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Biomedical subjects

R Meadows

Publications and source records attributed to R Meadows.

At least 19 recordsLinked to original sources

1H, 13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site.

The backbone 1H, 13C and 15N chemical shifts of cyclophilin (CyP) when bound to cyclosporin A (CsA) have been assigned from heteronuclear two- and three-dimensional NMR experiments involving selectively 15N- and uniformly 15N- and 15N,13C-labeled cyclophilin. From an analysis of the 1H and 15N chemical shifts of CyP that change upon binding to CsA and from CyP/CsA NOEs, we have determined the regions of cyclophilin involved in binding to CsA.

Amino Acid Isomerases

Cell cycle perturbations following DNA damage in the presence of ADP-ribosylation inhibitors.

Cell cycle analysis by DNA flow cytofluorimetry and autoradiography has been utilized to investigate the effects of 3-methoxybenzamide (MBA), a potent inhibitor of ADP-ribosylation reactions, on cell cycle progression in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated C3H10T1/2 cells. Following a dose of 6.8 microM MNNG, the presence of MBA resulted in an increased length of S phase from approximately 6.5 h to 10 h and in an accumulation of cells in G2 with a mitosis delay of 12 h. Progression to the next S phase occurred 5-10 times more slowly and the cells ultimately accumulated in G2. Increasing the dose of MNNG resulted in a complete block in cell division in the absence of ADP-ribosylation. These results suggest that ADP-ribosylation reactions, which do not seem to be necessary for DNA excision repair in nondividing cells, are essential for coordinating the events of DNA excision repair with DNA replication and events related to progression through the cell cycle.

Animals

Effect of nicotinamide analogues on recovery from DNA damage in C3H10T1/2 cells.

The effects of nicotinamide analogues on cellular recovery following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment have been characterized in the transformable cell line, C3H10T1/2. The recovery of cell division potential was measured under conditions which allow simultaneous quantification of intracellular levels of poly(adenosine diphosphate ribose), nicotinamide adenine dinucleotide, and rates of RNA, DNA, and protein synthesis. 3- Methoxybenzamide (MBA), 3-aminobenzamide, and benzamide, which are effective inhibitors of adenosine diphosphate ribosyltransferases , blocked recovery of cell division following treatment with 34 microM MNNG, while the noninhibitors , 3- methoxybenzoate and benzoate, had no effect. In the presence of MBA, cells progressively lost the ability to resume cell division during the first 24 to 36 hr following DNA damage. The intracellular levels of poly(adenosine diphosphate ribose) increased approximately 7-fold within 20 min following MNNG treatment, and 1 mM MBA inhibited this increase by approximately 82%. In the presence of MBA, a dramatic decrease in the rate of DNA synthesis occurred approximately 16 hr after MNNG treatment, while RNA and protein synthesis continued at rates similar to those in cells treated with MNNG alone.

Animals

Acute post-streptococcal glomerulonephritis in adults: a long-term study.

The long-term outcome after acute post-streptococcal glomerulonephritis was studied in 57 patients (52 aged 16 or over) followed for a period of one to 14 years (mean seven years). All patients presented with hypertension, haematuria and proteinuria. The antistreptolysin-0 titre was raised or the serum complement was low in all cases at the initial episode. All patients had histological evidence of a diffuse proliferative and exudative glomerulonephritis at onset. Follow-up renal biopsy was performed in 33 patients; in 18 patients this was carried out five years or more after the initial illness. Five patients died beyond two years, only two having had abnormal renal function at the time or death. Four patients were found to be mildly hypertensive without other clinical abnormalities. Eleven patients had proteinuria, haematuria or abnormal renal function; in three of these repeat renal biopsy was normal, incomplete resolution was reported in five, obsolescent glomeruli in one, and two others were not biopsied. No patient who had normal renal function at the time of follow-up had abnormal renal histology on biopsy. Obsolescent glomeruli were present in two other biopsies in association with evidence of incomplete resolution. It was concluded that the majority of patients with acute PSGN have a good prognosis. Histological resolution of the renal lesion may not occur for nine years.

Acute Disease

Acute interstitial nephritis following ampicillin hypersensitivity.

A case of acute anuric renal failure following hypersensitivity to ampicillin is presented. Renal biopsy showed severe interstitial nephritis. Treatment with prednisolone and heparin, together with supportive measures and peritoneal dialysis, was followed by rapid recovery of renal function. It is concluded that hypersensitivity to ampicillin can cause acute interstitial nephritis, analogous to that seen with penicillin and methicillin.

Acute Disease

IgA-associated glomerulonephritis.

Mesangial IgA depostiiton was detected by routine fluorescent microscopy of 19 cases of glomerulonephritis. Twelve patients had a variable degree of diffuse mesangial proliferative glomerulonephritis. The heterogeneous histological findings in the other seven patients show that mesangial IgA deposition alone does not have diagnostic specificity. However, when interpretation of the mesangial IgA deposition is complemented by clinical and histological information, a group of patients with the characteristic combined features can be distinguished.

Adolescent