Clinical problem-solving. A square peg in a round hole.
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Anorexia↗
Biomedical subjects
S Saha
Publications and source records attributed to S Saha.
Role of conformational constraints of position 7 of the disulphide bridge of h-alpha-CGRP derivatives in their agonist versus antagonist properties.
Previous structure-activity studies have shown that the disulphide bridge of calcitonin gene-related peptide (CGRP) is important for the highly potent, CGRP receptor-mediated effects of this peptide. In this study penicillamine (Pen) was substituted for one or both of the cysteinyl residues to determine conformational and topographical properties of the disulphide bridge favourable for binding to CGRP receptors and/or receptor activation. Pen constrains the conformational flexibility of disulphide bridges in other peptides. Binding affinities were measured using a radioligand binding assay with membranes prepared from pig coronary arteries and 125I-h-alpha-CGRP. Functional effects were characterized using a previously reported pig coronary artery relaxation bioassay. The binding affinity of [Pen2]h-alpha-CGRP was not significantly different from that of h-alpha-CGRP. All other analogues showed reduced affinity for CGRP receptors. [Pen2]h-alpha-CGRP also caused relaxation of coronary arteries. The remaining analogues either caused relaxation with significantly reduced potency or failed to relax the arteries at concentrations up to 1 x 10(-5)M. All analogues that did not relax coronary arteries contained a D-Pen in position 7 and inhibited CGRP-induced relaxation. [D-Pen2,7]h-alpha-CGRP was the most potent antagonist with a K8 value of 630 nM. This affinity is similar to that of the classical CGRP receptor antagonist, h-alpha-CGRP(8-37), on these arteries (KBs 212 nM). These studies show that modifying the topography of the disulphide bridge can cause large and variable effects on ligand binding and activation of CGRP receptors. The contribution of position 7 to the conformation and topography of the disulphide bridge of h-alpha-CGRP is crucial to the future design of agonists of CGRP receptors. Furthermore, position 7 is important for the development of new CGRP receptor antagonists with structures based on the whole sequence of h-alpha-CGRP.
Animals↗
Mutations in the Res subunit of the EcoPI restriction enzyme that affect ATP-dependent reactions.
The Res subunits of the type III restriction-modification enzymes share a statistically significant amino acid sequence similarity with several RNA and DNA helicases of the so-called DEAD family. It was postulated that in type III restriction enzymes a DNA helicase activity may be required for local unwinding at the cleavage site. The members of this family share seven conserved motifs, all of which are found in the Res subunit of the type III restriction enzymes. To determine the contribution, if any, of these motifs in DNA cleavage by EcoPI, a type III restriction enzyme, we have made changes in motifs I and II. While mutations in motif I (GTGKT) clearly affected ATP hydrolysis and resulted in loss of DNA cleavage activity, mutation in motif II (DEPH) significantly decreased ATP hydrolysis but had no effect on DNA cleavage. The double mutant R.EcoPIK90R-H229K showed no significant ATPase or DNA restriction activity though ATP binding was not affected. These results imply that there are at least two ATPase reaction centres in EcoPI restriction enzyme. Motif I appears to be involved in coupling DNA restriction to ATP hydrolysis. Our results indicate that EcoPI restriction enzyme does not have a strand separation activity. We suggest that these motifs play a role in the ATP-dependent translocation that has been proposed to occur in the type III restriction enzymes.
Adenosine Triphosphate↗
Fertility of sperm from a tetraparental chimeric bull.
