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Biomedical subjects

L Binder

Publications and source records attributed to L Binder.

At least 55 records · Page 3Linked to original sources
PubMed1990

Stimulation of glucose metabolism in human blood cells by inhibitors of carnitine-dependent fatty acid transport.

According to a well accepted hypothesis, increased fatty acid oxidation can lead to hyperglycaemia by stimulating gluconeogenesis and reducing glycolysis. Therefore, inhibitors of fatty acid metabolism should cause hypoglycaemia by inhibiting gluconeogenesis and activating glycolysis. Various substances were tested to validate this hypothesis with regard to glucose oxidation in human mononuclear leukocytes and thrombocytes. 2-(3-Methyl-cinnamyl-hydrazono)-propionate, an inhibitor of the carnitine acyltransfer system was found to cause hypoglycaemia in whole animals and to inhibit gluconeogensis in the perfused guinea pig liver, while the acetyl-CoA/CoASH ratio was decreased. This substance stimulated the metabolism of glucose to CO2 in human mononuclear leukocytes and especially in platelets. This effect could be potentiated if concanavalin A and 2-(3-methyl-cinnamyl-hydrazono)-propionate were applied simultaneously. Under these conditions, however, fatty acid oxidation was no longer inhibited. From these results, it can be concluded that the activation of glucose oxidation by 2-(3-methyl-cinnamyl-hydrazono)-propionate is independent of its effect on fatty acid metabolism. Other inhibitors of fatty acid metabolism which were also investigated behaved similarly.

Blood Glucose↗
PubMed1989

Indication of different lactogen and somatogen binding sites in the human growth hormone molecule as probed with monoclonal antibodies.

The relationship between the structure of human growth hormone (hGH) and the hormone-receptor interaction has been investigated using as probes monoclonal antibodies (Mabs) to hGH of defined epitope specificity profile. Seven high affinity Mabs were studied for their ability (i) to inhibit the binding of 125I-hGH to Nb2-SP rat lymphoma cells and to IM-9 human lymphocytes possessing lactogen and somatogen type receptors, respectively; and (ii) to interfere with the hormone (hGH or Met8Leu hGH)-induced proliferation in Nb2-11C lymphoma cells. The ability of these Mabs to inhibit the 125I-hGH binding and the hormone-induced proliferation in Nb2-11C cells was negatively correlated with the ability of these Mabs to cross-react with met14 hGH. Furthermore, Mabs Nos. 3 and 7, which cross-reacted minimally (0.2-0.4%) with Met8Leu hGH, were unable to interfere with the mitogenic activity of Met8Leu hGH in Nb2-11C cells. These results indicate that the first 13 amino acids of the N-terminal region of hGH are necessary for its lactogen activity. The inhibition of 125I-hGH binding to IM-9 cells by these Mabs was similar to those observed in Nb2-SP cells, except for Mabs Nos. 19 and 1. These Mabs inhibited more strongly the binding of 125I-hGH to IM-9 than to Nb2 cells and recognized antigenic epitopes close to the C-terminal part of the molecule. These results suggest that the somatogen receptor binding site of hGH may be located on two sites, one at the N-terminal and the other one close to the C-terminal, while the lactogen receptor is mainly confined to the N-terminal part.

Animals↗
PubMed1989

Chimeric bovine-human growth hormone prepared by recombinant DNA technology: binding properties and biological activity.

A chimeric bovine GH (amino acids Met-Asp-Gln-greater than 1-23) and human GH (hGH) (amino acids 24-191) plasmid was constructed and expressed in Escherichia coli. The purified protein (chimeric GH) exhibited a 2-3 order of magnitude lower affinity toward lactogenic receptors in Nb2 lymphoma cells, microsomal fractions from bovine mammary gland and male rat liver. The affinity towards somatogenic receptors in IM-9 human lymphocytes and male rat liver was decreased to a much lesser degree. This diminished affinity towards lactogenic receptors was accompanied by a parallel decrease in the ability of the chimeric GH to stimulate proliferation of Nb2-11C lymphoma cells and the lipogenesis in bovine mammary gland. This implies that occupation of the respective receptors by either chimeric GH or hGH leads to identical postreceptoral effects. The chimeric GH was also capable of down-regulating the lactogenic receptors in Nb2 lymphoma cells and was recognized by three anti-hGH monoclonal antibodies. These and previously published results indicate that the N-terminal part of hGH is essential for the high affinity binding to lactogenic receptors and subsequent biological effect. Removal or replacement by a corresponding part of bovine GH converts the hormone, respectively to weak antagonist or agonists. Analysis of our data, based on hydropathy index leads us to suggest that the high affinity binding site of the hGH towards lactogenic receptors is mainly confined to amino acids nos. 8-18.

