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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 145 records · Page 8Linked to original sources
PubMed2001

Percutaneous permeation and skin irritation of JP-8+100 jet fuel in a porcine model.

JP-8 is the major jet fuel used by US Air Force. JP-8+100 is a new jet fuel recently introduced by the US Air Force, which contains JP-8 plus three performance additives [butylated hydroxytoluene (BHT), metal deactivator (MDA) and 8Q405]. The purpose of the present study was to investigate the percutaneous permeation of JP-8+100 across pig ear skin in vitro and to study the effect of JP-8+100 exposure on the skin barrier function, moisture content and irritation in Yucatan minipigs. The influence of performance additives on the permeation of JP-8 was studied by adding each additive individually to JP-8. The percutaneous permeation and skin irritation data obtained with JP-8+100 were compared with that of JP-8. JP-8+100 spiked with 5.0 microCi of radiolabeled [14C]tridecane, nonane, naphthalene or toluene (selected components of JP-8+100) was used for the in vitro percutaneous permeation studies. For skin irritation studies, 250 microl of JP-8+100 was placed in a Hill top chamber and affixed over the marked treatment area for 24 h. The components of JP-8+100 such as tridecane, nonane, naphthalene and toluene permeated readily through pig ear skin without any apparent lag time. Compared to JP-8, the permeation of tridecane, toluene and nonane from JP-8+100 was significantly lower (P<0.05). However, the permeation of naphthalene from JP-8+100 was significantly higher than from JP-8. When BHT was added to JP-8, the permeation of all four chemicals were significantly decreased (P<0.05). Though the addition of 8Q405 to JP-8 decreased the permeation of all four chemicals, the values were not significantly different (P>0.05) from that of JP-8. Addition of MDA did not show any significant change in the permeation of the selected chemicals from JP-8. Application of JP-8+100 increased the transepidermal water loss (TEWL) about three times compared to the baseline level. The skin moisture content decreased consistently after the application of JP-8+100, though it was not significantly different (P>0.05) from the baseline level. JP-8+100 caused a moderate erythema (score: 1.60) and a moderate to severe edema (score: 2.60). These results suggest that JP-8+100 produces significant changes in the barrier function of the skin and a local irritant effect upon occlusive dermal exposure. However there was no significant difference in the skin irritation data observed from JP-8 and JP-8+100.

Administration, Cutaneous↗
PubMed2001

A novel bioadhesive intranasal delivery system for inactivated influenza vaccines.

The aim of the current studies was to evaluate a bioadhesive delivery system for intranasal administration of a flu vaccine, in combination with a mucosal adjuvant (LTK63). A commercially available influenza vaccine, containing hemagglutinin (HA) from influenza/A Johannesberg H1N1 1996, and LTK63 or LTR72 adjuvants, which are genetically detoxified derivatives of heat labile enterotoxin from Escherichia coli, were administered IN in a bioadhesive delivery system, which comprised esterified hyaluronic acid (HYAFF) microspheres, to mice, rabbits and micro-pigs at days 0 and 28. For comparison, additional groups of animals were immunized intranasally with the HA vaccine alone, with soluble HA+LTK63, or IM with HA. In all three species, the groups of animals receiving IN immunization with the bioadhesive microsphere formulations, including LT mutants, showed significantly enhanced serum IgG responses (P<0.05) and higher hemagglutination inhibition (HI) titers in comparison to the other groups. In addition, the bioadhesive formulation also showed a significantly enhanced nasal wash IgA response (P<0.05). Most encouragingly, in pigs, the bioadhesive microsphere vaccine delivery system induced serum immune responses following IN immunization, which were significantly more potent than those induced by traditional IM immunization at the same vaccine dose (P<0.05).

Administration, Intranasal↗
PubMed2001

Gene elements that affect the longevity of rbcL sequence-containing transcripts in Chlamydomonas reinhardtii chloroplasts.

