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Biomedical subjects

A Amin

Publications and source records attributed to A Amin.

At least 37 records · Page 2Linked to original sources
PubMed2001

Activation of stress-activated protein kinase in osteoarthritic cartilage: evidence for nitric oxide dependence.

OBJECTIVE: We have demonstrated in bovine chondrocytes that nitric oxide (NO) mediates IL1 dependent apoptosis under conditions of oxidant stress. This process is accompanied by activation of c-Jun NH2-terminal kinase (JNK; also called stress-activated protein kinase). In these studies we examined activation of JNK in explant cultures of human osteoarthritic cartilage obtained at joint replacement surgery and we characterized the role of peroxynitrite to act as an upstream trigger. DESIGN: A novel technique to isolate chondrocyte proteins (<10% of total cartilage protein) from cartilage specimens was developed. It was used to analyse JNK activation by a western blot technique. To examine the hypothesis that chondrocyte JNK activation is a result of increased peroxynitrite, in vitro experiments were performed in which cultured chondrocytes were incubated with this oxidant. RESULTS: Activated JNK was detected in the cytoplasm of osteoarthritis (OA) affected chondrocytes but not in that of controls. In vitro, chondrocytes produce NO and superoxide anion. IL-1 (48 h), which induces nitric oxide synthase, resulted in an activation of JNK; this effect was reversed by N-monomethylarginine (NMA). TNFalpha treated chondrocytes at 48 h produce superoxide anion (EPR method). Exposure of cells to peroxynitrite led to an accumulation of intracellular oxidants, in association with JNK activation and cell death by apoptosis. CONCLUSION: We suggest that JNK activation is among the IL-1 elicited responses that injure articular chondrocytes and this activation of JNK is dependent on intracellular oxidant formation (including NO peroxynitrite). In addition, the extraction technique here described is a novel method that permits the quantitation and study of proteins such as JNK involved in the signaling pathways of chondrocytes within osteoarthritic cartilage.

Animals↗
PubMed2000

Selection of antibiotic-resistant bacterial mutants: allelic diversity among fluoroquinolone-resistant mutations.

To obtain a general framework for understanding selection of antibiotic-resistant mutants, allelic diversity was examined with about 600 fluoroquinolone-resistant mutants of mycobacteria. Selection at low fluoroquinolone concentration produced many low-level resistance mutants. Some of these contained mutations that conferred unselected antibiotic resistance; none contained alterations in the quinolone-resistance-determining region of the GyrA protein, the principal drug target. As selection pressure increased, a variety of GyrA variants became prevalent. High concentrations of antibiotic reduced the variety to a few types, and eventually a concentration was reached at which no mutant was recovered. That concentration defined a threshold for preventing the selection of resistance. The pattern of variants selected, which was also strongly influenced by antibiotic structure, readily explained the variants present in clinical isolates. Thus, resistance arises from selection of mutants whose identity depends on drug concentration and structure, both of which can be manipulated to restrict selection.

Alleles↗
PubMed2000

Therapy and drug resistance in malaria.

The aim of this study was to highlight the high degree of clinical resistance of P. falciparum and also of P. vivax to chloroquine and also the importance of early diagnosis and prompt treatment. Ninety cases of smear positive malaria aged between 6 months to 14 years were studied with regards to clinical manifestations, management and outcome. Criteria for drug resistance were absence of clearance of parasitemia and/or persistance of fever after 72 hours of therapy. Chloroquin resistance was noted in 15 (62.5%) cases of falciparum malaria and 15 (51.7%) cases of vivax malaria. The resistant and complicated cases were treated with quinine. Four (6.6%) cases were resistant to quinine and responded to artemether. There was no mortality. Early reporting of cases, frequent sampling malarial parasite, prompt diagnosis of falciparum malaria, early institution of appropriate therapy and awareness of choloquine and/or quinine resistance helps in salvaging lives.

Adolescent↗
PubMed2000

Retinal vein thrombosis associated with chronic hepatitis C: a case series and review of the literature.

