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Biomedical subjects

S John

Publications and source records attributed to S John.

At least 19 recordsLinked to original sources

[Spontaneous kidney rupture as an early complication of Wegener's granulomatosis].

A 51-year-old woman had been suffering from blood-stained purulent sinusitis and antibiotic-resistant bouts of fever for 4 months. She had microhematuria and serological evidence of inflammation (erythrocyte sedimentation rate [ESR] 92/135 mm, C-reactive protein 5.0 mg/dl). When she was admitted to hospital suspected of having postinfectious glomerulonephritis she complained of spontaneous colic-like pains in the left flank. Within one day the haemoglobin concentration fell from 10 to 6.5 g/dl. Ultrasound and computed tomography demonstrated a large space-occupying lesion around the left kidney. At operation this was found to be a rupture of the kidney with perirenal bleeding which was treated without removing the kidney. No biopsy was taken, but serological tests showed antineutrophil cytoplasmatic antibodies (cANCA), indicating Wegener's granulomatosis as the cause of the compensated renal insufficiency and spontaneous renal rupture. Under immunosuppressive treatment the inflammatory signs (ESR 18/44 mm), fever, chronic maxillary sinusitis, raised serum creatinine concentration and the ANCA titre all regressed, while proteinuria of about 4 g/24 h persisted. There was no recurrence during a follow-up period of 15 months. Serological signs of marked inflammatory activity, urinary sediments of nephritis and spontaneous retroperitoneal bleeding should suggest that, in addition to lupus erythematodes and panarteritis nodosa, Wegener's granulomatosis be included in the differential diagnosis.

Acute Disease

Histone hyperacetylation does not alter the positioning or stability of phased nucleosomes on the mouse mammary tumor virus long terminal repeat.

Activation of mouse mammary tumor virus transcription by the hormone-bound glucocorticoid receptor results in disruption of a nucleosome that is specifically positioned on the promoter. Limited treatment of cells with the histone deacetylase inhibitor sodium butyrate prevents receptor-dependent promoter activation and nucleosome disruption [Bresnick, E. H., John, S., Berard, D. S., LeFebvre, P., & Hager, G. L. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3977-3981]. On the basis of this observation, we undertook a series of experiments to compare the structure of normal and hyperacetylated mouse mammary tumor virus chromatin. Although butyrate prevents hormone-induced restriction enzyme cutting specifically in the B nucleosome region, chromatin containing hyperacetylated histones does not differ from normal chromatin in general sensitivity to restriction enzymes. Indirect end-labeling analysis of micrococcal nuclease digested chromatin reveals that nucleosomes are identically phased on the mouse mammary tumor virus long terminal repeat in normal and hyperacetylated chromatin. A synthetic DNA fragment spanning the B nucleosome region was reconstituted into a monosome by using core particles containing normal or hyperacetylated histones. Analysis of the structure of reconstituted monosomes by nondenaturing polyacrylamide gel electrophoresis, salt stability, thermal stability, restriction enzyme accessibility, and exonuclease III or DNase I footprinting reveals no effect of histone hyperacetylation on monosome structure. These observations suggest that histone hyperacetylation does not induce a major change in the structure of mouse mammary tumor virus chromatin, such as nucleosome unfolding.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation

Glucocorticoid receptor-dependent disruption of a specific nucleosome on the mouse mammary tumor virus promoter is prevented by sodium butyrate.

Our laboratory has previously developed cell lines derived from mouse NIH 3T3 fibroblasts and C127 mammary tumor cells that stably express mouse mammary tumor virus (MMTV) long terminal repeat fusion genes in bovine papillomavirus-based episomes. Glucocorticoid hormone strongly activates transcription from episomes and induces the disruption of a single nucleosome in an array of phased nucleosomes on the MMTV promoter. Sodium butyrate inhibits the glucocorticoid hormone-dependent development of a nuclease-hypersensitive site that is due to the displacement of this nucleosome, and inhibits induction of RNA transcripts from episomes. Saturation binding studies show that butyrate treatment does not significantly affect the amount or the hormone-binding affinity of the glucocorticoid receptor. In a transient transfection assay, glucocorticoid hormone can activate transcription from a MMTV long terminal repeat-driven luciferase gene construct equivalently in untreated and butyrate-treated cells, indicating that the soluble factors necessary for transactivation of the MMTV promoter are unaffected by butyrate. The differential effect of butyrate on the induction of stable chromatin templates and transiently expressed plasmids suggests that butyrate prevents nucleosome displacement and represses transcription by inducing a modification of chromatin.