The chloroplast gene rbcL encodes the large subunit of the CO(2)-fixing enzyme ribulose-bisphosphate carboxylase. In previous work a target for photo-accelerated degradation of Chlamydomonas reinhardtii rbcL transcripts in vivo was found to lie within the first 63 nucleotides, and a sequence element required for increasing the longevity of transcripts of rbcL-reporter genes was found to occur between nucleotides 170 and 350. Photo-accelerated degradation of rbcL transcripts has been found to require nucleotides 21 to 41. Transcript nucleotides lying between 329 and 334 and between 14 and 27 are essential for stabilizing transcripts in vivo; mutations in either region reduce the longevity of transcripts. It is postulated that the effectiveness of photo-accelerated endonuclease attacks on the nucleotide 21 to 41 region is reduced by physical blockage or distortion of the target sequence by interacting proteins that associate with nucleotides in the 14 to 27 and 329 to 334 regions of the transcripts. Both the nucleotide +329 to +334 stabilizing sequence of rbcL and a transcription enhancing sequence that lies between +126 and +170 encode well conserved (cyanobacteria through angiosperms) amino acid sequences; the evolution of expression control elements within the protein coding sequence of rbcL is considered.

Animals↗
PubMed2001

Controlled release of recombinant insulin-like growth factor from a novel formulation of polylactide-co-glycolide microparticles.

The purpose of the current study was to develop a controlled-release delivery system for recombinant insulin-like growth factor (rhIGF-I). Polylactide-co-glycolide (PLG) microparticles with entrapped rhIGF-I were prepared by a novel emulsion based solvent evaporation process. Microparticles with two loading levels of rhIGF-I were prepared (4 and 20% w/w). The integrity of released rhIGF-I was characterized by RP-HPLC, SDS-PAGE and a bioactivity assay. In vitro and in vivo release profiles of rhIGF-I from these microparticles were also evaluated. Reproducible batches of microparticles with 4% and 20% w/w loading of rhIGF-I were prepared, with excellent encapsulation efficiency (81 and 85% of total protein respectively entrapped). The protein retained integrity after the microencapsulation process as evaluated by RP-HPLC, SDS-PAGE and bioactivity assay. The in vitro profiles exhibited a significant burst release of rhIGF-I (20-30%), followed by controlled release of protein for up to 28 days. A similar level of burst release was observed in vivo, followed by controlled release of protein for 14-18 days. In addition, there was a surprisingly close correlation between in vitro and in vivo release rates. PLG microparticles with entrapped rhIGF-I are a promising delivery system which may allow rhIGF-I to be used for a broad range of therapeutic indications.

Animals↗
PubMed2001

Levels of antibodies against C1q and 60 kDa family of heat shock proteins in the sera of patients with various autoimmune diseases.

Previously a strong positive correlation was found between antibodies to C1q (C1qAb) and antibodies against human heat shock protein (hsp60) and mycobacterial hsp65 in HIV infected patients. Here the levels of these antibodies were measured in the sera of patients with different autoimmune diseases (122 systemic lupus erythematosus (SLE), 55 systemic sclerosis, 33 undifferentiated connective tissue disease (UCTD), 27 primary Raynaud syndrome, 21 rheumatoid arthritis (RA), 14 polymyositis/dermatomyositis (PM/DM), and 192 healthy blood donors. The prevalence of IgG C1qAb was found to be high (P<0.0001 as compared to the healthy controls) only in the SLE group. The levels of the anti-hsp60 (P=0.0094) and anti-hsp65 (P=0.0108) antibodies were high only in the UCTD patients. No correlation was found between the C1qAb and anti-hsp antibodies in any group except a significant (P=0.011) positive correlation between C1qAb and hsp65 antibodies in the patients with UCTD. These findings indicate that the autoantibodies against C1q are heterogeneous: in different diseases different types of C1qAb may dominate.

Adult↗
PubMed2001

Microwave induced synthesis and antibacterial activity of cephalosporin derivatives using solid support.

Reaction of 7-amino-3-[5'-methyl-1',3',4'-thiadiazol-2'-ylthiomethyl]cephalo-sporanic acid with heterocyclic amines using basic alumina under microwave irradiation (MWI) afforded new cephalosporin analogs in shorter reaction time with improved yield as compared to conventional heating. All the synthesised compounds were tested for their in vitro antibacterial activity, using cefotaxime and cephalothin as reference drugs. All compounds showed significant in vitro antibacterial activity against E. herbicola, P. vulgaries, and Z. mobilis.

