Renovascular Hypertension: Pathophysiology,Diagnosis, and Treatment

Renovascular hypertension can result from renal artery lesions involving the main renal artery, or its branches. It is generally felt that the elevation of blood pressure results from excessive systemic vasoconstriction secondary to enhanced renin secretion by one or part of one kidney. Renin secretion is enhanced because of constriction of the renal artery and resultant intrarenal ischemia. Clinically patients cannot be distinguished from those with essential hypertension and diagnosis must be made with arteriography although urography and isotope renography may suggest the diagnosis. Surgical cure can be predicted if differential renal vein renin ratios lateralize but a non-lateralizing study does not necessarily mean that surgery will fail. In properly selected patients, surgical results are excellent.     

An Ly-like specificity with extensive nonlymphoid expression

The characteristics of a strong mouse alloantigen with renal, bone marrow, and lymphoid expression were studied. This antigen is probably identical to that currently designated Ly-6.2. It was defined by the high-titered (1:1000) cytotoxic activity of three different antisera against peripheral lymphocyte target cells from DBA/2, DBA/1, and a variety of other strains. In the F₂ and four backcross generations the genetic control of this specificity segregated as a single autosomal dominant gene. In lymphoid tissues the predominant expression was on T cells but 10–30% of B cells were lysed by these antisera. The specificity was expressed strongly in kidney, as shown by sequential absorption, in amounts equal to or greater than the amount in lymphoid tissues. Comparison to the rate of absorption of H-2 by kidney indicated that this antigen may be expressed in amounts comparable to an H-2 antigen in kidney. Immunization with kidney tissue resulted in a strong cytotoxic antibody response. The number of bone marrow cells expressing this antigen (40–50%) was well beyond what could be accounted for by T lymphocytes in bone marrow. In addition, a nonlymphoid tumor, the P815Y mastocytoma, was positive by cytotoxicity and by absorption. The extensive nonlymphoid expression and antigenic strength of Ly-6.2 raises the possibility that this serologically defined lymphocyte alloantigen will have histocompatibility effects when allografts of the appropriate tissues are examined.     

Distribution of the genus Leptospira in soil and water

The distribution of the aerobic spirochetes Leptospira in surface waters, soil, and aquatic animals was investigated. Isolates from water and soil exhibited physiological characteristics common to members of the "biflexa complex," none were capable of infecting experimental animals, and leptospires could not be isolated from the eight genera of aquatic animals examined. The isolation frequencies from surface waters were: stream, 100%; lake, 65%; spring, 28%; bog lake, 5%; and marsh, 0%. With the exception of the stream, more isolations were obtained from the soil adjacent to the water than from the water. Leptospires were most frequently associated with soils of high moisture and organic matter content.     

Studies on the mode of action of calciferol: Biological activity of 1α,24R,25-trihydroxyvitamin D3 in the chick

The biological activity of 1α,24R,25-trihydroxyvitamin D₃ [1α,24R,25(OH)₃D₃] was elevated in comparison to the hormonally active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ [1α,25(OH)₂D₃], in the rachitic chick in terms of its ability to (a) stimulate intestinal calcium absorption, (b) mobilize bone calcium, (c) induce intestinal calcium binding protein, (d) modulate the level of enzyme activity of the renal 25-OH-D₃-1-hydroxylase system, and (e) interact with the intestinal cystosol-chromatin receptor system for the 1α,25(OH)₂D₃ receptor system. In each of these assays, the relative ratio of activity of 1α,24R,25(OH)₃D₃ to 1α,25(OH)₂D₃was (a) 25–50, (b) ca. 20, (c) 10, (d) 50, and (e) 36%, respectively.     

