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Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 307 records · Page 17Linked to original sources

Spinal and supraspinal effects of pertussis toxin on opioid analgesia.

The effects of in vivo pertussis toxin (PTX) treatment on the functional effects of opioid agonists were examined in the mouse. Mice were injected intracerebroventricularly (ICV), or intrathecally (IT), or IT and ICV with PTX, and dose-response studies of the antinociceptive action of systemic (SC) morphine, fentanyl, and etorphine were conducted 10 days later. IT PTX decreased the potency (approximately 4.5-fold) of morphine more than ICV administration (approximately 1.5-fold), whereas the combination of IT and ICV administration produced an additive effect. When PTX was administered spinally and supraspinally, the potency of morphine, fentanyl, and etorphine was reduced similarly (approximately 5-7-fold), indicating that the effect of PTX does does not vary considerably among agonists of different intrinsic efficacies. These studies indicate that in vivo PTX can reduce the potency of opioid agonists with different intrinsic efficacies, and that spinal mechanisms appear to be more sensitive to PTX treatment.

Analgesics↗

Opioid antagonist-induced receptor upregulation: effects of concurrent agonist administration.

The present study examined whether opioid antagonist-induced receptor upregulation could be antagonized by simultaneous treatment with opioid agonists. Mice were treated concurrently with opioid agonists (morphine, fentanyl, etorphine) and antagonists (naloxone, naltrexone) over a period of 7-8 days. Concurrent morphine (1 or 4, 75 mg SC implanted pellets), fentanyl (5.0 mg/kg/day, infusion) or etorphine (0.25 mg/kg/day, infusion) administration were unable to inhibit upregulation of mu opioid (DAMGO) receptors by either naloxone (1 mg/kg/day, infusion) or naltrexone (15 mg or 2 mg SC implanted pellet). Only a very high infusion dose of etorphine (10 mg/kg/day) inhibited upregulation by naltrexone (2mg SC implanted pellet). These results indicate that antagonist-induced upregulation is a robust, receptor-mediated phenomenon.

Animals↗

The Drosophila dgq gene encodes a G alpha protein that mediates phototransduction.

We examined the roles of the Drosophila Gq alpha proteins (DGq) in the phototransduction pathway. The DGq proteins immunolocalized to the ocelli and all eight retinular photoreceptor cell rhabdomeres. An affinity-purified anti-DGq alpha immunoglobulin blocked the light-dependent GTP hydrolysis activity associated with Drosophila head membranes in vitro, suggesting that rhodopsin stimulated DGq. Dominantly active DGq1 mutants exhibited a light-independent GTPase activity and abnormal electrophysiological light responses, such as reduced retinal sensitivity and slow response kinetics compared with wild-type flies. Dominant DGq2 mutants exhibited a light-independent GTPase activity with normal electrophysiological light responses. Retinas of double mutants of DGq1, but not DGq2, with the light-dependent retinal degeneration mutant rdgB degenerated even in the dark. DGq1 stimulation of rdgB retinal degeneration in the dark was norpA-dependent. These results indicate that DGq1 mediates the stimulation by light-activated rhodopsin of the norpA-encoded phospholipase C in the visual transduction cascade.

Alternative Splicing↗

A national policy on asthma management for schools. The Asthma Special Interest Group, Thoracic Society of Australia and New Zealand.

Since asthma is the most common chronic illness in childhood, many of the problems associated with this condition will impact on the child's education. Because of widespread concerns regarding the management of asthma in schools, a subcommittee of the Thoracic Society of Australia and New Zealand, Asthma Special Interest Group, was convened to draw up national guidelines for school staff in order to provide optimal management of asthma in the school setting. We used current medial literature and the clinical experience of the authors who have dealt with children and adolescents suffering from asthma in the hospital, community and school environment. A number of issues had been identified, including: the availability of an asthma first aid kit; correct use of bronchodilator aerosols by puffer and spacer devices; and clear instructions as to when to notify parents and when to call an ambulance to the school.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Recognition and crisis management of asthma in schools.