Animals↗
PubMed1989

Failure of prediction of liver function test abnormalities with the urine urobilinogen and urine bilirubin assays.

A prospective observational study of 229 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. Both urine tests exhibited remarkably similar characteristics overall once they were adjusted to maximize accuracy and predictive values (occurring at a normal or abnormal "threshold," respectively, of 3.4 or 5.07 mumol/d for urobilinogen and 0 or 1+ for urine bilirubin). The percentage of cases correctly identified were 81% to 83% for serum bilirubin assays, 68% to 72% for other LFTs, but only 62% to 63% for screens for cases with at least one abnormal LFT finding. Poor sensitivities (47% to 49%) limited the detection of abnormal findings by the screen; both screens were reasonably specific (79% to 89%), but negative predictive values were suitable (89%) for serum bilirubin results only and were prohibitively lower (49% to 50%) in predicting all patients without LFT abnormalities. We conclude that spot urine urobilinogen and urine bilirubin determinations, although good screens for isolated serum bilirubin elevations, have unacceptable statistical properties as predictors of other LFT results due to a high proportion of false-negative results.

Bilirubin↗
PubMed1988

Inhibition of the proliferation of Nb2 cells by femtomolar concentrations of cholera toxin and partial reversal of the effect by 12-O-tetradecanoyl-phorbol-13-acetate.

One hour of exposure to cholera toxin is sufficient to elicit a significant delay in the initiation of DNA synthesis and cell division in lactogenic hormone-dependent Nb2-11C lymphoma cells. The inhibitory effect occurs already at very low concentrations of cholera toxin (5-50 fM), at which it is not accompanied by a detectable increase in intracellular cAMP, or ADP-ribosylation of the alpha subunit of Gs, the stimulatory guanine nucleotide binding protein of adenylate cyclase; IBMX, the phosphodiesterase inhibitor, acts synergistically to cholera toxin, indicating that a minute increase in cAMP may be sufficient for the inhibition. This indication is substantiated by the finding that dibutyryl cAMP also inhibits cell proliferation. Phorbol diester reverses partially the inhibitory activity of cholera toxin. It is most likely that this effect does not result from blocking the increase in cAMP, but rather from some subsequent, yet unidentified, events. The inhibitory effect of cholera toxin is not dependent on the concentration of the proliferation-stimulating lactogenic hormone and cannot be abolished or reduced by excess of the hormone. Cholera toxin also inhibits the autonomous proliferation of a lactogenic hormone-independent cell line (Nb2-SP); however, in this case the inhibition is not affected by TPA.

Animals↗
PubMed1988

Epitopes that span the tau molecule are shared with paired helical filaments.

Tau protein has been shown to be an integral component of Alzheimer paired helical filaments (PHF). However, the extent to which tau is incorporated into PHF has not been clear because the antibodies used to label PHF generally do not have precisely defined epitopes. Here we define the antigenic sites for five monoclonal antibodies that react with tau and cross-react with SDS-extracted neurofibrillary tangles. The reactive sites were determined by screening a lambda gt11 sublibrary expressing small fragments of the tau sequence. The mapped epitopes were found to span almost the entire length of tau, suggesting that PHF contains tau in its entirety or nearly in its entirety. One antibody was found to cross-react with microtubule-associated protein 2, implying some degree of homology between the two proteins.

Alzheimer Disease↗
PubMed1988

Abnormalities of urine urobilinogen and urine bilirubin assays and their relation to abnormal results of serum liver function tests.

