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Biomedical subjects

H Kessler

Publications and source records attributed to H Kessler.

At least 199 records · Page 11Linked to original sources

Prevention of phalloidin-induced lesions on isolated rat hepatocytes by novel synthetic analogues of somatostatin.

Exposure of freshly isolated hepatocytes to phalloidin produced blebs on their surfaces: this phenomenon was time- and dose-dependent and irreversible. When hepatocytes were pretreated with somatostatin or with some of its synthetic analogues, formation of blebs was dramatically reduced. This cytoprotective effect was dose-dependent: the dose-response profiles enabled the determination of the CD50 values, i.e., the concentrations of analogues that yielded 50% cytoprotection. The analogues with sequences of amino acids in the retro form, compared to those in somatostatin-14, exhibited higher cytoprotection; the retro hexapeptide, cyclo(-Phe-Thr-Lys-D-Trp-Phe-D-Pro-), was 27 times more active than somatostatin-14. Specificity of cytoprotection was examined by pretreating hepatocytes with biologically active peptide hormones prior to exposure to phalloidin. On a molar basis, prolactin and thyroid-stimulating hormone possessed activity comparable to that of somatostatin-14, whereas glucagon was twice as active. Insulin, vitamin A and propranolol exercised less than 10% protection. The synthetic analogues of somatostatin are potent protective agents against cell lesions induced by phalloidin. Formation of blebs on hepatocytes by toxins and their prevention by agents of interest may serve as a suitable morphological assay for screening of cytotoxicity and cytoprotection.

Animals↗

Modified somatostatins as inhibitors of a multispecific transport system for bile acids and phallotoxins in isolated hepatocytes.

Somatostatin inhibits the uptake of phallotoxins and of cholic acid in isolated liver cells in a concentration-dependent manner. The inhibition is independent on the preincubation period and fully reversed by switching to a somatostatin-free buffer. Concentrations needed for 50% inhibition decreased 30-80-fold when somatostatin was modified by variation of its amino acid sequence. Some cyclic hexa- or penta-peptides inhibited both kinds of transport more strongly as the original (14 amino acid) somatostatin did. Three of the analogs showed a 2-3-fold higher potency than the others. The most potent compound (cyclo (Phe-Thr-Lys-Trp-Phe-D-Pro) 1 was studied in detail. The IC50 for the initial uptake of phallotoxin (6 microM) or of cholate (6 microM) was 1.5 or 3 microM, respectively. 1 inhibited the uptake of cholate in a competitive manner. The inhibition was independent on the preincubation time, but in contrast to somatostatin not fully reversible after a preincubation of 35 min. Somatostatin as well as its analogs prevented binding of isothiocyanatobenzamido [3H]cholate (an affinity label of the cholate transporter) to isolated plasma membranes from rat liver. The transport inhibition of cholate uptake is unlikely to be a hormonal effect of somatostatin, because the concentrations needed are approx. 1000-fold higher than circulating levels; however, it is apparently possible to increase the inhibitory potency on the tested transport system by modification of the sequence without increase of the well-known hormonal effects (Designing Activity and Receptor-Selectivity in Cyclic Peptide Hormone Analogs, Kessler, H., 18th Ervag Conference, Brussels, 1983).

Amanitins↗

The radiographic evaluation of spinal trauma.

The authors describe a systematic approach to the radiographic evaluation of spinal trauma, discussing cervical spine anatomy, the mechanism of injury, and classification of injuries, and then discuss several specific injuries of the cervical and thoracolumbar spine and their radiographic evaluation.

Cervical Vertebrae↗

Psychological aspects of genetic counseling. III. Management of guilt and shame.

Reactions of guilt and shame are conspicuous in the context of genetic counseling, and the relief of their distressing aspects is a widely held goal of genetic counselors. They are in a unique position to accomplish this; however, guidelines as to how one might proceed are not readily available. We have considered guilt and shame responses and have attempted to differentiate them, dynamically and developmentally, and have pointed out how each might be manifested in the course of genetic counseling. The major counseling tactics by means of which the alleviation or reduction of feelings of guilt and shame might be achieved are outlined and case illustrations are provided in which actual and potential counseling situations are explored and discussed.

Adult↗

Ovarian melanoma. An interesting case.

A rare case of metastatic melanoma of the ovary and extension to the omentum is reported. The tumor was discovered 25 years following enucleation of one eye for malignant melanoma of the choroid.

Choroid Neoplasms↗

Survey of 24-hour, 7-day/week hospital pharmacy service.

Emergency after-hour pharmacy services in many hospitals have been replaced by 24-hour, 7-day/week pharmacy services. A survey questionnaire was published in Hospital Pharmacy, February 1983, to be completed by hospital pharmacies that provide a pharmacist in the hospital 24 hours a day, 7-days a week. Usable responses were received from 185 hospitals. The type of hospitals and the number of beds of these hospitals varied greatly. The differing responses concerning staffing, scheduling, hours of the post-midnight shift, arrangement of vacations and holidays, the factors used in selling the concept to administration, and the handling of compensation are presented.

Emergencies↗

Non-A, non-B hepatitis in persistent carriers of hepatitis B virus.

There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees. Elevation of alanine aminotransferase was accompanied by fourfold reduction in one chimpanzee and sixfold reduction in the other in the plasma levels of HBV-associated DNA polymerase activity and simultaneously by twofold reduction in the concentration of hepatitis B surface antigen in both chimpanzees. A mediator may account for these changes in markers of hepatitis B virus infection, and this mechanism may also explain the occurrence of spontaneous regression in some persistently infected carriers. The significance of transient red cell anaemia in non-A, non-B hepatitis, which was observed in one of the chimpanzees, is yet to be established.