Under-reporting of asthma and inappropriate management at school can hamper a child's academic progress. The aim of this study was to assess asthma reporting and crisis management, following implementation of a Primary School Asthma Programme. The intervention covered 12 primary schools with 5093 students in an area of high unemployment with a large proportion of the community from a non-English background. The programme included School Asthma First Aid Kits, training workshops for school staff and individual Crisis Management Plans for students with asthma. Registration of students with asthma at school increased from 6.2% before the intervention in 1989 to 12.7% in 1992. School Asthma Crisis Plans were completed appropriately by the child's doctor and parents and returned by 68% of the students with asthma. Teachers' asthma knowledge and confidence with the management of acute asthma at school improved following asthma education workshops. It was concluded that asthma reporting and acute crisis management of asthma at school can be achieved by a programme undertaken by school medical services.

Child↗

Disease susceptibility genes and the sib-pair method: a review of recent methodology.

There is now a considerable body of literature which describes and analyses various methods of testing for the presence of disease susceptibility genes by examining the degree of HLA haplotype sharing of parental haplotypes over random expectations amongst affected siblings. We here survey a number of improvements, generalizations and extensions of the earlier reported methods with the aim of bringing them to the attention of those who are collecting HLA or other haplotype data on familial disease.

Family↗

The distribution of Q: a powerful sibship test of association.

Non-random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, called Q, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well-known test, the N-test of haplotype concordance, are given. This is because Q is a modification of N to deal with the case when information on unaffected siblings is also available.

Genetic Diseases, Inborn↗

Variability of sonic scaling tip movement.

The sonic scaler operates at frequencies of 2 to 6 kHz and is powered by pressurised air from the dental unit. Variables likely to affect how these instruments perform include the air pressure input and load applied by the operator. Other variables include the brand of scaler used and the clinical technique of the operator. The aim of this study was to investigate differences in instrument performance within a dental teaching hospital. Light microscopy was used to measure the displacement amplitudes in air of 32 Sonic scalers which were in regular clinical use in three departments (Periodontal Unit, Restorative Unit and School of Hygiene). During operation, the air pressure was kept at a constant 2.8 kg cm-2 and measurements were made on each instrument with three scaling tips (universal, sickle and periodontal). The periodontal scaling tip exhibited the greatest vibration although this was not significant (p > 0.1). There was a significant difference in performance between the different clinical environments where the scalers were used (p < 0.01). 4 new sonic scaling instruments made by different manufacturers were selected for displacement amplitude measurements. One brand of sonic scaler demonstrated a significantly greater displacement amplitude in comparative measurements between instruments (p < 0.01). This study demonstrated differences in the oscillation of sonic scalers which should be recognised by clinicians when using these instruments, since they may influence clinical performance.

Calibration↗

Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives.

Islet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers > or = 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICA-positive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.

Adolescent↗

Addisonian crisis following pericardiectomy.

In developing countries tuberculosis is a common cause of constrictive pericarditis and its involvement of other organs may sometimes complicate the surgical management of such patients. A case is reported of constrictive pericarditis in which the patient developed protracted hypotension which was unresponsive to inotropic therapy, following pericardiectomy. On investigation the cause of hypotension was diagnosed as acute adrenocortical insufficiency, secondary to adrenal tuberculosis. The patient was successfully treated with corticosteroids. Low cardiac output after pericardiectomy, which is not uncommon, should not necessarily be attributed to a 'myocardial factor'. Patients with tuberculous pericarditis may have co-existent Addison's disease.

Addison Disease↗

Ethanol-responsive genes in neural cells include the 78-kilodalton glucose-regulated protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) molecular chaperones.

