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Biomedical subjects

A K Sharma

Publications and source records attributed to A K Sharma.

At least 127 records · Page 7Linked to original sources
PubMed2000

Need for bringing in a change in biochemistry curriculum to make it clinically oriented?

OBJECTIVES: This study was conducted to (a) assess the views of medical students and doctors regarding relevance of biochemistry training, (b) explore if they have any suggestion to bring in any improvement in contents of biochemistry curriculum and mode of teaching. METHODS: In 1997-98, a structured questionnaire was filled up by 114 medical students and 118 doctors. RESULTS: As many as 62/114 (55%) medical students and 40/118 (34%) doctors believed that it is not important to remember minute details of biochemical reactions (p value < 0.0001). Among medical students, 108/110 (98.2%) agree that a clinician should be invited to seminars for developing skills of interpretation of laboratory investigations; whilst 110/118 (93.2%) doctors expressed similar view, p value ns. Approximately 92% responders favored that departments biochemistry and physiology should co-ordinate on the topics of common interest in order to save time and effort. What is the most informative and effective way of teaching biochemistry?' in response to this question only 0.9% responders opted lecture as the best option. Seminars with active participation of medical students was preferred by 93.2% responders. About 6.9% responders reckoned that symposium prepared by a more than one teacher. In response to the question whether it is possible to cover pre-clinical subjects in 12 months so as to allow spiral mode of curriculum, 73% of all the responders agreed that it would be good idea, there was no difference of opinion among the doctors and medical students. On the other hand, 27% were strongly opposed to this suggestion. CONCLUSIONS: We suggest that there is a need to modify the contents, methods of teaching, and curriculum organization of training in clinical biochemistry. How best the curriculum can be made problem oriented needs to be debated among medical educationists.

Biochemistry↗
PubMed2000

Analysis of the activity of promoters from two photosynthesis-related genes psaF and petH of spinach in a monocot plant, rice.

The subunit III of photosystem I and ferredoxin-NADP(+)-oxidoreductase are encoded by nuclear genes, namely psaF and petH. The activity of their promoters from spinach has been evaluated in transgenic tobacco earlier. Evaluation of the activity of these Dicotyledoneae-specific promoters has been carried out in a monocot system (i.e. rice) by transient gene expression system, based on electroporation-mediated gene delivery into protoplasts from leaves and roots. It has been found that various promoter deletions show higher activity in leaf protoplasts and elements for quantitative response are widely distributed. Transgenic rice has also been produced with a petH promoter and gus reporter gene construct. Although petH promoter is a weak promoter in comparison to the 35S promoter, it expresses well in green tissues and could be useful for plant genetic engineering.

Bacterial Proteins↗
PubMed1999

Three-dimensional structure of mare diferric lactoferrin at 2.6 A resolution.

Lactoferrin is a monomeric glycoprotein with a molecular mass of approximately 80 kDa. The three-dimensional structure of mare diferric lactoferrin (mlf) has been determined at 2.6 A resolution. The protein crystallizes in the space group P 212121with a=85.2 A, b=99.5 A, c=103.1 A with a solvent content of 55 % (v/v). The structure was solved by the molecular replacement method using human diferric lactoferrin as the model. The structure has been refined using XPLOR to a final R -factor of 0.194 for all data in the 15-2.6 A resolution range. The amino acid sequence of mlf was determined using a cDNA method. The final refined model comprises 5281 protein atoms, 2 Fe3+, 2 CO32-and 112 water molecules. The overall folding of mlf is similar to that of other proteins of the transferrin family. The protein folds into two globular lobes, N and C. The lobes are further divided into two domains, N1 and N2, and C1 and C2. The iron-binding cleft is situated between the domains in each lobe. The N lobe appears to be well ordered and is more stable than the C lobe in mlf unlike in other lactoferrins, where the C lobe is the more stable. The opening of the binding cleft in the N lobe of mlf is narrower than those in other proteins of the transferrin family. This is very unusual and is found only in mare lactoferrin. Apart from certain hydrophobic interactions at the mouth of the cleft, one salt-bridge (Lys301 . . . . . . . . Glu216) crosses between the two walls of the cleft. The two lobes are connected covalently by a three-turn alpha-helix involving residues 334-344. The N lobe displays a highly ordered structure with appreciably low temperature factors. The iron coordination is more symmetrical in the N lobe than in the C lobe. There are only 16 intermolecular hydrogen bonds in the structure of mlf.