Anti-Bacterial Agents↗
PubMed2001

Malignant pericardial effusion and cardiac tamponade in endometrial adenocarcinoma.

BACKGROUND: Malignant pericardial effusion as a complication of gynecological cancers is a rare occurrence. A review of the literature revealed only two cases of pericardial effusion secondary to endometrial adenocarcinoma. We describe another patient with FIGO stage IIIA endometrial cancer who developed malignant pericardial effusion with cardiac tamponade. CASE: A 57-year-old woman with a history of endometrial carcinoma presented with pericardial effusion and cardiac tamponade. The patient had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by three cycles of radiotherapy postoperatively. Chest X ray and echocardiogram confirmed the presence of pericardial effusion with impending cardiac tamponade. Pericardial biopsy revealed adenocarcinoma. The treatment consisted of emergency pericardial window and subsequent therapy with tamoxifen. A follow-up after 6 months revealed the patient to be asymptomatic. CONCLUSION: Patients with cancer may develop a pericardial effusion for different reasons. Early diagnosis of the specific cause is not only useful but also essential in determination of the mode of therapy and estimation of prognosis.

Adenocarcinoma↗
PubMed2001

Possible role of nitric oxide and mast cells in endotoxin-induced cardioprotection.

The present study is designed to investigate the role of nitric oxide (NO) and cardiac mast cells in the cardioprotective effect of endotoxin in isolated rat heart subjected to 30 min of global ischaemia and 30 min of reperfusion. Endotoxin (2.5 mg kg(-1); i.p.) was administered 8 h before subjecting the heart to global ischaemia. Endotoxin pretreatment markedly reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), markers of cardiac injury, in coronary effluent and the percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Endotoxin pretreatment significantly increased the release of nitrite prior to and after global ischaemia. On the other hand, endotoxin pretreatment decreased the release of mast cell peroxidase (MPO) during the reperfusion phase. The cardioprotective and antiarrhythmic effect of endotoxin pretreatment was abolished by dexamethasone (3 mg kg(-1); i.p.) or l -canavanine (20 mg kg(-1); i.p.) given 1 h before the administration of endotoxin. It is proposed that the cardioprotective and antiarrhythmic effect of the endotoxin may be ascribed to the induction of nitric oxide synthase (NOS) and subsequent increase in the release of NO. NO may stabilize cardiac mast cells and consequently decrease the release of cytotoxic mediators from these cells. Prevention of degranulation of cardiac mast cells may be responsible for the cardioprotective and antiarrhythmic effects of the endotoxin.

Animals↗
PubMed2001

Vertebrate LTR retrotransposons of the Tf1/sushi group.

LTR retrotransposons of the Tf1/sushi group from a diversity of vertebrates, including fish, amphibians, and mammals (humans, mice, and others), are described as full-length or partial elements. These elements are compared, and the mechanisms involved in self-priming of reverse transcriptase and programmed phase shifting are inferred. Evidence is presented that in mammals these elements are still transcriptionally active and are represented as proteins. This suggests that members of the Tf1/sushi group are present as functional elements (or incorporated as partial elements into host genes) in diverse vertebrate lineages.

Amino Acid Sequence↗
PubMed2001

Production of selenomethionine-labelled proteins using simplified culture conditions and generally applicable host/vector systems.

The amino acid analogue selenomethionine (SeMet) is shown to be efficiently incorporated into recombinant proteins expressed in Escherichia coli grown in a simple minimal medium without the addition of synthetic amino acids. Furthermore, satisfactory SeMet incorporation is obtained with a methionine-prototrophic strain transformed with commonly used vector systems. As examples, purified tryparedoxin 1 from Crithidia fasciculata, alkylhydroperoxide reductase (AhpC) from Mycobacterium marinum and the 16-kDa antigen from M. tuberculosis are shown to be efficiently labelled with SeMet, using the culture conditions and the host/vector systems described here. Enzymatic analysis reveals no differences between native and SeMet-labelled tryparedoxin 1 enzyme. Both proteins yield crystals under similar conditions. The culture conditions and host vector systems described greatly facilitate selenium-labelling of proteins for 3-D structure determination.