The role of procoagulant autoantibodies in hepatitis C virus (HCV) infection is unclear. Three individuals with HCV infection and a unique genetic hypercoagulable state developed retinal vein thrombosis (RVT) in association with interferon-alpha (IFN-alpha) therapy. It is probable that a combination of active HCV infection in a genetically susceptible individual receiving IFN-alpha accounted for the observed RVT.

Adult↗
PubMed2000

Epidermal growth factor receptor signaling activates orthodenticle expression during Drosophila head development.

The relation between signal transduction pathways and the genes that specify regional identity remains poorly understood. We investigated the interaction between the epidermal growth factor receptor (EGFR) pathway and the homeobox gene orthodenticle (otd), which specifies cell fate during head development. Previous studies of head formation in Drosophila melanogaster demonstrated that reducing either EGFR signaling or otd expression in the imaginal primordium of the dorsal head capsule eliminates the ocelli and other dorsal head structures. Here, we show that blocking EGFR signaling reduces otd expression and that activating EGFR signaling outside this primordium induces ectopic otd expression. We also demonstrate that loss of EGFR can be rescued by constitutive otd expression. Our results indicate that otd is a downstream target of the EGFR pathway during head development.

Animals↗
PubMed2000

Negligible genetic diversity of mycobacterium tuberculosis host immune system protein targets: evidence of limited selective pressure.

A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sites were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis.

Acyltransferases↗
PubMed2000

Characterization of Mycobacterium tuberculosis isolates from patients in Houston, Texas, by spoligotyping.

Mycobacterium tuberculosis isolates (n = 1,429) from 1,283 patients collected as part of an ongoing population-based tuberculosis epidemiology study in Houston, Texas, were analyzed by spoligotyping and IS6110 profiling. The isolates were also assigned to one of three major genetic groups on the basis of nucleotide polymorphisms located at codons 463 and 95 in the genes (katG and gyrA) encoding catalase-peroxidase and the A subunit of DNA gyrase, respectively. A total of 225 spoligotypes were identified in the 1,429 isolates. There were 54 spoligotypes identified among 713 isolates (n = 623 patients) assigned to 73 IS6110 clusters. In addition, among 716 isolates (n = 660 patients) with unique IS6110 profiles, 200 spoligotypes were identified. No changes were observed either in the IS6110 profile or in the spoligotype for the 281 isolates collected sequentially from 133 patients. Five instances in which isolates with slightly different spoligotypes had the same IS6110 profile were identified, suggesting that in rare cases isolates with different spoligotypes can be clonally related. Spoligotypes correlated extremely well with major genetic group designations. Only three very similar spoligotypes were shared by isolates from genetic groups 2 and 3, and none was shared by group 1 and group 2 organisms or by group 1 and group 3 organisms. All organisms belonging to genetic groups 2 and 3 failed to hybridize with spacer probes 33 to 36. Taken together, the results support the existence of three distinct genetic groups of M. tuberculosis organisms and provide new information about the relationship between IS6110 profiles, spoligotypes, and major genetic groups of M. tuberculosis.

Bacterial Proteins↗
PubMed1999

Measurement of blood flow and oxygen tension in adjacent tissues in pedicled and free flap head and neck reconstruction.

The purpose of this study was to evaluate blood flow and transcutaneous partial oxygen pressure (TcPO(2)) in adjacent tissues to free and pedicled flaps following reconstructive procedures used in conjunction with radical surgery for head and neck cancers. Fifty patients were included. Fourteen patients had reconstruction with pedicled flaps and 36 with free flaps. For each patient, TcPO(2) and laser Doppler flow measurements were taken at the center of the flap, in adjacent tissue, and in a corresponding contralateral site. Three laser Doppler measurements were performed at each site and a mean value recorded. All patients had undergone reconstruction up to 6 months prior to the time of the measurements. The collected data were analyzed using a Wilcoxon signed rank test. There were no statistically significant differences in partial oxygen tension or laser Doppler values between tissues adjacent to free compared to pedicled flaps. Although there is strong evidence to support that free flaps have improved blood flow and partial oxygen tension over pedicled flaps, further study is required to evaluate adjacent tissues. Flap choice may assist with alteration in blood flow in less favorable defects such as those in previously irradiated fields and those resulting from burn scars or chronic infections.