Amino Acid Sequence↗
PubMed1999

Perineal-mound defects.

Perineal-mound (PMD) and genital-fold defects cause anorectal malformations (ARM) in both sexes. They are common in females and usually present as a low anomaly (except rectovestibular fistula). They are rare in males and present as an intermediate anomaly. A common embryological explanation for these defects with varied presentation in males and females is discussed. These anomalies should be grouped separately in the classification of ARM. We present five male patients with PMD, three of whom had imperforate anus with rectobulbar fistula and perineal hypospadias and two who had imperforate anus with rectoperineal fistula.

Anus, Imperforate↗
PubMed1999

Megalourethra with posterior urethral valves.

A case of scaphoid megalourethra associated with the posterior urethral valves was seen in a 4-year-old male. The embryology of the anomaly and its management are discussed with a review of the literature.

Child, Preschool↗
PubMed1999

Perineurial abnormalities in the spontaneously diabetic dog.

Structural abnormalities of the perineurium from six spontaneously diabetic dogs (diabetes duration 4-8 years and six control animals were quantified using detailed electron microscopic morphometric methods on superficial peroneal nerve biopsy specimens. Total perineurial sheath thickness (microm) was significantly increased in diabetic (8.8+/-0.6) compared to control animals (6.2+/-0.3) (P < 0.02). This was attributed to a significant increase in the mean perineurial lamellar width in diabetic (0.49+/-0.03) compared to control (0.40+/-0.01) (P < 0.04) animals. The number of lamellae also showed a non-significant increase in diabetic animals (7.8+/-0.4) compared to controls (6.9+/-0.13) (P < 0.06). There was no change in the mean interlamellar space in diabetic (0.7+/-0.05) compared to control (0.6+/-0.06) (P = 0.15) animals. The total interlamellar space was increased in diabetic (5.7+/-0.5) compared to control (4.1+/-0.36) (P < 0.04) animals. The perineurial cell basement membrane thickness (nm) was significantly increased in diabetic (126.9+/-9.8) compared to control (62.8+/-6.1) (P < 0.005) animals. The current study has demonstrated significant abnormalities of the perineurium in the spontaneously diabetic dog, which may have relevance to the pathogenesis of diabetic neuropathy.

Animals↗
PubMed1999

Reliability of the Tone Assessment Scale and the modified Ashworth scale as clinical tools for assessing poststroke spasticity.

OBJECTIVES: To establish reliability of the Tone Assessment Scale and modified Ashworth scale in acute stroke patients. SETTING: A North Liverpool university hospital. PATIENTS: Eighteen men and 14 women admitted with acute stroke and still in hospital at the study start date (median age, 74 yrs; median Barthel score, 8). MAIN OUTCOME MEASURES: The modified Ashworth scale and the Tone Assessment Scale. STUDY DESIGN: The 32 patients were examined with both scales on the same occasion by two raters (interrater comparison) and on two occasions by one rater (intrarater comparison). RESULTS: The reliability of the modified Ashworth scale was very good (kappa = .84 for interrater and .83 for intrarater comparisons). The reliability of the Tone Assessment Scale was not as strong as the modified Ashworth scale, with marked variability in the assessment of posture (kappa = .22 to .50 for interrater and .29 to .55 for intrarater comparisons) and associated reaction (kappa/kappaW = -.05 to .79 for interrater and .19 to .83 for intrarater comparisons). However, those aspects of the Tone Assessment Scale that addressed response to passive movement and that are scored similarly to the modified Ashworth scale showed good to very good interrater reliability (kappaW = .79 to .92) and good to very good intrarater reliability (kappaW = .72 to .86), except for the question related to movement at the ankle where agreement was only moderate (kappaW = .59). CONCLUSIONS: The modified Ashworth scale is reliable. The section of the Tone Assessment Scale relating to response to passive movement is reliable at various joints, except the ankle. It may assist in studies on the prevalence of spasticity after stroke and the relationship between tone and function. Further development of a measure of spasticity at the ankle is required. The Tone Assessment Scale is not reliable for measuring posture and associated reactions.

Aged↗
PubMed1999

The effects of bovine respiratory syncytial on normal ovine lymphocyte responses to mitogens or antigens in vitro.