The purpose of the present study was to examine the ability of a tetraparental Chimera in producing IVF embryos. Cumulus oocytes complexes (COCs) were matured in vitro for 22 h. Frozen-thawed sperm of a Chimera (CH), as well as Japanese Black (JB), Limousin (L), Japanese Brown (JBr), Holstein (H) bulls were used for IVF. The chromosome preparations were made from peripheral lymphocytes. Based on chromosome analysis the Chimera had apparently normal chromosomes (29 acrocentric pairs, one large sub metacentric X chromosome and one small sub metacentric Y chromosome). The proportion of acrosome reacted spermatozoa after 1 h incubation was higher (P < 0.01) with the Chimera (CH) than with the Holstein and in Japanese Brown bulls, but did not differ from Japanese Black and Limousin bull sperm (79.0%, 71.2%, 72.5%, 57.8% and 57.0% for CH, JB, L, JBr and H sperm, respectively). Fertilization rates observed after 5 h of sperm-oocyte incubation with Chimera (O-CH) sperm were higher (P < 0.05) than with Japanese Brown (O-JBr) and (P < 0.01) than with Holstein (O-H) sperm, but did not differ from Japanese Black (O-JB) and Limousin (O-L) sperm (36/44, 81.8%; 28/35, 80.0%; 25/36, 69.4%; 19/43, 44.2% and 6/33, 18.2% for O-CH, O-JB, O-L, O-JBr and O-H, respectively). The cleavage rates of IVM oocytes inseminated with Chimera sperm were also higher (P < 0.001) than in Holstein, (P < 0.01) Japanese Brown and (P < 0.05) Limousin, but did not differ from Japanese Black sperm (181/239, 75.7%; 123/171, 71.9%; 108/186, 58.1%; 80/196, 40.8% and 30/186, 16.1% for O-CH, O-JB, O-L, O-JBr and O-H, respectively). The blastocyst rates of IVM oocytes inseminated with sperm were higher (P < 0.05) than in Limousin, Japanese Brown and Holstein, but did not differ from Japanese Black (69/181, 38.1%; 48/123, 39.0%; 27/108, 25.0%; 7/30, 23.3% and 16/80, 17.8% for O-CH, O-JB, O-L, O-JBr and O-H, respectively). Three findings suggested the sperm from this tetraparental Chimeric bull were able to be used for producing bovine IVF embryos.
Acrosome↗
The effect of sperm-oocyte incubation time on in vitro embryo development using sperm from a tetraparental chimeric bull.
The present study was designed as 5 x 4 factorial to investigate the effects of using sperm from 5 bulls, and varied sperm-oocyte incubation times (5, 10, 15 and 20 h) on the fertilization, cleavage rates and blastocyst formation on an in vitro bovine embryo production system. The bulls included a tetraparental Chimera, its sires (Japanese Black and Limousin), its maternal grand-sires (Japanese Brown and Holstein). The proportion of polyspermy, 2-pronuclei formation, fertilization, cleavage and development to blastocyst were affected (P < 0.001) by the duration of sperm-oocyte incubation, as well as by the interaction between bulls and their corresponding sperm-oocyte incubation time. Blastocyst rate observed after 5 h in oocytes inseminated with Chimera, Japanese Black and Limousin were higher (p < 0.05) than those observed at 20 h incubation. The proportion of blastocysts from oocytes inseminated with Japanese Black observed at 10 h of incubation did not differ from that of Chimera, but both were higher (p < 0.05) than those observed for the Limousin, Japanese Brown and Holstein sires. The present study showed that there was an effect by the duration of sperm-oocyte incubation on in vitro embryo development. The optimal time of sperm-oocyte incubation for the Chimera was similar to that of its sires (Japanese Black and Limousin) but differed from its maternal grand-sires (Japanese Brown and Holstein). The fertilization rates for the sperm from the Holstein bull increased up to 15 h suggesting that this might be the only bull that would benefit from a long incubation period for insemination.
Animals↗
Vitrification of in vitro produced bovine embryos at different ages using one- and three-step addition of cryoprotective additives.
The effect of embryo age on development and ratio of live: dead cells after vitrification and warming was examined. One-step and three-step addition of cryoprotectants in vitrification solution (40% ethylene glycol, 0.3 M trehalose and 12% polyvinylpyrrolidone) were compared using in vitro produced (IVP) bovine blastocysts and expanded blastocysts. Rates of development and hatching were 74.2% and 41.9% for Day 7, 57.8% and 23.8% for Day 8, 33.7% and 6.1% for Day 9 embryos with one-step addition. In three-step addition, those rates were 86.2% and 77.3% for Day 7, 72.3% and 39.0% for Day 8, 47.3% and 10.5% for Day 9 embryos. Day 7 embryos showed highest (P < 0.01) development and hatching rates with one exception. Hatching rate of Day 7 embryos with three-step addition was higher (P < 0.01) than with one-step addition. The ratio of live:dead cells differed between one-step (94%) and three-step (97%) additions for Day 7 embryos (P < 0.05). The results indicate the higher resistance of younger IVP bovine embryos against vitrification and the potential for three-step addition of cryoprotectants to yield a higher survival rate after warming than with one-step addition.
Animals↗
Decreasing trend of multiresistant Salmonella typhi in Bangladesh.
