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Biomedical subjects

T Shah

Publications and source records attributed to T Shah.

At least 19 recordsLinked to original sources
PubMed1994

An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3)

We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and MIC2 within the pseudoautosomal region in 85 families with two or more siblings suffering from schizophrenia or schizoaffective disorder. A maximum lod score of 2.44 was reached at MIC2, with a dominant model of inheritance at a recombination fraction of 0.367 in females and 0.046 in males (a F:M sex ratio > 1, i.e. opposite to that expected with a pseudoautosomal locus). Evidence consistent with linkage (P = 0.01) was also obtained with a sibling pair analysis at the MIC2 locus. These data do not support (although they do not definitively exclude) a locus within the pseudoautosomal region; they are consistent with the presence of a gene that predisposes to schizophrenia in the sex-specific regions of the X and Y chromosomes.

Adult↗
PubMed1994

Methods in pathology. Optimization of proliferating cell nuclear antigen immunohistochemical staining by microwave heating in zinc sulfate solution.

Immunohistochemical staining of routinely processed formalin-fixed, paraffin-embedded archival tissue sections with proliferating cell nuclear antigen (PCNA) monoclonal antibody has facilitated the understanding of the regulation of cell proliferation. However, false-negative staining due to masking or poor preservation of antigen epitopes by fixatives or other unknown conditions has been a major problem in PCNA immunohistochemical studies. Microwave heating (MWH) has been used to retrieve antigen in archival tissue. However, optimal staining conditions have not yet been defined. We therefore investigated the effect of MWH with or without a metal solution (zinc sulfate) on routinely processed paraffin-embedded tissue to determine the optimal conditions for retrieval of PCNA. The results were compared with routine immunohistochemical staining. We found that MWH in 1% zinc sulfate solution successfully retrieved PCNA; the optimal MWH time was 7.5 mins. In contrast, when MWH was performed in water, the specific intensity of PCNA expression was not increased because MWH not only enhanced the intensity of the antigen staining but also increased the background staining. In summary, MWH technique in zinc-sulfate solution allowed successful PCNA retrieval from formalin-fixed archival tissue and thus facilitated accurate immunohistochemical evaluation of cell proliferative activity in cancers.

Antibodies, Monoclonal↗
PubMed1992

Inherited prion disease with 144 base pair gene insertion. 1. Genealogical and molecular studies.

Genealogical and molecular studies were carried out in four families in which early onset dementia is inherited as an autosomal dominant. These studies indicated that the four families derive from four siblings whose parents were born in the late 18th century in South-East England. The disease was found to be closely linked to a 144 bp insertion within the open reading frame of the prion protein (PrP) gene with a maximum LOD score of 11.02 at zero recombination. Within the general population the PrP gene is polymorphic at codon 129 (allele frequency approximately 30% valine, 70% methionine). The insertion in this family is always within a methionine-129 allele. The age at death of affected individuals whose normal allele encoded methionine at codon 129 was significantly lower than those whose normal allele encoded valine. The clinical features which were very variable and the neuropathological findings, which sometimes included spongiform encephalopathy, but which often did not, are described fully in the accompanying article (Collinge et al., 1992).

Base Sequence↗
PubMed1991

Insertions in the prion protein gene in atypical dementias.

A number of mutations have been demonstrated in the open reading frame (ORF) of the prion protein (PrP) gene in patients with familial Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome. On the basis of detecting an insertion in the ORF of the PrP gene in a patient originally suspected to be suffering from familial Alzheimer-type dementia, we screened 101 individuals with atypical dementias for the known PrP gene mutations. Insertions were found in five individuals, whereas none of the other reported mutations in the PrP gene was detected in the present study. One of the five insertions was larger than that described previously, suggesting that the individuals with these mutations are unlikely to be all lineally related and that insertions in the PrP gene may not be uncommon in prion diseases.

Alzheimer Disease↗
PubMed1991

Extracorporeal shock wave lithotripsy for urinary tract stones using MPL 9000 spark gap technology and ultrasound monitoring.

