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Biomedical subjects

R Henning

Publications and source records attributed to R Henning.

At least 73 records · Page 4Linked to original sources

Timolol and hydrochlorothiazide-amiloride in primary hypertension.

Fifty-five patients with primary hypertension, World Health Organization (WHO) stages I and II, were randomly allocated to a 9-mo multicenter, controlled, double-blind, crossover study with timolol, a nonselective beta adrenoceptor blocker, and hydrochlorothiazide combined with the potassium-sparing drug amiloride (AHCT). In 54% of the patients the blood pressure responded to timolol, in 87% to AHCT, and in 91% to a combination of the two. The diurectic was more effective than the beta blocker in patients with low-renin hypertension, who all responded to AHCT. Overall, there was no correlation between pretreatment plasma renin activity (PRA) and hypothensive effect of either drug. Timolol reduced PRA by 58% and plasma aldosterone (PA) by 23% while AHCT increased these levels threefold. Combination therapy increased PA while PRA returned towards baseline, suggesting greater aldosterone stimulation by the diuretic component. Serum triglycerides rose during timolol treatment alone and in combination. Both timolol and AHCT are effective antihypertensives. In combination they normalize blood pressure in most patients with primary hypertension (WHO stages I and II). Determination of PRA is useful as a guide to the choice of the first treatment in searching out low-renin hypertensive patients, who are best treated with diuretics.

Adult↗

Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ.

Simian virus 40 (SV40)-transformed monolayer cells were analyzed in situ by indirect immunofluorescence microscopy for the postulated cell surface location of SV40 T-antigen-related molecules. With antisera prepared against purified, sodium dodecyl sulfate-denatured SV40 T-antigen, positive surface staining was obtained when the cells had been treated with formaldehyde before immunofluorescence analysis. In contrast, living SV40-transformed cells analyzed in monolayer were surface fluorescence negative. The fixation procedure developed in this study combined with a double staining immunofluorescence technique allowed the simultaneous analysis of the same cells for the expression of both SV40 T-antigen-related surface antigen and nuclear T-antigen. The localization of SV40 T-antigen-related surface antigen on the outer surface of the plasma membrane of formaldehyde-fixed SV40-transformed cells was demonstrated directly by the protein A-mediated binding of Staphylococcus aureus bacteria on formaldehyde-fixed SV40-transformed cells precoated with antiserum against sodium dodecyl sulfate-denatured T-antigen. Both cell surface staining and S. aureus binding were found to be highly specific for SV40 T-antigen-related binding sites. These results indicate that T-antigen-related molecules in a cryptic form are located on the surface of SV40-transformed monolayer cells and can be detected in situ after modification of the cell surface architecture.

Animals↗

Massive thrombosis of the superior mesenteric, splenic, and portal veins. Report of a case.

A 19-year-old previously healthy youth developed a deep venous thrombosis and a pulmonary embolism in connection with rupture of a ligament of the left ankle. Two months later, while on effective (thrombotest value 21%) oral anticoagulant therapy, the patient had massive thrombosis of the superior mesenteric splenic and portal veins and died. There was no known predisposition to thrombosis, such as tumour, infection, or trauma. A later examination of a 12-year-old brother revealed decreased fibrinolytic activity in the vessel wall as well as a decreased fibrinolytic response to venous occlusion. Since decreased fibrinolytic activity in the vessel wall is sometimes familial, it seems reasonable to suspect that the same defect might have occurred in the patient with the fatal massive thromboembolic disease.

Adult↗

Identification of murine leukemia viral antigens detected on mouse cells by H-2 alloantisera.

H-2 alloantisera have been previously reported to contain antibodies against murine leukemia viral antigens, but the nature of the viral antigens on mouse cells which interact with these antibodies has not been established. We have found that H-2 alloantisera recognize components of molecular weight 70 000-80 000 mouse lymphocytes and leukemia cells. These components were also detected by a goat antiserum against the murine leukemia virus (MuLV) glycoprotein (gp 70) and are therefore closely related to or identical with that viral protein. Although most H-2 alloantisera detected gp 70-like molecules on lymphocytes and leukemia cells from a great variety of mouse strains, only one H-2 alloantiserum was found to interact with a gp 70 component on cells from C57BL/10 and C57BL/6 mice. Animals such as C57BL/10 mice that lacked the component reacting with most H-2 alloantisera showed increased serum levels of anti-MuLV antibodies after injection of B10.A spleen cells having a gp 70 component detectable by other H-2 alloantisera. In contrast, strains with cells reactive to antiviral antibodies in the H-2 alloantisera had low responses to MuLV antigens after a similar immunization procedure. Serum levels of anti-MuLV antibodies in both groups of mice, however, were increased after injection of Freund's adjuvant. These observations suggest that anti-MuLV antibodies in mouse alloantisera may arise from a response to viral antigens on the immunizing cells and general stimulation of the immune system.

Animals↗

Subunit structure, cell surface orientation, and partial amino-acid sequences of murine histocompatibility antigens.

Detergent and papain solubilized murine histocompatibility (H-2) antigens have been compared by gel exclusion chromatography, ultracentrifugation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and amino-acid sequence analysis. From these data, we propose a molecular model for the H-2 antigens that includes the size and arrangement of the subunits on the cell surface and in solution, and we provide evidence for the orientation of these molecules on the cell surface. Detergent solubilized H-2 antigens (molecular weight 116,000) consist of two disulfide-linked heavy chains (46,000 daltons) and two monocovalently associated light chains (12,000 daltons). Alkylation with iodoacetamide prior to extraction prevented the formation of a disulfide linkage between the two heavy chains. A water-soluble 51,000-dalton molecule (Fs) consisting of a 39,000-dalton fragment (FH) of the heavy chain and one intact light chain was obtained by papain digestion of cells or detergent extracts. Therefore, the disulfide linkage between the heavy chains is located in the remaining membrane-associated portion (Fm). Amino-acid sequence analysis of the FH fragment of H-2Kb by radiochemical techniques showed that it is identical to the detergent solubilized H-2Kb heavy chain in eight positions for the three amino acids tested. These data indicate that the fragment FH derives from the amino-terminus of the heavy chain and suggest that it projects outward from the cell surface, while the carboxyl-terminal region is associated with the plasma membrane. The described amino-terminal sequence data have been found constant in H-2Kb, H-2Kd, H-2Kk, H-2Db, and H-2Dd gene products. These data support the hypothesis that the K and D products of the major histocompatibility antigen complex have evolved by gene duplication.

Amino Acid Sequence↗

pH gradient across the lysosomal membrane generated by selective cation permeability and Donnan equilibrium.

The pH within isolated Triton WR 1339-filled rat liver lysosomes was determined by measuring the distribution of [14C]methylamine between the intra- and extralysosomal space. The intralysosomal pH was found to be approximately one pH unit lower than that of the surrounding medium. Increasing the extralysosomal cation concentration lowered the pH gradient by a cation exchange indicating the presence of a Donnan equilibrium. The lysosomal membrane was found to be significantly more permeable to protons than to other cations. The relative mobility of cations through the lysosomal membrane is H+ greater than Cs+ greater than Rb+ greater than K greater than Na+ greater than Li+ greater than Mg2+, Ca2+. The presented data suggest that the acidity within isolated Triton WR 1339-filled lysosomes is maintained by: (1) a Donnan equilibrium resulting from the intralysosomal accumulation of nondiffusible anions and (2) a selective permeability of the lysosomal membrane to cations.

Animals↗