Search PubMed⌕ Search

Biomedical subjects

A Siddiqui

Publications and source records attributed to A Siddiqui.

At least 73 records · Page 4Linked to original sources
PubMed1996

Hemophilus influenzae septic arthritis and pneumonia in an adult as the first presentation of multiple myeloma.

We describe an apparently healthy woman who presented with monoarthritis of the right knee and a history of respiratory infection. The synovial fluid cultures grew beta lactamase-negative H. influenzae. Chest roentgenogram showed patchy densities throughout the right lung. Investigations for a predisposing factor for this H. influenzae infection revealed underlying multiple myeloma. As H. influenzae pyoarthrosis is extremely rare in adults, we suggest that an underlying systemic cause be sought in all such patients.

Aged↗
PubMed1996

Prevalence of seromarkers of HBV and HCV in health care personnel and apparently healthy blood donors.

Ninety-five health care workers and 91 controls were screened for seromarkers of both HBV (HBsAg, HBeAg, Anti-HBc) and HCV (anti-HCV) by ELISA. The control group showed a much higher frequency of seromarkers for both the viruses. HBsAg was positive in 5% of study group (health care personnel) and 14% of controls. Anti-HBc as a marker of past HBV-exposure was positive in 28% of study group as compared to 36% of controls. Overall, 33% of study group and 48% of control showed one or the other marker of HBV Anti-HCV was positive in 4% of study group and 14% of controls. This study suggests that health care workers are not particularly a high risk group as compared to rest of the population.

Adult↗
PubMed1995

Hepatitis B virus transactivator protein X interacts with the TATA-binding protein.

Several viral transcriptional activators have been shown to interact with the basal transcription factor TATA-binding protein (TBP). These associations have been implicated in facilitating the assembly of the transcriptional preinitiation complex. We report here that the hepatitis B virus protein X (pX) specifically binds to TBP in vitro. While truncations of the highly conserved carboxyl terminus of TBP abolished this binding, amino-terminal deletions had no effect. Deletion analysis suggests that a domain consisting of 71 aa in the highly conserved carboxyl-terminal region of TBP is necessary for its interaction with pX. The minimal region in pX sufficient for its interaction with TBP includes aa 110-143. Furthermore, TBP from phylogenetically distinct species including Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, and Solanum tuberosum (potato) bound to pX. The pX-TBP interaction was inhibited in the presence of nonhydrolyzable analogs of ATP, suggesting a requirement for ATP. These results provide an explanation for the promiscuous behavior of pX in the transactivation of a large repertoire of cellular promoters. This study further implicates a fundamental role for pX in modulating transcriptional regulatory pathways by interacting with the basal transcription factor TBP.

Amino Acid Sequence↗
PubMed1995

Pestivirus translation initiation occurs by internal ribosome entry.

The role of the 385 nucleotide 5' noncoding region (NCR) in the translation of the pestivirus genome was investigated. In vitro translation of an RNA transcript containing the 5' NCR of the bovine viral diarrhea virus (BVDV) genome followed by the coding sequence of the first gene product (p20) of the BVDV large open reading frame resulted in the synthesis of a 20-kDa polypeptide. Results from hybrid-arrest translation studies identified a region involving a predicted RNA stem-loop structure spanning nucleotides 154-261 within the 5' NCR that was important for p20 synthesis. An additional inhibitory oligonucleotide was complementary to the sequence at the base of this stem-loop and encompassed the initiating AUG at nucleotide 386. Antisense oligonucleotides both upstream and downstream of those that were inhibitory had no effect on p20 translation. RNA from a dicistronic expression vector in which the BVDV 5' NCR was inserted between two reporter genes, CAT and LUC, showed strong expression of the second (LUC) cistron upon in vitro translation. This expression was dramatically reduced in an analogous construct in which nucleotides 173-236 of the 5' NCR were deleted. Similar results were obtained when RNA from these same vectors was evaluated for expression after transfection into BHK cells. These results suggest that the BVDV 5' NCR contains an internal ribosome entry site for translation initiation. This translational mechanism is similar to that shown for hepatitis C virus, further demonstrating the close relationship between viruses of these two genera within the family Flaviviridae.

Animals↗
PubMed1995

Cation-induced efflux of calcium from the mitochondria of Hymenolepis diminuta.

