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Biomedical subjects

S Rahman

Publications and source records attributed to S Rahman.

At least 91 records · Page 5Linked to original sources
PubMed2000

Randomised comparison of antero-lateral versus antero-posterior paddle positions for DC cardioversion of persistent atrial fibrillation.

We designed a prospective, randomised, single-blind trial to compare the relative efficacy of antero-lateral versus antero-posterior paddle positions for DC cardioversion of persistent atrial fibrillation. A total of 59 patients were randomised to cardioversion using standard gel pads placed either in the antero-lateral (AL) or antero-posterior (AP) positions. The first synchronised shock was given at 360 J; if this was unsuccessful, a second shock of 360 J was given in the alternative position. We compared cardioversion success rate and energy requirements with each strategy. With the first 360 J DC shock, a significantly greater proportion of patients were restored to sinus rhythm from the antero-lateral position (18/30) compared to the antero-posterior position (10/29) (P=0.048). For those patients remaining in atrial fibrillation, there was no difference in the proportions cardioverted from the antero-lateral position (4/19) compared to the antero-posterior position (5/12) with the second 360 J DC shock (P=0. 22). The total cardioversion success rate was 23/30 (77%) for antero-lateral followed by antero-posterior shocks compared to a success rate of 14/29 (48%) for antero-posterior followed by antero-lateral shocks, and this difference was significant (P=0.024). There was no significant difference in the mean energy delivered for patients randomised to an initial antero-lateral shock (504 J), compared to patients given an initial antero-posterior shock (583 J) (P=0.1). We conclude that the antero-lateral paddle position appears more effective for DC cardioversion of persistent atrial fibrillation.

Aged↗
PubMed2000

Induction of the urokinase plasminogen activator system by oncostatin M promotes endothelial migration.

Oncostatin M (OSM) is an inflammatory cytokine produced by activated macrophages and T-lymphocytes. We have previously demonstrated that OSM-induced endothelial cell migration, unlike endothelial cell proliferation and spindle formation, is independent of basic fibroblast growth factor expression (Wijelath et al. [1997] J. Cell. Sci. 110:871-879). To better understand the mechanism of OSM-induced endothelial cell migration, this study examined the potential role of the plasminogen activator system in promoting OSM mediated endothelial cell migration. OSM stimulated increased mRNA levels of urokinase-plasminogen activator (uPA) and urokinase-plasminogen activator receptor (uPAR) in a time and dose-dependent manner. Transcriptional run-off and mRNA stability analysis demonstrated that the increase in uPA and uPAR mRNA levels was due to both increased gene transcription and mRNA stability. The increase in mRNA correlated with increased protein levels of both uPA and uPAR. This increase was reflected in elevated levels of membrane-bound plasmin activity. OSM-induced endothelial cell migration was only partially dependent on plasmin activity since incubating endothelial cells without plasminogen or, in the presence of aprotinin, resulted in suppression of endothelial cell migration, indicating that OSM promoted endothelial cell migration through both a plasmin-dependent and -independent mechanism. Our results imply a role for OSM in promoting endothelial cell migration via a plasmin-dependent pathway and a uPAR-mediated pathway. Together, these and other recent studies support a role for OSM in modulating the different phases of angiogenesis.

Cells, Cultured↗
PubMed2000

Differential recognition of snake venom proteins expressing specific Arg-Gly-Asp (RGD) sequence motifs by wild-type and variant integrin alphaIIbbeta3: further evidence for distinct sites of RGD ligand recognition exhibiting negative allostery.

