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Biomedical subjects

M Ahmad

Publications and source records attributed to M Ahmad.

At least 163 records · Page 9Linked to original sources
PubMed1998

The effect of atlas anterior translation and rotation on axis canal size. A computer-assisted anatomic study.

Eighteen adult paired atlas and axis specimens were used in conjunction with computer analysis to determine the average transverse canal area of the axis after different degrees of anterior translation and three types of rotation of the atlas. After each displacement, the remaining transverse canal area of the axis was calculated. The data showed that the mean transverse canal area of the axis was 351.5 +/- 8.8 mm2 for males and 276.9 +/- 8.6 mm2 for females, respectively. After a 3-, 4-, and 5-mm anterior translation of the atlas, the mean transverse canal area of the axis decreased to 300.4 +/- 5.1 mm2 (85.5%) for males and 238.0 +/- 2.1 mm2 (85.9%) for females, 283.9 +/- 5.9 mm2 (80.8%) for males and 228.5 +/- 3.1 mm2 (82.5%) for females, and 260.4 +/- 4.2 mm2 (74.1%) for males and 216.4 +/- 2.8 mm2 (78.2%) for females, respectively. After a 40 degree rotation, 40 degree rotation with 4-mm anterior translation, and 40 degree rotation with 8-mm anterior translation of the atlas, the mean transverse canal area of the axis for both sexes decreased approximately to 58%, 42%, and 23%, respectively. This study confirmed that the size of the transverse canal area of the axis was consistently correlated with the degrees of the anterior translation and rotation of the atlas.

Adult↗
PubMed1997

Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.

We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 activation. Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.

Amino Acid Sequence↗
PubMed1997

Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL.

A human receptor for the cytotoxic ligand TRAIL (TRAIL receptor-1, designated DR4) was identified recently as a member of the tumor necrosis factor receptor family. In this report we describe the identification of two additional human TRAIL receptors, TRAIL receptor-2 and TRAIL receptor-3, that belong to the tumor necrosis factor receptor family. Interestingly, TRAIL receptor-2 but not TRAIL receptor-3 contains a cytoplasmic "death domain" necessary for induction of apoptosis and is hence designated death receptor-5 (DR5). Like DR4, DR5 engages the apoptotic pathway independent of the adaptor molecule FADD/MORT1. Because of its lack of a death domain, TRAIL receptor-3 is not capable of inducing apoptosis. However, by competing for TRAIL, it is capable of inhibiting TRAIL-induced apoptosis. Thus, TRAIL receptor-3 may function as an antagonistic decoy receptor to attenuate the cytotoxic effect of TRAIL in most tissues that are TRAIL+, DR4+, and DR5+.

Adaptor Proteins, Signal Transducing↗
PubMed1997

The quantitative anatomy of the thoracic facet and the posterior projection of its inferior facet.

STUDY DESIGN: This study evaluated the dimensions of the thoracic facet from T1 to T12 and determined the posterior projection of the inferior facet using thoracic spine specimens. OBJECTIVES: To evaluate quantitatively the thoracic facet and determine the projection of the inferior facet on the posterior aspect of the lamina relative to facet hook placement in the thoracic spine. SUMMARY OF BACKGROUND DATA: Anatomic evaluation of the thoracic facet has not been extensively addressed. No detailed studies of the thoracic facet relative to posterior facet hook fixation exist. METHODS: Forty-three thoracic spines from T1 to T12 were directly evaluated for this study. Anatomic evaluation of the thoracic superior and inferior facets included the facet width, height, and angulation relative to sagittal plane. The projection of the inferior facet on the posterior aspect of the lamina was constructed and measured. RESULTS: In general, the male linear and angular parameters were larger than the female ones. The average transverse angle of the facets at T1-T12 for both men and women ranged approximately from 74 degrees to 88 degrees for the superior facet and 74 degrees to 108 degrees for the inferior facet. The average inferior thickness from T1 to T12 for both sexes ranged from 3 to 5 mm. The posterior projection height of the inferior facet was found to be 9 to 12 mm from T1 to T12 for both men and women. The distance between the posterior midline and the inferior facet projection ranged from 7 to 11 mm at T1-T12 for both sexes. CONCLUSIONS: This study may aid in the understanding of the location, angulation, and dimensions of the facet and proper placement of hooks into the thoracic facet joint.

Adult↗
PubMed1997

Bradykinin and endothelial-cardiac myocyte interactions in ischemic preconditioning.

