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Biomedical subjects

R Kahn

Publications and source records attributed to R Kahn.

At least 91 records · Page 5Linked to original sources
PubMed1989

Diagnosis of major depression by self-report.

The Symptom Checklist-90 (SCL-90), Millon Clinical Multiaxial Inventory (MCMI), and Minnesota Multiphasic Personality Inventory (MMPI) test profiles of inpatients and outpatients with DSM-III major depression (n = 48) were contrasted with the test profiles of a control group of patients with diverse psychiatric disorders (n = 68). In addition, the diagnostic efficiency of the relevant depression subscales for the diagnosis of major depression were examined. The results indicated that the three self-report tests may be used to diagnose DSM-III major depression, and that the depressed patients had characteristic test profiles.

Adult↗
PubMed1989

Molecular cloning, sequence analysis and mRNA expression of human ADP-ribosylation factor.

The ADP-ribosylation factor (ARF) is the small (21 kb) GTP-binding protein required for the efficient cholera toxin-catalyzed ADP-ribosylation of purified Gs, the stimulating regulatory component of adenylate cyclase. Human ARF cDNA clones were obtained from a human cDNA library by cross-species hybridization with bovine ARF1, and the nucleotide and deduced amino acid sequences were determined. Comparison of the sequences of human and bovine ARF1 showed 90% identity at the nucleotide level and 100% identity at the amino acid level, demonstrating the highly conserved nature of the ARF protein. Using human ARF cDNA as the probe, we have detected ARF messenger RNA (approximately 2.2-2.3 kb) in a wide variety of human tissues and tumor cell lines.

ADP-Ribosylation Factor 1↗
PubMed1989

Supravital dithizone staining in the isolation of human and rat pancreatic islets.

Dithizone, a zinc chelating agent, is known to selectively stain the islets of Langerhans in the pancreas. In the present study, we have used this stain to aid the identification of islets in material obtained by collagenase digestion of human pancreas. Islets were shown to rapidly and reversibly stain red on incubation with dithizone solution. Tissue selected on the basis of dithizone staining was shown to contain insulin-positive cells and to accumulate insulin in the medium during a subsequent period in tissue culture. Experiments with rat islets indicated that the dithizone treatment had no effect on insulin release in tissue culture, on acute responses to stimulatory glucose concentrations or on the insulin content of cells. These results suggest that dithizone staining can assist in the identification of islets from the human pancreas and may prove to be a useful tool in developing techniques for the large scale isolation of functionally intact human islets.

Animals↗
PubMed1988

Structure of tumour necrosis factor by X-ray solution scattering and preliminary studies by single crystal X-ray diffraction.

The structure of tumour necrosis factor has been investigated by X-ray small-angle scattering and X-ray diffraction using synchrotron radiation. The overall radius of gyration is 25.5 A. A plausible model accounting for the scattering curves consists of an elongated trimer with an axial ratio of 3 to 4 and a maximal chord with a lower limit of 80 A. Tumour necrosis factor has been crystallized in a trigonal space group. Our results are in favour of a single trimer in the asymmetric unit. The diffraction extends to 3.5 A.

Humans↗
PubMed1988

The role of serotonin in schizophrenia.

Studies examining serotonin (5-hydroxytryptamine; 5HT) in schizophrenia show variable and inconsistent findings, which might reflect the heterogeneity of the disease. When these studies are reviewed in the light of Crow's "two-syndrome" paradigm of schizophrenia, a new trend emerges. It appears that 5HT findings may be related to certain features of Type II schizophrenia such as negative symptoms, degenerative brain changes, and chronicity in the following manner: (1) 5HT2 antagonists, which have recently become available, have been shown to have an antipsychotic effect, particularly on the negative symptom cluster. (2) Decreased levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid have been found to be correlated with cortical atrophy or ventricular enlargement in schizophrenic patients. (3) A subgroup of chronic schizophrenic patients has been shown to have elevated levels of platelet or whole blood 5HT. We propose, then, that 5HT dysfunction might be related to Type II, or negative syndrome, schizophrenia, and that the nature of this dysfunction might involve 5HT postsynaptic receptor hypersensitivity. We further suggest that the pharmacotherapy of schizophrenia should include a 5HT-blocking component, as well as a dopamine-blocking component, and we propose that future research should address the role of selective 5HT receptor hypersensitivity in schizophrenia.