Several studies have demonstrated that the amino acid residues flanking the Arg-Gly-Asp (RGD) sequence of high-affinity ligands modulate their specificity of interaction with integrin complexes. Because of the absence of structural data for integrin complexes with bound ligand, the molecular basis for this specificity modulation remains obscure. In a previous paper [Rahman, Lu, Kakkar and Authi (1995) Biochem. J. 312, 223-232] we demonstrated that two genetically distinct venom-derived RGD proteins, kistrin and dendroaspin (both containing the sequence PRGDMP), were simple competitors, indicating the recognition of an identical binding site on the alpha(IIb)beta(3) complex. Furthermore, both kistrin and dendroaspin inhibited the binding of the disintegrin elegantin (containing the sequence ARGDNP) via a non-competitive mechanism, suggesting that the binding of elegantin to the alpha(IIb)beta(3) complex was at a remote site and down-regulated via an allosteric mechanism. Here we present further evidence for distinct RGD ligand recognition sites on the alpha(IIb)beta(3) complex that exhibit a negative allosteric relationship. A panel of well-characterized recombinant dendroaspin and elegantin derivatives were employed for this study. These recombinant molecules were constructed as glutathione S-transferase fusion proteins with either an Ala or Pro residue N-terminal to the RGD sequence in combination with either a Met or an Asn residue immediately C-terminal. Equilibrium competition experiments showed that elegantin binding to ADP-treated platelets was inhibited by derivatives Eleg. AM (ARGDMP) and Eleg. PM (PRGDMP) via an allosteric competitive mechanism, providing direct evidence that modulation of the RGD motif can alter competitive behaviour. In addition, recombinant kistrin and dendroaspin both inhibited elegantin binding via a non-competitive mechanism, confirming our previous observations. Further evidence for distinct binding sites employing an independent approach was obtained by analysing the binding of the panel of venom proteins to the functionally defective heterodimer alpha(IIb)beta(3) Ser(123)-->Ala expressed on Chinese hamster ovary cells. These studies demonstrated that simple competitors kistrin and dendroaspin bound with high affinity to the variant integrin complex. In contrast, the binding of elegantin and most significantly, recombinant Dendro. PN (PRGDNP) and Dendro. AN (ARGDNP) were abolished. These observations, taken together, are consistent with a model depicting the presence of distinct sites of RGD ligand recognition on the alpha(IIb)beta(3) complex that show the preferential recognition of specific RGD motifs. Competition experiments demonstrate a negative allosteric relationship between these RGD recognition sites.

Alanine↗
PubMed2000

The role of cardioplegia induction temperature and amino acid enrichment in neonatal myocardial protection.

BACKGROUND: Warm cardioplegic induction improves the ischemically "stressed" adult heart. However, it is rarely used in infants, despite the fact that many newborn hearts are stressed by other factors such as hypoxia. The need for amino acids as well as their mechanism of action has also not been studied. METHODS: We first assessed the role of cardioplegic induction temperature in 10 nonhypoxic neonatal piglets undergoing 70 minutes of multidose blood cardioplegic arrest. Five piglets (group 1) received a cold (4 degrees C) induction, and 5 (group 2) a warm (37 degrees C) induction. Twenty-six other piglets underwent ventilator hypoxia (fraction of inspired oxygen, 8% to 10%) for 60 minutes before cardiopulmonary bypass (stress). Six piglets (group 3) then underwent 70 minutes of cardiopulmonary bypass without ischemia (hypoxia controls), and 20 underwent 70 minutes of cardioplegic arrest. Five of these (group 4) received cold cardioplegic induction, and 15 received warm induction; in 5 of these (group 5), the warm cardioplegic solution contained amino acids, in 5 others (group 6), it was unsupplemented, and in the remaining 5 (group 7), nitroglycerin was added to determine the role of vasodilation. Myocardial function was assessed by pressure-volume loops (expressed as a percent of control), and coronary vascular resistance was measured with cardioplegic infusions. RESULTS: In nonhypoxic (normal) piglets, cold (group 1) and warm (group 2) induction completely preserved systolic function (end-systolic elastance, 100% versus 104%) and preload recruitable stroke work (100% versus 102%), with minimal increase in diastolic compliance (162% versus 156%). Hypoxia-reoxygenation alone (group 3) depressed systolic function (end-systolic elastance, 51%+/-2%) and preload recruitable stroke work (54%+/-3%), and raised diastolic stiffness (260%+/-15%). The detrimental effects of reoxygenation persisted (unchanged from reoxygenation alone) with cold induction (group 4) or warm induction without amino acids (groups 6 and 7). In contrast, warm induction with amino acids (group 5) restored systolic function (end-systolic elastance, 105%+/-3%; p < 0.001 versus groups 3, 4, 6, and 7) and preload recruitable stroke work (103%+/-2%; p < 0.001 versus groups 3, 4, 6, and 7), and decreased diastolic stiffness (154%+/-7%; p < 0.001 versus groups 3, 4, 6, and 7). However, there was no difference in myocardial oxygen consumption in hypoxic hearts receiving a warm induction (6.9 versus 6.5 versus 7.3 mL/g per 5 minutes) (groups 5, 6, 7), and coronary vascular resistance was lowest with nitroglycerin (group 7). CONCLUSIONS: Cardioplegic induction can be given either warm or cold in nonhypoxic neonatal hearts. In contrast, only warm induction with amino acids repairs the hypoxic injury, but the primary mechanism of action is not related to increased metabolic activity or vasodilation.

