S S Sumner MB, CHB, FRCS ED, DOMS.
Explore the source record for details and available documents.
SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Highly polyploid cells were detected in ganglia of Drosophila melanogaster larvae homozygous for the chbv40 mutation (78D) resulting from insertion of the P[lArB] construction. Frequency distribution of metaphases differing in chromosome number showed that the primary defect caused by the mutation involved formation of the unipolar chromosome spindle. This was confirmed directly by cytological analysis. Circular mitotic figures (CMF), i.e., circles of chromosomes with centromeres pointing inward and chromatid arms pointing outward, were also observed in neuroblasts of the homozygotes. Such structures are characteristic of polo and mgr mutations that alter the functions of the centrosome.
The phosphoenolpyruvate:glycose transferase system (PTS) is a prototypic signaling system responsible for the vectorial uptake and phosphorylation of carbohydrate substrates. The accompanying papers describe the proteins and product of the Escherichia coli N, N-diacetylchitobiose ((GlcNAc)(2)) PTS-mediated permease. Unlike most PTS transporters, the Chb system is composed of two soluble proteins, IIA(Chb) and IIB(Chb), and one transmembrane receptor (IIC(Chb)). The oligomeric states of PTS permease proteins and phosphoproteins have been difficult to determine. Using analytical ultracentrifugation, both dephospho and phosphorylated IIA(Chb) are shown to exist as stable dimers, whereas IIB(Chb), phospho-IIB(Chb) and the mutant Cys10SerIIB(Chb) are monomers. The mutant protein Cys10SerIIB(Chb) is unable to accept phosphate from phospho-IIA(Chb) but forms a stable higher order complex with phospho-IIA(Chb) (but not with dephospho-IIA(Chb)). The stoichiometry of proteins in the purified complex was determined to be 1:1, indicating that two molecules of Cys10SerIIB(Chb) are associated with one phospho-IIA(Chb) dimer in the complex. The complex appears to be a transition state analogue in the phosphotransfer reaction between the proteins. A model is presented that describes the concerted assembly and disassembly of IIA(Chb)-IIB(Chb) complexes contingent on phosphorylation-dependent conformational changes, especially of IIA(Chb).
Clinical and morphological features of chronic hepatitis B (CHB), C (CHC), and B+C (CHB+C) were studied in 283 renal graft recipients. High total bilirubin serum levels were detected significantly more often in CHB and CHB+C patients vs. CHC patients. High ALT activity was noted in 65% of CHB patients and only in 45% of CHC patients (p = 0.003). Stable low activity of hepatitis prevailed in renal recipients; it was noted in 56.7% of CHB patients, 66.2% of CHC patients, and 62% of CHB+C patients. The character of pathomorphological liver changes in chronic viral hepatitis was studied in 53 renal graft recipients using puncture biopsy. Histopathological activity index (HAI, Knodell R.G. et al., 1981) witnessed a more severe liver lesion in CHB vs. CHC and CHB+C. Thus, inflammatory activity in CHB was found to be minimal or low in 13 patients, and moderate or high in 11 patients, whilst a minimal or low activity in CHC or CHB+C was found in 16 and 10 patients, respectively, and a moderate activity was detected only in two and one, respectively (p = 0.016 and 0.024 compared with CHB). Advanced hepatic fibrosis or cirrhosis was significantly more frequent (p = 0.006) in CHB patients (eight out of 24) than in CHC ones (none out of 18). The rate of advanced sclerotic changes in CHB+C was lower (one out of 10 patients) than that in CHB, and similar to CHC. Thus, clinico-morphological manifestations were more prominent in renal graft recipients with CHB vs. CHC.
BACKGROUND: The purpose of this community-wide study was to describe a >2-decade-long experience (1975-97) in the incidence and death rates associated with complete heart block (CHB) in patients with acute myocardial infarction (AMI). Limited population-based data exist describing recent, and changes with time therein, incidence and case-fatality rates associated with CHB complicating AMI. METHODS: We conducted an observational study of 9082 metropolitan Worcester, Mass, residents (1990 census = 437,000) hospitalized with validated AMI in all greater Worcester hospitals during 11 1-year periods between 1975 and 1997. RESULTS: Overall, CHB developed in 5.0% of patients with AMI. The incidence rates of CHB declined in the periods studied (6.0% in 1975/78 vs 3.1% in 1997). Declines in the occurrence of CHB were noted in patients with anterior or inferior/posterior MI. These trends remained after adjustment for other factors that might affect the risk of CHB. Patients in whom CHB developed experienced significantly higher hospital death rates than patients in whom CHB did not develop (46.8% vs 14.6%). However, improving trends in the hospital survival rate of patients with CHB were observed between 1975/78 (47.4% surviving) and 1997 (61.3% surviving). Patients in whom CHB developed during hospitalization were not at increased risk for dying after hospital discharge. CONCLUSIONS: Our findings indicate that the incidence of CHB complicating AMI has declined with time. The hospital prognosis of patients in whom CHB developed has improved, but these patients remain at an increased risk of hospital mortality. The long-term prognosis of patients with inferior MI and CHB is similar to that of patients in whom CHB did not develop. Patients with anterior MI and CHB may be at an increased risk of long-term mortality.
