old) gave a greater and faster increase than controls in levels of both glucose and plasma insulin. At adult age (90 days) the response of blood glucose to an oral glucose load in offspring from ethanol-treated mothers was not different from that in offspring from controls, but the insulin response was higher. This abnormal insulin response, such a long time after the end of ethanol exposure, suggests either a permanent alteration in the pancreatic response, or a peripheral insulin resistance and/or differences in the rate of insulin degradation in these animals.     

Study of the veins of the foot by counter-current phlebography

83 CF phlebographies of the foot veins were carried out in varicose vein sufferers of both sexes in order to better understand the return venous circulation of the foot in detail, its abnormalities, and also to attempt to explain edema of the foot suffered by many varicose vein patients to varying degrees of severity after saphenous stripping. Films were obtained by direct needle puncture at different sites on the fore-foot, after a tourniquet was placed around the ankle. The route taken by the contrast medium injected was followed on a fluoroscop screen and photographed. Images obtained were classified under 4 headings: 1) slight, 2) moderate, 3) loaded and 4) overloaded opacification. In normal or slightly pathological cases (group 1 and 2), contrast medium was evacuated via a route ranging from level 1 (superficial) to level 3 (deep), this being the "usual evacuation circuit." In frankly pathological cases (groups 3 and 4), a "subsidiary evacuation circuit" may develop. It is also possible that after a degree of stagnation (by obstruction of the main veins of the foot) the contrast medium is very slowly evacuated by a number of small collateral veins. Edema of the foot as seen in some varicose vein patients as well as that which occurs post-operatively in the majority of patients undergoing varicose vein surgery is felt to be more often due to valve incompetence and to hypotonicity of the venous walls rather than to thrombosis of a deep vein of the foot.     

Biochemical and immunological properties of the human carcinoma antigen CAR-5 defined by the monoclonal antibody BD-5

The monoclonal antibody (MAb) BD-5 reacts with an epitope (CAR-5) expressed in 83% of the gastric carcinomas and in 51% of the ductal pancreatic carcinomas. This MAb reacts also with epithelial cells of colorectal mucosa, but does not react at all with normal adult gastric mucosa or normal adult pancreas. We report the biochemical and immunochemical characterization of CAR-5-bearing molecule. The epitope was found to be carried on a mucin of more than 400 kDa with a density of 1.45 g/ml, metabolically labelled with 35S-sulfate, 3H-glucosamine, 3H-mannose and 35S-methionine. Antigenicity survived metaperiodate oxidation and alkalinization, while it was fully destroyed by pronase or papain. Trypsin, although cleaving the molecule, did not affect its antigenic activity. CAR-5 epitope is thus carried on the protein moiety of a sulfo-mucin. On the basis of its biochemical properties, the antigen was purified by a 3-step procedure, consisting of perchloric acid extraction, molecular sieving on Sepharose CL-4B and affinity chromatography on wheat-germ agglutinin coupled to Sepharose 4B. Cross-competition experiments, together with the chemical properties displayed by the different epitopes, clearly indicate that CAR-5 is different from all previously characterized carcinoma-associated determinants. Cross-DDIRMA experiments performed with different "catcher" and "tracer" antibody combinations showed that CAR-5 epitope may be expressed on the same mucin bearing CA 19-9, MOv2, DU-PAN-2, Lewisa and Lewisb epitopes.     

A tumour-associated membrane antigen transiently expressed by normal cells during mitosis

Rabbit antisera raised against antigens solubilized from the membranes of a transplantable Balb/c adenocarcinoma precipitated an antigen that was not expressed by the normal resting mammary gland or any other normal mouse tissue. The same antisera were used to show the presence of this antigen in other mammary adenocarcinomas, although not in tumours of different histological types. The antigen was, however, transiently expressed by mammary gland cells during the hyperplasia that both precedes and accompanies lactation. A connection is sought between the existence of this antigen and the membrane structural changes that take place during mitosis.     

Myelolipoma: A New Adrenal Finding in Carney's Complex?