Previously we found that ethanol increases expression of the constitutive 70-kDa heat shock protein (Hsc70) in NG108-15 neuroblastoma x glioma cells. We suggested that known ethanol actions on cellular protein trafficking may relate to Hsc70 induction because Hsc70 functions as a molecular chaperone. Here we use a subtractive hybridization protocol to isolate ethanol-responsive genes (EtRGs). Northern blot hybridization verified ethanol-induced increases in mRNA abundance for five cDNA clones isolated from ethanol-treated NG108-15 neuroblastoma x glioma cells. DNA sequence analysis identified one EtRG as 94-kDa glucose-regulated protein (GRP94), a member of the "glucose-responsive" subgroup of stress proteins. Other identified EtRGs included an insulin-induced growth-response protein gene and an intracisternal A-type particle gene. Sequence analysis of the remaining two EtRGs showed no homology in DNA sequence databases. All EtRGs showed wide tissue expression, except SL64, which was not detected in Northern blot analyses of adult mouse or rat tissues. Ethanol also increased mRNA abundance for 78-kDa glucose-regulated protein (GRP78), a molecular chaperone known to function in glycoprotein trafficking and usually coordinately regulated with GRP94. However, ethanol induced GRP94 more than GRP78, a pattern distinct from those of other inducers of these genes. All EtRGs, including GRP94 and GRP78, showed similar ethanol concentration-dependent increases in mRNA abundance. In contrast, thapsigargin and other inducers of glucose-responsive proteins increased GRP94 and GRP78 mRNA levels without altering expression of other EtRGs. Our studies demonstrate that several molecular chaperones constitute a subset of EtRGs. Ethanol appears to regulate these EtRGs by a unique mechanism, rather than one shared by classical inducers of stress proteins.

Carrier Proteins↗

Hereditary pancreatitis.

Hereditary pancreatitis is an idiopathic form of chronic pancreatitis which affects multiple members of a family in an autosomal dominant mode of inheritance. Most of the case reports are in caucasians of European descent. In this report, we present our data on four affected members spanning three generations in a family from India. Current data on hereditary pancreatitis are summarized, to revive an interest in this rare form of chronic pancreatitis.

Adult↗

Anomalous growth of Staphylococcus epidermidis in the presence of Silastic and glycopeptide antibiotics.

In the presence of supra-inhibitory concentrations of the glycopeptide antibiotics vancomycin and teicoplanin, biofilms of Staphylococcus epidermidis on a Silastic surface produce anomalous growth. This takes the form of macroscopic, cohesive aggregates of cocci bound together with slime. This phenomenon was intermittent, independent of antibiotic concentrations between 20 and 50 micrograms ml-1, occurred more often with teicoplanin, and was found both with slime-positive and slime-negative strains.

Microscopy, Electron, Scanning↗

Organization, sequence, and expression of the murine S100 beta gene. Transcriptional regulation by cell type-specific cis-acting regulatory elements.

The organization, sequence, and transcriptional regulation of expression of the murine S100 beta gene are reported. The gene is approximately 9 kilobase pairs in length and is composed of three exons and two introns. The deduced murine S100 beta protein sequence differs from the human S100 beta protein by only 1 amino acid. The murine S100 beta gene contains a TATA box (AATAA) and a reverse CCAAT box (ATTGG) located at 30 nucleotides and 92 nucleotides upstream of the cap site, respectively. A 149-base pair DNA fragment (-157/-9) spanning the TATA box and the reverse CCAAT box functions as a promoter. The murine S100 beta promoter drives a 4-fold higher level of transcription in glial (C6) than in non-glial (3T3) cells, suggesting the existence of a potential cell type-specific regulatory element within the promoter region. The 5'-flanking region suppresses transcription from the homologous S100 beta as well as the heterologous SV40 promoters in an orientation-independent fashion. However, the 5'-flanking region exhibits cell type specificity when suppressing the S100 beta promoter-dependent transcription, indicating its involvement in the cell type-specific expression of S100 beta gene. In order to map cell type-specific regulatory elements, transcription analyses of various deletions of the 5'-region were carried out in C6 and 3T3 cells. Two cell type-specific negative regulatory elements, one active in non-glial cells and another active in glial cells, were mapped to the regions -1552/-1234 and -1234/-551, respectively. A strong negative regulatory element and a relatively weak negative element were located in the regions -551/-157 and -1669/-1552, respectively. The murine S100 beta gene is under complex transcriptional regulation involving tonic negative control exerted by combination of multiple cis-acting regulatory elements including cell type-specific elements.

Amino Acid Sequence↗