A high risk critical mitral valve stenosis with emergency management at Apollo Hospitals Dhaka.

Heart valve surgery in high-risk patients with severe jaundice, congestive hepatomegaly and renal impairment is associated with considerable morbidity and mortality. Without operation the consequences are invariably grave. A 35 years old gentleman with congestive cardiac failure was initially treated in coronary care unit (CCU). Mitral valve area was 0.5cm², pulmonary arterial systolic pressure (PASP) was 110mmHg, serum bilirubin was 20mg/dl, SGPT & SGOT were 1024iu/l and 1027iu/l respectively. Serum creatinine was 3.35mmol/l. Serum bilirubin gradually diminished to 3.1mg/dl after 12 days treatment in Coronary Care Unit but next day it increased to 3.6mg/dl. Mitral valve was replaced on an emergency basis. Echocardiogram on the 5th post operative day showed well functioning prosthetic mitral valve in situ. Serum bilirubin decreased to 2.2mg/dl, SGPT, SGOT and serum creatinine to 43iu/l, 40iu/l and 1.34mmol/l respectively. After 8 weeks of postoperative follow up his serum bilirubin decreased to 0.8mg/dl.

Insulin-like growth factor-1 gene polymorphism in rheumatoid arthritis patients.

OBJECTIVES: Insulin-like growth factor-1 (IGF-1) regulates several biological functions, and low plasma levels of IGF-1 are known to contribute towards the pathogenesis of rheumatoid arthritis (RA). In view of the biological significance of IGF-1, we investigated the association of RA with the polymorphism of a 192-bp allele which is cytosine-adenosine repeat located 1 kb upstream from the IGF-1 gene transcription site and is known to regulate serum IGF-1 levels. METHODS: Blood samples were collected from 52 healthy controls (HC) and 68 RA patients to measure the levels of IGF-1 and to isolate genomic DNA. Polymorphism of the IGF-1 gene was examined using polymerase chain reaction (PCR). Disease severity, duration, and activity were recorded for all RA patients. RESULTS: We observed that 97% of all the subjects who participated in this study showed the presence of a 192-bp allele of the IGF-1 gene. All healthy controls exhibited the presence of 192-bp wild-type allele. All non-carriers of the 192-bp allele were Arabs and had RA. Gender correlated significantly with allele frequencies as 14% of the male and only 2% of the female RA patients were non-carriers of 192-bp allele. Plasma IGF-1 levels were significantly lower (p < 0.01) in RA patients compared to HC, and all RA patients who were non-carriers of the 192-bp allele had a significantly high disease activity score. No correlation was found between the duration of RA and the presence or absence of this allele. CONCLUSIONS: This study suggests a possible association of the IGF-1 gene polymorphism with developing RA, particularly in males as non-carriers of the 192-bp allele.

Multiple comparisons of diversity indices invaded by Lantana camara.

Current study assessed the impact of Lantana camara invasion on native plant diversity in Pothohar region of Pakistan. The approach used for study was random samplings and comparisons of diversity indices [number of species (S), abundance (N), species richness (R), evenness (Jꞌ), Shannon diversity index (Hꞌ) and Simpson index of dominance (λ)] with two categorical factors i.e., invaded and non-invaded (control). Control plots harboured by an average of 1.74 more species/10m2. The control category was diverse (Hꞌ=2.56) than invaded category (Hꞌ=1.56). The higher value of species richness in control plots shows heterogeneous nature of communities and vice versa in invaded plots. At multivariate scale, ordination (nMDS) and ANOSIM showed significant magnitude of differences between invaded and control plots at all sites. The decrease in studied diversity indices in invaded over control sites indicated that plant communities become less productive due to Lantana invasion.

Haptoglobin gene polymorphisms in sickle cell disease patients with different ßS-globin gene haplotypes.

