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Biomedical subjects

D Shah

Publications and source records attributed to D Shah.

At least 109 records · Page 6Linked to original sources

Thyroid-gonad relationship in systemic lupus erythematosus.

Thirty women with systemic lupus erythematosus (SLE) were examined to assess the thyroid-gonad relationship. Significant decreases in mean serum tri-iodo-thyronine and testosterone levels and increases in mean serum estradiol and luteinizing hormone levels were observed in SLE patients as compared to control subjects. The serum levels of thyroxine, thyrotropin, tri-iodo-thyronine uptake, free thyroxine index and prolactin were, however, not significantly different in both groups. The interpretation of these findings is unclear but SLE could be regarded as one of the nonthyroidal systemic illness since low serum tri-iodo-thyronine with normal thyrotropin levels were observed in our patients. Furthermore, high levels of estradiol and low levels of testosterone in our female patients may indicate involvement of sex steroids in the pathogenesis of SLE.

Adolescent↗

Lupus nephritis at the University Hospital of the West Indies, Kingston, Jamaica: a 10-year experience.

The case records of 75 patients who had systemic lupus erythematosus (SLE) and renal involvement on renal histology were reviewed. There were 70 females and 5 males, with a ratio of 14:1. The majority of the patients were in their second and third decades of life. SLE nephritis was distinctly uncommon in patients below 10 years of age and above 50 years of age. In nearly 80% of the patients, SLE nephritis was diagnosed within the year prior to presentation. The most common presenting clinical features were arthritis in 78% and a rash in 48%. The two most common renal features were proteinuria in 60% and renal failure in 55%. Of these patients, 20%, 12%, 48%, and 17% fell into Class II (mesangial GN), Class III (focal GN), Class IV (diffuse GN), and Class V (membranous GN), respectively, when the renal histological abnormalities were categorized according to the World Health Organization classification. The remaining 3% of patients had sclerosis and as a result were unclassifiable. The two major clinical manifestations in the Class IV patients were an acute nephritis syndrome in 83% and renal failure in 61%. The nephrotic syndrome was seen in 62% of Class V (membranous GN) cases. There was 100% survival in Classes II (mesangial GN) and V (membranous GN), and 62% percent in Classes III (focal GN) and IV (diffuse GN) combined.

Adolescent↗

Single-needle insertion in twin amniocentesis.

Amniocentesis in twin gestation is an uncommon event for most medical centers. The current technique used for this procedure includes two or more needle insertions and the introduction of dye into the first sac. A new approach that consists of a single insertion is proposed. The advantages of this alternate technique are that it requires only one insertion, it is a swifter procedure, it does not require the injection of dye, and it offers positive proof of tapping the two gestational sacs. Although this technique may have some potential risks, in our judgment the advantages outweight the potential risks, and this technique should be considered and its feasibility evaluated in cases of twin gestation requiring two-sac tapping.

Amniocentesis↗

Who gets radiotherapy?

This study investigated the use of radiotherapy for patients perceived to be unsuitable for curative therapy. Patients were grouped according to whether their cancer was considered curable or incurable and whether they received radical or palliative schedules of radiotherapy. The latter group was further evaluated to clarify current practice, to examine the problems in establishing guidelines for treatment and as a basis for prospective audit. Results confirmed that therapy guidelines within the unit were in line with national practice. Changes in standard therapy were proposed in view of resource limitations and recent results from other surveys. A second audit in 1989, together with a formal costing exercise, showed a reduction in the median number of fractions per course in both patient groups. This study suggests that palliative radiotherapy was used selectively for patients likely to receive significant benefit, and that consensus management was practised, and influenced, by informal internal audit. Results highlighted decision-making problems in the management of advanced non-metastasised cancer; confirmed doubts about the advisability of establishing rigid guidelines in palliative therapy; and clarified some of the difficulties in conducting meaningful cost-benefit analyses in this area.

Cancer Care Facilities↗

Warthin's tumour in Jamaica. Incidence, electron microscopy and immunoenzyme studies.