Brain↗
PubMed1988

Immunochemical studies of the 36-kDa common beta subunit of guanine nucleotide-binding proteins: identification of a major epitope.

Twenty-four of 24 rabbits immunized with the beta subunit common to guanine nucleotide binding proteins developed antibodies reactive on immunoblots with the 15-kDa (amino-terminal) tryptic fragment of beta. Only 2 of 24 developed antibodies reactive with the 26-kDa (carboxy-terminal) tryptic fragment. The 15-kDa fragment-reactive antibodies were also detected in several nonimmune sera. Antibodies reactive with the 15-kDa fragment could be affinity-purified from all beta-immune sera by adsorption to a fusion protein encoded by a cDNA clone identified by expression vector screening. The 15-kDa fragment antibodies in nonimmune sera did not bind to the fusion protein. Limited amino acid sequence homology between the 36-kDa beta subunit and the protein encoded by the cDNA clone suggested that the amino-terminal decapeptide of beta contains a major epitope. A synthetic decapeptide, corresponding to the amino terminus of the 36-kDa beta subunit, effectively and specifically blocked binding of antibodies in beta-immune sera (but not in beta-reactive nonimmune sera) to nitrocellulose-bound 15-kDa fragment. The 15-kDa fragment-reactive antibodies could be affinity-purified from beta-immune sera on a matrix containing bound decapeptide; affinity-purified antibodies reacted equally well with the 36- and 35-kDa forms of the beta subunit. Native transducin beta/gamma complexes readily blocked binding of 15-kDa fragment-reactive antibodies in immune but not nonimmune sera from binding to the nitrocellulose-bound fragment. The results show that nonimmune sera may contain antibodies directed against an epitope of the 15-kDa fragment that is buried in the native beta/gamma complex. In contrast, the amino terminal decapeptide of the beta subunit is exposed on the surface of the native protein and contains a major antigenic site in both the 35- and 36-kDa forms.

Amino Acid Sequence↗
PubMed1987

Hormonal probes of central serotonergic activity: do they really exist?

The response of a hormone allegedly under 5-hydroxytryptaminergic (5-HT-ergic) control to a compound stimulating or inhibiting serotonergic activity has been used as a measure of the functional state of central serotonergic systems. The relevant literature is reviewed, and based on that, it is concluded that, as yet, no reliable hormonal 5-HT probe exists. The main problems are nonselectivity of the challengers and noncomparability of individual studies because of variations in dose and route of administration. An acceptable hormonal 5-HT probe should at least have passed the following three tests. The influence of the challenger on catecholaminergic (CA) systems must be rendered unlikely in humans to avoid the pitfalls of, say, the 5-HT precursors whose CA-ergic influences have been overlooked. Dose-response relationships must be established to avoid the confusion caused by different investigators using the challenger in different doses. It must be demonstrated that the effect of the challenger is counteracted by its functional opponent.

Central Nervous System↗
PubMed1987

Therapeutic indications for serotonin-potentiating compounds: a hypothesis.

The original antidepressants, tricyclics and MAO inhibitors, increase the availability in the brain of both 5-HT and NA. Prompted by clinical findings suggestive of 5-HT disturbances in depression, drugs were developed that increase 5-HT selectively. Data are presented that suggest that broad-spectrum compounds may provide better conditions for antidepressant effects than the 5-HT-selective ones. The hypothesis is proposed that 5-HT potentiators are partial antidepressants, in that they predominantly reduce the anxiety/aggressive component of the depressive syndrome, and deserve to be tested in conditions with heightened anxiety and/or aggression irrespective of the nosological diagnosis. Tentative evidence relates diminished 5-HT metabolism to disordered impulse control. Based on these data, trials of 5-HT potentiators in impulse control disorders unrelated to aggressive drives seem warranted.

5-Hydroxytryptophan↗
PubMed1987

Transurethral ultrasonic ureterolithotripsy using a solid-wire probe.

A multicenter study evaluates a new technique for transurethral ultrasonic ureterolithotripsy utilizing a solid-wire probe. The transverse vibrations of the probe cause greater stone disintegration. A small ureteroscope is used and a basket is not required. There was a 96.6 per cent success rate in 118 cases. This technique has significantly improved ultrasonic lithotripsy. It has proved to be useful for upper ureteral stones not amenable to extracorporeal shock-wave lithotripsy and lower ureteral stones including "steinstrasse."