Myocardial ischemia results in the release of a variety of vasoactive substances from coronary vascular endothelial cells and/or from cardiac myocytes. Some of these substances appear to be protective and include nitric oxide and bradykinin. One hypothesis for the pronounced antiarrhythmic effects of preconditioning involves the early generation of bradykinin and, subsequently, nitric oxide. Evidence for early bradykinin release has come from clinical studies involving patients undergoing coronary angioplasty where, in 4 of 5 patients, there was evidence for elevated kinin levels in coronary sinus blood either during balloon inflation (i.e., ischemia) or deflation (reperfusion). The levels reached are sometimes considerable (increases 10-20 fold). The second piece of evidence comes from dogs subjected to a preconditioning stimulus (2 x 5 min periods of ischemia), followed 20 min later by occlusion of the same artery for a 25-min period. This preconditioning procedure markedly reduces ischemia-induced ventricular arrhythmias and, although under resting conditions there was little difference between arterial and coronary sinus bradykinin levels (125 +/- 22 and 157 +/- 41 pg/mL, respectively), there was a marked increase in coronary sinus levels in preconditioned dogs before the prolonged occlusion (637 +/- 293 pg/mL compared with 114 +/- 18 pg/mL in nonpreconditioned dogs); levels at the end of the prolonged occlusion in the preconditioned dogs were also higher (577 +/- 305 pg/mL compared with 162 +/- 34 pg/mL in control dogs). Other evidence for the involvement of bradykinin and nitric oxide comes from studies in which the generation, or effects, of these mediators have been suppressed (e.g., with the bradykinin B2 receptor blocking agent icatibant, with inhibitors of the L-arginine-nitric oxide pathway, and by methylene blue). The conclusion is that early bradykinin release is protective under conditions of ischemia, is presumably enhanced during therapy with angiotensin-converting enzyme (ACE) inhibitors and is suppressed under conditions of endothelial dysfunction.

Animals↗
PubMed1997

FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis.

We identified and cloned a novel human protein that contains FADD/Mort1 death effector domain homology regions, designated FLAME-1. FLAME-1, although most similar in structure to Mch4 and Mch5, does not possess caspase activity but can interact specifically with FADD, Mch4, and Mch5. Interestingly, FLAME-1 is recruited to the Fas receptor complex and can abrogate Fas/TNFR-induced apoptosis upon expression in FasL/tumor necrosis factor-sensitive MCF-7 cells, possibly by acting as a dominant-negative inhibitor. These findings identify a novel endogenous control point that regulates Fas/TNFR1-mediated apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed1997

CRADD, a novel human apoptotic adaptor molecule for caspase-2, and FasL/tumor necrosis factor receptor-interacting protein RIP.

FADD/MORT1 is a death domain (DD)-containing adaptor/signaling molecule that interacts with the intracellular DD of FAS/APO-I (CD95) and tumor necrosis factor receptor 1 and the prodomain of caspase-8 (Mch5/MACH/FLICE). FADD engagement of caspase-8 presumably activates this caspase and leads to apoptosis. Another DD-containing adaptor/signaling molecule, CRADD, was identified and was shown to induce apoptosis. CRADD has a dual-domain structure similar to that of FADD. It has an NH2-terminal caspase homology domain that interacts with caspase-2 and a COOH-terminal DD that interacts with RIP. CRADD is constitutively expressed in many tissues and thus could play a role in regulating apoptosis in mammalian cells.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Projection of the thoracic pedicle and its morphometric analysis.

STUDY DESIGN: This study defined the projection point of the thoracic pedicles on their posterior aspect and its relation to a reliable landmark. It also reported pedicle dimensions based on 43 thoracic spines. OBJECTIVES: To determine the projection point of the pedicle axis on the posterior aspect of the thoracic spine, quantitatively describe relations of the projection point to some reliable landmarks, and evaluate linear and angular dimensions of the thoracic pedicle. SUMMARY OF BACKGROUND DATA: Posterior segmental screw fixation is the current standard of internal fixation at the level of the second lumbar vertebrae or below. However, pedicular screw fixation in the thoracic spine, especially in the middle and upper thoracic region, is not common because the small dimensions of the pedicle in this region make screw insertion difficult. More information about pedicle axis projection (not pedicle zone) and its quantitative relationship to some reliable landmarks is essential. METHODS: Forty-three dry thoracic specimens (516 vertebrae) were obtained for study of the thoracic pedicle. Anatomic evaluation focused on the determination of the projection point of the thoracic pedicle axis on its posterior aspect and the anatomic relationship of this point to the lateral edge of superior facet and the midline of the transverse process. Also, pedicle dimensions, including linear and angular, were measured. The mean, range, and standard deviation were calculated for all of the specimens and for male and female specimens separately. RESULTS: Sexual difference was found to be significant statistically in more than half of parameters. For T1-T2, the projection point of the pedicle axis was approximately 7-8 mm medial to the lateral edge of the superior facet and 3-4 mm superior to the midline of the transverse process. For T3-T12, this point was 4-5 mm medial to the lateral margin of the facet and 5-8 mm superior to the midline of the transverse process. The transverse angle of the pedicle axis was found to be 30-40 degrees at T1-T2, 20-25 degrees at T3-T11, and 10 degrees at T12. CONCLUSIONS: This information, in conjunction with preoperative computed tomography evaluation, may enhance our knowledge of transpedicular screw fixation in the thoracic pedicle.