Adolescent↗
PubMed1999

Laser in situ keratomileusis for correction of myopia and astigmatism after penetrating keratoplasty.

PURPOSE: To determine the safety and effectiveness of laser in situ keratomileusis (LASIK) for visual rehabilitation of residual myopia and astigmatism after penetrating keratoplasty. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: LASIK was performed on 23 eyes of 22 patients unable to wear glasses or contact lenses after penetrating keratoplasty due to anisometropia, high astigmatism, and/or contact lens-intolerance. METHODS: All patients underwent LASIK for visual rehabilitation after penetrating keratoplasty. Uncorrected visual acuity and best spectacle-corrected visual acuity, degree of anisometropia, and corneal transplant integrity were recorded before surgery, as well as at 1 month, 3 months, 6 months, and 12 months after LASIK surgery. RESULTS: The mean spherical equivalent before surgery was -7.58+/-4.42 diopters (D), which was reduced to -1.09+/-2.01 D, -0.79+/-1.84 D, -0.77+/-1.25 D, and -1.57+/-1.20 D, respectively, at 1, 3, 6, and 12 months after LASIK. The mean cylinder before surgery was 3.64+/-1.72 D, which was reduced to 1.98+/-1.15 D, 1.64+/-1.14 D, 1.48+/-0.92 D, and 1.29+/-1.04 D, respectively, at 1, 3, 6, and 12 months after LASIK. Spherical equivalent anisometropia was reduced from a mean of 6.88+/-4.4 D to 1.42+/-1.05 D at the final examination. Best-corrected visual acuity remained the same or improved in 21 of 23 eyes and decreased by 1 and 3 lines in 2 patients. There were no surgical flap or corneal transplant complications. CONCLUSIONS: LASIK is a viable treatment alternative for myopia and astigmatism after penetrating keratoplasty in patients who are contact lens-intolerant. LASIK is more effective in treating myopia than astigmatism after penetrating keratoplasty.

Adult↗
PubMed1999

Identification of a Drosophila prolyl endopeptidase and analysis of its expression.

Prolyl endopeptidases (PEPs) are believed to be involved in the metabolism of neuropeptide hormones (reviewed in Mentlein [1988]). Genes encoding PEPs have been isolated from various species, but their expression patterns during development have not been determined. In this study, we isolated a gene encoding a predicted PEP from the fruitfly Drosophila melanogaster. The gene encodes a predicted 756-amino acid protein having extensive sequence similarity to human PEP. We demonstrated that the Drosophila gene (DPEP) is expressed in a spatially restricted pattern in imaginal discs and the larval brain. Our results suggest a role for DPEP in the regional specification of larval tissues. They also provide a starting point for a genetic analysis of the function of this enzyme during development.

Amino Acid Sequence↗
PubMed1999

Role of the ATP-binding domain of the human papillomavirus type 11 E1 helicase in E2-dependent binding to the origin.

Replication of the genome of human papillomaviruses (HPV) is initiated by the recruitment of the viral E1 helicase to the origin of DNA replication by the viral E2 protein, which binds specifically to the origin. We determined, for HPV type 11 (HPV-11), that the C-terminal 296 amino acids of E1 are sufficient for interaction with the transactivation domain of E2 in the yeast two-hybrid system and in vitro. This region of E1 encompasses the ATP-binding domain. Here we have examined the role of this ATP-binding domain, and of ATP, on E2-dependent binding of E1 to the origin. Several amino acid substitutions in the phosphate-binding loop (P loop), which is implicated in binding the triphosphate moiety of ATP, abolished E2 binding, indicating that the structural integrity of this domain is essential for the interaction. The structural constraints imposed on the E1 P loop may differ between HPV-11 and bovine papillomavirus type 1 (BPV-1), since the P479S substitution that inactivates BPV-1 E1 is tolerated in the HPV-11 enzyme. Other substitutions in the E1 P loop, or in two other conserved motifs of the ATP-binding domain, were tolerated, indicating that ATP binding is not essential for interaction with E2. Nevertheless, ATP-Mg stimulated the E2-dependent binding of E1 to the origin in vitro. This stimulation was maximal at the physiological temperature (37 degrees C) and did not require ATP hydrolysis. In contrast, ATP-Mg did not stimulate the E2-dependent binding to the origin of an E1 protein containing only the C-terminal domain (353 to 649) or that of mutant E1 proteins with alterations in the DNA-binding domain. These results are discussed in light of a model in which the E1 ATP-binding domain is required for formation of the E2-binding surface and can, upon the binding of ATP, facilitate and/or stabilize the interaction of E1 with the origin.

