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Biomedical subjects

N Saha

Publications and source records attributed to N Saha.

At least 19 recordsLinked to original sources

National Biometry Audit II.

PURPOSE: To determine the change in compliance with the Royal College of Ophthalmologists biometry guidelines since the last National Audit 2 years ago and in particular to quantify the adoption of modern methods of axial length measurement and customization of A constants. METHOD: A structured telephone questionnaire of individuals who perform biometry in all eye departments in the United Kingdom. RESULTS: A biometrist was interviewed in 94 of the 178 United Kingdom Ophthalmology departments. Compared with 2 years ago, nurses alone perform biometry more frequently (67 vs 51%) and junior doctors less frequently (9 vs 15%). More biometrists now attend external training courses (45 vs 37%). The Royal College of Ophthalmologists recommended intraocular lens calculation formulae (SRK-T, Hoffer Q, and Holladay) are used more commonly (30 and 15%) and audit of prediction error is being performed more frequently (78 vs 71%). The routine use of a partial coherence laser interferometry has increased from 35 to 61% in United Kingdom Ophthalmology departments. Currently, only one United Kingdom department is routinely using immersion ultrasound biometry. 'A' constants are customized in 47% of departments. CONCLUSION: Over the last 2 years, there has been improved implementation of the Royal College of Ophthalmologists guidelines on biometry. It is essential that the Royal College of Ophthalmologists guidelines are updated to include current best practice of routine use of partial coherence laser interferometry or immersion biometry and customization of A constants. A benchmark standard of 85-90% of patients achieving a final postoperative refraction within 1 dioptre of the predicted should be established.

Biometry↗

The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

Antigens↗

Coexistent partial anodontia and supernumerary tooth in the mandibular arch: a rare case.

Coexistent partial anodontia and supernumerary tooth in the lower jaw is a very uncommon condition. Very few cases have been reported in the literature of this condition, etiology of which is still obscure. Presented here is a rare case of simultaneous presence of single supernumerary tooth together with missing permanent central incisor teeth in the lower jaw without any associated systemic condition or syndrome.

Anodontia↗

Food reduces the bioavailability of lamotrigine.

BACKGROUND AND OBJECTIVE: Lamotrigine is a relatively newer antiepileptic drug used in the treatment of partial seizures. It has a narrow therapeutic index and hence the achieved blood level of the drug is closely related to the therapeutic efficacy and toxicity. The bioavailability of lamotrigine is affected by food, hence the present study was done to investigate the effect of two types of food on the bioavailability of lamotrigine. METHODS: A randomized, open-label, three treatment, three period, single dose and cross-over study was done in nine healthy male volunteers. A single dose of lamotrigine (100 mg) was administered at three occasions: after a north Indian diet (high calorie, high fat), after a south Indian diet (low calorie, low fat), and after an overnight fasting. Serial blood samples were collected up to 24 h post dose. Plasma lamotrigine concentrations were determined and pharmacokinetic parameters studied. RESULTS: A statistically significant decrease in rate and extent of absorption was observed with north Indian diet and south Indian diet when compared with fasting group. Presence of both types of food causes decrease in mean values of C(max), AUC((0-t)), and AUC((0-alpha)) thus reducing the bioavailability of lamotrigine at significant level (P<0.05). INTERPRETATION AND CONCLUSION: Lamotrigine should be taken preferably in fasting condition, as presence of food (low fat, low calorie or high fat, high calorie) decreases the bioavailability to a significant extent.

Adult↗

Anthelmintic efficacy of Flemingia vestita (Fabaceae): alteration in the activities of some glycolytic enzymes in the cestode, Raillietina echinobothrida.

The crude root-peel extract of Flemingia vestita, genistein and praziquantel were tested against some selected glycolytic enzymes--hexokinase (HK), phosphofructokinase (PFK), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH) and malic enzyme (ME)--of the fowl tape worm, Raillietina echinobothrida. Following exposure to the various treatments, the activities of HK, PFK, PEPCK and LDH increased by 33-39%, 41-125%, 44-49% and 55-67%, respectively, and that of PK decreased by 14-26% in the parasite at the time of paralysis. The MDH and ME activities of the tissue homogenate were also found to be higher by 22-43% and 28-59%, respectively, in the treatments. However, whereas the activity of both cytosolic and mitochondrial MDH increased by 33-58% and 43-73%, respectively, the cytosolic ME activity showed an increase of 33-39%, and there was no significant enhancement in the mitochondrial ME activity. Histochemically, the enhancement in the activities of HK, LDH and MDH was clearly discernible. The enhanced glycolytic activity seems to be a function of anthelmintic stress caused by the phytochemicals.