Adult↗
PubMed1997

Spodoptera frugiperda caspase-1, a novel insect death protease that cleaves the nuclear immunophilin FKBP46, is the target of the baculovirus antiapoptotic protein p35.

Employing the degenerate primer-dependent polymerase chain reaction approach used recently to clone human Mch2, we have identified and cloned the insect Spodoptera frugiperda target of the baculovirus antiapoptotic protein p35. This protein named Sf caspase-1 belongs to the family of caspases and is highly related to human Mch3 and CPP32 in sequence and specific activity. The proenzyme of Sf caspase-1 is 299 amino acids in length and can undergo autocatalytic processing in Escherichia coli to an active enzyme heterocomplex. Autoprocessing occurs at Asp-28, Asp-184, and Asp-195 to generate the large p19/p18 and small p12 subunits. Sf caspase-1 is able to induce apoptosis in Sf9 cells and is capable of cleaving p35 to similar sized fragments as observed with extracts from p35 null mutant baculovirus-infected Sf9 cells. Sf caspase-1 activity is potently inhibited by p35, suggesting that it is an important target of this antiapoptotic protein. Finally, the Sf9 nuclear immunophilin FKBP46 was identified as a death-associated substrate for Sf caspase-1.

Amino Acid Sequence↗
PubMed1997

Torn ascending aorta missed by transesophageal echocardiography.

Transesophageal echocardiography has become a commonly used screening tool for traumatic tears of the descending aorta. The role of transesophageal echocardiography for ascending aortic tears is not yet well-defined. We report an ascending aortic tear imaged by aortography but missed on transesophageal echocardiography.

Adult↗
PubMed1997

Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: epidemiological correlations.

To investigate the potential relationship of socioeconomic status with the prevalence of Epstein-Barr virus (EBV) and to understand the significance of del-LMP-1 within EBV+ cases of Burkitt's lymphoma (BL), we studied 10 cases of BL, 30 cases of diffuse large cell lymphoma (DLCL) arising in nonimmunocompromised patients, and 30 reactive tonsillar biopsy specimens from Pakistan. Each lymphoma was analyzed for EBV by EBER1 RNA in situ hybridization (EBV-RISH). Cases showing hybridization signal within neoplastic cells and all reactive tonsillar tissues were analyzed for EBV strain type by EBNA-2 polymerase chain reaction (PCR) and for the presence of a del-LMP-1 by PCR. Eight of 10 (80%) of BL were EBV+, each containing EBV strain A and a wild-type LMP-1 gene. In contrast, only 4 of 30 DLCL (13%) cases were EBV positive (three strain A, one strain B), each containing a wild-type LMP-1 gene. Fifteen of 30 tonsillar biopsy specimens contained EBV, all of which were strain A and wild-type for LMP1. The prevalence of EBV in BL from Pakistan is slightly lower than in BL in endemic regions, but significantly higher than in BL in North America. EBV positivity probably reflects the socioeconomic status of the patient population and age at seroconversion. The absence of del-LMP-1 within all EBV+ BL cases is consistent with the view that del-LMP-1 is not involved in the pathogenesis of BL, and the presence of del-LMP-1 in EBV+ cases of BL reported in other studies may likely reflect the prevalence of a viral strain containing the 30-bp deletion within the respective population studied.

Adolescent↗
PubMed1997

Pemphigus vulgaris autoantibody response is linked to HLA-DQB1*0503 in Pakistani patients.

Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. WE found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 (p = 0.01), DQA1*0101 (p = 0.02), and DQB1*0503 (p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 (p < 10(-6)), DQA1*0101 (p < 10(-5)) and DQB1*0503 (p < 10(-6)), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives' families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations.

Alleles↗
PubMed1997

The blue-light receptor cryptochrome 1 shows functional dependence on phytochrome A or phytochrome B in Arabidopsis thaliana.

