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Biomedical subjects

G Joseph

Publications and source records attributed to G Joseph.

At least 73 records · Page 4Linked to original sources

HLA-DR53 protects against thrombotic thrombocytopenic purpura/adult hemolytic uremic syndrome.

Class I and Class II HLA antigens were tested in patients treated for thrombotic thrombocytopenic purpura or hemolytic uremic syndrome (TTP/HUS) to determine whether there is a disease association. Based on the results of a pilot trial, retrospective HLA-typing of 18 patients with a diagnosis of TTP/HUS and prospective typing of 12 newly diagnosed patients with TTP/HUS were performed. Twenty-one patients were non-Hispanic Caucasians, 7 were African-Americans, and 2 were Hispanic-Caucasians. Of 30 patients tested, 28 were positive for DR52 (chi-squared = 5.14, P < 0.05), and only two were positive for DR53 compared to 57% of controls (chi-squared = 18.5, P < 0.0005). Diverse DR52 subtypes (DRB3*0101, DRB3*02, and DRB3*0301) were found by oligonucleotide testing in 15 patients, suggesting the association was not with DR52 but with absence of the DR53 antigen. The 2 patients with DR53 were not homozygous. This study suggests that the supertypic antigen, DR53, may govern susceptibility to TTP/HUS, since the relative risk of this disease among DR53 positives is reduced at 0.09 (95% confidence interval, 0.01-0.28). This finding indicates a possible immunogenetic component in the pathogenesis of TTP.

Adult↗

Propranolol for pulmonary oedema in mitral stenosis.

We report the case of a young adult with mitral stenosis and pulmonary oedema who did not respond to conventional antifailure therapy, but improved with intravenous propranolol and later underwent successful balloon mitral valvotomy. Intravenous beta blockade, though contraindicated in most cases of pulmonary oedema, may benefit patients with mitral stenosis and tachycardia.

Adolescent↗

Lack of correlation between coronary risk factors and CAD severity.

The coronary arterial lesions seen by angiography in 1666 consecutive male patients were converted to a score by the standardized scoring system advocated by Gensini. The resulting score, which allowed the disease to be expressed as a continuous variable, was effectively utilized to see the correlations between the severity of coronary arterial disease (CAD) and individual risk factors/risk markers. Significant correlations were seen between severity and age (P < 0.001), with a very low coefficient of correlation of 0.0873. On univariate analysis, no correlation was found between CAD severity and diabetes, smoking, positive family history of CAD, hypertension and other lipid fractions. On multiple regression analysis, significant correlations were found between severity and LDL Cholesterol, family history and total cholesterol after adjusting for other factors. The R2 for all these risk factors was only 14.1%. It is concluded that, although strong associations exist between risk factors and the occurrence of CAD, the small quantitative association detected between the presence of risk factors and the severity of disease is weak.

Adult↗

Middle generation roles and the well-being of men and women.

Sociological literature on gender, work, and families has focused on both conflict and benefits created by combining the spouse, parent, and paid worker roles, whereas research by family gerontologists has focused on stress experienced by those who provide care to frail elderly parents as well as other roles associated with being in the "middle generation." We examine consequences of adding middle generation roles to other major life roles during the middle years. We find that giving help to parents increases men's distress, while giving help to adult children enhances women's well-being. When help to biological parents is examined separately, it is found to increase both men's and women's distress. Women are unaffected by the multiplicity of roles while, for men, there is evidence of both role buffering and strain from conflicting demands. We discuss further directions for research on consequences of roles for well-being.

Adult↗

Primary pulmonary plasmacytoma.

BACKGROUND: A patient was diagnosed with an extramedullary plasmacytoma of the lung after complete resection of the mass at thoracotomy. Immunoperoxidase staining of the mass revealed monoclonal lambda chains. Screening for multiple myeloma identified a small amount of M-protein in the blood, but no other evidence of multiple myeloma was found. METHODS: A literature search was conducted to determine the prognosis and the best way to manage the patient. RESULTS: Nineteen cases of primary pulmonary plasmacytoma were found in the literature. The age range was 3-79 years. Most of these cases were diagnosed at thoracotomy and treated by surgical excision. Immunohistochemical evaluation of the lesion is essential for diagnosis but was done in only three cases. CONCLUSIONS: Surgery and radiation therapy seem to be equally effective forms of treatment. The role of adjuvant chemotherapy is unknown. Local recurrences are rare. Follow-up data were inadequate to determine disease-free survival, progression to multiple myeloma, and overall survival in primary pulmonary plasmacytoma. Close follow-up is needed to detect progression.

Adolescent↗

Classification of mutations at the HLA-A locus by use of the polymerase chain reaction.