Evaluation Studies as Topic↗
PubMed1987

Yeast tRNA(Asp)-aspartyl-tRNA synthetase complex: low resolution crystal structure.

Yeast aspartyl-tRNA synthetase, a dimer of molecular weight 125,000, and two molecules of its cognate tRNA (Mr = 24160) cocrystallize in the cubic space group I432 (a = 354 A). The crystal structure was solved to low resolution using neutron and X-ray diffraction data. Neutron single crystal diffraction data were collected in five solvents differing by their D2O content in order to use the contrast variation method to distinguish between the protein and tRNA. The synthetase was first located at 40 A resolution using the 65% D2O neutron data (tRNA matched) tRNA molecules were found at 20 A resolution using both neutron and X-ray data. The resulting model was refined against 10 A resolution X-ray data, using density modification and least-squares refinement of the tRNA positions. The crystal structure solved without a priori phase knowledge, was confirmed later by isomorphous replacement. The molecular model of the complex is in good agreement with results obtained in solution by probing the protected part of the tRNA by chemical reagents.

Amino Acyl-tRNA Synthetases↗
PubMed1987

Institutionalization of Alzheimer's disease patients: reducing precipitating factors through family counseling.

Although home-care of Alzheimer's disease (AD) patients is more cost-effective than institutionalization, there is limited knowledge concerning the causes and prevention of institutionalization. The goal of this project was to determine the circumstances related to institutionalization of AD patients and to determine if a family counseling program can reduce these precipitating factors. In Study 1, we surveyed 109 family members of institutionalized AD patients. Primary precipitating factors included difficulties with patient behavior, insufficient auxiliary help and respite, financial difficulties, and caregiver emotional and physical complaints. In Study 2 we evaluated the effectiveness of an enhanced counseling program which included specific intervention techniques to cope with precipitating factors. For 41 AD family members who were seriously contemplating institutionalization, the precipitating factors prior to counseling were similar to those found in Study 1. After six months of individual counseling, home visits, and participation in caregiver support groups, there was only one placement, and a consistent reduction in the precipitating factors. These preliminary results suggest that a specially designed counseling program may delay or forestall institutionalization.

Alzheimer Disease↗
PubMed1986

Detection of the major pertussis toxin substrate of human leukocytes with antisera raised against synthetic peptides.

Antisera raised against the carboxy-terminal decapeptide (KENLKDCGLF) of transducin-alpha detected the 40 kDa, major pertussis toxin substrate of human neutrophils. The antisera also detected this protein in undifferentiated HL-60 and U937 cells, and revealed an approx. 2-fold increase in protein/mg membrane protein with differentiation into mature phagocytic cells. The results provide direct immunochemical evidence for the presence of a novel, pertussis toxin-sensitive guanine nucleotide-binding protein in human leukocytes.

Antigen-Antibody Complex↗
PubMed1986

McN-A-343, a specific agonist of M1-muscarinic receptors, exerts antinicotinic and antimuscarinic effects in the rat adrenal medulla.

Pirenzepine, McN-A-343 and oxotremorine were used to determine the subtypes of muscarinic receptors involved in the secretion of catecholamines from the isolated perfused adrenal gland of the rat. In the presence of 0.1 microM pirenzepine, the concentration-secretion curve for muscarine was shifted in parallel to the right by almost one log unit. With 0.5 microM the shift was over two log units. The apparent dissociation constant for pirenzepine was about 1.12 X 10(-8) M. Perfusion with McN-A-343 (1-30 microM) did not evoke the secretion of catecholamines. A further increase to very high concentrations (100-1000 microM) caused only a modest secretion (about 50 ng/5 min with 300 microM as compared to the same amount of secretion obtained with 1 microM muscarine). Secretion evoked by nicotine was significantly reduced (30%) by 3 microM McN-A-343, and the inhibition increased (90%) with higher concentrations (100 microM). McN-A-343 also produced concentration-dependent inhibition of catecholamine secretion evoked by muscarine. A significant effect was observed at 30 microM and reached a maximum level at 300 microM. Oxotremorine, like McN-A-343 was a partial agonist on the muscarinic receptors; but unlike McN-A-343, did not block the stimulatory effects of nicotine. Although the pirenzepine data suggest that M1 receptors are responsible for the secretion of catecholamines in the rat adrenal medulla, this conclusion is not supported by the results obtained with the M1-receptor agonist, McN-A-343, which proved to be an effective blocker of muscarinic as well as nicotinic receptors.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