Adenosine↗
PubMed2000

Reducing postischemic reperfusion damage in neonates using a terminal warm substrate-enriched blood cardioplegic reperfusate.

BACKGROUND: In adult cardiac operations, a warm cardioplegic reperfusate ("hot shot") before removing the aortic cross-clamp improves postbypass myocardial function and metabolic recovery. This modality, however, is rarely used in infants, despite the fact that postbypass cardiac dysfunction remains problematic, especially in cyanotic ("stressed") patients. METHODS: To produce stress, 15 neonatal piglets underwent 60 minutes of ventilator hypoxia (fraction of inspired oxygen, 8% to 10%). All piglets then received similar protection with multidose cold blood cardioplegic solution during 70 minutes of arrest and were separated into three groups to examine the role of a warm reperfusate as well as possible augmentation by aspartate and glutamate enrichment. In 5 piglets (group 1), the cross-clamp was simply removed; in 5 (group 2), an unsupplemented warm blood cardioplegic reperfusate was given; and in 5 (group 3), the warm reperfusate was enriched with aspartate and glutamate. Myocardial function was assessed using pressure-volume loops and expressed as a percentage of control. RESULTS: Compared with hearts receiving reperfusion with unmodified blood (group 1), a warm unsupplemented cardioplegic reperfusate (group 2) slightly improved systolic contractility (end-systolic elastance, 41% versus 50%; p < 0.05 versus group 1) and preload recruitable stroke work (41% versus 52%; p < 0.05 versus group 1), reduced diastolic stiffness (263% versus 245%; p < 0.05 versus group 1), and increased adenosine triphosphate (10.7 versus 11.9 microg/g tissue, p < 0.05 versus group 1). However, if aspartate and glutamate was included in the warm reperfusate (group 3), there was complete recovery of systolic function (end-systolic elastance, 105%+/-3%; p < 0.001 versus all groups) and preload recruitable stroke work (103%+/-2%; p < 0.001 versus all groups), a minimal rise in diastolic stiffness (154%+/-7%; p < 0.001 versus all groups), and preservation of adenosine triphosphate (15.5+/-0.5 microg/g; p < 0.001 versus all groups). CONCLUSIONS: A warm cardioplegic reperfusate helps reduce the reperfusion injury, resulting in improved myocardial function and metabolic recovery in hypoxic (stressed) neonatal hearts, and this effect is maximized if the reperfusate is enriched with aspartate and glutamate, which completely preserves myocardial function.

Adenosine Triphosphate↗
PubMed2000

Lowering reperfusion pressure reduces the injury after pulmonary ischemia.