Blue-light responses in higher plants are mediated by specific photoreceptors, which are thought to be flavoproteins; one such flavin-type blue-light receptor, CRY1 (for cryptochrome), which mediates inhibition of hypocotyl elongation and anthocyanin biosynthesis, has recently been characterized. Prompted by classical photobiological studies suggesting possible co-action of the red/far-red absorbing photoreceptor phytochrome with blue-light photoreceptors in certain plant species, the role of phytochrome in CRY1 action in Arabidopsis was investigated. The activity of the CRY1 photoreceptor can be substantially altered by manipulating the levels of active phytochrome (Pfr) with red or far-red light pulses subsequent to blue-light treatments. Furthermore, analysis of severely phytochrome-deficient mutants showed that CRY1-mediated blue-light responses were considerably reduced, even though Western blots confirmed that levels of CRY1 photoreceptor are unaffected in these phytochrome-deficient mutant backgrounds. It was concluded that CRY1-mediated inhibition of hypocotyl elongation and anthocyanin production requires active phytochrome for full expression, and that this requirement can be supplied by low levels of either phyA or phyB.

Anthocyanins↗
PubMed1997

Aziridinyl steroid-induced lesions in DNA and apoptosis in promyelocytic leukemia cells.

Variety of synthetic steroids are reported to be mutagenic as well as carcinogenic. The mutagenic and carcinogenic nature of these compounds have been related to their potential of being reactive to genetic material and production of reactive oxygen species. Here we have analyzed the action of aziridinyl steroid on calf thymus DNA and human promyelocytic leukemia cell line HL-60 under in vitro conditions. Calf thymus DNA when treated with various doses of aziridinyl steroid induced a high degree of stand separation and sensitivity/susceptibility to S1 nuclease hydrolysis. The treatment also induced an increasing number of strand breaks per molecule of DNA as determined by alkaline unwinding assay. Relatively higher doses of steroid, however, displayed a reduced susceptibility to S1 nuclease hydrolysis and did not increase the number of strand breaks in DNA. Moreover, the high dose treatments result increased melting temperature and an enhanced rate of reanealing after thermal denaturation, indicating that interstrand crosslinks are induced at higher doses of steroid treatment. Moreover, steroid treatment caused cell death in human promyelocytic leukemia cell line HL-60 and induced DNA degradation, characteristic of apoptosis. The test steroid has the ability to produce reactive oxygen intermediates (ROI) as determined by chemical methods. Incorporation of oxygen radical scavengers into the system blocked the damaging effect of steroid in calf thymus DNA and HL-60 cells. These observations strongly suggest that aziridinyl steroid, a pharmaceutical, damages mammalian DNA and induces apoptosis by the production of ROI in the test system.

Animals↗
PubMed1997

An enzyme similar to animal type II photolyases mediates photoreactivation in Arabidopsis.

The important issue of photoreactivation DNA repair in plants has become even more interesting in recent years because a family of genes that are highly homologous to photoreactivating DNA repair enzymes but that function as blue light photoreceptors has been isolated. Here, we report the isolation of a novel photolyase-like sequence from Arabidopsis designated PHR1 (for photoreactivating enzyme). It shares little sequence similarity with either type I photolyases or the cryptochrome family of blue light photoreceptors. Instead, the PHR1 gene encodes an amino acid sequence with significant homology to the recently characterized type II photolyases identified in a number of prokaryotic and animal systems. PHR1 is a single-copy gene and is not expressed in dark-grown etiolated seedlings: the message is light inducible, which is similar to the expression profile for photoreactivation activity in plants. The PHR1 protein complements a photolyase-deficient mutant of Escherichia coli and thus confers photoreactivation activity. In addition, an Arabidopsis mutant that is entirely lacking in photolyase activity has been found to contain a lesion within this Arabidopsis type II photolyase sequence. We conclude that PHR1 represents a genuine plant photolyase gene and that the plant genes with homology to type I photolyases (the cryptochrome family of blue light photoreceptors) do not contribute to photoreactivation repair, at least in the case of Arabidopsis.

Amino Acid Sequence↗
PubMed1997

Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone-releasing factor (GRF) display enhanced duration of biological activity in vivo.

In the present study, human growth hormone-releasing factor (hGRF) and analogs were successfully pegylated at the carboxy-terminus using a novel solid- and solution-phase strategy. Following synthesis, these pegylated hGRF analogs were evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)-NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic biological activity), and then monopegylated via coupling to an activated dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular weight (MW) were examined to determine the effect of polymer weight on activity. Initial biological evaluations in vitro revealed that all C-terminally pegylated hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1, D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated in both pig and mouse models and found to be highly potent (in vivo potency range = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts, these two pegylated hGRF analogs exhibited enhanced duration of activity.

Animals↗