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Ampicillin↗
Meniscal allograft transplantation for unicompartmental arthritis of the knee.
Sixty-seven meniscal allografts were transplanted in the knees of 63 patients between 1988 and 1994. Before surgery, all patients experienced refractory disabling knee pain secondary to a prior total meniscectomy with advanced unicompartmental osteoarthritic changes as verified by arthroscopy. At a mean followup of 31 months (range, 1.0-5.5 years), 58 knees (86.6%) attained a good to excellent results-Twenty-one knees received isolated meniscal allografts, with 19 achieving good to excellent results (90.5%). Five knees received a medial or lateral meniscal allograft with an anterior cruciate ligament reconstruction, and 4 (80.0%) obtained good to excellent results. Thirty-four knees received a meniscal allograft in combination with either a valgus high tibial osteotomy, varus high tibial osteotomy, or varus distal femoral osteotomy to correct for preoperative varus or valgus deformities, with 29 (85.3%) attaining good to excellent results. The remaining 7 knees underwent a combined medial meniscal allograft, valgus high tibial osteotomy, and anterior cruciate ligament reconstruction with 6 (85.7%) attaining good to excellent results. The most frequent complication was a traumatic posterior horn tear in 6 knees at a mean of 21 months after surgery (range, 9-43 months), most likely the consequence of unsuccessful healing of the posterior horn of the graft.
Activities of Daily Living↗
Induction of a glucose-dependent insulin secretory response by the nonmetabolizable amino acid alpha-aminoisobutyric acid.
The effects of the nonmetabolizable amino acid alpha-aminoisobutyric acid (AIB) on insulin release were evaluated using beta cell-rich pancreatic islets from ob/ob mice. Both AIB and L-alanine promptly induced transient insulin release during column perifusion of islet cells. The secretory response was dependent on an elevated level of glucose and effectively suppressed by removal of Na+. The insulin release elicited by AIB fulfilled the criteria of a physiological event in being suppressed by clonidine or lowering of the temperature to 22 degrees C. AIB effectively promoted the increase in sodium (total as well as ionized cytoplasmic) obtained with ouabain blockage of the Na/K pump. When added to a medium containing 11 mM glucose, AIB altered cytoplasmic Ca2+ in terms of both an initial transitory rise and transformation of existing oscillations into a sustained elevation. It is concluded that amino acids can stimulate insulin release from mature beta cells by virtue of being cotransported with Na+.
Alanine↗
ECG coding by wavelet-based linear prediction.
This paper presents a novel coding scheme for electrocardiogram (ECG). Following beat delineation, the periods of the beats are normalized by multirate processing. After amplitude normalization, discrete wavelet transform is applied to each beat. Due to the period and amplitude normalization, the wavelet transform coefficients bear a high correlation across beats at identical locations. To increase the compression ratio, the residual sequence obtained after linear prediction of the significant wavelet coefficients is transmitted to the decoder. The difference between the actual period and the mean beat period, and that between the actual scale factor and the average amplitude scale factor are also transmitted for each beat. At the decoder, the inverse wavelet transform is computed from the reconstructed wavelet transform coefficients. The original amplitude and period of each beat are then recovered. The approximation achieved, at an average rate of 180 b/s, is of high quality. We have evaluated the normalized maximum amplitude error and its position in each cycle, in addition to the normalized root mean square error. The significant feature of the proposed technique is that, while the error is nearly uniform throughout the cycle, the diagnostically crucial QRS region is kept free of maximal reconstruction error.
Algorithms↗
Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23.
Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are mostly benign, slow-growing tumors of the head and neck region, inherited from carrier fathers in an autosomal dominant fashion subject to genomic imprinting. Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We ascertained a total of 11 North American PGL families and confirmed maternal imprinting (inactivation). In three of six families, linkage analysis provided evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the critical region to an approximately 4.5-Mb interval flanked by markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly different between fathers and children (Wilcoxon rank-sum test, P < .002). Affected children had an earlier age at onset of symptoms in 39 of 57 father-child pairs (chi2 = 7.74, P < .006). However, a more conservative comparison of the number of pairs in which a child had > or = 5 years earlier age at onset (n = 33) vis-a-vis that of complementary pairs (n = 24) revealed no significant difference (chi2 = 1.42, P > .2). Whether these data represent genetic anticipation or ascertainment bias can be addressed only by analysis of a larger number of father-child pairs.
