Antihypertensive drugs: proposed sites and mechanisms of action.
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Biomedical subjects
Publications and source records attributed to R D Smith.
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We report a previously undescribed association of severe short-limbed dwarfism and macular colobomas with histological changes of cartilage resembling to some extent those of diastrophic dysplasia. Chance occurrence of two rare disorders due to different causes is considered unlikely and the patient is presumed to have a syndrome of, as yet, unknown cause.
Described here are clinical, radiological, and morphological studies of two brothers with an apparently previously undescribed mental retardation syndrome.
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Short incubation of heparinized human leukemic bone-marrow cells in phosphate buffered saline containing colcemid and overnight chilling of fixed cells yields metaphases with elongated and well-spread chromosomes. This technique enables us to do trypsin-Giemsa banding of chromosomes obtained from leukemic marrow cells otherwise difficult to band.
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The osmium tetroxide method for demonstrating lipid in human or animal tissue (Manual of Histological Staining Methods, 1968) has been modified to virtually eliminate background staining. Sections prepared by this method are suitable for either manual or automated analysis of the amount of fat tissue.
HA/ICR mice injected intraperitoneally with an LD(10) of murine cytomegalovirus develop a transiet acute glomerulonephritis characterized by cytomegalic intranuclear inclusions limited to mesangial cells. Viruria and proteinuria occur on the 3rd day and usually subside by the 10th day, accompanied by resolution of the glomerular lesion. By electron microscopy, virus synthesized within mesangial cell nuclei accumulates in intercelluar channels that course through the mesangial matrix. Virus and cellular debris are also found in channels surrounded by matrix in the juxtaglomerular area and between the epithelial cells of the macula densa. By immunofluorescence, viral antigen first concentrated in glomerular mesangial cells on the 5th day is cleared centripetally, appearing as fine granules in the juxtaglomerular area by the 7th day after infection. By the 10th day, changes are restricted to the juxtaglomerular region, and thereafter hyalinization at the glomerular vascular pole or cellular disarray of the juxtaglomerular zone with lymphocytic infiltration extending into the renal interstitium from few glomeruli occurs in approximately 40 per cent of the mice associated with persistence of viral antigen in these foci. These findings indicate that at least one route of transport resulting in viruria involves the glomerular mesangium, juxtaglomerular zone, and the distal convoluted tubule. Persistence of viral antigen or other noxious substances along this route may result in a unique juxtaglomerular lesion and interstital nephritis.
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A total of 22 nonsplenectomized Hereford, Holstein-Friesian, and cross-bred 18-month-old cattle were used to assess the degree of protection conferred by previous infection with Babesia bovis or B bigemina against infection and disease from tick-borne challenge exposure with the heterologous species. Prior infection with B bigemina or B bovis did not significantly (P less than 0.05) reduce the susceptibility of cattle to tick-borne infection and disease caused by the heterologous species. Carrier infections were not activated during heterologous species challenge exposure, nor was the severity of the challenge-exposure infection aggravated. Immunologic cross reactivity in the indirect fluorescent antibody test was restricted to the period during and shortly after recovery. Homologous indirect fluorescent antibody titers persisted long after primary infections with B bovis, but gradually declined in B bigemina-immune cattle. Babesia bovis infections caused severe reactions characterized by high fever, pancytopenia, and death of 9 of 15 infected cattle. Total serum bilirubin and urea nitrogen values increased markedly within 24 hours preceding death and were often accompanied by clinical signs of CNS involvement (incoordination, opisthotonos, and paddling). Microscopic lesions were restricted largely to kidney, CNS, and liver parenchyma and were characterized by vascular congestion and aggregation of infected erythrocytes in small vessels. Babesia bigemina, in contrast, caused only mild fever and anemia despite prolonged parasitemia and marked thrombocytopenia. The absence of significant (P less than 0.05) heterologous species immunity indicated that protection of cattle from these 2 babesial parasites will require specific immunization against each species.
An evaluation of some system variables for the suspension-culture method of in vitro Babesia bovis cultivation has identified some variables as critical and suggested optimum values for others. Growth of Babesia was not affected by siliconizing the culture vessels or including HEPES buffer in the culture medium. THe culture pH, however, markedly influenced the growth rate. When supplemented with a large amount of serum, even Hanks's balanced salt solution was an adequate medium to support growth of B bovis, but growth improved with increasing medium complexity. A comparison of growth in the complex mammalian tissue culture mediums RPMI-1640, medium 199, and NCTC-135 showed no significant differences. Heparinized plasma (plasma with added heparin ) could not be substituted for serum. While serum could be stored by either freezing or refrigeration at 4 C for up to a week RBC rapidly lost their ability to support growth of B bovis when stored at 4 C. Preliminary experiments with the gaseous environment indicated that CO2 is required and that the optimum oxygen tension was near the normal atmospheric level of about 20%.
Babesia bovis was isolated from an experimentally infected calf (No. 1) and was maintained in vitro for 32 days by subculturing 14 times, using a total dilution of 192,000. A splenectomized calf was inoculated with subculture Babesia (isolate B). The agent (isolate C) was isolated and maintained in vitro for 17 days prior to inoculation of a third splenectomized calf. Babesia organisms (isolate D) were isolated and retained in vitro for 270 days. After 85 days in vitro, organisms from this third isolation (isolate D) were injected into a fourth splenectomized calf to test for infectivity. Responses of the three calves to cultural inoculation were similar to those responses that occurred from inoculation of infected bovine blood (calf 1). There was no observed change in the microscopic appearance of the Babesia in vitro with time.
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Nine cases of peliosis hepatis are reported: five of these were associated with the administration of androgen or anabolic androgenic steroids and a sixth with large doses of medroxy-progesterone acetate. In five instances, neoplasm was present as an underlying disease. Antemortem evidence of liver disease was detected in six of seven cases but was not severe and had not contributed to death. The pathogenesis of blood-filled cystic cavities is discussed and the literature reviewed. Angiopathy of hepatic sinusoids in patients with wasting diseases or in those receiving androgens in coexistence with passive congestion of the liver appear to be factors in the pathogenesis of pleiosis hepatis.