We have previously reported that Ca2+ influx into the mitochondria of Hymenolepis diminuta, a rat intestinal cestode, takes place through an electrophoretic uniport system. Sodium and lithium were found to induce efflux of 45Ca2+ from the mitochondria of H. diminuta. The two cations induced the efflux in a hyperbolic and linear fashion, respectively. The efflux as well as an exchange of external Ca2+ with internal 45Ca2+ was inhibited by lanthanum. The type of Ca2+ transport system in the cestode organelle has been discussed and compared with that of the host (mammalian) counterpart.

Animals↗
PubMed1995

Thoracoscopic implantation of cancer with a fatal outcome.

A case is presented in which an indeterminate lung lesion was extracted through an accessory incision during a video-assisted thoracic surgical lung biopsy. The lesion was malignant, and a completion lobectomy was performed. An incisional recurrence developed 5 months later, and this was treated with a wide chest wall resection and reconstruction. However, there was a second massive chest wall recurrence that proved fatal. We believe that tumor seeding to the chest wall occurred at thoracoscopy. To prevent such tumor seeding, thoracoscopic biopsy specimens should be removed in some sort of receptacle when cancer is suspected.

Adenocarcinoma↗
PubMed1995

Tumor targeting and pharmacokinetics of unmodified and modified F(ab)2 fragments of an anti-CEA murine monoclonal antibody (Immu-14).

Pharmacokinetic studies were performed with two different 111In-labeled F(ab)2 fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-14). Unmodified F(ab)2 and modified Fab-BMH-Fab fragments were compared in nude mice bearing a LS-174T human colon carcinoma tumor xenograft. Tumor accumulation is significantly higher for modified fragments than for unmodified fragments at all time points. At 24 h post injection, tumor uptake for modified and unmodified fragments reached 40 and 25% ID g, respectively. The retention of radioactivity in the liver was approx. 2-fold higher for modified fragments. Kidney uptake of modified fragments was at least 2-fold lower than that of unmodified fragments. Although blood radioactivity decreased rapidly for both fragments, the cumulative tumor activity was 40% higher for Fab-BMH-Fab fragment. Modified F(ab)2 fragments can deliver higher radiation doses to the tumor.

Animals↗
PubMed1995

Biodistribution and tumor localization of 111In-labeled unmodified and modified F(ab')2 fragments of human monoclonal IgM (16.88) in a nude mouse model.

Unmodified F(ab')2 and modified Fab'-BMH-Fab' fragments of human monoclonal IgM (16.88) were compared for biodistribution and tumor localization in nude mice bearing LS-174T human colon carcinoma xenografts. Although both unmodified and modified fragments of IgM cleared rapidly from the blood, the radioactivity retentions for each fragment in liver and kidney were significantly different. Kidney uptake of the modified fragment was about 4-fold lower than kidney uptake of the unmodified fragment. Radioactivity uptake in liver was 2-4-fold higher for the modified fragment. Lower liver and higher kidney uptake of unmodified fragments reflected the labile disulfide linkage of F(ab')2 in their hinge region and the subsequent behavior of the Fab' fragments resulting from the reduction of the disulfide linkage. Higher liver and lower kidney retention of modified fragments, on the other hand, resulted from the different cleavage mechanism of the stable thioether linkage. Tumor targeting was similar for unmodified and modified fragments at approx. 4% of injected dose per gram. These results indicate that the changes in fragment linkage chemistry may provide different pharmacokinetic patterns in vivo and improve the therapeutic application of radiolabeled fragments in human patients.

Animals↗
PubMed1995

Object size as a determinant of grasping in infancy.

The early development and patterns of development of prehensile ability were examined. Infants 5, 7, and 9 months old were presented five objects, 0.5, 1.0, 3.5, 7.0, and 14.0 cm in diameter. The findings revealed that infants as young as 5 months old were able to differentiate grip configurations as a function of object size. The number of grasps involving the two or three most radial digits (thumb, index finger, and long finger) increased greatly over this age span. At 9 months of age these kinds of grasps were 10 times more frequent than at 5 months of age. However, at each age level, when only the two or three most radial digits were used, the reaches were typically directed at the two smallest objects. These findings suggest that it was not a perceptual problem that the younger infants were facing, nor was the problem knowing when to use different kinds of grasps; rather, the problem was one of cortico-motoneural connections, which are better established in older infants. The findings also suggest that traditionally described sequential development of infants' prehension is rigid and conservative. The discrepancy with earlier results may also be attributed to the difference in the objects' sizes and the way they were presented.

