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Biomedical subjects

C D West

Publications and source records attributed to C D West.

At least 91 records · Page 5Linked to original sources

Assessment of 11beta-hydroxylase activity with plasma corticosterone, deoxycorticosterone, cortisol, and deoxycortisol: role of ACTH and angiotensin.

UNLABELLED: In this study we evaluated the role of ACTH and angiotensin on regulation of activities of 11beta-hydroxylases of the adrenal cortex. The ratio of the plasma concentrations of 11 deoxycorticosterone (DOC) to plasma corticosterone (B) reflected the activity of the enzyme of the B and/or aldosterone pathways, and the ratio of plasma 11-deoxycortisol (S) to plasma cortisol (F) as the activity of the enzyme in the F pathway. In normal subjects, both ratios were significantly lower at 0800-0900 h (Doc to B, .01+/-.004, mean+/-SE, n=10; and S to F, .01+/-.003) than at 2000 h (DOC to B, .028+/-.024 and S to F, .015+/-.005). The plasma levels of DOC, B, S and F were all significantly lower at 2000-2100 h than at 0800-0900 h. In contrast 9 patients with Cushing's syndrome exhibited no diurnal change in the ratios. The ratios increased substantially following dexamethasone or metyrapone administration. A high or low salt diet and an angiotensin infusion produced no significant effect on the ratios. The plasma concentration of all four steroids was increased by more than 50% by an infusion of angiotensin. Four hours after administration of 80 mg of Lasix at 0800 h to 10 normal subjects, the ratios of DOC to B and S to F increased significantly (P less than .02), an effect possibly related to a decreased secretion of ACTH. CONCLUSIONS: 1) 11beta-hydroxylase activity of the B and/or aldosterone and F pathways appears to change in parallel with ACTH secretion, and 2) although angiotensin stimulates steroidogenesis of the pathways, it has no apparent effect on 11beta-hydroxylase activity.

17-Hydroxycorticosteroids↗

Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane.

Seven patients with a form of membranoproliferative glomerulonephritis distinct in its glomerular ultrastructure from other forms are described. The use of silver impregnated electron micrographs revealed contiguous subepithelial and subendothelial deposits associated with basement membrane disruption, replication and layering of lamina densalike material. By light and fluorescence microscopy the appearance was distinctive but not diagnostic. Immunohistology consistently showed abundant C3 and properdin in a granular pattern while immunoglobulins and Clq were variably present. Low serum C3 concentrations were observed at some time in each patient, often accompanied by low levels of properdin, whereas the concentrations of Clq and C4 were normal. The patients were indistinguishable in their clinical course from those with other types of MPGN.

Basement Membrane↗

Correlations between serum factor B and C3b inactivator levels in normal subjects and in patients with infections, nephrosis and hypocomplementaemic glomerulonephritis.

In normal subjects, factor B and C3b inactivator (KAF) levels were linearly related (r = 0-71); factor B levels in subjects with low normal levels of KAF were significantly lower than in those with high normal levels of KAF. This relationship is postulated to be the result of modulation by the level of KAF of the availability of nascent, spontaneously formed, C3b, in turn responsible for a constant low-grade activation of the C3b feedback which determines in part the level of factor B. The correlation did not obtain in patients with infections; levels of KAF and, to a greater extent, factor B were elevated. In patients with glomerulonephritis and hypocomplementaemic because of in vivo classical pathway activation, KAF and factor B levels were also poorly correlated, presumably because many factors were influencing the levels of these proteins transcending the modulating effect of the concentration of KAF. On the other hand, in patients with nephrosis and with MPGN Type II, KAF and factor B levels were low but were directly correlated. In nephrosis the correlation may be the combined result of an equal rate of catabolism of these proteins and of modulation of factor B levels by the level of KAF as in normal subjects. In MPGN Type II, the correlation may reflect the fact, noted in in vitro studies, that with alternative pathway activation, the level of KAF influences the extent of factor B and C3 conversion to a greater extent than when complement is activated by the classical pathway.

Analysis of Variance↗

The effect of a low protein diet on the anatomical development of the rat brain.

