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Biomedical subjects

P Grob

Publications and source records attributed to P Grob.

At least 73 records · Page 4Linked to original sources

Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies.

The nerve growth factor (NGF) receptor was characterized by using a new series of anti-receptor monoclonal antibodies (MAbs). These MAbs (i) showed significantly greater reactivity with a melanoma cell line expressing higher levels of NGF receptor, (ii) inhibited the binding of 125I-labeled NGF to its receptor, and (iii) immunoprecipitated both metabolically labeled and 125I-labeled NGF affinity-labeled receptor. These experiments defined the receptor as a 75-kDa cell-surface protein. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of human nevi, melanomas, neurofibromas, a pheochromocytoma, and peripheral nerves. Uniform staining of the cytoplasm suggests that, in addition to cell-surface NGF receptors, there is a population of intracellular receptors.

Affinity Labels↗

[Hepatitis B virus infection and hepatocellular carcinoma: indication for a possible causal connection even in non-endemic Switzerland].

62 patients with histologically proven hepatocellular carcinoma have been investigated for the presence of serological markers of hepatitis B virus infection, and the findings have been related to alpha 1-fetoprotein measurements and to the nature of the basic disease process affecting the liver. The results document a statistically significant increase in the prevalence of hepatitis B virus markers as compared to patients with cirrhosis of the liver only, pointing to a probable etiological relationship between hepatitis B virus infection and hepatocellular carcinoma even in areas of the world where the infection is not endemic. Early detection of hepatocellular carcinoma is limited by the remarkably high percentage of patients who have no, or only marginal, elevation of serum alpha 1-fetoprotein.

Adult↗

Transsynaptic retrograde labeling in the oculomotor system of the monkey with [125I]tetanus toxin BIIb fragment.

The injection of radioactive [125I]tetanus toxin BIIb fragment into the extraocular eye muscles of monkeys led to strong retrograde labeling of motoneurons. In addition, two patterns of weaker labeling were found: (1) discrete deposits of silver grains associated with cell soma, and (2) diffuse deposits unrelated to cell bodies. The discrete cell soma labeling was found in all areas known to make synaptic contact with the retrogradely filled motoneurons, and is indicative of transsynaptic retrograde transport. The use of tetanus toxin as a transsynaptic retrograde tracer substance is shown here for the first time at the light microscopic level.

Animals↗

Papain-derived fragment IIc of tetanus toxin: its binding to isolated synaptic membranes and retrograde axonal transport.

The papain-derived fragment IIc of tetanus toxin, which is immunologically identical to the B-IIb fragment, has previously been shown to bind gangliosides. As could be expected from its analogy with the B-IIb fragment, the IIc fragment was also found to bind to isolated synaptic membranes and to be transported retrogradely from the axonal endings within muscle to the motoneuronal perikarya. It is concluded that the IIc fragment--like the B-IIb fragment--might also serve as a specific carrier for chemical and chemotherapeutical agents into the central nervous system.

Afferent Pathways↗

[Prophylaxis and therapy of acute viral hepatitis. 10 questions and answers].

The authors set out to answer the following ten questions regarding acute viral hepatitis: 1. Are serologic tests a prerequisite for prophylaxis and treatment of acute viral hepatitis? 2. What serologic markers are available? 3. What hygienic measures are of use in avoiding contact infections? 4. What general therapeutic measures can be recommended? 5. Does a pharmacotherapy for acute viral hepatitis actually exist? 6. What is the position regarding passive immunization in hepatitis A? 7. What is the position regarding passive immunization in hepatitis B? 8. Are vaccines available for active immunization? 9. Who should undergo active immunization? 10. What has been the most important advance of recent years in the field of prophylaxis and treatment of acute viral hepatitis?

Acute Disease↗

Involvement of cyclic AMP in the regulations of lymphokine induced glia cell stimulation.

T and B lymphocytes of human or murine origin were found to secrete a factor which increases the DNA and RNA synthesis of cultured glia cells. This factor, termed glia cell stimulating factor (GSF), is released upon stimulation of such immune cells by mitogen or antigen qualifying it as a lymphokine. In this communication we report on the role of cyclic AMP (cAMP) in regulating the effect of GSF on glia cells. Prostaglandin E1 (PGE1), isoproterenol and theophylline were effective in suppressing the GSF-induced increase of the glia cell proliferation. No inhibition of DNA synthesis and no decrease in cell number was observed when testing these substances on glia cells not being activated by GSF. The drugs were found to induce an increase in cAMP concentrations of glia cells. A partial desensitization of the glia cells to these drug induced elevations of cAMP was detected after pretreatment of the glia cell cultures with GSF. It is suggested that stimulated lymphocytes not only release GSF but also low molecular weight proteins such as PGE1 which regulate the effects of GSF on glia cells by activating their adenylate cyclase.