Adolescent↗
Role of midbrain ventro-lateral tegmental area (VTA) adrenergic mechanisms in facilitation of hypothalamically-induced predatory attack behaviour.
Bipolar concentric electrodes were implanted in extreme lateral regions of hypothalamus having coordinates (A12.5 mm, L 3.5-3.7 mm, V 3.0-3.7 mm). These sites were electrically stimulated using biphasic square wave pulses (1 ms, 60 Hz) at a current strength ranging from 300-800 microA to evoke predatory attack on an anaesthetized rat. At lower current strengths of 300 microA only altertness with pupillary dilatation was produced. Gradual increase in the current strength led to recruitment of somatic and affective components and a full blown predatory attack on a rat was produced at a mean current strength of 700 microA. A scoring system allowed the construction of stimulus response curve, which remained fairly constant when repeated over a period of 3-4 weeks. In ventrolateral tegmental area (VTA), bilateral microinjections of norepinephrine (NE 10 micrograms in 0.5 microliter saline, pH 7.4) lowered the mean threshold current strength to 100 microA while predatory attack was produced at 500 microA. Clonidine (5 micrograms in 0.5 microliter propylene glycol, pH 7.4) an alpha-2 agonist similarly lowered the mean threshold to 100 microA and predatory attack threshold to 400 microA. The effects of clonidine appeared within 20 min of microinjection and persisted up to 6 hr. Yohimbine, an alpha-2 antagonist (4 micrograms in 0.5 microliter propylene glycol. pH 7.4) when microinjected into the same locus (VTA), completely blocked predatory attack behaviour for 3 days, the peak period of the blocking effects were between 3-8 hr, after microinjection. Isoproterenol (beta agonist), propranolol (beta blocker), prazosin (alpha-1 antagonist) and phenoxybenzamine (alpha antagonist) failed to produce any effect. Normal saline and propylene glycol in similar volumes served as controls. The excitatory effects of NE and clonidine and inhibitory effects of Yohimbine were significant at P < 0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present study indicates the involvement of alpha-2 adrenoceptive mechanisms operating at the midbrain (VTA) level in the elicitation of predatory attack from lateral hypothalamus.
Adrenergic alpha-Agonists↗
Biomedical ethics and the biomedical engineer: a review.
Biomedical engineering is responsible for many of the dramatic advances in modern medicine. This has resulted in improved medical care and better quality of life for patients. However, biomedical technology has also contributed to new ethical dilemmas and has challenged some of our moral values. Bioengineers often lack adequate training in facing these moral and ethical problems. These include conflicts of interest, allocation of scarce resources, research misconduct, animal experimentation, and clinical trials for new medical devices. This paper is a compilation of our previous published papers on these topics, and it summarizes many complex ethical issues that a bioengineer may face during his or her research career or professional practice. The need for ethics training in the education of a bioengineering student is emphasized. We also advocate the adoption of a code of ethics for bioengineers.
Animal Testing Alternatives↗
Breast feeding practices in a teaching hospital of Calcutta before and after the adoption of BFHI (Baby Friendly Hospital Initiative).
A comparative study has been made on two groups of 102 mothers each who delivered children in the postnatal ward of obstetrics and gynaecology department of Calcutta National Medical College before and after the introduction of BFHI (Baby Friendly Hospital Initiative). The study revealed that only 14.3% of the babies who were delivered normally were given their first breast feed in time, the ideal time of half an hour, while not a single baby delivered by caesarean section were given their breast feed within the stipulated time period of 4-6 hours. However, there has been a significant overall reduction in the time gap between the birth and the first breast feed in all types of delivery. BFHI has also made significant reduction of prelacteal feeds and in-between feeds in the newborns especially those delivered normally. The fact that babies of first order and those delivered by caesarean section are lagging behind as far as exclusive breast feeding is concerned has been highlighted in the study.
Breast Feeding↗
Implant diameter and bone density: effect on initial stability and pull-out resistance.