Age Factors↗
PubMed1995

Retinoid X receptor alpha transactivates the hepatitis B virus enhancer 1 element by forming a heterodimeric complex with the peroxisome proliferator-activated receptor.

The hepatitis B virus enhancer 1 contains a retinoic acid responsive element (RARE). We have previously demonstrated that retinoid X receptor alpha (RXR alpha) transactivates enhancer 1 by binding to the RARE. The present study has revealed that a heterodimeric complex composed of RXR alpha and peroxisome proliferator-activated receptor (PPAR) interacts with the hepatitis B virus RARE. Transient transfection studies, in conjunction with in vitro DNA binding data, support the hypothesis that the RXR alpha-PPAR heterodimer transactivates enhancer 1.

Base Sequence↗
PubMed1995

Interaction of polypyrimidine tract-binding protein with the 5' noncoding region of the hepatitis C virus RNA genome and its functional requirement in internal initiation of translation.

Initiation of translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry into the 5' noncoding region (5'NCR) in a cap-independent manner. The internal ribosome entry site of the HCV 5'NCR has been previously defined to encompass almost the entire 5'NCR. Here we report the interaction of polypyrimidine tract-binding protein (PTB) at three distinct regions within the 5'NCR by UV cross-linking assays. All three regions contain a consensus polypyrimidine tract motif. The evidence for the interaction of recombinant PTB at multiple sites within the 5'NCR is based on the use of 5'NCR mutants as competitors and by direct UV cross-linking of the mutant RNAs. Furthermore, the PTB isomers from HeLa nuclear extracts interact with the HCV 5'NCR, as shown by immunoprecipitation of a UV cross-linked complex with anti-PTB serum. Immunodepletion of PTB from translation lysates suggested the functional requirement for PTB during translation initiation of the HCV RNA. Addition of purified PTB to immunodepleted lysates did not restore translation mediated by the HCV 5'NCR, indicating the requirement of PTB-associated factors that were removed during immunodepletion.

Base Sequence↗
PubMed1995

An RNA pseudoknot is an essential structural element of the internal ribosome entry site located within the hepatitis C virus 5' noncoding region.

Translation of the human hepatitis C virus (HCV) RNA genome occurs by a mechanism known as "internal ribosome entry." This unusual strategy of translation is employed by naturally uncapped picornaviral genomic RNAs and several cellular mRNAs. A common feature of these RNAs is a relatively long 5' noncoding region (NCR) that folds into a complex secondary structure harboring an internal ribosome entry site (IRES). Evidence derived from the use of dicistronic expression systems, combined with an extensive mutational analysis, demonstrated the presence of an IRES within the HCV 5'NCR. The results of our continued mutational analysis to map the critical structural elements of the HCV IRES has led to the identification of a pseudoknot structure upstream of the initiator AUG. The evidence presented in this study is based upon the mutational analysis of the putative pseudoknot structure. This is further substantiated by biochemical and enzymatic probing of the wild-type and mutant 5'NCR. Further, the thermodynamic calculations, based upon a modified RNAKNOT program, are consistent with the presence of a pseudoknot structure located upstream of the initiator AUG. Maintenance of this structural element is critical for internal initiation of translation. The pseudoknot structure in the 5'NCR represents a highly conserved feature of all HCV subtypes and members of the pestivirus family, including hog cholera virus and bovine viral diarrhea virus.

Base Sequence↗
PubMed1995

Translation of hepatitis C virus genome.

Translation of the human hepatitis C virus (HCV) RNA genome occurs by internal ribosome entry through the 5' end (5' noncoding region) in a cap-independent fashion. The relatively long stretch of this noncoding region contains multiple initiation codons that are apparently not used for translation. Translation of the HCV polyprotein is initiated instead from an AUG located at nt 342. Using computer-assisted analysis (and subsequently substantiated by enzymatic probing), a complex secondary and tertiary structure of the 5' noncoding region (5'NCR) has been predicted. Based on an RNA folding model proposed by Brown et al. (1992), a detailed mutational analysis carried out identified the key secondary structural regions that are of functional significance in translational control. Maintenance of a helical structural element relevant to an oligopyrimidine tract is essential for internal initiation. A putative coaxial stacking or a pseudoknot structure upstream of the initiator AUG seems to be central to an internal ribosome entry site (IRES)-mediated translation of the HCV RNA genome.

Hepacivirus↗
PubMed1994

Detection of phencyclidine in urine using a polarization fluoroimmunoassay.