OBJECTIVE: To investigate the prevalence of haptoglobin (Hp) gene alleles in Kuwaiti sickle cell disease (SCD) patients, who generally have a mild phenotype, and compare the pattern to Nigerian SCD patients whose SCD phenotype is more severe. SUBJECTS AND METHODS: Hp genotyping was carried out in a group of 82 and 54 SCD patients from Kuwait and Nigeria, respectively, and appropriate Hb AA controls. The Hp genotyping was done using a PCR technique followed by agarose gel electrophoresis. RESULTS: The frequency of the Hp-2 allele was 73.8% among Kuwaiti SCD patients, while the Hp-1 allele predominated among Nigerian patients (60.7%). However, the differences were not significant (p > 0.05) when the allele distributions were compared between Kuwaiti SCD and their AA counterparts or between Nigerian SCD and their AA controls. There was no association of Hp-2 allele with frequent vaso-occlusive crisis among the Kuwaiti SCD patients. CONCLUSION: The distribution of Hp alleles appears to follow ethnic and geographical trends. Their role in the pathophysiology of pain crisis is not clear.

Prevalence of angiotensin-converting enzyme gene insertion-deletion polymorphism in patients with primary knee osteoarthritis.

OBJECTIVE: Angiotensin converting enzyme (ACE) plays an important role in a number of inflammatory and immune related disorders. This study was undertaken to investigate an association between Angiotensin converting enzyme (ACE) gene insertion- deletion (I/D) polymorphism and primary knee osteoarthritis (OA) in Kuwait and to explore a correlation between clinical subgroups of OA and ACE I/D polymorphism genotypes. PATIENTS AND METHODS: The prevalence of ACE gene I/D polymorphism was determined in 115 patients with primary knee OA and 111 ethnically matched healthy controls by using polymerase chain reaction (PCR) of the genomic DNA. The association of ACE gene I/D polymorphism genotypes was also studied with age of disease onset, function and radiological grading. RESULTS: No significant difference was detected in the frequency of ACE gene I/D polymorphism genotypes and alleles between knee OA patients and the controls. The frequency of ACE gene polymorphism genotypes was also studied in subgroups on the basis of clinical parameters of age of onset of disease, function and radiological grading and no significant difference was detected between subgroups of OA patients and the controls. This is in sharp contrast to a previous report from Korea in which a significant association has been reported between ACE gene polymorphism and knee OA. CONCLUSION: This study did not find an association between ACE gene I/D polymorphism genotypes in Kuwaiti patients with primary knee osteoarthritis and the onset or severity of the disease, which is very different from Korean knee OA patients in which an association has been reported.

Angiotensin-converting enzyme gene polymorphism in Kuwaiti patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in patients with systemic lupus erythematosus (SLE), and to study the correlation between I/D polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement, lupus nephritis and disease severity. METHODS: The frequency of ACE gene I/D polymorphism genotypes was determined in 92 patients with SLE from Kuwait, and compared to that in 100 ethnically matched healthy controls using the polymerase chain reaction. RESULTS: The distribution of ACE I/D polymorphism and allele frequencies in SLE patients was not significantly different from controls. Further analyses of SLE patients showed that there was a significant association between DD genotype and Raynaud's phenomenon (p=0.008, odd ratio=5.4, 95% confidence interval: 1.6-18.6). However, there was no significant association between the ACE genotype and lupus nephritis or disease severity. CONCLUSION: No difference was found between the distribution of the ACE genotype in SLE patients and the general pop-ulation in Kuwait. However, the presence of the DD genotype may confer susceptibility to the development of vascular morbidity.

Multiple comparisons of diversity indices invaded by Lantana camara / Análises múltiplas de índices de diversidade da invasiva Lantana camara

Abstract Current study assessed the impact of Lantana camara invasion on native plant diversity in Pothohar region of Pakistan. The approach used for study was random samplings and comparisons of diversity indices [number of species (S), abundance (N), species richness (R), evenness (Jꞌ), Shannon diversity index (Hꞌ) and Simpson index of dominance (λ)] with two categorical factors i.e., invaded and non-invaded (control). Control plots harboured by an average of 1.74 more species/10m2. The control category was diverse (Hꞌ=2.56) than invaded category (Hꞌ=1.56). The higher value of species richness in control plots shows heterogeneous nature of communities and vice versa in invaded plots. At multivariate scale, ordination (nMDS) and ANOSIM showed significant magnitude of differences between invaded and control plots at all sites. The decrease in studied diversity indices in invaded over control sites indicated that plant communities become less productive due to Lantana invasion.

