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Biomedical subjects

J Roth

Publications and source records attributed to J Roth.

At least 667 records · Page 37Linked to original sources
PubMed1979

Conventional supervoltage irradiation is an effective treatment for acromegaly.

Forty-seven acromegalic patients were treated with conventional supervoltage irradiation (4000-5000 rads) and were followed-up at 2, 5, and 10 yr after treatment. The mean fall in the GH concentrations 5 years after treatment was 77%, and GH was less than 10 ng/ml in 73% of the cases. In the majority, GH continued to fall over the 5- to 10-yr interval after treatment, so that by 10 yr, plasma GH was less than or equal to 10 ng/ml in 81% and less than or equal to 5 ng/ml in 69% of the patients. Also, the subjective (acral and facial changes) and the objective (metabolic) effects of GH excess all showed significant improvement with time, and the improvement roughly paralleled the fall in plasma GH concentrations. After therapy, no patient developed extrasellar extension, and headaches improved in the majority of patients. The prevalence of hypopituitarism, which was low before treatment, increased progressively throughout the follow-up period. Significant loss of vision was observed in only one patient, who received 5600 rads and had severe systemic sarcoidosis. The only other complication was temporal hair loss. Conventional super-voltage irradiation by 5-10 yr produces the same fall in plasma GH as all other forms of treatment for acromegaly, including transphenoidal microsurgery. The rate of fall in plasma GH after conventional irradiation is comparable to that of more aggressive forms of irradiation and is slower than that achieved by surgical methods but probably conventional irradiation has fewer serious side effects.

Acromegaly↗
PubMed1979

Regulation of receptor by homologous hormone enhances sensitivity and broadens scope of radioreceptor assay for human growth hormone.

In standard competitive binding assays (including radioreceptor assays) unlabeled ligand (hormone) competes with labeled ligand (hormone) for binding to a fixed number of binding (receptor) sites. Detection of the unlabeled ligand occurs when the occupancy of binding sites by the unlabeled ligand is sufficient to reduce the binding of labeled ligand. A common feature of the hormone-receptor interaction is the ability of the hormone to regulate the affinity and/or the concentration of its homologous receptor. In the present study, by exploiting the ability of human GH to regulate by negative feedback the concentration of its own receptors, we have enhanced the sensitivity of the human GH radioreceptor assay 5-fold. The ability of hormone to regulate receptor concentration and affinity affords wide opportunities to broaden the scope as well as to enhance the sensitivity of radioreceptor assays.

Binding, Competitive↗
PubMed1979

Insulin-induced receptor loss in the cultured human lymphocyte: quantitative morphological perturbations in the cell and plasma membrane.

When cultured human lymphocytes (IM-9) are exposed to 10(-6) M procine insulin for 6 h, washed, and incubated with 125I-insulin, the ability of the cell to bind the labelled hormone is reduced by a mean of 78%. Under these experimental conditions that induce insulin-receptor loss in this cell there is a mean 95% increase in microinvaginations in the plasma membrane revealed by electron microscopy on freez-fractured replicas of the cell. At the same time, horseradish peroxidase uptake, a marker of endocytosis, is increased in the cells incubated with insulin. Coupled with our recent EM autoradiographic evidence that labelled insulin is acutely internalized by this cell, these studies are consistent with the possibility that endocytosis represents a mechanism by which receptor is removed from the cell surface.

Cell Line↗
PubMed1979

Receptor binding studies on A1-(2-nitro-4-trimethylammoniophenyl)insulin.

The results are presented from receptor binding studies and isolated fat cell assays on A1-(2-nitro-4-trimethylammoniophenyl)insulin. In the former tests, the derivative is shown to have properties similar to native insulin and the fat cell assays afford a value of 76 +/- 4%. The importance of a charged, hydrophilic moiety attached at A1-glycine is discussed in the light of the above findings.

Adipose Tissue↗
PubMed1979

Regulation of insulin receptors in normal and abnormal physiology in humans.

Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect.

Acanthosis Nigricans↗
PubMed1979

[Significance of bronchial hyperreactivity (tested with acetylcholine) and ventilatory inhomogeneity for the early detection and differentiation of chronic nonspecific lung disease (CNSLD) (author's transl)].