In an effort to investigate the potential of cyclic peptides as carriers for cytotoxic agents, we synthesized four cyclic peptide-chlorambucil conjugates: cyclo[Lys(CHB)-Lys(CHB)-Gaba-] (peptide Y), cyclo[Lys(CHB)-Gly-Lys(CHB)-Gaba-] (peptide A), cyclo[Lys(CHB)-beta-Ala-Lys(CHB)-Gaba-] (peptide B) and cyclo[Lys(CHB)-Gaba-Lys(CHB)-Gaba-] (peptide C). The cyclic peptides were synthesized by coupling protected amino acid residues in solution and the subsequent cyclization was performed by the pentafluorophenyl ester method as described previously (Sheh et al., 1990, 1993a,b). After deblocking the lysyl-carbobenzyloxy protecting group (Z), the conjugation was achieved by reaction with the pentafluorophenyl ester of chlorambucil (CHB). These cyclic peptides differ from one another in ring size and are disubstituted with CHB via the epsilon-amino group of the lysyl residue. The various conjugates were designed to study the effect of ring size on the mode of DNA binding and alkylation. A DNA-binding assay using lambda-DNA with ethidium bromide showed that whereas peptide Y and CHB have no observable binding affinity, the apparent binding constants for peptide A, peptide B and peptide C on lambda-DNA were determined to be 2.36 x 10(5), 1.27 x 10(5) and 3.50 x 10(5), respectively. Thus, it is suggested that cyclic peptides bearing aliphatic side chains attached to a ring larger in size than 14 members would be more favourable as regards augmenting the binding affinity. DNase I footprinting showed that no footprinting patterns were observed for the 253-mer fragment and 117-mer fragment with peptide A, but two new bands corresponding to G69 and G80 were observed for the 117-mer fragment. DNA alkylation studies using a piperidine cleavage assay on the 117-mer DNA fragment showed that the sequence selectivity, judged by reaction intensity observed with peptide A, peptide B and peptide C, was similar to that seen with CHB alone. The selectivity of alkylation for both CHB and its peptide derivatives appears to be: 3'-Pur-G-Pyr-5' > 3'-Pyr-G-Pyr-5' > 3'-Pyr-G-Pur-5' = 3'Pur-G-Pur-5'. However, there are apparent differences in the intensity of alkylation by peptides A, B, C and CHB at certain guanine residues.
Acute and subacute complete heart block (CHB) are sequelae of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy. Temporary pacemakers are routinely placed at the time of ASA, but there are no widely accepted guidelines for their management. This study examined acute predictors of subacute CHB in 52 consecutive ASA procedures in 48 patients without preexisting permanent pacemakers. Acute CHB occurred during 32 ASA procedures (62%), with the return of atrioventricular conduction on the day of ASA in all cases. New intraventricular conduction defects (IVCDs) were noted after 32 procedures (62%); in 9 of these, there was new first-degree atrioventricular block as well. CHB recurred subacutely 36 +/- 22 hours after 13 ASA procedures (25%). In 5 of these cases, there was absent or inconsistent ventricular escape rhythm. Subacute CHB did not occur in 9 cases without acute CHB during ASA or new IVCDs after ASA. Acute CHB during ASA, new IVCDs after ASA, and new first-degree atrioventricular block after ASA incrementally increased the risk for subacute CHB. In conclusion, patients with acute CHB during ASA or new IVCDs after ASA are at high risk for developing subacute CHB, sometimes without a reliable escape rhythm; these patients should therefore have temporary pacing support for > or = 48 hours after ASA or the last occurrence of CHB. Patients without acute CHB during ASA or new IVCDs after ASA are at low risk for subacute CHB.