Warthin's tumour has traditionally had a strong male association, and has been said to be rare in Blacks. Current studies describe a new trend; a rise in females, strongly linked to cigarette smoking. The tumour has eosinophilic epithelial cells packed with distinctive mitochondria, and a lymphoid stroma. Immunological investigations have demonstrated polyclonal B cells, T cells and macrophages. Views differ as to whether B or T cells predominate. Between 1958 and 1989, the Jamaica Cancer Registry recorded 491 benign and malignant salivary gland tumours. There were 18 cases of Warthin's tumour (3.7%), with a male: female ratio of 5:1. The low proportion of females is similar to the trend for female lung cancer in Kingston & St. Andrew. A case of Warthin's tumour was studied by light and electron microscopy and immunoenzyme methods. The epithelial cells contained numerous mitochondria with stacked cristae, as previously described. Similar morphology occurs in oncocytic tumours; riboflavin-deficient rats and mice; rats given non-lethal doses of hypoglycin; dogs treated with annatto extracts; and hibernating or starving frogs. The mitochondrial changes may be an adaptive response. The immunoenzyme studies utilized newly available monoclonal antibodies: UCHL1, L26, 4KB5, MT1 and LN2. The reaction patterns indicate a distribution of B and T cells in a manner expected in a lymph node. The interaction between mitochondrial changes, adaptive metabolic pathways, the immune cells and tobacco raises some interesting questions.

Adenolymphoma↗

Fine needle aspiration biopsy in the diagnosis of breast cancer.

A prospective study of 176 Fine Needle Aspiration Biopsies (FNAB) in 172 patients was carried out to assess the accuracy of FNAB in diagnosing breast cancer at the University Hospital of the West Indies. The results showed 99 per cent and 97 per cent accuracy and sensitivity rates, respectively. There were no false positives and a one per cent false negative rate. FNAB provides a rapid, safe and cheap method of accurately diagnosing breast cancer.

Biopsy, Needle↗

31P NMR of covalent phosphorylated derivatives of alpha-chymotrypsin.

The structures of various covalent phosphorylated derivatives of alpha-chymotrypsin (alpha-CT) have been studied by 31P NMR spectroscopy. Diisopropylphosphoryl-alpha-chymotrypsin (alpha-DIPCT) shows a single 31P signal at ca. 0.0 ppm (pH 4). At low pH, the 31P NMR spectrum of alpha-DIPCT gradually changed with the appearance of one or two additional peaks. The ratio of the peaks varied with pH, time, and concentration. One of these two new downfield peaks (both at ca. 2.0 ppm) has been previously identified by Markley and co-workers (Markley, 1979; Porubcan et al., 1979) and van der Drift et al. (1985) as an aged monoisopropylphosphoryl-alpha-chymotrypsin (alpha-MIPCT) and is confirmed by our studies. A new additional downfield signal, separate from the alpha-MIPCT signal, is attributed to a dimer of the phosphorylated alpha-DIPCT. Phosphorylation of the enzyme with diphenyl chlorophosphate yields a monophenylphosphoryl-alpha-chymotrypsin (alpha-MPPCT) that also showed a single 31P signal at -2.1 ppm (pH 7). However, the spectrum did not change as a function of pH, incubation time, or concentration. Comparison of the 31P chemical shifts of the native and denatured phosphorylated derivatives of alpha-chymotrypsin suggests changes in the conformation about the P-O ester bonds are at least partially responsible for the various 31P chemical shift differences.

Chymotrypsin↗

An evaluation of the Takeda UA751 automatic sphygmomanometer.

The Takeda UA751, a simple automatic blood pressure measuring device, was compared with standard osciltatory measurement. There was little or no systematic difference in pressure determined by the automatic or manual method and the correlation between the two devices for both systolic and distolic pressure was satisfactory. This suggests that the Takeda UA751 is an appropriate device for patient self monitoring of blood pressure or as a measure of pressure in group outcome trials. The results essential replicate an evaluation by Steptoe and Molineux (Behav. Res. Ther. 24 223-226, 1986) of an earlier version of the Takeda (the Copal UA251) that used a different method for determining blood pressure.

Adolescent↗

Prenatal diagnosis of sickle cell anemia. Hemoglobin electrophoresis versus DNA analysis.

The prenatal diagnosis of sickle cell anemia (hemoglobin SS) can be established by DNA analysis using two highly sensitive techniques (Southern blot and polymerase chain reaction [PCR]). Hemoglobin electrophoresis provides a third, simpler and more rapid, technique to analyze blood from a fetus at risk for sickle cell anemia. The authors present examples of prenatal diagnostic studies using both DNA analysis techniques and hemoglobin electrophoresis. Hemoglobin electrophoresis of fetal hemolysate can provide a simple and rapid alternative method to PCR analysis for the prenatal exclusion of sickle cell anemia, and it is especially useful in cases in which rapid results are needed because of advanced gestational age.