It is well known that the standard diameter dental implant so often utilized is often inadequate in patients with poor bone quality or quantity, and larger diameter implants have been utilized to overcome this deficiency. The objective of this study was to compare the pull-out resistance of small and large diameter (3.25- and 4.5-mm) dental implants and the relationship of these implants to bone density. Two groups of implants, consisting of 18 implants of each diameter, were placed in the mandibles of five embalmed humans. The bone mineral density of the area surrounding the implant site in the coronal cross section was measured by quantitative computed tomography (QCT). Initial implant stability was tested with a periodontium diagnostic device and pull-out resistance was tested with a mechanical testing system. Results showed the same initial stability for the two implants. The maximum pull-out force required for the large diameter implants was 15% greater than that required for the small diameter implants, although given the small number of samples, this difference was not statistically significant. There were significant positive correlations between the pull-out resistance and the bone density for both the large and small diameter implants (p < 0.05, p < 0.01). We conclude that larger diameter implants appear to have advantages over smaller ones; however, more extensive testing is needed to determine quantitatively the increased load-carrying capacity.
Aged↗
Primary squamous cell carcinoma of bone.
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Adult↗
Identifying sick children requiring referral to hospital in Bangladesh.
The object of this study was to evaluate and improve the guidelines for the Integrated Management of Childhood Illness (IMCI) with respect to identifying young infants and children requiring referral to hospital in an area of low malaria prevalence. A total of 234 young infants (aged 1 week to 2 months) and 668 children (aged 2 months to 5 years) were prospectively sampled from patients presenting at a children's hospital in Dhaka, Bangladesh. The study paediatricians obtained a standardized history and carried out a physical examination, including items in the IMCI guidelines developed by WHO and UNICEF. The paediatricians made a provisional diagnosis and judged whether each patient needed hospital admission. Using the paediatrician's assessment of a need for admission as the standard, the sensitivity and specificity of the current and modified IMCI guidelines for correctly referring patients to hospital were examined. The IMCI's sensitivity for a paediatrician's assessment in favour of hospital admission was 84% (95% confidence interval (CI): 75-90) for young infants and 86% (95% CI: 81-90) for children, and the specificity was, respectively, 54% (95% CI: 45-63) and 64% (95% CI: 59-69). One fourth or more in each group had a provisional diagnosis of pneumonia, and the IMCI's specificity was increased without lowering sensitivity by modifying the respiratory signs calling for referral. These results show that the IMCI has good sensitivity for correctly referring young infants and children requiring hospital admission in a developing country setting with a low prevalence of malaria. The guidelines' moderate specificity will result in considerable over-referral of patients not needing admission, thereby decreasing opportunities for successful treatment of patients at first-level health facilities. The impact of the IMCI guidelines on children's health and the health care system must be judged in the light of current treatment practices, health outcomes and referral patterns.
Algorithms↗
Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in areas with and without malaria.
The object of this study was to assess the ability of pallor and other clinical signs, including those in the Integrated Management of Childhood Illness (IMCI) guidelines developed by WHO and UNICEF, to identify severe anaemia and some anaemia in developing country settings with and without malaria. A total of 1226 and 668 children aged 2 months to 5 years were prospectively sampled from patients presenting at, respectively, a district hospital in rural Uganda and a children's hospital in Dhaka, Bangladesh. The study physicians obtained a standardized history and carried out a physical examination that included pallor, signs of respiratory distress, and the remaining IMCI referral signs. The haematocrit or haemoglobin level was determined in all children with conjunctival or palmar pallor, and in a sample of the rest. Children with a blood level measurement and assessment of pallor at both sites were included in the anaemia analysis. Using the haematocrit or haemoglobin level as the reference standard, the correctness of assessments using severe and some pallor and other clinical signs in classifying severe and some anaemia was determined. While the full IMCI process would have referred most of the children in Uganda and nearly all the children in Bangladesh with severe anaemia to hospital, few would have received a diagnosis of severe anaemia. Severe palmar and conjunctival pallor, individually and together, had 10-50% sensitivity and 99% specificity for severe anaemia; the addition of grunting increased the sensitivity to 37-80% while maintaining a reasonable positive predictive value. Palmar pallor did not work as well as conjunctival pallor in Bangladesh for the detection for severe or some anaemia. Combining "conjunctival or palmar pallor" detected 71-87% of moderate anaemia and half or more of mild anaemia. About half the children with no anaemia were incorrectly classified as having "moderate or mild" anaemia. Anaemia was more easily diagnosed in Uganda in children with malaria. Our results show that simple clinical signs can correctly classify the anaemia status of most children. Grunting may serve as a useful adjunct to pallor in the diagnosis of severe anaemia. Conjunctival pallor should be added to the IMCI anaemia box, or the guidelines need to be adapted in regions where palmar pallor may not readily be detected.
Anemia↗