Pigmented nodular cortical hyperplasia, a rare cause of Cushing’s syndrome, is characterized by resistance to inhibition with dexamethasone and normal sized adrenal glands with multiple, small pigmented nodules. The disorder may be a component of a syndrome inherited as an autosomal dominant pattern that includes intra- and extracardiac myxomas, lentiginous lesions, blue nevi, other functional endocrine tumors, and peripheral nerve tumors (Carney’s complex). We report a patient in whom bilateral myelolipomas were found, in addition to the usual features of this complex. A 29-yr-old man was admitted to the hospital for Cushing’s syndrome of probably more than 15 yr duration. Physical examination showed diffuse facial hyperchromatic macules, 0.2–0.5 cm, predominantly around the lips and on the palmar surfaces of the fingers. Results with dexamethasone suppression nocturnal testing (1 and 8 mg) were compatible with an adrenal adenoma. The computed tomography (CT) of the sella turcica was normal. Adrenal CT showed a tumor in the left gland with a double component: one solid and another suggestive of fat, consistent with an angiomyelolipoma. Following 5 wk treatment with ketoconazole, 800 mg per day po, serum cortisol decreased to 5.9 μg/dL, morning and evening, respectively. Bilateral adrenalectomy was performed. Pathologic examination revealed pigmented nodular cortical hypersplasia and a dominant myelolipoma in the left adrenal. A microscopic myelolipoma was identified in the right adrenal. An echocardiogram showed a mass on the posterior wall of the left ventricle which was a myxoma. Study of the patient's family disclosed two sisters with facial lentigines. Echocardiograms were performed on all available first degree relatives: all were normal. Nocturnal inhibition with dexamethasone revealed that one of the patient’s sisters with lentigines also had hypercortisolism. Myelolipoma has been reported in association to Cushing syndrome in humans and experimentally after pituitary extracts in animals. The relationship between this finding and the Carney’s complex remain elusive.     

Distribution of glycoconjugates during cochlea development in mice: light microscopic lectin study

During development, different epithelial cells in the mouse cochlea express different cell surface glycoconjugates, which may reflect membrane specialization. Some of the lectins tested in this study (SBA, succ-WGA, and PSA) labeled the sensory cells of the cochlea around birth. Other lectins (WGA, Con A, RCA-II, and PHA-E) labeled surfaces of the sensory cells, particularly the stereocilia, from early stages of development (gestation day (GD) 16) through 21 days after birth. These may be adhesion molecules needed to attach the newly forming tectorial membrane (TM) to the stereocilia. Lectin staining of the developing TM revealed that the substructures of the TM are biochemically distinct. Lectin staining also showed the temporal sequence of the expression of cytoplasmic glycoconjugates of the cochlear epithelium during development. Biochemical changes during development are probably the result of different cells being involved in the production of glycoconjugates, and may have functional significance, specifically with regard to the expression of adhesion and/or signaling molecules.     

Cytogenetic and molecular studies of a familial renal cell carcinoma.

In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using DNA sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene.     

E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells

In Hereditary Diffuse Gastric Cancer syndrome, E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between alpha-catenin and beta-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype-phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidence that motility is neither necessary nor sufficient for cells to invade. Our data give new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer.     

Modulation of mechanosensory responses by motoneurons that regulate skin surface topology in the leech

Central regulation of somatosensory signals has been extensively studied, but little is known about their regulation in the periphery. Given the widespread exposure of the skin sensory terminals to the environment, it is of interest to explore how somatosensory sensitivity is affected by changes in properties of the skin. In the leech, the annuli that subdivide the skin can be erected under the control of the annulus erector (AE) motoneurons. To analyze whether this surface change influences mechanosensory sensitivity, we studied the responses of low threshold mechanosensory T cells to mechanical stimulation of the skin as AE motoneurons were activated. In segments of the body wall connected to the corresponding ganglion and submerged in an aqueous environment, T cells responded to localized bubbling on the skin and to water flow parallel to its surface. Excitation of AE motoneurons diminished these responses in a way that depended on the motoneuron firing frequency. Video recordings established that the range of AE firing frequencies that produced effective annulus erection coincided with that influencing T cell responses. In isolated ganglia, AE firing had no effect on T cell excitability, suggesting that annulus erection diminished T cell responsiveness to mechanical input. Counteracting this effect, mechanosensory inputs inhibited AE motoneurons. However, because depolarization of AE cells caused a decrease in their input resistance, the more active the motoneuron, the less sensitive it became to inhibitory signals. Thus when brought to fire, AE motoneurons would stay "committed" to a high activity level, and this would limit sensory responsiveness to incoming mechanical signals.