Adult↗

Correlation of beta-bend conformations of tetrapeptides with their activities in CD4-receptor binding assays.

Conformational analysis, based on ECEPP (Empirical Conformational Energy Program for Peptides) using the chain build-up procedure, was applied to determine the low-energy conformations for a series of tetrapeptides. The tetrapeptides are components of larger peptides which have been found to bind to the CD4 receptor of monocytes. Several previous studies have implicated the tetrapeptide units investigated here as being critical to the biological activities of the full peptides. Five such tetrapeptides were studied: Ser-Ser-Asn-Tyr (from ribonuclease A), Thr-Thr-Asn-Tyr (from peptide T, known to block human immunodeficiency virus from attaching to CD4+ T cells), Thr-Ile-Asn-Tyr (from polio virus coat protein, which is less active than the other peptides in binding to CD4 receptors), Ser-Ser-Ala-Tyr (from the gp 120 coat protein of human immunodeficiency virus, a variant of the peptide T sequence, active in blocking viral attachment to CD4+ cells), and the tetrapeptide from an active synthetic pentapeptide, Asn-Thr-Lys-Tyr (from Asn-Thr-Lys-Tyr-Thr). Using a 7 kcal/mol cutoff, the low-energy conformations for each peptide were computed. Approximately 20,000 conformations were computed for each tetrapeptide. Residue probability profiles were determined for each tetrapeptide. All tetrapeptides except for the polio sequence showed flexibility in the sense that many low-energy conformations were possible. In previous studies, it was postulated that the critical tetrapeptide units would adopt conformations similar to the one observed in a segment of ribonuclease A, residues 22-25, a beta-bend, which is part of an octapeptide segment (residues 19-26) that is homologous to the sequence of peptide T.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Clinical and experimental evaluation of aortic polytetrafluoroethylene grafts for aneurysm replacement.

The aortic expanded polytetrafluoroethylene bifurcation graft has a unique taper design. This was studied in an in vitro model using hydrogen bubbles and colored dyes to assess its hemodynamic significance compared with a conventional nontapered graft model. Under conditions of nonpulsatile flow the only significant differences were seen with a high percentage of occlusions of one outflow limb. Clinical experience with this new graft for infrarenal aneurysm replacement was accumulated in 163 elective cases and 53 emergency cases. The results with this new graft were compared with those obtained in the same time frame with alternative Dacron grafts. No detrimental problems with the graft have appeared in its use up to 78 months following aneurysm bypass or replacement.

Aged↗

The use of early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal fragile X chromosome diagnosis.

Early simultaneous percutaneous umbilical blood sampling (PUBS) and amniocentesis for prenatal diagnosis were undertaken for the first time in a 17-week gestation fetus at risk for the fragile X [fra (X)] syndrome. Metaphase spreads from 300 fetal lymphocytes were examined within 5 days following PUBS, while approximately 5 weeks were required for the analysis of 148 amniocytes. The chromosomes were interpreted as normal (46,XX) and the fetus as fragile X-negative at the time of prenatal diagnosis. This was cytogenetically confirmed after delivery of a healthy term female infant. Our results suggest that early PUBS may become a useful adjunct to amniocentesis because of shorter culture time and earlier diagnosis.

Amniocentesis↗

The fluid-phase binding of human C4 and its genetic variants, C4A3 and C4B1, to immunoglobulins.

Covalent binding of the fourth complement protein, C4, to immune complexes is an important first step in the complement mediated processing of the complexes. Many of the initial encounters between the proteins of the complement system and antigen and antibody occur in solution, and prior to this report, studies of the interactions between them have focused on complement binding to preformed immune precipitates that most likely are not found in vivo. We have characterized the covalent binding of C4b to immunoglobulin molecules in a fluid-phase system consisting only of antibody in solution and purified C4 and C1s. We demonstrate that human C4b binds to IgG in the fluid phase, that its covalent binding is predominantly to the heavy chain of IgG, and that the covalent linkage is by either amide or acyl ester bonds. In addition, we compare the covalent binding efficiencies of two genetic variants of C4, C4A3 and C4B1, to IgG. C4A3 binds 3-4 times more IgG than C4B1 over a range of C4 concentrations, and C4A3 has a higher binding efficiency than C4B1 for IgM, IgA, IgG2a and F(ab')2 as well as for a protein antigen, BSA. Furthermore, we found that whereas C4A3 is bound to immunoglobulins in the fluid-phase predominantly by amide linkage, C4B1 is bound by either amide or acyl ester bonds. The results presented here suggest that the covalent binding efficiency of C4A3 and C4B1 to IgG is similar to that reported for their covalent binding to small molecules.