We investigated whether the polymerase chain reaction (PCR) could be used to determine the mechanism of mutation in lymphocyte clones mutated at the HLA-A locus. Three polymorphisms, at Factor XIIIA, D6S109, and intron 3 of the HLA-A gene, were used to study a series of clones previously characterised by Southern blotting (SB) at multiple loci on chromosome 6. For detection of loss of heterozygosity, the results of PCR and SB were concordant in 140 of 141 clones when polymorphism in the Factor XIIIA region was studied and in 144 of 145 clones when polymorphism in the HLA-A gene was studied. For classification of the mechanism of mutation, PCR and SB gave the same result in 88 of 92 clones (96%) when a combination of the HLA-A and Factor XIIIA polymorphisms was used and in 46 of 47 clones (98%) when a combination of the HLA-A and D6S109 polymorphisms was used. The results indicate that PCR provides a simple and reliable method for categorising mutations at the HLA-A locus as arising from mitotic recombination, deletion, or from presumptive minor changes within the gene. Rare events such as gene conversion, nondisjunction, or large deletions extending to the telomere will be misclassified. However, such events are rare for mutations at this locus.

Base Sequence↗

Using mitotic recombinant mutant clonal lymphocytes for physical mapping of polymorphic loci on the short arm of human chromosome 6.

Immunoselection has been used to identify human lymphocytes that have undergone spontaneous mutation resulting in the loss of expression of one of the codominant HLA-A alleles. Approximately 35% of such mutations are the consequence of mitotic recombination events. Mitotic recombination is the result of nonsister chromatid exchange that leaves the mutated cell homozygous for all loci distal to the crossover point. The location of the crossover has been regionalized for 99 independently derived mutant lymphocyte clones by identification of their loss or retention of heterozygosity at seven reference polymorphic loci on chromosome 6. If a polymorphic locus of unknown map position is studied in clones from this ordered set of mitotic recombinants, and clones that display loss of heterozygosity and retention of heterozygosity of the locus are observed, then the map position of the locus is between the appropriate reference loci of the ordered set. The newly mapped locus becomes a reference locus in turn. In this way the mitotic recombinant mutant clones can be used to generate an ordered set of crossover points with a theoretical resolution limited only by the number of mutants generated. In this paper such a set of mutants is used to refine or confirm the map position of eight polymorphic loci on chromosome 6.

Chromosome Mapping↗

High-dose chlorambucil and dexamethasone for relapsed non-Hodgkin's lymphomas.

Twenty patients with relapsed or refractory non-Hodgkin's lymphoma were treated with high-dose chlorambucil (14 mg/m2 every 6 hours for 6 doses) and dexamethasone (40 mg/day for 5 days). There was a 45% response rate with 17% complete responses. The median duration of complete response was 7 months. The regimen was well tolerated and had minimal toxicity.

Adult↗

Left ventricular diastolic function--pulsed Doppler echocardiography versus radionuclide angiography.

Fifty five consecutive patients diagnosed to have coronary artery disease by coronary angiography had their left ventricular (LV) diastolic functions evaluated by pulsed doppler (PD) methods and radionuclide angiography (RNA). Using PD, the peak velocities of the early filling wave 'E' and the late filling wave 'A' of mitral inflow were measured. LV diastolic dysfunction, defined as E/A ratio less than 1.0, was present in 31 of 38 patients with low RNA peak filling rates (PFR) of 2.3 EDV/sec or less (sensitivity 81.6%). Normal E/A ratios (> 1.0) were seen in 13 of 17 patients with normal RNA PFR of > 2.3 EDV/sec (specificity 76.5%). Both methods were in agreement in 44 of 55 patients (accuracy 80%). There was good direct correlation between RNA PFR and PD E/A ratio (correlation coefficient r = 0.51, P < 0.01). It is concluded that PD echocardiography is a simple and reliable method of identifying diastolic dysfunction in patients with ischaemic heart disease.

Coronary Disease↗

Concerted activities of the RNA recognition and the glycine-rich C-terminal domains of nucleolin are required for efficient complex formation with pre-ribosomal RNA.

Nucleolin is an abundant nucleolar protein which is involved in the early stages of ribosome assembly. The central 40-kDa domain of nucleolin comprises four RNA recognition motifs (RRM) which are presumed to be involved in specific interactions with pre-rRNA. In order to examine in detail the role of this central domain and the contribution of the N-terminal and C-terminal domains of nucleolin to RNA binding, we have used an Escherichia coli expression system to synthezise polypeptides corresponding to various combinations of the three domains and their subdomains. By means of an in-vitro binding assay and a synthetic RNA corresponding to a specific recognition site in pre-rRNA we have been able to demonstrate conclusively that the central 40-kDa domain is indeed responsible for the specificity of RNA recognition and that the N-terminal domain can be removed without affecting RNA binding. Most interestingly, it appears that the C-terminal 10-kDa domain, which is rich in glycine and arginine residues, is essential for efficient binding of nucleolin to RNA, but does not itself contribute to the specificity of the interaction. Circular dichroic spectroscopic probing of the RNA component shows that the C-terminal domain significantly modifies the RNA-binding properties of the central RRM core. Finally, infrared spectroscopic studies reveal that the central 40-kDa domain is structured in alpha helices and beta sheets and that the interaction with the specific pre-rRNA site induces subtle changes in the beta sheet conformation.