A prospective observational study of 324 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. High positive predictive values (88% for at least one abnormal LFT) make the evaluation of positive urine screens detected during routine health care maintenance examinations imperative. Because extraneous factors may influence both urine and serum test results, however, urine assays obtained as a screening parameter in clinical presentations (abdominal pain, jaundice, constitutional symptoms, etc) have only limited clinical utility. The high proportion of false-negative results for both urine assays renders their statistical properties unacceptable as screens in these clinical situations.

Adolescent↗
PubMed1988

Effects of 2-(3-methyl-cinnamyl-hydrazono)-propionate on fatty acid and glucose oxidation in the isolated rat diaphragm using 14C-labelled substrates. Hydrazonopropionic acids, a new class of hypoglycaemic substances, VIII.

The influence of 2-(3-methyl-cinnamyl-hydrazono)-propionate on the utilization of various substrates in isolated rat hemidiaphragms was investigated in comparison with other hypoglycaemic compounds. The effect of 2-(3-methyl-cinnamyl-hydrazono)-propionate was concentration-dependent. At a concentration of 0.5 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate, glucose utilization increased from 0.276 +/- 0.043 mumol.g-1.l-1 to 0.894 +/- 0.303 mumol.g-1.l-1 (p less than 0.05). Pyruvate and lactate utilization were stimulated to a lesser extent, while acetate utilization remained nearly constant. At a concentration of 2 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate, the oxidation of palmitate decreased from 0.214 +/- 0.017 mumol.g-1.l-1 to 0.060 +/- 0.005 mumol.g-1.l-1, while the oxidation of octanoate was not decreased. These findings point to a stimulation of the glycolytic flux by inhibition of long-chain fatty acid oxidation.

Animals↗
PubMed1987

[Therapeutic possibilities in diseases caused by intestinal parasites].

Compatible and efficient drugs for the therapy, caused by protozoal- or helminthic-infections, are available today. Many of them are not registered in Austria. Metronidazole, Mebendazole and Praziquantel are particularly effective. Most protozoal-infections can be treated with metronidazole. Mebendazole can be used against numerous nematode-infections (Ascariasis, Trichuriasis, Oxyuriasis, Ancylostomiasis), Niclosamide against cestode-infections (Taeniasis, Hymenolepiasis, Diphyllobothriasis), whereas, Praziquantel is applied against trematode-infections.

Anthelmintics↗
PubMed1987

Inhibition of mitochondrial carnitine acylcarnitine translocase-mediated uptake of carnitine by 2-(3-methyl-cinnamyl-hydrazono)-propionate. Hydrazonopropionic acids, a new class of hypoglycaemic substances, VI.

The rate of mitochondrial carnitine-carnitine exchange mediated by carnitine acylcarnitine translocase was measured by following the uptake of L-[methyl-14C]carnitine. It was demonstrated that the hypoglycaemic compound 2-(3-methyl-cinnamyl-hydrazono)-propionate causes a concentration-dependent decrease in the rate of the translocase-mediated transport of carnitine in guinea pig liver mitochondria. Apparent initial influx rates were decreased by 20% at 0.3 mmol/1 2-(3-methyl-cinnamyl-hydrazono)-propionate, 38% at 0.5 mmol/l, and 75% at 2.0 mmol/l of this compound. This finding may explain the previously observed inhibitory effects of this substance on long-chain fatty acid oxidation, ketone body production and gluconeogenesis.

Animals↗
PubMed1986

Hemorrhagic disease of the newborn: an unusual etiology of neonatal bleeding.

Emergency physicians may encounter presentations of bleeding in the neonate that have multifactorial etiologies. A case of a 15-day-old male infant with umbilical bleeding that exhibited many of the characteristic features of hemorrhagic disease of the newborn (nonmedically attended birth, breastfeeding, no definite history of Vitamin K administration, bleeding from iatrogenic puncture sites, and isolated prolongation of the prothrombin time and partial thromboplastin time) is presented. A differential diagnosis and laboratory evaluation of bleeding in the newborn are summarized, and treatment recommendations for hemorrhagic disease of the newborn are discussed.

Blood Coagulation Tests↗
PubMed1986

Immunocytochemical localization of tubulin and microtubule-associated protein 2 during the development of hippocampal neurons in culture.