A polarization fluoroimmunoassay was developed for the detection of phencyclidine in urine and the reagents were adapted for use on the Abbott TDx analyser. The assay was used to look for evidence of phencyclidine abuse, over a 6 month period, amongst patients attending drug abuse clinics in the East End of London. Although over 2000 patients' samples tested negative, the assay successfully detected phencyclidine in an external quality control scheme.

Animals↗
PubMed1994

A conserved helical element is essential for internal initiation of translation of hepatitis C virus RNA.

Translation of hepatitis C virus (HCV) RNA is initiated by cap-independent internal ribosome binding to the 5' noncoding region (NCR). To identify the sequences and structural elements within the 5' NCR of HCV RNA that contribute to the initiation of translation, a series of point mutations was introduced within this sequence. Since the pyrimidine-rich tract is considered a characteristic feature of picornavirus internal ribosome entry site (IRES) elements, our mutational analysis focused on two putative pyrimidine tracts (Py-I and Py-II) within the HCV 5' NCR. Translational efficiency of these mutant RNAs was examined by in vitro translation and after RNA transfection into liver-derived cells. Mutational analysis of Py-I (nucleotides 120 to 130), supported by compensatory mutants, demonstrates that the primary sequence of this motif is not important but that a helical structural element associated with this region is critical for HCV IRES function. Mutations in Py-II (nucleotides 191 to 199) show that this motif is dispensable for IRES function as well. Thus, the pyrimidine-rich tract motif, which is considered as an essential element of the picornavirus IRES elements, does not appear to be a functional component of the HCV IRES. Further, the insertional mutagenesis study suggests a requirement for proper spacing between the initiator AUG and the upstream structures of the HCV IRES element for internal initiation of translation.

Base Sequence↗
PubMed1994

The effect of cardiopulmonary bypass on gastric and colonic mucosal perfusion: a tonometric assessment.

In a study to assess the potential effect of nonpulsatile hypothermic cardiopulmonary bypass (CPB), intramucosal pH (pHi) of the gastric and colonic mucosae was determined by tonometry (n = 8). During the hypothermic phase of CPB, gastric and colonic pHi did not change significantly. Forty minutes after the start of rewarming, despite increases in the cardiac index and mean arterial blood pressure, gastric pHi fell from 7.53 +/- 0.02 to 7.31 +/- 0.03 (p = 0.017) and colonic pHi fell from 7.50 +/- 0.02 to 7.32 +/- 0.03 (p = 0.028). Forty minutes after the end of CPB both the colonic (p = 0.017) and gastric (p = 0.046) pHi remained depressed below pre-CPB values. The difference in the arterial (pHa) and the gastric mucosal pH changed from -0.097 before CPB to 0.016, 40 minutes after the end of CPB (p = 0.027). This alteration in the pHa-pHi underlines the importance of measuring intramucosal pH by tonometry, since the pHa and pHi may move in opposite directions during episodes of haemodynamic stress. Both the gastric and colonic pHi were found to have a linear correlation with the pHa, although changes in the gastric pHi (r = 0.41, p = 0.018) were more strongly correlated with the pHa than the colonic pHi (r = 0.23, p = 0.19) in the rewarming phase of CPB and the immediate post-CPB period when there was a tendency towards intramucosal acidosis. The development of intramucosal acidosis in the rewarming and immediate post-CPB phases following hypothermic nonpulsatile CPB may impair the gut barrier and predispose patients to the absorption of luminal toxins.

Blood Pressure↗
PubMed1994

The cutaneous signs of eating disorders.

Anorexia nervosa and bulimia nervosa are common yet occult eating disorders which each affect between 1 and 2% of young adult women in the UK (1). Cutaneous signs may provide valuable clues allowing earlier diagnosis. Eating disorders may both imitate (Table I) and complicate other medical illnesses, resulting in unnecessary and expensive investigations. Organic diseases that may be complicated by eating disorders are Crohn's disease (2), diabetes mellitus (3, 4) and human immune deficiency virus disease (5). The concurrence of an additional eating disorder will destabilize the primary medical condition. In anorexia nervosa the mortality rate has been found to be between 15 and 18% (6, 7). Early diagnosis and treatment are essential to reduce the morbidity and mortality of these concealed conditions. This report describes a patient who exhibited excoriations and scars over the dorsum of her hands, leg ulceration and loss of teeth as cutaneous signs of an eating disorder.

Adult↗