In the present study peripheral blod mononuclear cells (MNC) obtained from normal uninfected lambs were used to study the possible effects of bovine respiratory syncytial virus (BRSV) on lymphocyte responses to the mitogens, phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) in vitro. Live BRSV had a depressive effect on the proliferative responses of normal MNC to PHA, Con A and PWM. Inactivated BRSV and a commercial preparation of prostaglandin E2 were also found to depress the proliferative responses of normal ovine MNC to PHA but recombinant tumour necrosis factor-alpha (TNF-alpha) had no such effect. Serum samples obtained from BRSV-infected lambs contained substances inhibitory to PHA-driven lymphocyte blastogenesis. Memory blastogenic responses to border disease virus (BDV) of lymyphocytes obtained from lambs previously primed with BDV were significantly reduced when lymphocytes were exposed to infectious BRSV.

Animals↗
PubMed1999

The immunohistochemical expression of desmoplakin and its role in vivo in the progression and metastasis of breast cancer.

Desmoplakin (DP) is a protein located at the inner plaque of desmosomes where it associates with the desmosomal cadherins to form a cell adhesion complex. Reduced expression of DP has been correlated with the progression of several cancers, but its role in in vivo breast cancer is yet to be established. The aim of this present paper was to determine the immunohistochemical (IHC) expression of DP in breast cancer specimens (n = 75) in comparison with ductal carcinoma in situ (DCIS) (n = 26), tumour associated normal (n = 29) and normal breast tissue (n = 7). DP expression was correlated with that of desmosomal cadherin, Desmoglein 2 (Dsg2) and other clinical and IHC prognostic markers. DP staining occurred at the sub-plasma membrane level. There was no significant correlation between the level of DP (as assessed by the H-score) and that of Dsg. Significantly stronger staining was demonstrated in normal breast tissue and well differentiated tumours compared with more moderately or poorly differentiated tumours (P = 0.04). A significant inverse correlation was seen between DP staining and tumour size (P = 0.01). In a limited series of 8 cases, primary tumours demonstrated significantly stronger staining than the matched metastatic lymph nodes (P = 0.046). Of all the IHC markers examined, only Ki-67 showed a significant inverse relationship with DP staining (P = 0.01). In summary, the data suggest that loss of DP may be of potential importance in progression of breast cancer in vivo from normal, DCIS, well differentiated through to poorly differentiated, large tumours. In addition, this loss may be associated with metastasis.

Breast Neoplasms↗
PubMed1999

Chromoblastomycosis in India.

BACKGROUND: Four patients with chromoblastomycosis are presented. An additional 30 infected Indian patients are reviewed. RESULTS: These 34 patients ranged in age from 12 to 80 years with a male to female ratio of 5.8 : 1. Onset before the age of 20 years was seen in 24% of cases which was comparatively high. Culture was positive in 72% of cases and sclerotic bodies were observed in 84% of cases. A relatively higher prevalence (15%) of Fonsecaea compacta was observed. Unusual cutaneous sites afflicted were the penile shaft, vulva, and ala of the nose, and unusual extracutaneous spread was seen in the pleural cavity, ileocecal region, laryngotracheal area, and tonsils. Extracutaneous involvement was seen in 24% of cases. Overlapping infection with another fungus, Geotrichum candidum, was seen in one case. CONCLUSIONS: Combination therapy with two azoles was attempted with some success for clinical cure.

Adolescent↗
PubMed1999

Serum transferrin receptor assay in iron deficiency anaemia and anaemia of chronic disease in the elderly.

The most common cause of anaemia in the elderly is anaemia of chronic disease (ACD). However, iron deficiency anaemia (IDA) may coexist, and can be difficult to diagnose. The serum transferrin receptor (sTfR) blood test may be a better indicator of iron status as it is not affected by inflammation nor by advancing age. We evaluated it in four groups (10 males, 10 females each): 'young' controls, 'elderly' controls, IDA and ACD. All patients in the IDA group had elevated sTfR levels (mean +/- SD 65.2 +/- 17.7 nmol/l). All 'young' controls had normal sTfR (22.3 +/- 7.3 nmol/l) and ferritin levels (92.7 +/- 61.1 micrograms/l). Although all subjects in the 'elderly' controls and ACD group had normal, and raised or normal serum ferritin, respectively (88 +/- 62.3 micrograms/l; 631.2 +/- 509.5 micrograms/l), three (15%) 'elderly' controls and four (20%) ACD patients had raised sTfR levels, suggesting depleted iron stores. Bone-marrow aspirates were available in 3/4 ACD patients with raised sTfR. Haemosiderin was absent in two. The sTfR blood test is comparable to serum ferritin in diagnosing IDA in the elderly but also seems capable of differentiating ACD from IDA. Its potential as a non-invasive test of iron status, especially in elderly anaemic patients, deserves further evaluation.