Albino rats were conceived and suckled by mothers maintained on a 8% or an isocaloric 25% casein diet. After weaning, pups were maintained on their respective diets ad libitum. By most parameters of CNS maturation, rats on the low protein diet closely resembled their age-matched controls. only by the parameter of the ratio of brain weight to body weight did they resemble rats of a younger age. Camera lucida drawings of comparable Rapid Golgi-impregnated cortical neurons of 10-day-old control and experimental rats were nearly identical to each other. A similar finding was also noted in 30-day-old rats. However, with quantitative studies, the 30-day-old experimental animals showed a decrease in synaptic spine density and reduced dendritic length for some but not all dendritic processes. At all ages, experimental animals closely resembled age matched controls in the proportion of their brain weight that was neocortex, archicortex, and cerebellum. In these results we concur with Dobbing and Sands that developmental timetables for the brain are not affected by undernutrition, though extent of development may be.

Age Factors↗

Cushing's syndrome in a patient with an empty sella turcica and a microadenoma of the adenohypophysis.

A patient with Cushing's syndrome and an empty sella turcica is presented. A pituitary microadenoma was removed by the transsphenoidal approach. The Cushing's syndrome was alleviated, and the function of the other pituitary trophic hormones has remained normal eight months after surgery. It is emphasized that an empty sella turcica does not rule out a pituitary tumor. The therapeutic implications are discussed.

Adenoma↗

Shunt nephritis: the nature of the serum cryoglobulins and their relation to the complement profile.

The serum complement profiles of four patients with shunt nephritis indicated classical pathway activation of the complement system. The presence of mixed cryoglobulins was correlated with disease activity and the cryoglobulins were shown to be complement reactive. Antisera to two of the cryoglobulins recognized antigens of the infecting organism, and a specific bacterial antibody was identified in one cryoglobulin, giveing evidence that the cryoglobulins contained immune complexes. Bacterial antibody without detectable antigen was demonstrable in the sera indicating antibody excess. Renal morphology demonstrated mesangial proliferation and interposition with subendothelial and mesangial deposits. Parallels are drawn with active lupus nephritis.

Antigens, Bacterial↗

Gonadal function, testicular histology, and meiosis following cyclophosphamide therapy in patients with nephrotic syndrome.

Gonadal function, histology, and meiosis were studied in patients after puberty who had received cyclophosphamide in the treatment of nephrotic syndrome. Four males with minimal lesion nephrotic syndrome received cyclophosphamide, 2 to 4 mg/kg/24 hr, during periods ranging from 49 to 60 days and had normal semen at 15 3/12 to 22 3/12 years of age. Four males who received cyclophosphamide, 2 to 5 mg/kg/24 hr, during 89 to 489 days were azoospermic at 15 6/12 to 21 11/12 years of age. Plasma testosterone levels were normal in both groups. LH and FSH levels were elevated in the azoospermicgroup. Light and electron microscopy and meiotic analysis of testicular tissue were normal in two normospermic patients tested. Germinal cells were absent but Leydig and Sertoli cells were present in three azoospermic patients tested. No neoplasia was observed. Two preadolescent and two postadolescent males received 64 to 129 mg/kg of cyclophosphamide during 14 to 45 days and have since fathered normal children. One preadolescent female received 182 mg/kg of cyclophosphamide during 49 days and later bore a normal child. Two preadolescent females who died of complications of their nephrotic syndrome during childhood after courses of cyclophosphamide had normal preadolescent ovaries.

Adolescent↗

Classical complement pathway activation in membranoproliferative glomerulonephritis.

Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results compared with the levels in normal subjects. Although C3 and C5 concentrations were comparably depressed in type I and type II, the levels of Clq and C4 were lower in type I and the correlation coefficients between Clq vs. C4 and C4 vs. C3 were higher than in type II. The profile was highly suggestive of classical pathway activation. In contrast, in type II MPGN, factor B levels were lower and C3NeF activity was more frequently detectable and higher. A feature of interest was that type I, as compared to type II, was characterized by significantly lower serum concentrations of properdin, higher and more significant correlation coefficients between serum properdin concentrations and those of Clq, C4 and C3, and consistent glomerular deposition of properdin. The involvement of properdin in type I may reflect recruitment of a pathway resembling the C1 bypass mechanism, said to involve C1, properdin, factor B and C3-9.

Adult↗

Mesangiocapillary glomerulonephritis: changes in glomerular morphology with long-term alternate-day prednisone therapy.