BACKGROUND: Controlled reperfusion with a modified solution limits pulmonary injury following ischemia. Our initial studies infused this modified reperfusate at a pressure of 40 to 50 mm Hg to insure distribution. However, perhaps a lower pressure, which is closer to the normal physiologic pressure in the lung, would improve results by decreasing sheer stress. METHODS: Fifteen adult pigs underwent 2 hours of lung ischemia by clamping the left bronchus and pulmonary artery. Five (group 1) then underwent uncontrolled reperfusion by removing the vascular clamps and allowing unmodified blood to reperfuse the lung at a pulmonary artery pressure of 20 to 30 mm Hg. The other 10 pigs underwent controlled reperfusion by mixing blood from the femoral artery with a crystalloid solution, and infusing this modified reperfusate into the ischemic lung through the pulmonary artery for 10 minutes before removing the arterial clamp. In 5 (group 2), the modified solution was infused at a pressure of 40 to 50 mm Hg, and in 5 (group 3) 20 to 30 mm Hg. Lung function was assessed 60 minutes after reperfusion and expressed as percentage of control. RESULTS: Compared to uncontrolled reperfusion (group 1), controlled reperfusion at a pressure of 40 to 50 mm Hg (group 2) significantly improved postreperfusion pulmonary compliance (77% versus 86%; p<0.001 versus group 1), and arterial/alveolar ratio (a/A) ratio (27% versus 52%; p<0.001 versus group 1); as well as decreased pulmonary vascular resistance (PVR) (198% versus 154%; p<0.001 versus group 1), lung water (84.3% versus 83.5%; p<0.001 versus group 1), and myeloperoxidase (0.35 versus 0.23 optical density/min/mg protein). Reducing the pressure of the modified reperfusate to 20 to 30 mm Hg further improved postreperfusion compliance (92%+/-1%; p<0.001 versus groups 1 and 2) and a/A ratio (76%+/-1%; p<0.001 versus groups 1 and 2); and lowered PVR (133%+/-2%; p<0.001 versus groups 1 and 2), lung water (82.7%+/-0.1%; p<0.001 versus groups 1 and 2), and myeloperoxidase (0.16%+/-0.01%; p<0.001 versus groups 1 and 2). CONCLUSIONS: After 2 hours of pulmonary ischemia, a severe lung injury occurs following uncontrolled reperfusion, controlled reperfusion with a modified solution reduces this reperfusion injury, and lowering the pressure of the modified reperfusate to more physiologic levels (20 to 30 mm Hg) further reduces the reperfusion injury improving pulmonary function.

Animals↗
PubMed2000

Interleukin-1 and IL-1 receptor antagonist in gingival crevicular fluid.

BACKGROUND/AIMS: This study aimed to investigate the cytokine IL-1beta and its receptor antagonist IL-1ra in gingival crevicular fluid (GCF), in patients with adult periodontitis. METHOD: A total of 40 GCF samples were harvested from 10 subjects with moderate to severe adult periodontitis and 10 healthy controls. Subjects were selected from both genders, with all the upper anterior teeth present, and with no relevant systemic illness, pregnancy or recent medication. All subjects were non-smokers and had not received any periodontal therapy within the preceding 3 months. Deep bleeding sites, deep non-bleeding sites and healthy sites were investigated in relation to upper anterior teeth. Clinical measurements were recorded for each site, after obtaining a GCF sample. IL-1beta and IL-1ra were quantified using new commercially available ELISA kits (Quantikine), and could be detected in all samples. RESULTS: The mean concentration for IL-1beta was 0.11 (SD 0.14) pg/microl for bleeding periodontitis sites, 0.04 (0.05) pg/microl for non-bleeding periodontitis sites, and 0.01 (0.03) pg/microl for healthy sites (p<0.001). In contrast, the mean concentration for IL-1ra was 6.99 (9.78) pg/microl for healthy sites, 0.59 (0.44) pg/microl for non-bleeding periodontitis sites, and 0.44 (0.36) pg/microl for bleeding periodontitis sites (p<0.001, except for comparisons between bleeding and non-bleeding periodontitis sites, p>0.05). For healthy sites, a strong inverse relationship was found between IL-1beta and IL-1ra levels in GCE. CONCLUSIONS: The results suggest a strong relationship between the severity of adult periodontitis and the increasing GCF levels of IL-1beta and decreasing levels of IL-1ra.

Adult↗
PubMed2000

Feedback control of mesolimbic somatodendritic dopamine release in rat brain.