Resumo O presente estudo avaliou o impacto da invasão de Lantana camara na diversidade de plantas nativas na região de Pothohar, no Paquistão. A abordagem utilizada para o estudo foram a amostragem aleatória e a comparação de índices de diversidade, como número de espécies (S), abundância (N), riqueza de espécies (R), equitabilidade (Jꞌ), índice de diversidade de Shannon (Hꞌ) e índice de dominância de Simpson (λ), com dois fatores categóricos, ou seja, invadidos e não invadidos (controle). As parcelas não invadidas tinham, em média, 1,74 espécie a mais / 10 m2 que parcelas invadidas. A categoria controle foi mais diversa (Hꞌ = 2,56) do que a categoria invadida (Hꞌ = 1,56). O maior valor da riqueza de espécies em parcelas de controle mostra a natureza heterogênea das comunidades, e vice-versa, em parcelas invadidas. Na escala multivariada, ordenação (nMDS) e ANOSIM mostraram magnitude significativa das diferenças entre as parcelas invadidas e controle em todos os locais. A diminuição nos índices de diversidade estudados em locais invadidos por controle indicou que as comunidades de plantas se tornam menos produtivas por causa da invasão de Lantana.

Mechanism of action of Bacillus thuringiensis insecticidal delta-endotoxin: interaction with phospholipid vesicles.

Bacillus thuringiensis (Bt) crystal delta-endotoxin from three subspecies and the product of a cloned crystal protein gene were activated in vitro and their interaction with phospholipid liposomes studied. Despite their diverse spectrum of activity, all these toxins were found to cause a rapid increase in the light scattering of liposome suspensions, which reflects a morphological change in the lipid bilayer. When liposomes loaded with radioactive markers were incubated with B. thuringiensis aizawai IC1 toxin, a relatively rapid release of more than 70% of the trapped markers occurred after an initial lag. Activated Bta IC1 and B. thuringiensis israelensis toxins were shown to bind to phospholipid vesicles. Two of the five conserved domains (D1-D5) detectable in the sequence of a range of Bt toxins are predicted to be highly hydrophobic. It is suggested that these, together with an additional conserved hydrophobic region showing structural homology and two predicted amphiphilic helices, play a major part in the interaction of these toxins with target membranes.

Functional mapping of an entomocidal delta-endotoxin. Single amino acid changes produced by site-directed mutagenesis influence toxicity and specificity of the protein.

Mutagenesis has been used to investigate the toxicity and specificity of a larvicidal protein from Bacillus thuringiensis aizawai IC1 that is toxic to both lepidoptera and diptera and differs by only three residues from a monospecific lepidopteran toxin from B. thuringiensis berliner. Site-directed mutagenesis was used to investigate the contribution of these residues to the dual specificity of the aizawai protein. The results suggest that changes in the identity of residues adjacent to Arg544 and Arg567 on the C-terminal side may convert a monospecific toxin into a dual specificity toxin by altering the protease sensitivity of the arginyl peptide bond. A series of deletion mutants was constructed and their protein products analysed for toxicity in vitro and in vivo and for their ability to perturb phospholipid bilayers. The results indicate a different functional role for various protein segments in the toxin's mode of action and suggest that two separate regions close to the C terminus of the active toxin are important in conferring dual specificity on the aizawai IC1 toxin. A model suggesting a basis for the activity of monospecific and dual-specificity B. thuringiensis toxins is presented, which postulates that association of sequences at the C terminus of the active toxin with regions near the N terminus may be responsible for determining toxin specificity.