Animals↗
PubMed2001

Do Blastocystis hominis colony forms undergo programmed cell death?

Ultrastructural observations were made on colony forms of the protozoan parasite, Blastocystis hominis. Cross-sections of entire colonies were observed by TEM. Cells within a colony were heterogeneous in morphology, consisting of vacuolar, amoeboid, multivacuolar and unusual forms. Dying cells appeared to be in the process of fragmenting into numerous membranebound vesicles, giving rise to empty spaces within the colony. Interestingly, older colonies appeared to show cell fragmentation which resulted in larger, membranebound structures. Numerous cytoplasmic inclusions were present in the central vacuole of some cells, with many containing mitochondria. Amoeboid forms were observed to harbour small membrane-bound vesicles in endosome-like compartments. Other unusual features included margination of chromatin material and distinct blebbing of nuclei. These ultrastructural features suggest that B. hominis colony forms perhaps undergo a form of programmed cell death.

Animals↗
PubMed2001

Exposure of Blastocystis species to a cytotoxic monoclonal antibody.

A recently described cytotoxic monoclonal antibody (mAb 1D5) raised against Blastocystis hominis isolate B, was tested for reactivity with 13 different isolates of Blastocystis. The isolates used were previously isolated from humans, rats and reptiles and were maintained as axenised cultures throughout the course of this study. Five B. hominis isolates (B, C, E, G and H) were found to react with mAb 1D5 in immunoblotting studies and the indirect fluorescence antibody test. The pattern of fluorescence observed for all five isolates was diffuse and patchy. Immunoblotting studies revealed that mAb 1D5 reacted with a 29-30-kDa protein found in all five isolates. Results of a cytotoxic assay showed that the mAb exhibited a complement-independent cytotoxic effect on all the exposed isolates. Microscopic observations showed differences in morphology between the Blastocystis cells exposed and unexposed to mAb. Acridine orange staining performed on both exposed and unexposed cells showed similar internal structures when viewed under fluorescence microscopy.

Animals↗
PubMed2001

Blastocystis hominis: evidence for caspase-3-like activity in cells undergoing programmed cell death.

We have shown previously that the human intestinal protozoan, Blastocystis hominis, undergoes apoptosis-like programmed cell death (PCD) when exposed to a cytotoxic monoclonal antibody (mAb), 1D5. In the present study, ELISA and immunoblot assays employing chicken anti-CPP32 antibody suggest that caspase-3-like antigens exist in B. hominis. Using colorimetric and flow cytometric assays for caspase-3 activity, we also observed an increase in activity between 1 h and 6 h after exposure to mAb 1D5, with greatest activity at 6 h. These findings suggest that caspase-3-like proteases play an important role in B. hominis undergoing PCD, similar to the phenomenon in higher eukaryotic organisms.

Animals↗
PubMed2001

Cloning and sequence characterisation of falcipain-2 from Plasmodium falciparum Gombak A strain (Malaysia).

In this study, the genome of the Plasmodium falciparum Gombak A strain was examined for the presence of a gene encoding falcipain-2, a cysteine protease, using homology-based polymerase chain reaction cloning. The nucleotide sequence obtained from the gene cloned (designated pFG1) is approximately 99% homologous to other falcipain-2 genes from different strains. Comparatively, it is 69% homologous to falcipain-3 genes. Direct cloning of the falcipain-2 gene and its resemblance to the reported corresponding mRNA transcript suggests the absence of introns in this gene. Sequence alignment and comparison revealed four amino acid differences at positions 15, 51, 59 and 414 in the falcipain-2 from P. falciparum Gombak A as compared to other falcipain-2 proteins from different strains.

Amino Acid Sequence↗
PubMed2001

Essential genes in proximal 3L heterochromatin of Drosophila melanogaster.