Alanine Transaminase↗

Ultrastructural changes in the liver in experimental non-A, non-B hepatitis.

Factor VIII, a blood-clotting derivative prepared from pooled human plasma, previously shown to cause a short-incubation-period non-A, non-B hepatitis in patients and in chimpanzees, was studied further to establish the nature of the pathological lesions associated with this infection. Percutaneous liver biopsy specimens were examined in detail. Cytoplasmic changes in the hepatocytes were observed on the 7th day after inoculation in one instance and after 13 days in the second, and persisted in the biopsy specimens for 13 weeks after infection. Abnormalities in hepatocyte nuclei, including aggregates of irregularly shaped particles 15-20 nm in size, were observed about 1 week after the onset of the cytoplasmic changes. The ultrastructural changes are described and their nature and significance discussed. Attention is drawn to somewhat similar cytoplasmic and nuclear changes occurring in other disease entities.

Animals↗

Non-A/non-B hepatitis in experimentally infected chimpanzees: cross-challenge and electron microscopic studies.

Inoculation of eight chimpanzees with factor VIII, factor IX, or "H" strain plasma resulted in enzymatic and histopathologic evidence of non-A/non-B hepatitis in all eight animals. Challenge of two chimpanzees convalescent from factor VIII-induced disease with either factor IX or "H" strain plasma resulted in non-A/non-B hepatitis only in the animal inoculated with factor IX materials. Reciprocal cross-challenge of a chimpanzee convalescent from factor IX-induced disease with factor VIII also produced unequivocal enzymatic and histopathologic evidence of non-A/non-B hepatitis. Cross-challenge of a chimpanzee convalescent from "H" strain-induced non-A/non-B hepatitis with factor VII did not cause a second bout of non-A/non-B hepatitis. These findings suggest the factor VIII materials and "H" strain plasma used in these studies share a common etiologic agent (or agents), but that factor VIII and factor IX may contain two distinct agents. Electron microscopic (EM) examination of thin-sectioned, acute-phase liver biopsies from all but one of the chimpanzees receiving the primary inocula revealed the presence of abnormal hepatocyte cytoplasmic structures previously shown to be associated with non-A/non-B hepatitis. Crystalline structure containing 25 to 30 nm particles were visualized by EM in the cytoplasm of endothelial or Kupffer cells in acute-phase liver biopsies obtained from three chimpanzees inoculated with either factor VIII materials or "H" strain plasma.

Animals↗

Rates of block by procaine and benzocaine and the procaine-benzocaine interaction at the node of Ranvier.

1. Action potentials and their maximum rates of rise, VA, were measured in single myelinated nerve fibres of the frog, Rana esculenta at room temperature. 2. On applying 1 mM procaine (pH 7.2) at 20 Hz stimulus frequency, half of the final VA reduction was reached at ton = 0.27 s; on applying 0.5 mM benzocaine (pH 7,2) at 50 HZ, ton was 0.12 s. Increasing the stimulus frequency between 2 and 50 HZ increased the rate of block by procaine but not by benzocaine. 3. Recovery in Ringer solution (pH 7.2) from 30-s treatment with 1 mM procaine (pH 7.2), the equieffective 0.15 mM procaine (pH 8.9) and from 0.5 mM benzocaine (pH 7.2) was 54%, 31% and 70%, respectively, within 1 s. 4. Changing between alkaline Ringer solution (pH 8.9) and 1 mM procaine (pH 7.2) led to transitory excessive block. Changing between 1 mM procaine (pH 7.2) and acid Ringer solution (pH 6.0) and washing out 10 mM procaine (pH 5.5) with neutral Ringer solution also led to a non-monotonic change in VA. 5. If hyperpolarizing pulses (30 ms, 20 mV) preceded the stimuli, changing the frequency of the pulse pairs led to a gradual moderate relief of block in procaine, turning off prepulses (at 10 HZ) to a gradual increase of block. In benzocaine changing from 1 to 10 HZ had no effect but turning off prepulses led to a prompt large increase of block. In procaine + benzocaine the membrane responded much as in benzocaine alone. At 1 HZ (prepulses) VA in 0.4 mM procaine was smaller than in 0.4 mM procaine + 0.3 mM benzocaine. 6. These phenomena can be explained on the assumption of voltage-dependent binding of benzocaine and procaine to a common receptor. The rate of block appears to be limited by access to the receptor, more in the case of benzocaine than of procaine.

Action Potentials↗

Delayed hypersensitivity and lymphocytic transformation in patients with Hodgkin's disease and granulomas.

Noncaseating, sarcoid-like granulomas were found in the tissues of 9 out of 31 patients with Hodgkin's disease. In vivo and in vitro cell-mediated immunity was evaluated in patients with and without granulomas and compared to a group of 20 normal controls. Hodgkin's disease patients of both groups showed a significantly reduced in vivo and in vitro response when compared to the control group. However, when patients in stages IIIB and IV were eliminated and patients in stages I, II, and IIIA examined separately, a positive skin test response to one or more antigens was elicited in 85.7% of patients with granulomas, while a markedly decreased-dose dependent response was observed in patients without granulomas. In vitro lymphocyte blastic transformation by phytohemagglutinin (PHA) was severely impaired in both groups of patients as determined by dose-responses curves. These results indicate that Hodgkin's disease patients with granulomas have a significantly better skin test response than those without granulomas.

Adolescent↗