Alprostadil↗

Glia cell response to bacterial lipopolysaccharide: effect on nucleotide synthesis, its genetic control and definition of the active principle.

Cell types sensitive to lipopolysaccharides (LPS) include macrophages, polymorphonuclear leukocytes, platelets, B-lymphocytes and fibroblasts. Earlier observations that during endotoxemia or intracerebral injection of LPS morphological and functional alterations of the central nervous system develop, suggest that LPS may also interact with brain cells. The effects of bacterial products on nucleotide synthesis of cultured murine glia cells are examined in this study. LPS extracted from the outer cell wall of gram-negative bacteria were found to cause an increased RNA synthesis and an inhibition of DNA synthesis in the cultured glia cells. The inhibitory effect of LPS on DNA synthesis is not due to an LPS-mediated increase of the cAMP content in the glia cells or contact inhibition of the monolayer culture. Within the structure of LPS lipid A was found to be the active part. On the basis of the LPS-induced increase of RNA synthesis, the glia cells of C3H/HeJ mice are low responders to low doses of LPS. We conclude that in the presence of fetal calf serum glia cells are sensitive to the lipid A part of LPS, the sensitivity being under genetic control.

Animals↗

Prevalence of various degrees of hypothyroidism among patients of a general medical department.

We have measured basal thyrotropin (TSH) in 945 consecutive patients of a general medical department. Additional thyroid tests were carried out in patients with elevated TSH. Thirty patients (3.1%) had subclinical hypothyroidism, i.e. an elevated TSH with no clinical signs and with a normal free thyroxine index. A cause was found in only fifteen of these thirty patients. Thirteen additional patients (1.37%) had mild or overt primary hypothyroidism, three of which were already diagnosed. This prevalence is three times higher than that found in a retrospective survey at the same hospital. Of the ten newly-detected cases five were discharged on thyroid hormone replacement. In two patients the antithyroid drugs which were the cause of hypothyroidism were discontinued. The remaining three patients had severe non-thyroidal illnesses and thyroid hormone was not prescribed. A cause for the hypothyroidism (autoimmune thyroid disease, post-radioiodine, post-thyroidectomy or antithyroid drugs) was established in all but two cases. The data suggest that thyroid function tests (preferably a TSH) should be performed on any patient with prior treatment to the thyroid and, in addition with very broad indications, perhaps even routinely, in all women over 50 years of age.

Adult↗

Use of the B-IIb tetanus toxin derived fragment as a specific neuropharmacological transport agent.

It has been previously demonstrated that the non-toxic B-IIb tetanus toxin-derived fragment is transported retrogradely within neurons of the rat peripheral nervous system. In the present work we have shown that when a foreign polypeptide, in this case the Ibc tetanus toxin fragment, is coupled to B-IIb by a disulfide bond, it is transported retrogradely from the axonal endings within muscle to the motoneuronal perikarya. In contrast, Ibc fragment alone was found not to be transported. From these results we draw the conclusion that fragments like B-IIb may serve as specific carriers for chemical and chemotherapeutic agents into the central nervous system.

Animals↗

In vitro stimulation of glia cells by a lymphocyte-produced factor.

The factors responsible for the activation of astrocytes surrounding inflammatory brain tissues are unknown. The present study was designed to examine the ability of lymphocytes to produce astrocyte stimulating activity in cell culture. Normal rat lymphocytes stimulated with Concanavalin A, or sensitized lymphocytes, challenged with antigen in vitro, activate cultured rat glia cells by a soluble mediator which we have termed glia stimulating factor (GSF). In undifferentiated glioblasts both RNA synthesis, as measured by [5-3H]uridine uptake, and DNA synthesis, as measured by [6-3H]thymidine uptake, were stimulated by the presence of GSF. Preliminary characterisation showed the GSF to be non-dialysable and heat stable at 56 degrees C for 30 min, but not stable at 80 degrees C for 30 min. To study the effect of this factor on differentiated glia cells, brain cell cultures were treated with dibutyryl cyclic AMP (db-cAMP) which induces a morphologic transformation of glioblasts to multipolar cells that have a characteristic astrocytic appearance. After addition of GSF to db-cAMP treated astrocytes only an increase in RNA synthesis was observed. The significance of this in vitro phenomenon, mediated by a glia stimulating factor, to activation of astrocytes and astrocytic gliosis in human brain diseases is discussed.

Animals↗