Animals

Valve replacement in the young patient with rheumatic heart disease. Review of a twenty-year experience.

During a 20-year period 303 young subjects between 9 and 20 years of age (mean, 16.2 +/- 2.72 years) with rapid and relentlessly progressive valvular disease from rheumatic fever underwent valve replacements. The Starr-Edwards ball valve prosthesis remains the device of choice, although other valves have been implanted. The overall hospital mortality rate was 9.6% in the mitral valve, 3.5% in the aortic valve, and 4.2% in the double valve replacement groups. Actuarial survival at 10, 15, and 20 years was 78.4% (+/- 3.3%), 70.0% (+/- 5.8%), and 59.3% (+/- 11.1%), respectively, for patients with mitral valve replacement. The rates for aortic valve replacement were 85.9% (+/- 4.6%) at 10 and 15 years and 72.7% (12.8%) at 20 years. In the double valve replacement group the survival rates after 5 and 10 years were 79.9% (+/- 5.1%). The incidence of thromboembolism was 0.41, 0.59, and 1.04 per 100 patient-years for the mitral, aortic, and double-valve prostheses, respectively. The prospect of childbearing seems promising in those young women who were subsequently married. Our favorable and gratifying experience in this review bears testimony to the physiologic advantages of the Starr-Edwards valve as the device of choice in the rehabilitation of patients with advanced and severe valvular disease after rheumatic fever.

Adolescent

Surface expression of the T cell receptor complex requires charged residues within the alpha chain transmembrane region.

The T cell receptor (TcR) complex is a multi-subunit glycoprotein comprising at least five transmembrane polypeptides. An unusual characteristic of each of the transbilayer domains is the presence of charged amino acids. To examine the importance of these residues for the association and consequent surface expression of the components of the complex, a TcR alpha chain containing either charged or neutral residues within its transbilayer segment was introduced into the human T cell line MOLT-4, and the appearance of the TcR complex at the cell surface was assayed. Surface expression was observed only in MOLT-4 cells transfected with the alpha chain containing charged transbilayer residues. Thus, these residues most probably play a crucial role in the assembly process.

Amino Acids

Early and late results of pericardiectomy in 118 cases of constrictive pericarditis.

The medical records of 118 patients (86 male, 32 female, age 10-50 (mean 27) years) who underwent pericardiectomy for constrictive pericarditis at the Christian Medical College Hospital, Vellore, from 1954 to 1985 were reviewed. All had appreciable pericardial constriction. Preoperatively 97 of the 118 were in class III or IV of the New York Heart Association classification and 100 had peripheral oedema or ascites. Tuberculosis was proved as the cause in 72 patients. Pericardiectomy was accomplished through a standard anterolateral thoracotomy (107 cases), median sternotomy (3 cases), or bilateral thoracotomy (8 cases). Postoperatively an apparent low cardiac output state was seen in 34 patients, 12 of whom died. Hospital mortality in the last 12 years was 11%. Mortality was higher in NYHA class III and IV patients. The improved surgical results recently may be related to increased use of inotropic support and prolonged ventilation. At follow up there were 72 patients in whom functional capacity could be assessed; 63 were in class I or II. The poor results of pericardiectomy in some patients are likely to be related to advanced preoperative disability and early pericardiectomy is therefore recommended.

Adolescent

Molecular structure of the gap junctional channel.