Adenosine Triphosphate↗
PubMed1999

Hedgehog activates the EGF receptor pathway during Drosophila head development.

The Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in pattern formation and cell proliferation in invertebrates and vertebrates. In this study, we demonstrate a direct link between these two pathways in Drosophila melanogaster. Hh and EGFR signaling are each required for the formation of a specific region of the head of the adult fruitfly. We show that hh and vein (vn), which encodes a ligand of the Drosophila EGFR (Schnepp, B., Grumbling, G., Donaldson, T. and Simcox, A. (1996) Genes Dev. 10, 2302-13), are expressed in adjacent domains within the imaginal primordium of this region. Using loss- and gain-of-function approaches, we demonstrate that Hh activates vn expression. We also show that Hh activation of vn is mediated through the gene cubitus interruptus (ci) and that this activation requires the C-terminal region of the Ci protein. Finally, we demonstrate that wingless (wg) represses vn expression, thereby limiting the domain of EGFR signaling.

Animals↗
PubMed1998

Murine HIP/L29 is a heparin-binding protein with a restricted pattern of expression in adult tissues.

Heparin/heparan sulfate (Hp/HS)-binding proteins are implicated in a variety of cell biological processes including cell adhesion, modulation of blood coagulation, and cytokine/growth factor action. Hp/HS-interacting protein (HIP) has been identified in various adult tissues in humans. HIP supports high affinity, selective binding to Hp/HS, promotes cell adhesion, and modulates blood coagulation activities via Hp/HS-dependent mechanisms. Herein, a murine ortholog of human HIP is described that is 78.8% identical to human HIP and 99.8% identical at the cDNA level and identical at the amino acid level to a previously described murine ribosomal protein, L29. Western blot analyses and immunohistological staining with affinity-purified antibodies generated against two distinct peptide sequences of murine HIP/L29 indicate that HIP/L29 is differentially expressed in adult murine tissues and cell types. In the normal murine mammary epithelial cell line, NMuMG, HIP/L29 is enriched in the 100,000 x g particulate fraction. HIP/L29 can be solubilized from the 100,000 x g particulate fraction with 0.8 M NaCl, suggesting that it is a peripheral membrane protein. HIP/L29 directly binds 125I-Hp in gel overlay assays and requires 0.75 M NaCl for elution from Hp-agarose. In addition, recombinant murine HIP expressed in Escherichia coli binds Hp in a saturable and highly selective manner, compared with other glycosaminoglycans including dermatan sulfate, chondroitin sulfate, keratan sulfate, and hyaluronic acid. Collectively, these data indicate that murine HIP/L29, like its human ortholog, is a Hp-binding protein expressed in a restricted manner in adult tissues.

Amino Acid Sequence↗
PubMed1998

Latex exposure and allergy: a survey of general dental practitioners and dental students.

Gloves are now worn routinely by most general dental practitioners and dental students while treating patients, with latex being the most commonly used glove material. By means of a questionnaire, this study surveyed 160 students in one dental school and 300 randomly selected general dental practitioners in respect of their exposure to latex. Response rates were 74.4 per cent and 57.3 per cent for dental students and practitioners respectively. Adverse skin reactions to the wearing of latex gloves was reported by 18.5 per cent of dental students and 22.8 per cent of practitioners. Analysis of the data indicated that there was an association between student year and adverse skin reaction to latex, an association between years in dental practice and adverse skin reaction to latex and a strong relationship between dentist's gender and adverse skin reaction to latex. Respondents who suffered from eczema or food allergies were more likely to have experienced an adverse skin reaction to latex glove wearing. It is concluded that adverse reactions to latex occur in significant numbers of dental students and dental practitioners, with those who reported personal and familial atopy being more likely to be affected.

Adolescent↗