The objective of this study was to examine the role of dopamine (DA) receptors in the nucleus accumbens (ACB) in controlling feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats using ipsilateral dual-probe in vivo microdialysis. Perfusion of the ACB for 60 min with the DA uptake inhibitor GBR-12909 (10-1,000 microM) or nomifensine (10-1,000 microM) dose-dependently increased the extracellular levels of DA in ACB and concomitantly reduced the extracellular levels of DA in the VTA. Coperfusion of 100 microM nomifensine with either 100 microM SCH-23390 (SCH), a D1 antagonist, or 100 microM sulpiride (SUL), a D2 receptor antagonist, produced either an additive (for SCH) or a synergistic (for SUL) elevation in the extracellular levels of DA in the ACB, whereas the reduction in the extracellular levels of DA in the VTA produced by nomifensine alone was completely prevented by addition of either antagonist. Application of 100 microM SCH or SUL alone through the microdialysis probe in the ACB increased the extracellular levels of DA in the ACB, whereas the extracellular levels of DA in the VTA remained unchanged. Overall, the results suggest that (a) increasing the synaptic levels of DA in the ACB activates a long-loop negative feedback pathway to the VTA involving both D1 and D2 postsynaptic receptors and (b) terminal DA release within the ACB is regulated directly by D2 autoreceptors and may be indirectly regulated by D1 receptors, possibly on interneurons and/or through postsynaptic inhibition of the negative feedback loop.

Animals↗
PubMed2000

Complete resolution of hypertension after decompression of Chiari I malformation.

The Chiari I malformation has not been previously linked to sustained hypertension. Other forms of medullary compression have, however, been shown to be associated with elevated arterial pressure. This association has been demonstrated through numerous studies that have implicated compression of the rostral ventrolateral medulla, usually by vascular structures, as a factor responsible for hypertension. We present a case of a young man with a 2-year history of hypertension who was found to have a Chiari I malformation. No other cause for hypertension was found. After subsequent surgical decompression, his hypertension resolved immediately. No other therapeutic options were activated. This is the first reported case linking Chiari I malformation and sustained hypertension. This case presents further evidence linking medullary compression and elevation of hemodynamic tone.

Case Reports↗
PubMed2000

Cytochrome oxidase immunohistochemistry: clues for genetic mechanisms.

Cytochrome c oxidase (COX) is encoded by three mitochondrial and nine nuclear genes. COX deficiency is genetically heterogeneous but current diagnostic methods cannot easily distinguish between mitochondrial and nuclear defects. We hypothesized that there may be differential expression of COX subunits depending on the underlying mutation. COX subunit expression was investigated in five patients with known mtDNA mutations. Severe and selective reduction of mtDNA-encoded COX subunits I and II was consistently observed in all these patients and was restricted to COX-deficient fibres. Immunostaining of nuclear-encoded subunits COX IV and Va was normal, whilst subunit VIc, also nuclear-encoded, was decreased. Twelve of 36 additional patients with histochemically defined COX deficiency also had this pattern of staining, suggesting that they had mtDNA defects. Clinical features in this group were heterogeneous, including infantile encephalopathy, multisystem disease, cardiomyopathy and childhood-onset isolated myopathy. The remaining patients did not have the same pattern of immunostaining. Fourteen had reduced staining of all subunits, whilst 10 had normal staining of all subunits despite reduced enzyme activity. Patients with COX deficiency secondary to mtDNA mutations have a specific pattern of subunit loss, but the majority of children with COX deficiency do not have this pattern of subunit loss and are likely to have nuclear gene defects.

Adolescent↗
PubMed2000

The structure and expression of the wheat starch synthase III gene. Motifs in the expressed gene define the lineage of the starch synthase III gene family.

The endosperm of hexaploid wheat (Triticum aestivum [L.]) was shown to contain a high molecular weight starch synthase (SS) analogous to the product of the maize du1 gene, starch synthase III (SSIII; DU1). cDNA and genomic DNA sequences encoding wheat SSIII were isolated and characterized. The wheat SSIII cDNA is 5,346 bp long and contains an open reading frame that encodes a 1,628-amino acid polypeptide. A putative N-terminal transit peptide, a 436-amino acid C-terminal catalytic domain, and a central 470-amino acid SSIII-specific domain containing three regions of repeated amino acid similarity were identified in the wheat gene. A fourth region between the transit peptide and the SSIII-specific domain contains repeat motifs that are variable with respect to motif sequence and repeat number between wheat and maize. In dicots, this N-terminal region does not contain repeat motifs and is truncated. The gene encoding wheat SSIII, designated ss3, consists of 16 exons extending over 10 kb, and is located on wheat chromosome I. Expression of ss3 mRNA in wheat was detected in leaves, pre-anthesis florets, and from very early to middle stage of endosperm development. The entire N-terminal variable repeat region and the majority of the SSIII-specific domain are encoded on a single 2,703-bp exon. A gene encoding a class III SS from the Arabidopsis genome sequencing project shows a strongly conserved exon structure to the wheat ss3 gene, with the exception of the N-terminal region. The evolutionary relationships of the genes encoding monocot and dicot class III SSs are discussed.