A STABLE ISOTOPE METHOD FOR MEASUREMENT OF THYMIDINE INCORPORATION INTO DNA

A method has been developed for the measurement of DNA synthesis in vivo using the incorporation of multilabeled, non-radioactive thymidine. Simultaneous intraperitoneal injection of hexalabeled thymidine and tritiated thymidine into a normal adult rat resulted in the incorporation of both labeled nucleosides into the DNA of cells undergoing replication. The DNA of several tissues and organs was analysed, including liver, thymus, spleen, bone marrow, and small intestine. Following extraction with hot trichloroacetic acid, acid hydrolysis, and thin-layer chromatography of the hydrolysates, the isotopic compositions of the thymine products were determined by field ionization mass spectrometry and by scintillation counting. The relative incorporation of radioactive and stable isotope-labeled thymidine was similar in all tissues, and corresponded to the ratio of the two labeled nucleosides in the injected material. These results indicate the feasibility of utilizing thymidine multilabeled with stable isotopes for measurement of cellular proliferation rates in conjunction with cancer therapy.     

Cellulose acetate electrophoresis of protein kinases: Detection of the active forms using various substrates

Electrophoresis on cellulose acetate strips was used to analyze protein kinases from normal rat liver. In addition to already well-characterized cAMP-dependent protein kinases type I and II and cAMP-independent casein kinases I and II, this method enabled the detection of several supplementary bands corresponding to kinases which were investigated according to their substrate specificity, activation by cAMP, and inhibition by the specific inhibitor of the catalytic subunit of cAMP-dependent protein kinases or by heparin. Using this rapid, sensitive, and resolutive electrophoretic method, different isozyme patterns could be obtained starting from minute amounts of different types of biological material.     

Calorimetric studies of flavin-binding proteins: FMN and FAD binding to hen egg riboflavin-binding proteins

Systematic thermodynamic studies have been conducted for flavin (FMN, FAD) binding to purified riboflavin-binding proteins from hen egg white and egg yolk. These studies were conducted under a variety of temperature (14, 26, and 38 °C), pH (4.5, 5.5, 6.5, 7.4, and 9.0), and buffer conditions, and an extensive thermodynamic profile was constructed. Enthalpies of binding FMN to white riboflavin-binding protein and yolk riboflavin-binding protein were ?19.3 and ?14.4 kcal/mol, respectively, at pH 7.4 and 38 °C. FAD bound to white and yolk riboflavin-binding proteins under the same conditions with ΔH values of ?11.7 and ?6.0, respectively. Binding constants of about 10⁵ and 10⁴ were obtained for FMN and FAD, respectively, and were the same for both proteins under all conditions studied. Using established thermodynamic relationships, we were able to calculate entropy and free energy changes. Entropies indicated a large degree of ordering in the system upon flavin binding with FMN (about ?40 cal/mol/ °C) twice as large as FAD (about ?15 to ?25 cal/mol/ °C), which may indicate a structured solvent interaction with the charged phosphate group, or steric limitations placed on the ribityl side chain in the bound state. Our thermodynamic data support the idea that flavin binding is a mixture of forces, with no one predominant. Analysis of the data suggests that the nucleotide may bind both as the mono- or dianion, that flavin binding occurs with no significant change in the pK of any functional group in the system, except at low pH for FAD binding, and that the temperature variation of the enthalpy change is quite small. These findings are combined with other published data to outline a general scheme of flavin binding with a histidine residue implicated in hydrogen bonding to the adenine portion of FAD, which may be in the unstacked form.     

Purification and reconstitution of the 32Pi-ATP exchange activity of bovine chromaffin granule membrane

Ghosts derived from bovine chromaffin granules have a ³²P_i-ATP exchange activity which is associated with the H⁺ pump of that membrane. This activity was low when compared to bacteria, chloroplasts or submitochondrial particles, but had similar properties (K_m for ATP and P_i, ATP/Mg²⁺ ratio, pH profile, inhibition by dicyclohexylcarbodiimide and tributyltin) to the ATPase from above membranes. The ³²P_i-ATP exchange activity was solubilized by cholate/octylglucoside mixtures. The soluble extract was lipid depleted by ammonium sulfate fractionation and partially purified by sucrose gradient centrifugation. The purified preparation was reconstituted with phospholipids by freeze-thawing. The reconstituted vesicles had a ³²P_i-ATP exchange sensitive to dicyclohexylcarbodiimide and trybutyltin and an ATPase with a sensitivity to the inhibitors which varied with the reconstitution conditions. The α- and β-subunits of F₁-ATPase were major components of the preparation.