1-Cyano-2-hydroxy-3-butene (CHB), an aliphatic nitrile found in cruciferous vegetables, causes a two- and sevenfold elevation in reduced glutathione (GSH) in rat liver and pancreas, respectively, after oral administration of 200 mg/kg. While this dose is also associated with pancreatotoxicity, a single 100 mg/kg dose or multiple lesser doses show the same effect, although somewhat reduced in magnitude, with no concomitant toxicity. In an attempt to identify the mechanism of this increase, we investigated the effect of CHB on GSH synthesis by examining the effect of buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, on CHB-induced GSH elevation. Male Fischer 344 rats received 3 mmol BSO/kg ip 24 and 34 hr following CHB or corn oil. The CHB-mediated elevation in hepatic and pancreatic GSH was eradicated by BSO, suggesting that increased synthesis was responsible. The rate-limiting step in synthesis is gamma-glutamyl cysteine synthetase (GCS); the limiting substrate is cysteine. Therefore, CHB effects on GCS activity and hepatic and pancreatic cysteine equivalents were investigated. When rats were treated by gavage with CHB (100 mg/kg), hepatic GCS mRNA concentrations were increased 24 hr after treatment and hepatic cysteine equivalents were significantly elevated 4 hr following CHB. No significant elevation in hepatic GCS activity was observed, however, even 24 hr following CHB. Pancreatic cysteine equivalents were elevated at both 4 and 8 hr after CHB treatment. However, there was no detectable GCS mRNA or activity in pancreas, in either control or treated animals. Furthermore, CHB had no direct effect on the activity of GCS purified from kidney, regardless of whether GSH was present or absent. These results suggest that the mechanism of CHB-mediated induction of GSH may involve early increases in GSH precursors as well as a later increase in GCS mRNA. The mechanism of GSH elevation identified in these studies may hold therapeutic or prophylactic implications.
As part of a community-based study of patients hospitalized with acute myocardial infarction (AMI) in the Worcester, Massachusetts, metropolitan area, changes over time in the incidence rates of complete heart block (CHB) complicating AMI, and the prognostic impact of CHB on the in-hospital and long-term survival of these patients were examined. In all, 4,762 patients with validated AMI hospitalized at 16 hospitals in the Worcester metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988 constituted the study sample. The incidence rates of CHB complicating AMI remained relatively stable at 5.8% over the 13-year (1975 to 1988) period studied. The incidence rates of CHB were approximately twice as high in patients with inferior/posterior wall AMI (7.7%) as in those with anterior wall AMI (3.9%). Use of a multivariate regression analysis to control for factors affecting the incidence rates of CHB revealed that patients were at highest risk for developing CHB during the latter 2 study years (1986 and 1988). Patients with AMI developing CHB had higher in-hospital case fatality rates than did those without CHB overall, as well as during each of the 6 periods studied. The in-hospital survival associated with CHB did not improve over time. After use of a multivariate regression analysis to control for additional prognostic factors, the independent effect of CHB on in-hospital prognosis remained (adjusted risk of dying = 2.10; 95% confidence intervals = 1.37, 3.21). Patients with inferior wall AMI complicated by CHB were at significantly increased risk of dying during hospitalization compared with those without CHB (adjusted risk of dying = 2.71; 95% confidence intervals = 1.60, 4.59).(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To describe the incidence, time to onset and extent of anaemia occurring in patients with prostate cancer receiving combined hormone blockade (CHB) and the timing and extent of recovery from anaemia in those patients where CHB was discontinued. PATIENTS AND METHODS: Patients with prostate cancer were evaluated prospectively by physical examination and laboratory tests at baseline and at routine intervals while receiving CHB. Of 142 patients who received CHB, 133 were evaluable for the assessment of anaemia; CHB was discontinued in 76 patients, of whom 64 were assessable for recovery from their anaemia. RESULTS: Haemoglobin levels declined significantly in all patients from a mean baseline of 149 g/L to means of 139 g/L, 132 g/L and 131 g/L at 1, 2 and 3 months, respectively. Haemoglobin levels continued to decline during CHB to a mean nadir of 123 g/L at a mean of 5.6 months of CHB, representing a mean absolute haemoglobin decline at nadir of 25.4 g/L. In 120 of the 133 (90%) patients, the relative decline in haemoglobin at nadir was > or = 10% and was > or = 25% in 17 (13%) others, representing a mean absolute haemoglobin decline in this subset of 42.7 g/L. Significant symptoms related to anaemia occurred in 17 patients (13%). Anaemia and symptoms in these patients were easily corrected with the subcutaneous administration of recombinant human erythropoietin. CONCLUSIONS: The anaemia associated with androgen deprivation is significant and occurs routinely in men receiving CHB. It is normochromic, normocytic, temporally-related to the initiation of androgen blockade and usually resolves after CHB is discontinued. We suggest that patients receiving CHB undergo haematological testing at baseline, 1-2 months after initiating CHB and periodically thereafter. Patients developing anaemia should be questioned about symptoms reflecting physiological compromise (e.g. angina, dyspnoea on exertion). In the absence of other causes, CHB should be suspected in the development of anaemia in patients receiving this treatment.