Bronchial hyperreactivity (tested with 0.01% acetylcholine ultrasonic aerosol) and ventilatory inhomogeneity (tested with V2/V1-parameter of the flow-volume diagram) using the pneumotest apparatus were studied. Patients with high bronchial reactivity are frequently showing not only ventilatory disorders of distribution but sometimes also an additional increase due to the bronchial provocation. Bronchial reactivity testing combined with the flow-volume diagram allows to estimate the predominant site of the bronchospastic response either centrally or also in the more peripheral parts of the bronchial system. By testing bronchial reactivity persons without any symptoms and with no evident spirometric alterations can be separated in dependence on the relative increase of total airway flow resistance as well on smoking habits. That does not succeed with the appliance of the inhomogeneity parameters V2/V1. The results obtained in this study are of value for preventive measures, for early detection of risk factors in premorbid stages, for assessment of prognosis in chronic nonspecific lung disease, for an adequate therapy and also for the rehabilitation of patients in jobs with inhalation of noxious dusts.

Acetylcholine↗
PubMed1979

[Season-related incidence of Yersinia enterocolitica in fecal material of healthy slaughterhouse pigs (author's transl)].

In the period July 1976 to June 1977 a total of 1358 fecal specimens and 165 mesenteric lymphnodes of healthy slaughterhouse pigs were examined for Yersinia enterocolitica (Y.e.). The animals originated from 215 farms in 86 localities of Northern Bavaria. Y.e. was found in fecal specimens of 371 pigs (27.3%). A total of 408 strains was isolated including 35 double and one triple infections. Most cultures belonged to serogroups O:6...(186 strains), O:7...(78 strains), and O:5...(71 strains, Table 3). The serogroups O:3 and O:9 which in Europe are most frequently associated with human disease were isolated from 26 animals (1.9%). Lymphnodes were positive in two instances only (1.2%). Besides aerobic subculture on SS-agar after cold enrichment in phosphate buffered saline anaerobic incubation was performed simultaneously during the last 8 months of the study. This method rendered more than twice as many isolations due to an effective inhibition of environmental bacteria with oxidative metabolism (mainly Pseudomonas spp.; Tables 3 and 4). The incidence of asymptomatic infections was markedly related to season. The lowest incidence was observed during the summer months (August 1976:0%) but increased steadily to a maximum in April 1977 (71.2%; Table 4). With one exception the serogroups O:3 and O:9 were only isolated during October to December (Fig. 1). Despite the frequent occurrence of Y.e. in healthy pigs the significance of these animals for human yersiniosis remains to be clarified. Especially the frequency of disease in infants and young children would not suggest porc meat as an important vehicle of transmission. It is imaginable that the human pathogenic serogroups O:3 and O:9 might be simultaneously adapted to several hosts with independent cycles of infection. Future investigations will mainly have to consider the elucidation of the hitherto unknown mode of transmission of human yersiniosis.

Abattoirs↗
PubMed1978

Autoantibodies to the insulin receptor activate glycogen synthase in rat adipocytes.

Autoantibodies to the insulin receptor mimic the effects of insulin on glycogen synthase and phosphorylase. The interaction of antibodies with adipocyte cell surface insulin receptors seems sufficient to promote stable changes in the activities of these intracellular enzymes, suggesting that internalization or processing of insulin is not important in the generation of these biological responses.

Adipose Tissue↗
PubMed1978

[Effect of bronchial reactivity on the whole-body plethysmographic inhomogeneity parameter REmax/RE0 and its value in the early diagnosis of chronic nonspecific lung diseases].

Examinations performed with the help of the body-plethysmographic inhomogeneity parameter REmax/RE0 prove the close connection between the development of chronic unspecific pulmonary diseases and the appearance of disturbances of the ventilatory distribution. The functional disturbance metioned is further increased by the bronchial provocation and may partly be demonstrated in a characteristic way also in inconspicuous initial findings. The body-plethysmographic inhomogeneity parameter REmax/RE0 is, however, not suited for the early diagnosis of chronic unspecific pulmonary diseases, since with its help the verification of disturbances of the ventilatory distribution is successful only then, when the total resistance is already increased. For the final judgment of the aptitude of the bronchial reactivity test for the increase of the valency of methods of the distribution analysis in the early diagnosis further examinations are necessary.