Adult↗
PubMed1999

Structure of mare apolactoferrin: the N and C lobes are in the closed form.

The structure of mare apolactoferrin (MALT) has been determined at 3. 8 A resolution by the molecular-replacement method, using the structure of mare diferric lactoferrin (MDLT) as the search model. The MDLT structure contains two iron-binding sites: one in the N-terminal lobe, lying between domains N1 and N2, and one in the C-terminal lobe between domains C1 and C2. Both lobes have a closed structure. MALT was crystallized using the microdialysis method with 10%(v/v) ethanol in 0.01 M Tris-HCl. The structure has been refined to a final R factor of 0.20 for all data to 3.8 A resolution. Comparison of the structure of MALT with that of MDLT showed that the domain arrangements in these structures are identical. However, the structure of MALT is very different to the structures of human apolactoferrin (HALT) and duck apo-ovotransferrin (DAOT), in which the domain associations differ greatly. In HALT, the N lobe adopts an open conformation while the C lobe is in the closed form. On the other hand, in DAOT both the N and the C lobes adopt the open form. These results indicate the domain arrangements in these proteins to be an important structural feature related to their specific biological functions. Based on the structures of MALT, HALT and DAOT, it can be stated that the native apoproteins of the transferrin family adopt three forms: (i) with both the N and the C lobes in closed forms, as observed in MALT, (ii) with the N lobe open and the C lobe closed, as observed in HALT, and (iii) with both the N and the C lobes open, as found in DAOT. All these proteins attain a convergent form when iron is bound to them, suggesting an efficient and unique form of iron binding. The interface between the N and C lobes, which is formed by N1-C1 contact in the core of the molecule, does not change significantly.

Animals↗
PubMed1999

Structure of oxalate-substituted diferric mare lactoferrin at 2.7 A resolution.

Lactoferrin binds two Fe(3+) and two CO(2-)(3) ions with high affinity. It can also bind other metal ions and anions. In order to determine the perturbations in the environments of the binding sites in the N and C lobes and elsewhere in the protein, the crystal structure of oxalate-substituted diferric mare lactoferrin has been determined at 2.7 A resolution. The final model has a crystallographic R factor of 21.3% for all data in the resolution range 17.0-2.7 A. The substitution of an oxalate anion does not perturb the overall structure of the protein, but produces several significant changes at the metal-binding and anion-binding sites. The binding of the oxalate anion is symmetrical in both the N and C lobes, unlike in diferric dioxalate human lactoferrin, where the oxalate anion binds the metal ion symmetrically in the C lobe and asymmetrically in the N lobe.

Animals↗
PubMed1999

Lactoferrin-metal interactions: first crystal structure of a complex of lactoferrin with a lanthanide ion (Sm3+) at 3.4 A resolution.

Lactoferrin is an important member of the transferrin family. A characteristic property of transferrins is their ability to bind very tightly (K(app) approximately/= 10(20)) but reversibly two Fe(3+) ions. The structural consequences of binding a metal other than Fe(3+) have been examined by crystallographic analysis at 3.4 A resolution of mare samarium-lactoferrin (Sm(2)Lf). The structure was refined to an R factor of 0.219 for 8776 reflections in the resolution range 17.0-3.4 A. The samarium geometry (distorted octahedral coordination) is similar in both lobes. However, the anion interactions are quite different in the two lobes. In the N lobe, the anion is able to form only two hydrogen bonds instead of the four observed in the C lobe of Sm(2)Lf and the six observed in Fe(2)Lf. This is because Arg121, Thr117 and Gly124 have moved away from the anion as a consequence of the binding of the Sm(3+) ion. The protein ligands in the binding cleft of Sm(2)Lf show large displacements, but the overall protein structure remains the same. The binding of Sm(3+) by lactoferrin shows that the protein is capable of sequestering ions of different sizes and charges, though with reduced affinity. This conclusion should be true of other transferrins also.

Animals↗
PubMed1999

Cor triatriatum in adults: three new cases and a brief review.

We report 3 cases of cor triatriatum that were diagnosed late, in the 4th and 5th decades of life. The presentations of these 2 men and 1 woman varied substantially, both in anatomic and symptomatic aspects. The woman had an associated complex congenital anomaly, which is not uncommon in cases of cor triatriatum. We present our cases, along with a review of this rare congenital cardiac anomaly.

Adult↗