Amino Acid Sequence↗
PubMed2000

Adaptive noise cancellation in a multimicrophone system for distortion product otoacoustic emission acquisition.

This study focuses on adaptive noise cancellation (ANC) techniques for the acquisition of distortion product otoacoustic emissions (DPOAEs). Otoacoustic emissions (OAEs) are very low level sounds produced by the outer hair cells of normal cochleas, spontaneously or in response to sound stimulation as a byproduct of a frequency and threshold sensitivity increasing mechanism. Current OAE recording systems rely on test probe noise attenuation and synchronous ensemble averaging for increasing signal-to-noise ratios (SNRs). The efficiency of an ANC algorithm for noise suppression was investigated using three microphones: one placed in the test ear, one in the nontest ear for internal noise reference; one near the subject's head for external noise reference. The system proposed was tested with simulations, off-line averaging and real-time implementation of the ANC algorithm. Simulation results showed that the technique had a potential noise reduction capability of 24 dB for complex multifrequency noise signals. Off-line results were positive, with a mean SNR improvement of 4.9 dB. Real-time results indicated that the use of an ANC algorithm in combination with standard averaging methods can reduce noise levels by as much as 10 dB beyond that obtained with standard noise reduction methods and probe attenuation alone.

Algorithms↗
PubMed2000

Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression.

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.

Animals↗
PubMed2000

Knowledge, attitudes, and practices regarding sexually transmitted infections among general practitioners and medical specialists in Karachi, Pakistan.

OBJECTIVES: To determine the knowledge, attitudes, and practices regarding diagnosis and treatment of sexually transmitted infections (STIs) among specialists--that is, dermatologists, gynaecologists and urologists, and general practitioners (GPs) in Karachi, Pakistan. METHODS: Interviewers administered structured questionnaires to doctors conducting outpatient clinics at tertiary hospitals and/or private clinics in Karachi. All private clinics within a 10 km radius of the Aga Khan University, and all tertiary hospitals having more than 100 inpatient beds were included in the study. RESULTS: 100 doctors (54 specialists and 46 GPs) responded. 80 doctors reported seeing at least one STI patient/month. The most commonly diagnosed STI the doctors reported was urethritis/cervicitis syndrome. 50% of the doctors knew the recommended antibiotics for gonorrhoea though only 46% of these knew the correct dosage. Specialists were three times more likely to recognise the clinical presentation of herpes and twice as likely to treat chlamydia, syphilis, and herpes with appropriate antimicrobials than GPs. 85% of the doctors advised their STI patients regarding condom usage; 36% thought that STI patients had loose sexual morals; 43% believed STI patients were drug addicts. Over 90% of the physicians were willing to attend educational sessions and follow a national STI treatment protocol. CONCLUSION: Doctors in Karachi, especially GPs, are deficient in appropriately managing and counselling STI patients. Among the specialists, urologists and dermatologists were more likely to manage STIs correctly than gynaecologists. Karachi doctors should be educated in the correct management and counselling of STIs to prevent further spread of STIs including AIDS.

Attitude of Health Personnel↗
PubMed2000

The genes encoding granule-bound starch synthases at the waxy loci of the A, B, and D progenitors of common wheat.