Between November 7, 1988 and December 31, 1989, 881 treatments were given with the MPL 9000 lithotriptor to 513 sites in 510 renal units in 464 patients. Of the stones 447 (87.1%) were in the kidney, 64 (12.5%) in the ureter and 2 (0.4%) in the bladder. Stone size was up to 2 cm. in 58.5% of the cases, greater than 2 to 3 cm. in 25.8% and more than 3 cm. in 15.7%, including complete or partial staghorn, or multiple stones. Of the patients 54.2% received only 1 treatment, 17.6% received 2 treatments and 28.2% received more than 2 treatments (re-treatment was necessary in 45.8%). The number of shocks used varied from 610 to 4,000 at 14 to 24 kv., the usual energy used being 18 kv. Of the stones 30.2% were treated after Double-J stents were inserted. A patient was declared stone-free only when no stone particle was visible on a plain abdominal x-ray (or ultrasound if the stone was radiolucent). X-rays 3 months after extracorporeal shock wave lithotripsy (ESWL) were available for review in 397 patients (79.9%) and 72.8% were stone-free (with the aforementioned criteria) at 6 months (61.5% without ancillary procedures and 11.3% after ancillary procedures). Of a subset of 106 patients 84% were stone-free within 3 months when ESWL was restricted to a smaller stone burden, the number of shock waves administered was increased and energy was restricted to 14 to 18 kv. Over-all, 9.1% of the patients needed ancillary measures, including percutaneous nephrostomy in 1.6%, push-back for ESWL in 1.9%, ureterorenoscopy in 5.4%, percutaneous nephrolithotomy in 0.6% and pyelolithotomy/ureterolithotomy in 2.8%. The MPL 9000 device has the unique combination of electrohydraulic shock wave generation and ultrasound monitoring. The latter attribute has the distinct advantage of avoiding radiation to allow for visualization of nonopaque renal and gallbladder calculi. In addition, because there is continuous stone visualization during fragmentation accurate stone targeting can be maintained. The combination of ultrasound monitoring and spark gap technology allows for effective stone fragmentation.

Adolescent↗
PubMed1990

Reaction of thiol groups of gizzard myosin heavy chains with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole.

Chicken gizzard myosin treated with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) resulted in a 65% inhibition of the K(+)-ATPase (myosin ATP phosphohydrolase (actin translocating), EC 3.6.1.32) activity and 3.5 mol of the reagent was bound per 4.7 x 10(5) g protein. The labeling was limited to the heavy chain region and none of the light chains were lost. MgATP had no effect on the inactivation or labeling pattern. Thiolysis of NBD-myosin with dithiothreitol restored the K(+)-ATPase activity and concurrently, 1 mol of the NBD group was removed from the heavy chain region. Cysteine residues were modified in NBD-myosin at sites other than the active site when the enzyme activity was inhibited. There was a difference in the extent of NBD-Cl modification of gizzard myosin at 0.6 M KCl (6 S elongated state) when compared to that at 0.15 M KCl (10 S folded state). This was also seen in the heavy meromyosin-like chymotryptic fragments and tryptic fragments of NBD-myosin. The reagent NBD-Cl can detect changes in the conformation of gizzard myosin by way of its reaction with thiol groups of the heavy chain region.

4-Chloro-7-nitrobenzofurazan↗
PubMed1990

An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease.

In a pedigree with Creutzfeldt-Jakob disease we identified a 144-bp insertion in the open reading frame of the prion protein (PrP) gene. The insertion is in-frame and codes for 6 extra uninterrupted octapeptide repeats in addition to the 5 that are normally present in the N-terminal region of the protein. The possibility that this mutation may prove relevant to elucidating the mechanism of horizontal transmission of the spongiform encephalopathies is discussed.

Amino Acid Sequence↗
PubMed1989

Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis.

The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease. 2 members of a family in whom GSS was not previously suspected had a 0.15 kb insertion of similar size to that found in another kindred with pathologically proven spongiform encephalopathy. GSS may be more common than is currently realised; PrP gene analysis is potentially useful for diagnosis and genetic counselling in familial dementias and ataxias.

Adult↗
PubMed1989

A two-institution study of transfusion practice in 78 consecutive adult elective open-heart procedures.

Blood salvage techniques and increasingly conservative physician transfusion practice in cardiac surgery have led to reports of homologous blood exposure in as few as 10% of patients having elective cardiac revascularization surgery (Ann Thorac Surg 1985;40:380). To identify current prevailing transfusion practice between centers, the authors prospectively audited 49 and 29 consecutive adult elective open-heart surgery cases (78 total) at two centers. Thirty-six of 49 patients (73%) received 245 homologous blood units (HBs) at institution 1 (m = 5.0). Fifteen of 29 (52%) received 84 HBs at institution 2 (m = 2.9, P less than 0.05). Sex, age, duration of surgery, intraoperative blood salvaged, preoperative hematocrit (Hct), nadir Hct, and nadir platelet counts, and the surgeon were all found to be determinants of transfusion practice at institution 1 but not at the other. The data indicate that (1) determinants of homologous blood exposure are not consistent between institutions and instead reflect "prevailing practice" rather than need; (2) a prospective multi-institution audit of prevailing transfusion practice in cardiac revascularization is needed to address this; (3) autologous blood pre-deposit is underused in open-heart surgery.

Blood Transfusion↗
PubMed1989

Serum neopterin patients with X-linked and acquired 'common variable' hypogammaglobulinaemia.

Serum neopterin was measured in patients with acquired 'common variable' hypogammaglobulinaemia (CVH), X-linked agammaglobulinaemia (XLA) and healthy subjects. There was a highly significant increase in neopterin levels in the CVH patients as compared with that of the other groups, particularly in those CVH patients with non-A non-B or granulomatous hepatitis. There was no association between raised neopterin levels and chronic infective lung disease. Since chronic viral infections are associated with raised serum neopterin, this data add some support to a viral aetiology for CVH.