Chemical Phenomena↗

Conformational analysis of possible biologically active (receptor-bound) conformations of peptides derived from cholecystokinin, cerulein and little gastrin and the opiate peptide, Met-enkephalin.

Possible biologically active (receptor-bound) conformations of peptides derived from cholecystokinin (CCK) have been deduced using conformational analysis combined with comparative studies of their biological specificities. Two peptides, the completely active carboxyl terminal heptapeptide from CCK (CCK-7), whose sequence is Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2, and the carboxyl terminal heptapeptide from cerulein (CER-7) which has the same sequence as for CCK-7 except for replacement of Met 2 with a Thr 2, both stimulate peripheral receptors in gall bladder, pancreas, and pylorus in the gastrointestinal system. In contrast, two other very similar peptides, the last four residues of CCK (CCK-4) whose sequence is Trp-Met-Asp-Phe-NH2, and the carboxyl terminal hexapeptide of little gastrin (LGA-6, Tyr-Gly-Trp-Met-Asp-Phe-NH2, i.e., residue 2 deleted relative to CCK-7 and CER-7 sequences), interact specifically with gastrin receptors and not at all or very weakly with peripheral receptors. All of these peptides react with CCK receptors in the central nervous system, especially in forebrain. The results in the GI tract suggest that the peptides active on peripheral receptors adopt structures that are significantly different from those of the peptides that interact with gastrin receptors. We have generated all of the many low energy conformations for each of these peptides. By retaining only the conformations that are the same for peptides within the same group and then rejecting those resulting conformations that are the same for the peptides in the two different groups, we can greatly reduce the possible active conformations for the peptides within each class.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

On the biologically active structures of cholecystokinin, little gastrin, and enkephalin in the gastrointestinal system.

The biologically active conformations of a series of four peptides [four cholecystokinin (CCK)-related peptides and enkephalin] in their interactions with gastrointestinal receptors have been deduced using conformational computational analysis. The two peptides that interact exclusively with peripheral-type CCK receptors are the heptapeptide COOH-terminal fragment from CCK (CCK-7) and the analogous sequence from cerulein (CER-7) in which threonine replaces the methionine proximal to the NH2 terminus. The two peptides that interact exclusively with the gastrin receptor in the stomach are the active COOH-terminal fragment of little gastrin and the COOH-terminal tetrapeptide sequence common to all of these peptides, CCK-4. We find that preferred conformations for the peripherally active peptides CCK-7 and CER-7 are principally beta-bends, whereas little gastrin and CCK-4 are fundamentally helical. In the class of lowest energy structures for both CCK-7 and CER-7, the aromatic rings of the tyrosine and phenylalanine lie close to one another whereas the tryptophan indole ring points in the opposite direction. This structure is superimposable on the structures of a set of rigid indolyl benzodiazepine derivatives that interact with complete specificity and high affinity with peripheral CCK receptors further suggesting that the computed beta-bends are the biologically active conformation. The biologically active conformation for CCK-4 and the little gastrin hexapeptide has also been deduced. By excluding conformations common to CCK-7 and CCK-4, which do not bond to each other's receptors, and then by selecting conformations in common to CCK-4 and the gastrin-related hexapeptide, which do bind to each other's receptors, we deduce that the biologically active conformation at the gastrin receptor is partly helical and one in which the indole of tryptophan and the aromatic ring of phenylalanine are close to one another while the methionine and aspartic acid side chains point in the opposite direction. These major differences in preferred structures between the common CCK-7/CER-7 peptides and the common CCK-4/little gastrin peptides explain the mutually exclusive activities of these two sets of peptides. We have observed that [Met]enkephalin strongly antagonizes the action of the naturally occurring peripherally active CCK-8 (CCK-7 with an NH2-terminal aspartic acid residue added). The computed lowest energy structures for this opiate peptide closely resemble key features of the computed CCK-7/CER-7 structure, further supporting the proposed structure.

Amino Acid Sequence↗