In all of eight patients with mesangiocapillary glomerulonephritis who received prednisone in an alternate-day schedule for 3 to 9 hr, the glomerule showed a marked reduction in mesangial cellularity and complete regression of mesangial interposition. Subendothelial deposits disappeared but intramembranous dense deposits, when present previously, persisted. Repair was incomplete in that a few mesangial deposits were still present, immunoflourescence was unchanged, and several of the patients developed focal mesangial scarring and increased numbers of global bodies. Functional glomerule and glomerular tuft segments, however, showed greatly improved morphology. There was no evidence of deterioration of renal function over a follow-up period of 5 to 11.5 yr.

Azathioprine↗

Single-dose metyrapone test: review of a four-year experience.

Subnormal plasma 11-deoxycortisol (compound S) responses to metyrapone were found in patients with adrenal insufficiency or with Cushing syndrome caused by adrenal tumors and in those receiving long-term glucocorticoid or diphenylhydantoin sodium therapy. High normal or exaggerated responses were seen in women receiving oral contraceptives, patients with Cushing syndrome caused by adrenal hyperplasia, and those with untreated hypothyroidism. Diabetes mellitus, hypoglycemia, congestive failure, and obesity also were associated with exaggerated responses. Subnormal plasma S responses were observed in 15 patients who responded normally to a repeat test or to the standard metyrapone test. The abnormal response resulted from insufficient metyrapone, administration at the wrong time, or delay in obtaining the blood sample. The single-dose metyrapone test may be the procedure of choice in screening for adrenal insufficiency.

Adenoma, Chromophobe↗

A serum factor in chronic hypocomplementemic hephritis distinct from immunoglobulins and activating the alternate pathway of complement.

Nephritic factor (C3NeF) has been isolated from plasma of patients with hypocomplementemic chronic glomerulonephritis (HCG) by ion exchange and molecular sieve chromatography. This material was further treated with solidified anti-Ig antiserum. The purified material failed to react with antiserum to human IgG, IgG3, Fab, Fc, and kappa and lambda chains, but retained full C3NeF activity. The nonidentity of C3NeF with IgG was further demonstrated by Ouchterlony analysis using anti-IgG and anti-C3NeF. Isolated C3NeF was found to be a protein with a sedimentation coefficient of 7S and a mol wt of 150,000 daltons, which on microzone electrophoresis and gel electrophoresis at pH 8.6 behaved as a gamma-globulin. C3NeF is not a C1q precipitin and does not activate the classical complement pathway. Unlike cobra venom factor, it failed to enter into a complex with C3 proactivator (C3PA) when incubated with normal human serum (NHS) and then subjected to sucrose density gradient ultracentrifugation. The action of isolated C3NeF on C3 requires C3PA, C3PA convertase (C3PAse), and properdin (P). Similarly, C3PA conversion by C3NeF requires P, C3PAse, and C3. Total hemolytic activity was lost by incubation of 64 microg of C3NeF/1 ml NHS at 37 degrees C for 30 min. Both C3a and C5a anaphylatoxin could be generated by C3NeF in serum previously depleted of anaphylatoxin inactivator. Anti-C3NeF was found to detect an antigen in all NHS tested. Treatment of NHS with solidified anti-C3NeF caused impairment of the alternate complement pathway. It failed to sustain lysis of glutathione-treated human erythrocytes initiated by inulin. It is conceivable that the normal serum constituent which is removed by anti-C3NeF constitutes the inactive precursor of C3NeF, and a heretofore unrecognized component of the alternate pathway.

Adsorption↗

Hypocomplementemic and normocomplementemic acute nephritis in children: a comparison with respect to etiology, clinical manifestations, and glomerular morphology.

Of 182 patients with acute glomerulonephritis, 20 had normal C3 levels at onset. Normocomplementemic and hypocomplementemic patients were similar with respect to incidence and site of preceding streptococcal infection, elevation of ASO titer, distribution by age, sex, race, season, and year,\and glomerular morphology by light and electron microscopy. They differed in that the normocomplementemic patients tended to have normal serum C5 levels and, for reasons not clear, reduced serum albumin and elevated cholesterol levels. The consistent absence by immunofluorescence of IgG in the glomeruli of five hypocomplementemic patients and its presence in five normocomplementemic patients was considered a chance observation. The data suggest that in each group the nephritis was poststreptococcal and that the mechanism producing poststreptococcal glomerulonephritis is capable of acting independently of that activating circulating C3.

Acute Disease↗