Binding Sites↗

The glycine-rich domain of nucleolin has an unusual supersecondary structure responsible for its RNA-helix-destabilizing properties.

Nucleolin, a major nucleolar protein implicated in preribosome assembly and transcriptional regulation, possesses a C-terminal domain unusually rich in glycine, arginine, and phenylalanine residues. A polypeptide (p10), corresponding to this domain, has been synthesized by means of an Escherichia coli expression system and purified to homogeneity. Nitrocellulose binding assays have clearly shown that this domain of nucleolin is capable of interacting with RNA, and indeed all nucleic acids tested, in an efficient but nonspecific manner. A combination of circular dichroism and infrared spectroscopy provide strong evidence that repeated beta-turns are a major structural component of this polypeptide, which is entirely consistent with its amino acid composition and above all the presence of repeat motifs such as RGGF. Circular dichroism technique also shows that the interaction of p10 with RNA involves an unstacking of the nucleotide bases and an unfolding of the RNA secondary structure. While the role of the C-terminal domain of nucleolin in vivo has yet to be established, our findings suggest that it may act to unfold regions of ribosomal RNA so that a second domain of nucleolin has access to its specific binding site.

Amino Acid Sequence↗

Interactions of praseodymium and neodymium with nucleosides and nucleotides: absorption difference and comparative absorption spectral study.

The interactions of praseodymium(III) and neodymium(III) with nucleosides and nucleotides have been studied in different stoichiometry in water and water-DMF mixtures by employing absorption difference and comparative absorption spectrophotometry. The 4f-4f bands were analysed by linear curve analysis followed by gaussian curve analysis, and various spectral parameters were computed, using partial and multiple regression method. The magnitude of changes in both energy interaction and intensity were used to explore the degree of outer and inner sphere coordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Crystalline complexes of the type [Ln(nucleotide)2(H2O)2]- (where nucleotide--GMP or IMP) were characterized by IR, 1H NMR, 31P NMR data. These studies indicated that the binding of the nucleotide is through phosphate oxygen in a bidentate manner and the complexes undergo substantial ionisation in aqueous medium, thereby supporting the observed weak 4f-4f bands and lower values for nephelauxetic effect (1-beta), bonding (b) and covalency (delta) parameters derived from coulombic and spin orbit interaction parameters.

Guanosine Monophosphate↗

GM-CSF in the treatment of Felty syndrome.

Many therapeutic agents have been tried with variable success in the treatment of Felty neutropenia, but the reports are anecdotal. We now describe the second trial of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), in a splenectomized, infected patient with Felty syndrome.

Felty Syndrome↗

In vitro susceptibility of Brucella melitensis to antibiotics.

The in vitro susceptibilities of 86 recent clinical isolates of Brucella melitensis to minocycline, streptomycin, co-trimoxazole, rifampin, and six fluoroquinolones were determined. Minocycline exhibited the lowest MIC and was followed by rifampin and streptomycin. Among the quinolones, WIN 57273 and ciprofloxacin were the most active agents. No antibiotic combination of these agents exhibited synergy against 15 selected isolates. In killing rate experiments, streptomycin exhibited the most rapid kill (less than 12 h), while a complete kill with minocycline, rifampin, and ciprofloxacin was delayed up to 48 h. The combinations of streptomycin with each of minocycline, rifampin, or ciprofloxacin exhibited the fastest kills (within 2 h), while with the other combinations, a complete kill was delayed up to 96 h. These results demonstrate the discrepancy between the results of various in vitro methods in evaluating the antibiotic susceptibility of B. melitensis.

Anti-Bacterial Agents↗

Demands on tertiary care for cardiovascular diseases in India: analysis of data for 1960-89.

Data on 43,544 consecutive patients with cardiac disorders admitted to one hospital were analysed under four etiological groups to study the changing trend in the demand for tertiary care between 1960 and 1989. While rheumatic fever went down in frequency, rheumatic valvular disease remained at an average of 40% of total cardiac admissions, coronary heart disease steadily increased from 4% in 1960 to about 33% in 1989, and congenital heart cases accounted for 24% of cardiac admissions. While other etiological groups have varied, coronary heart disease has shown an almost linear increase. The demand for cardiac surgery also has risen almost linearly. The implications of these findings on the health needs and health planning in the whole country pose a great challenge to planners.

Cardiac Rehabilitation↗

A new algorithm for the diagnosis of polycythemia.

A new algorithm for the diagnostic evaluation of erythrocytosis is presented. This algorithm is based on principles of decision-making analysis and on the pathophysiology of erythrocytosis. The initial task is to identify smokers, because of the high probability that they have "smoker's" polycythemia. The current diagnostic criteria for polycythemia vera may be insufficient when the probability of disease is low but may be too rigorous when the probability of disease is high.

Algorithms↗