Cloning and heterologous expression of an insecticidal delta-endotoxin gene from Bacillus thuringiensis var. aizawai IC1 toxic to both lepidoptera and diptera.

Bacillus thuringiensis var. aizawai IC1 synthesises an insecticidal protein delta-endotoxin (130-135 kDa) that is toxic to both lepidopteran and dipteran larvae, and cross-reacts immunologically with certain monospecific lepidopteran toxins. A 166-kb plasmid from this bacterium was found to hybridise with an intragenic probe derived from the clone B. thuringiensis var. sotto lepidopteran-specific delta-endotoxin gene. A strongly hybridising 5.2-kb SstI fragment from var. aizawai plasmid DNA was cloned in pUC18. After subcloning of this DNA in Escherichia coli, recombinants were obtained that synthesised large amounts of a 130-135-kDa protein. The protein was deposited in the cytoplasm as microscopically visible inclusion bodies and lysates of these cells were found to be toxic to both lepidopteran and dipteran larvae by comparison with controls. The structural basis for the dual specificity of this var. aizawai toxin is now amenable to further study.

Human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti Arabs with schizophrenia.

The frequency of human leukocyte anti- gen DRB1 alleles was determined in a cohort of 194 Kuwaiti Arabs consisting of 80 schizophrenia patients and 114 ethnically matched healthy controls, using a polymerase chain reaction-sequence specific primers method. A total of 12 DRB1 alleles were identified in this Kuwaiti cohort. A statistically significant difference was detected in the frequency of alleles DRB1(*)04 and DRB1(*)13 between the schizophrenia patients and controls. Allele frequency of DRB1(*)04 in schizophrenia patients was 14% compared with nearly 7% in controls (P = 0.028). For DRB1(*)13, the allele frequency was found to be 18% in schizophrenia patients compared with 9% in the controls (P = 0.015). For alleles, DRB1(*)03, DRB1(*)07, and DRB1(*)16 the frequency was higher in controls compared with schizophrenia patients. The frequency of DRB1(*)01, DRB1(*)08, DRB1(*)10, DRB1(*)11, and DRB1(*)15 alleles was almost identical in schizophrenia patients and controls. For the remaining alleles, the differences between the two groups were not statistically significant. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:870-872, 2000.

Delineation of the toxin coding fragments and an insect-specificity region of a dual toxicity Bacillus thuringiensis crystal protein gene.

A series of deletion mutants have been constructed from the dual toxicity Bacillus thuringiensis aizawai IC1 (Bta IC1) crystal protein gene. The mutant toxin genes were expressed in Escherichia coli, their protein products purified and the authenticity of these mutant proteins confirmed immunologically. Analysis of the toxicity spectra of these mutants revealed that lepidopteran toxicity is located on the N-terminal region of the toxin between residues Ile30-Glu595. 3' deletion of a further 37 residues from Glu595 of the lepidopteran-specific toxin abolished lepidopteran toxicity but the resulting protein consisting of residues Ile30-Gly558 was still fully toxic to dipteran larvae and cells. Another mutant crystal protein gene truncated to encode residues between Ile30-Gly563 was toxic only to diptera. These data indicate that the determinants of lepidopteran specificity in the Bta IC1 toxin are located between residues Gly558-Glu595 and that the N-terminal portion of the toxin between Ile30-Gly558 is sufficient to express dipteran toxicity.

Role of human leukocyte antigen DRB1*0307 and DRB1*0308 in susceptibility to juvenile rheumatoid arthritis.