Adolescent↗
PubMed1978

Properties and partial purification of the detergent-solubilized insulin receptor: a demonstration of negative cooperativity in micellar solution.

Turkey erythrocytes possess insulin receptors with binding properties very similar to those of mammalian insulin receptors. In the present study, the insulin receptor of the avian erythrocyte has been solubilized in Triton X-100, extensively characterized and partially purified, and its properties compared to those of the membrane-bound receptor. The solubilized insulin receptor has a Stokes radius of 70 A and an apparent molecular weight of 300 000 in 0.05% Triton. The binding of insulin to the soluble receptor was very similar to the binding observed with the membrane-bound receptor. Thus, binding was markedly temperature dependent for both the soluble and membrane-bound forms, although the kinetics of binding were slower with the soluble receptor. Both forms of the receptor also showed a sharp pH optimum; however, solubilization produced a shift from maximal binding at pH 7.8 to pH 7.3. The soluble receptor also retained insulin analog specificity, ion sensitivity and negative cooperativity. The soluble receptor did not appear to degrade either bound or free insulin. On DEAE-cellulose chromatography the receptor eluted as a single peak. The specific activity of this partially purified preparation was 25--30 pmol/mg protein (about 500-fold enrichment over crude extract and 5-fold over highly purified membranes). Extensive attempts to purify further the receptor by gel filtration, carboxymethyl-cellulose chromatography and affinity chromatography resulted in either a very low yield or only modest enrichment. Purification was also complicated because the receptor was easily denatured; about 40% of the activity was lost after a 90-min exposure to 3 M urea or pH 4.5. These data suggest that the insulin receptor retains its properties in the absence of the lipid bilayer of the membrane. Complete purification will be difficult due to a lack of stability under a number of conditions.

Animals↗
PubMed1978

Conjugation of lectins with fluorochromes: an approach to histochemical double labeling of carbohydrate components.

Methodical investigations on the coupling of lectins (Con A, LcL, WGA, RcA) to tetramethylrhodamine isothiocyan ate (TRITC) are reported. 20-microgram of TRITC per mg of lectin were found to be the optimal amount of TRITC for the conjugation. With this fluorochrome: protein ratio conjugates were produced which resulted in a specific and brilliant fluorescence in tissue staining. The optimally conjugated lectins were separated on DEAE-Sephadex-A 50. Using two different lectins which were conjugated with TRITC or FITC, respectively, a double labeling of different lectin-binding sites in tissue sections was achieved.

Animals↗
PubMed1978

[Evaluation of weather-dependent dyspnea by means of body plethysmographic study of bronchial reactivity].

By body plethysmographic investigations including the test of the bronchial reactivity (ultrasound aerosol of a 0.01% acetylcholine solution) was demonstrated that in dependence on the degree of the manifest disturbance of ventilation the frequency of the bronchial hyperreactivity (increase of the total resistance by at least 3.0 cm H2O/l/s compared with the initial position) increases. The constellation of findings mentioned leads to a large increase of dyspnoea depending on weather.

Acetylcholine↗
PubMed1978

Mapping of the residues responsible for the negative cooperativity of the receptor-binding region of insulin.

Insulin binding to its receptor leads to negatively cooperative interactions among the receptor sites. Studies with 29 insulin analogues (animal insulins and proinsulin, insulin-like growth factor and chemically modified insulins) which vary 1,000-fold in their affinity for the receptor and in their biological potency, suggest that a discrete invariable region on the surface of the insulin monomer is responsible for including the negative cooperativity. This domain comprises some of the eight carboxy-terminal residues of the B-chain and the A21 asparagine. Burying of this 'cooperative site' in the dimerisation of insulin leads to a loss of negative cooperativity. A revised mapping of the insulin molecule is proposed, featuring distinct bioactive and cooperative sites.

Allosteric Site↗