The proteins in various gap junctional preparations from rodent liver have been analysed by two-dimensional peptide mapping and immunoblotting. Only the protein of relative molecular mass (Mr) 16,000 (16K) is found in all gap junctional isolates, and it is unrelated to the 27K protein. The absence of the 27K protein and any of its fragments from trypsin-treated preparations suggests that this protein does not directly contribute to gap junctional structure. Peptide mapping and immunoblotting of the 16K proteins isolated from various tissues and species and of the arthropod 18K protein present in gap junctional preparations from Nephrops norvegicus show that these proteins constitute a family of related junctional proteins. A site-specific antiserum raised against the N-terminal octapeptide of the 16K protein from mouse liver cross-reacts with all 16K and 18K forms of the junctional protein so far tested, suggesting that this particular antigenic determinant is highly conserved. Immuno-localization studies show that the N-terminus is most likely located on the cytoplasmic aspect of the junction and is available to Pronase digestion.

Animals

A new polymorphic marker of the T-cell antigen receptor alpha chain genes in man.

The restriction fragment length polymorphism of the unrearranged T-cell antigen receptor (Tcr) alpha chain gene was investigated. Taq I digests, when probed with a Tcr alpha chain cDNA probe, revealed polymorphic bands of 7.0, 2.0, and 1.4 kb, due to variations around the C alpha gene, and the V gene cluster. Family studies confirmed the segregation of these polymorphic bands as allelic markers. These polymorphisms provide a new marker for the analysis of genetic variation of the Tcr alpha chain, and the influence of variation of the Tcr genes on the immune response.

Alleles

Coexistent mitral valve disease with left-to-right shunt at the atrial level: clinical profile, hemodynamics, and surgical considerations in 67 consecutive patients.

Between January, 1963, and June, 1985, 67 patients underwent corrective surgery for this complex anomaly. Symptoms and signs of atrial septal defect were dominant in the majority of subjects. History of rheumatic fever (46%), paroxysmal nocturnal dyspnea (33%), presence of an opening snap, mitral diastolic murmur, or pansystolic murmur provided clinical clues to document associated mitral valve disease. Open mitral valvotomy was accomplished in 39 subjects, while in the remainder (28 subjects) the valve required replacement. Partial anomalous venous connection was encountered in 12 subjects. Recognition and attention to the associated tricuspid incompetence is a high priority, and 21 subjects underwent concomitant annuloplasty. The overall hospital mortality was 13.4%, with no deaths in the last 22 consecutive patients. The period of follow-up ranged from 1 year to 22 years, with a mean +/- SD of 9.34 +/- 6.61 years. We believe, with other authors, that since the hemodynamic and therapeutic considerations are very similar, both the stenotic and regurgitant lesions should be included in the same syndrome.

Adolescent

Surgical treatment of ruptured aneurysms of the sinus of Valsalva.

Aneurysms of the sinus of Valsalva are usually congenital in origin. When they rupture, it is generally into the right atrium or the right ventricle. Signs of a left-to-right shunt, aortic runoff, and cardiac decompensation are the cardinal features. Early diagnosis and surgical correction result in cure. We report our experience with 28 patients. In all patients, we used a combined aortocameral approach, and we recommend a sandwich patch for the repair. Aortic valve replacement is needed only in patients with severe degenerative changes. The overall operative mortality was 21.4%, but in the last 10 years, mortality was only 11.7%. The causes of operative and late mortality are discussed.

Adolescent

The clinical profile and surgical treatment of tetralogy of Fallot in the adult: results of repair in 200 patients.

This report describes our 17-year experience with intracardiac repair in 200 patients older than 14 years with tetralogy of Fallot. Congestive failure, hemoptysis, and cerebral abscess were present in 15, 10, and 3% of patients, respectively. Prior palliative shunts had been performed in 24.5% only. Polycythemia with a hematocrit greater than 60% was noted in 100 patients but was not considered an incremental risk factor (p greater than 0.05). A transannular gusset was utilized in 74% of patients in the last 5 years of the study. Hospital mortality was 1.3% in the last 5 years. Ninety-seven percent of survivors at follow-up are asymptomatic and leading an active life. Recatheterization data from 86 patients revealed excellent or good results in 88%. The incidence of residual ventricular defect was 1% overall, with a zero incidence in the last 12 years. On the basis of this review, we consider that easier and hemodynamically satisfactory repair has been achieved in the adolescent and older patient compared with the child. The ultimate longevity, however, must await the results of long-term functional and serial hemodynamic evaluation.

Actuarial Analysis