Three genes encoding granule-bound starch synthase (wx-TmA, wx-TsB, and wx-TtD) have been isolated from Triticum monococcum (AA), and Triticum speltoides (BB), by the polymerase chain reaction (PCR) approach, and from Triticum tauschii (DD), by screening a genomic DNA library. Multiple sequence alignment indicated that the wx-TmA, wx-TsB, and wx-TtD genes had the same extron and (or) intron structure as the previously reported waxy gene from barley. The lengths of the three wx-TmA, wx-TsB, and wx-TtD genes were 2834 bp, 2826 bp, and 2893 bp, respectively, each covering 31 bp in the untranslated leader and the entire coding region consisting of 11 exons and 10 introns. The three genes had identical lengths of exons, except exonl, and shared over 95% identity with each other within the exon regions. The majority of introns were significantly variable in length and sequence, differing mainly in length (1-57 bp) as a result of insertion and (or) deletion events. The deduced amino acid sequence from these three genes indicated that the mature WX-TMA, -TSB, and -TTD proteins contained the same number of amino acids, but differed in predicted molecular weight and isoelectric point (pI) due to amino acid substitutions (13-18). The predicted physical characteristics of the WX proteins matched the respective proteins in wheat very closely, but the match was not perfect. Furthermore the exon5 sequences of the wx-TmA, wx-TsB, and wx-TtD genes were different from a cDNA encoding a waxy gene of common wheat previously reported. The striking difference was that an insertion of 11 amino acids occurred in the cDNA sequence that could not be observed in the exons of the A, B, and D genes. It was noted, however, that the 3' end of intron4 of these genes could account for the additional 11 amino acids. The sequence information from the available waxy genes identified the intron4-exon5-intron5 region as being diagnostic for sequence variation in waxy. The sequence variation in the waxy genes provides the basis for primer design to distinguish the respective genes in common wheat, and its progenitors, using PCR.

Amino Acid Sequence↗
PubMed2000

Mitochondrial DNA point mutation T9176C in Leigh syndrome.

Leigh syndrome is a progressive neurodegenerative disease frequently associated with mitochondrial abnormalities. The mitochondrial DNA T9176C mutation in the adenosine triphosphatase 6 gene has recently been described as a cause of Leigh syndrome. Leukocyte DNA from 59 children with Leigh syndrome was screened for the T9176C mutation by conventional polymerase chain reaction methods. Two unrelated patients were found to be homoplasmic for this mutation in blood. Both patients had similar clinical and biochemical features. They had first presented acutely at 3 and 5 years, respectively, with ataxia and slurred speech. Magnetic resonance imaging changes were consistent with Leigh syndrome, and the cerebrospinal fluid lactate was elevated. They have both had relatively stable disease since the time of diagnosis. The mother of one of the children had presented at age 29 years with sudden onset of ataxia, headache, and blurred vision. She was heteroplasmic for the T9176C mutation. The T1976C is an important cause of Leigh syndrome especially in the subgroup of patients with more stable disease and normal respiratory chain enzyme analysis.

Adenosine Triphosphatases↗
PubMed1999

Cerebellar cortical AMPA-kainate receptor blockade prevents performance of classically conditioned nictitating membrane responses.

Classical conditioning of the nictitating membrane-eye blink response of rabbits is a simple form of associative motor learning. Lesion studies have shown that performance of learned responses is dependent on the cerebellum, but they have not shown whether there is storage of memories within the cerebellum or distinguished the roles of the cerebellar cortex and nuclei. Reversible inactivations of the cerebellar nuclei have directly implicated the cerebellum in the acquisition of nictitating membrane conditioning, but previously the cerebellar cortex has not been reversibly inactivated to assess its contribution to the performance or acquisition of conditioned responses. Here we use the water-soluble disodium salt of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reversibly to block cerebellar cortical AMPA-kainate receptors in lobule HVI and quantitative autoradiography to map its distribution. Conditioned responses are completely, but reversibly, abolished for 10-60 min depending on the concentration of the CNQX infusion and its location within HVI. Zebrin immunohistochemistry was used to define the optimal cortical infusion site that, we suggest, corresponds to the location of the eye blink control regions. We confirm that areas in HVI are essential for the expression of classically conditioned nictitating membrane responses, and we establish a method to analyze the role of cerebellar cortex in the acquisition of this form of motor learning.

6-Cyano-7-nitroquinoxaline-2,3-dione↗