We have further characterized essential loci within the centric heterochromatin of the left arm of chromosome 3 (3L) of Drosophila melanogaster, using EMS, radiation and P element mutagenesis. We failed to find any new essential genes, a result that suggests a lower-than-average gene density in this region. Mutations affecting expression of the most proximal gene [lethal 1, l1 or l(3)80Fj] act as dominant suppressors of Polycomb (Pc), behavior which is consistent with a putative trithorax group (trx-G) gene. The third gene to the left of the centromere [lethal 3, l3 or l(3)80Fh] is likely to correspond to verthandi (vtd), a known trx-G gene that plays a role in the regulation of hedgehog (hh) expression and signalling. The intervening gene [lethal 2, l2 or l(3)80Fi] is required throughout development, and mutant alleles have interesting phenotypes; in various allelic combinations that survive, we observe fertility, bristle, wing, eye and cuticle defects.

Animals↗
PubMed2001

Lateral preferences among indian school children.

In the first study, 718 children from India, aged 4 to 11 years, were observed for their hand preference for ten common unimanual activities. The prevalence of left-handedness was found to be only 3.2 percent, i.e. one-third of that (9.6%) observed in a French study using a similar procedure. The degree (weak to strong) but not the direction of hand preference was found to be related to the children's age, with stronger preference among older children. The factor structure of handedness items was similar in France and India. In the second study, 400 schoolchildren from India, aged 6 to 18 years, were examined for handedness, footedness, eyedness, use of hand in space, and absolute and relative hand skill assessed by a peg-moving task and a dot-filling task. Prevalence of left-handedness was 4.2%. A sex difference was observed for handedness, footedness, use of hand in space. and relative hand skill, with higher proportions of right preferences and higher degree of lateralization (i.e., relative between hands asymmetry) in females. The degree of hand skill asymmetry increased with age. These results are discussed in relation to findings from previous studies in other countries using similar procedures.

Adolescent↗
PubMed2001

Effect of abciximab on the outcome of emergency coronary artery bypass grafting after failed percutaneous coronary intervention.

OBJECTIVE: To evaluate the outcome of coronary artery bypass grafting (CABG) for failed percutaneous coronary intervention (PCI) in patients who had received abciximab. PATIENTS AND METHODS: In this retrospective study, we analyzed the records of patients who had PCI at our institution between January 1994 and December 1998 and identified those who had urgent or emergency CABG within 48 hours after PCI. CABG was performed for failed PCI in patients who had ongoing ischemia, hemodynamic compromise, or both. These patients were categorized into 2 groups depending on whether they had been given abciximab during PCI. We compared blood product transfusion requirements, bleeding complications, and frequency of in-hospital adverse events of the 2 groups. RESULTS: Of 5636 patients who had PCI, 77 (1.4%) had urgent or emergency CABG within 48 hours, including 11 who were given abciximab (abciximab group) during PCI and 66 who were not given abciximab (no abciximab group). The 2 groups had similar baseline characteristics. The mean +/- SD time to surgery was 8.4 +/-8.0 hours (median, 6 hours) for the abciximab group vs 12.1 +/- 12.5 hours (median, 4 hours) for the no abciximab group. Major bleeding (Thrombolysis in Myocardial Infarction criteria) occurred in 9 (90%) of 10 patients in the abciximab group vs 48 (77%) of 62 patients in the no abciximab group. The total volumes of intraoperative autotransfusion and transfusion of red blood cells and fresh frozen plasma tended to be higher for the abciximab group. Also, this group received a mean of 13.9 U of platelets vs 3.2 U for the no abciximab group (P<.001). However, no in-hospital deaths occurred among patients in the abciximab group, and adverse events were infrequent and comparable between the 2 groups. No difference was noted between the 2 groups in the frequency of surgical reexploration for bleeding. CONCLUSION: Transfusion requirements are higher for patients who undergo emergency or urgent CABG after having received abciximab during PCI. However, in-hospital adverse events are infrequent and comparable to those for patients who do not receive abciximab.

Abciximab↗