In dissociated-cell cultures prepared from the embryonic rat hippocampus, neurons establish both axons and dendrites, which differ in geometry, in ultrastructure, and in synaptic polarity. We have used immunocytochemistry with monoclonal antibodies to study the regional distribution of beta-tubulin and micro-tubule-associated protein 2 (MAP2) in hippocampal cultures and their localization during early stages of axonal and dendritic development. After development for a week or more in culture, when axons and dendrites were well-differentiated, the distribution of these two proteins was quite different. Beta-tubulin was present throughout the nerve cell, in soma, dendrites, and axon. It was also present in all classes of non-neuronal cells, astrocytes, fibroblasts, and a presumptive glial progenitor cell. In contrast, MAP2 was preferentially localized to nerve cells; within neurons, MAP2 was present in soma and dendrites, but little or no immunostaining was detectable in axons. Both beta-tubulin and MAP2 were present in nerve cells at the time of plating. From the earliest stages of process extension, beta-tubulin was present in all neuronal processes, both axons and dendrites. Surprisingly, MAP2 was also initially present in both axons and dendrites, extending as far as the axonal growth cone. With subsequent development, MAP2 staining was selectively lost from the axon so that after 1 week in vitro little or no axonal staining remained. Taken together with earlier results (Cáceres et al., 1984a), these data indicate that the establishment of neuronal polarity, as manifested by the molecular differentiation of the axonal and dendritic cytoskeleton, occurs largely under endogenous control, even under culture conditions in which cell interactions are greatly restricted.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Multiple component agraphia in a patient with atypical cerebral dominance: an error analysis.

A 52-year-old man with atypical cerebral dominance (left-handed for writing but mixed handedness for other tasks) suffered an extensive right hemisphere stroke, resulting in a combination of deficits that has not been previously reported. There were profound visual constructive and visual perceptual disturbances and a spatial agraphia, which were consistent with a nondominant hemisphere lesion. There was also a severe apraxic agraphia, which is typically associated with a dominant hemisphere lesion, but no other signs of dominant hemisphere dysfunction such as linguistic disturbance or limb-motor apraxia were present. This case serves to highlight the functional and anatomical relationship between handwriting and other forms of praxis; the various sources of error in letter formation; the need to be specific in labeling and describing agraphias ; and the role of a detailed analysis of writing errors in delineating the neuropsychological processes involved in handwriting.

Agraphia↗
PubMed1984

MAP2 is localized to the dendrites of hippocampal neurons which develop in culture.

The distribution of the microtubule-associated protein MAP2 in cultured hippocampal neurons was studied using immunocytochemistry with monoclonal antibodies. MAP2 was preferentially localized to dendritic, but not axonal, processes even in single isolated cells which developed without making intercellular contacts. Hence regional differences in the molecular composition of the neuronal cytoskeleton can develop independently of cell interactions. The presence of MAP2 may be a useful marker for identifying dendrites in cell culture.

Animals↗
PubMed1984

Pediatric gastrointestinal foreign body ingestions.

One hundred twenty-five consecutive emergency department cases of pediatric gastrointestinal foreign body ingestions were analyzed retrospectively to tabulate data, identify high risk ingestions, and draw conclusions regarding the standard of care. Eleven patients (9%) were admitted for endoscopy or observation of high risk situations. Twenty patients (16%) were managed invasively, 19 with esophageal foreign bodies; 17 of 20 attempts at invasive management were successful. There was a 2% incidence of minor complications; no major complications (perforation, obstruction, bleeding, or mediastinal infection) or complications of invasive procedures were observed. High risk factors identified included the following: 1) the ingestion of rounded objects (esophageal impaction); 2) the presence of social, developmental, or psychiatric risk factors (29.6% incidence); and 3) esophageal disease (significantly associated with recurrent foreign bodies and frequent endoscopy or other surgical procedures). We conclude that, while asymptomatic gastric and intestinal foreign bodies can be managed with outpatient observation, hospitalization is indicated for endoscopic management and for symptom complexes suggestive of complication. Immediate endoscopy is recommended for removal of esophageal foreign bodies and for direct evaluation of the esophagus.

Adolescent↗