OBJECTIVE: To study the prevalence of Human Leukocyte Antigen (HLA) DR alleles in children with juvenile rheumatoid arthritis (JRA). METHODS: DNA samples from 64 children with oligoarticular and seronegative polyarticular JRA and 64 controls of the same ethnic background were analyzed using PCR-sequence specific primers (PCR-SSP) method. Analysis took into account the onset subtype, the presence of antinuclear antibodies (ANA) and the presence of chronic anterior uveitis, a recognised serious complication of JRA. RESULTS: A high prevalence of DR3 alleles were detected in children with oligoarticular JRA compared to controls (p < 0.05). DR3 alleles were the commonest also in patients with positive ANA as well as those with chronic anterior uveitis. The interesting finding in this study is the absence of two DR3 alleles, namely DRB1*0307 and DRB1 *0308 in the control group while present in significant proportion in children with JRA. DRB1*0307 was present in 16% of children with oligoarticular subtype and 15% of those with polyarticular JRA. DRB1*0308 was only detected in children with oligoarticular JRA, none of the children with polyarticular JRA or the controls had this allele. CONCLUSION: These findings support earlier observations linking these two DR3 alleles, namely 0307 and 0308, to the genetic susceptibility to JRA.

Gene deletions in Arab patients with spinal muscular atrophy.

Spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of lower motor neurons. We have investigated the presence of survival motor neuron gene and neuronal apoptosis inhibitory protein gene deletions in 17 Arab and 1 Indian families with spinal muscular atrophy (15 type I and 3 type II). Homologous deletions were detected in exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene in all patients with type I spinal muscular atrophy. Exon 13 of the neuronal apoptosis inhibitory protein gene was deleted in only one patient with type I spinal muscular atrophy. In two patients with type II spinal muscular atrophy, only exons 7 and 8 of the survival motor neuron gene were deleted whereas exons 5 and 13 of the neuronal apoptosis inhibitory protein gene were present. In another patient with spinal muscular atrophy type II, exons 7 and 8 of the survival motor neuron gene and exon 5 of the neuronal apoptosis inhibitory protein gene were deleted. This latter patient also had the Pierre Robin syndrome. No deletion was detected in healthy siblings or the parents. The deletions found in our patients are similar to those reported in other population groups.

Effect of testosterone on epididymal proteins in castrated rhesus monkeys.

The effect of testosterone on regulation of epididymal protein synthesis has been investigated in castrated rhesus monkeys (Macaca mulatta). The proteins in the treated monkeys were characterized using polyacrylamide gel electrophoresis (under nondenaturing and denaturing conditions) and electrofocusing. At least four distinct proteins have been shown to be synthesized by the monkey epididymis under testosterone influence. Two of these proteins were detected following two days of testosterone treatment while the other two proteins were detected after a six-day treatment period. None of these proteins was detectable in monkeys treated with estradiol for six days. Electrofocusing of epididymal cytosol proteins from untreated and testosterone-treated and castrated monkeys also confirmed the presence of four androgen-dependent proteins in this species. The isoelectric points of these proteins were shown to range between 5.8 and 6.4. The molecular weights of these proteins were found to vary between 47,500 and 66,000. The in vitro incorporation of 3H-labeled amino acids was markedly greater in the androgen-primed epididymis as compared with the control tissue.

Effect of chemotherapy on circulating steroid hormone levels in postoperative premenopausal breast cancer patients.

Serum levels of 17-beta oestradiol, testosterone and progesterone were determined in postoperative premenopausal breast cancer patients. In patients receiving chemotherapy circulating 17-beta oestradiol values decreased significantly compared to control group during the sampling/drug regimens employed. Among the control group, however, the oestradiol levels remained high throughout the sampling period. Testosterone levels in patients were also significantly low compared to control group throughout the sampling regimen up to 28 days. In contrast the levels of progesterone in patients were elevated and remained high compared to the corresponding controls. A positive correlation was found between the drop in serum oestradiol and testosterone levels following the initiation of chemotherapy and the regression of the tumour size. Steroid hormone levels in the serum of breast cancer patients receiving chemotherapy can serve as clinical tools to monitor the progress of the disease and response to therapy.