Adolescent↗
PubMed1988

Dipeptidyl peptidase IV--subcellular localization, activity and kinetics in lymphocytes from control subjects, immunodeficient patients and cord blood.

Dipeptidyl peptidase IV (DPIV), a T cell enzyme, has been implicated in the regulation of lymphocyte proliferation in response to lectins and allogeneic cells. A sensitive fluorimetric assay has been established for the enzyme and used to investigate DPIV activity, kinetics and the subcellular localization in lymphocytes from control subjects, cord blood and patients with common variable hypogammaglobulinaemia (CVH) and chronic lymphatic leukaemia (CLL). Using sucrose density gradient centrifugation and organelle marker enzyme assays, in conjunction with digitonin as a selective plasma membrane perturbant and diazotized sulphanilic acid as a non-permeant enzyme inhibitor, DPIV was shown to be a plasma membrane ecto-enzyme. A significant decrease in lymphocyte DPIV activity was observed in cord blood and in patients with CVH and CLL compared to controls. Kinetic analysis showed a marked decrease in the Vmax of lymphocyte DPIV from cord blood and patients with CVH and CLL compared to controls. The apparent Km for the substrate was unaffected in cord blood and patients with CLL. However, in patients with CVH the Km was significantly reduced. Various enzyme inhibitors showed no differences between control subjects and CVH lymphocyte activities. The decreased Km for DPIV provides further evidence for a stem cell defect rather than cell immaturity in CVH.

Agammaglobulinemia↗
PubMed1988

Adenine nucleotide concentrations in peripheral blood lymphocytes from patients with common variable hypogammaglobulinaemia and B-cell chronic lymphatic leukaemia.

The adenine nucleotide profiles (AMP, ATP, NAD and NADH2) of peripheral blood lymphocytes isolated from patients with common variable hypogammaglobulinaemia (CVH) were similar to those in control cells. AMP and ATP levels were also similar in the lymphocytes of patients with chronic lymphatic leukaemia (CLL). Since CVH and CLL patients have reduced activity of plasma membrane ecto-5'-nucleotidase, our data suggests that this enzyme does not regulate the levels of intracellular adenine nucleotides, at least in "resting" cells.

Adenine Nucleotides↗
PubMed1987

Binding of adenosine and receptor-specific analogues to lymphocytes from control subjects and patients with common variable immunodeficiency.

Studies were performed on the binding of tritiated adenosine and its analogues, 5'-N-ethylcarboxamide adenosine (NECA) and N6-phenylisopropyladenosine (PIA), to human peripheral blood lymphocytes. These revealed binding only of adenosine (Kd, 1-10 microM, 14,000 binding sites/cell), which was abolished by dipyridamole, a specific adenosine transport inhibitor, suggesting that the binding is to the nucleoside transporter. The absence of high affinity (Kd less than or equal to 1 microM) binding of adenosine or of the two analogues. NECA and PIA suggests that the previously reported effects of adenosine on cAMP formation are not mediated by cell surface specific nucleoside receptors. Binding of adenosine to the carrier in lymphocytes from patients with common variable immunodeficiency was similar to those from control subjects.

Adenosine↗
PubMed1986

Uptake of free adenosine and adenosine from adenosine monophosphate by human peripheral blood lymphocytes: possible kinetic role for ecto-5'-nucleotidase in the regulation of intracellular adenosine.

The role of 5'-nucleotidase in the uptake of adenosine from AMP was investigated in lymphocytes from normal subjects and patients with common variable hypogammaglobulinaemia (CVH) and chronic lymphatic leukaemia (CLL). At physiological pH, the Km values for the uptake of adenosine and of adenosine from AMP by intact cells were one order of magnitude higher than the Km values for 5'-nucleotidase. The Vmax values for the hydrolysis of AMP by 5'-nucleotidase were two orders of magnitude greater than for the uptake of adenosine itself or the uptake of adenosine from AMP by normal lymphocytes. 5'-Nucleotidase activity is clearly not rate-limiting in normal lymphocytes for uptake of adenosine from AMP in steady state conditions. Patients with common variable hypogammaglobulinaemia showed a low Vmax for 5'-nucleotidase assayed at pH 7.4 in intact cells as compared to values from control subjects. Michaelis constants (Km) for the uptake of free adenosine and adenosine from AMP as well as 5'-nucleotidase were similar compared to those obtained for controls. The uptake of adenosine moiety from AMP in CLL lymphocytes with a low Vmax for 5'-nucleotidase was also reduced, although not to the same extent as the reduction in 5'-nucleotidase activity. One CLL patient with supranormal levels of 5'-nucleotidase activity showed elevated uptake of adenosine moiety from AMP and of free adenosine. These results suggest that 5'-nucleotidase can influence the salvage of purine by lymphocytes from extracellular nucleotides but only when the enzyme activity is greatly reduced.

5'-Nucleotidase↗