Multiple comparisons of diversity indices invaded by Lantana camara

Abstract Current study assessed the impact of Lantana camara invasion on native plant diversity in Pothohar region of Pakistan. The approach used for study was random samplings and comparisons of diversity indices [number of species (S), abundance (N), species richness (R), evenness (J), Shannon diversity index (H) and Simpson index of dominance ()] with two categorical factors i.e., invaded and non-invaded (control). Control plots harboured by an average of 1.74 more species/10m2. The control category was diverse (H=2.56) than invaded category (H=1.56). The higher value of species richness in control plots shows heterogeneous nature of communities and vice versa in invaded plots. At multivariate scale, ordination (nMDS) and ANOSIM showed significant magnitude of differences between invaded and control plots at all sites. The decrease in studied diversity indices in invaded over control sites indicated that plant communities become less productive due to Lantana invasion.

Resumo O presente estudo avaliou o impacto da invasão de Lantana camara na diversidade de plantas nativas na região de Pothohar, no Paquistão. A abordagem utilizada para o estudo foram a amostragem aleatória e a comparação de índices de diversidade, como número de espécies (S), abundância (N), riqueza de espécies (R), equitabilidade (J), índice de diversidade de Shannon (H) e índice de dominância de Simpson (), com dois fatores categóricos, ou seja, invadidos e não invadidos (controle). As parcelas não invadidas tinham, em média, 1,74 espécie a mais / 10 m2 que parcelas invadidas. A categoria controle foi mais diversa (H = 2,56) do que a categoria invadida (H = 1,56). O maior valor da riqueza de espécies em parcelas de controle mostra a natureza heterogênea das comunidades, e vice-versa, em parcelas invadidas. Na escala multivariada, ordenação (nMDS) e ANOSIM mostraram magnitude significativa das diferenças entre as parcelas invadidas e controle em todos os locais. A diminuição nos índices de diversidade estudados em locais invadidos por controle indicou que as comunidades de plantas se tornam menos produtivas por causa da invasão de Lantana.

The prevalence of human leukocyte antigen (HLA) DR/DQ/DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis.

We have determined the prevalence of human leukocyte antigen (HLA)-DR, DQ and DP alleles in Kuwaiti children with oligoarticular juvenile idiopathic arthritis (OA-JIA) and healthy controls using the PCR-SSP (sequence specific primers) method. The analysis took into account the presence of antinuclear antibodies and chronic anterior uveitis. DRB1*03 (RR 2.20, P<0.001), DRB1*08 (RR 5.280, P<0.026), DQA1*0501 (RR 1.930, P<0.001), DQB1*0304 (RR 7.920, P<0.002), DQB1*0501 (RR 3.080, P<0.007) and DPB1*0101 (RR 8.8, P<0.001) were the main HLA alleles associated with OA-JIA in Kuwaiti Arabs in this study. DRB1*03 was detected in 71% of children with positive ANA, and in 50% of children with anterior uveitis. DQA1 alleles *0501, *0103 and *0105 (P<0.001; 0.029 and 0.024 respectively) were found to be associated with OA-JIA. In contrast, DQA1*0301 and DQA1*0302 alleles appear to be protective in Kuwaiti children (RR 0.153, P<0.001 and RR 0.278, P<0.016 respectively). The DQB1 alleles *0304 and *0501 were associated with OA-JIA (P<0.002 and P<0.007 respectively). In the case of DPB1, only one allele (*0101) was associated with OA-JIA (P<0.001). Most Kuwaiti Arab patients with OA-JIA who carried a DQ or DP susceptibility allele also had an accompanying DRB1*03 or *8 allele.

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head.

Strong associations have been established between various HLA alleles and different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03 allele was shown to be associated with susceptibility to stroke while the HLA-DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI) are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head (AVNFH) is quite common. The modulatory association factors must still be elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68 Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed by magnetic resonance imaging. A group of 167 apparently healthy age- and sex-matched individuals served as controls. Comparison of the HLA alleles between the whole SS group and the controls showed a significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant differences in the allele frequencies in the SS patients with or without AVNFH were observed. It therefore appears that the HLA-DRB1 locus does not play a significant role in the pathogenesis of AVNFH Kuwaiti patients.