Animals↗

National biometry audit.

PURPOSE: To determine compliance with the Royal College of Ophthalmologists' (RCOphth) biometry guidelines. METHOD: A structured telephone questionnaire of individuals who perform biometry in all eye departments in the United Kingdom (UK). RESULTS: A biometrist was interviewed in 107 of the UK's 178 eye departments. Nurses alone run the biometry service in 58% of departments, orthoptists alone in 13%, junior doctors alone in 6%, optometrists alone in 3%, and a combination of staff in 20%. Of the staff interviewed, 37% had been on external biometry training courses. One intraocular lens (IOL) calculation formula was used for all eyes in 61% of departments with 17% using the obsolete SRK II formula, 36% of departments used two or more formulae and only 4% adhered to the RCOphth guidelines to use Hoffer Q in eyes with axial lengths <22.0 mm, an average of all three formulae in eyes between 22.0 and 24.5 mm, Holladay in eyes between 24.6 and 26.0 mm, and SRK/T in eyes >26.0 mm. Audit of refractive results was claimed by 71% of units but in only 17 (16%) did the biometrist know the percentage of eyes with a prediction error <or=1 D. CONCLUSION: This study demonstrates poor awareness and/or implementation of the RCOphth biometry guidelines and indicates that audits are either not highlighting poor results or are not resulting in a change in practice. The guidelines should be updated to emphasise the importance of customising A constants and to set benchmark standards for prediction error.

Biometry↗

STM imaging of flux line arrangements in the peak effect regime.

We present the results of a study of vortex arrangements in the peak-effect regime of 2H-NbSe2 by scanning tunneling microscopy. By slowly increasing the temperature in a constant magnetic field, we observed a sharp transition from collective vortex motion to positional fluctuations of individual vortices at the temperature which coincides with the onset of the peak effect in ac susceptibility. We conclude that the peak effect is a disorder driven transition, with the pinning energy winning against the elastic energy.

Journal Article↗

Genotype associations of factor VII gene with plasma factor VII coagulant activity and antigen levels in healthy Chinese.

A raised plasma factor VII (FVII) level is one of the risk factors for coronary artery disease. The R353Q polymorphism at codon 353 and the 10 base pair (bp) insertion (0/10 bp) polymorphism of the FVII gene have been reported to be associated with plasma FVII levels in several populations. We investigated these two polymorphisms in 209 male and 214 female healthy Chinese. The allele frequencies of 10 bp and Q were 0.036 and 0.045, respectively. Strong linkage disequilibrium was observed between these two sites (Delta = 0.85, P < 0.001). There were significant genotype associations of these two loci with FVII coagulant activity (FVIIc) and antigen (FVIIAg) levels. Heterozygous individuals had lower FVIIc and FVIIAg levels than those homozygous for the common alleles. When analyzed separately by gender, the 0/10 bp polymorphism was strongly associated with FVIIAg levels in males and females. However, both polymorphisms were significantly associated with FVIIc levels only in the females. The effect of 0/10 bp polymorphism predominated over that of the R353Q polymorphism in a two-way analysis of variance procedure. In the Chinese, the 10 bp insertion may reduce transcription of the FVII gene, leading to the decreased synthesis of FVII protein and thus FVIIc.

Adult↗

Effects of alanine cluster mutations in the D12 subunit of vaccinia virus mRNA (guanine-N7) methyltransferase.

The (guanine-N7)-methyltransferase domain of the vaccinia virus mRNA capping enzyme is a heterodimer composed of a catalytic subunit D1(498-844) bound to a stimulatory subunit D12. To identify structural elements of the 287-amino-acid D12 subunit that participate in binding and activation of the catalytic subunit, we introduced 12 double-alanine mutations at vicinal residues that are conserved in the D12 homologs of other vertebrate poxviruses. His-tagged D12 mutants were coexpressed in bacteria with the D1(498-544) subunit, and the recombinant D1(498-844)/His-D12 heterodimers were purified. Eight of the mutants (K111A-R112A, N120A-N121A, N126A-N127A, F141A-R142A, K223A-D224A, H260A-S261A, E275A-N276A, and R280A-R281A) had no significant effect on methyltransferase activity. Three of the mutants (L61A-K62A, F176A-K177A, and F245A-L246A) displayed an intermediate level of cap methylation (35-50% of wild-type activity). Only one mutation, N42A-Y43A, elicited a significant loss of the methyltransferase activation function (<20% of the wild-type activity). Nine of the D12-Ala/Ala proteins were produced individually in bacteria and tested for reconstitution of methyltransferase activity in vitro by mixing with the catalytic subunit. K111A-R112A, N120A-N121A, F176A-K177A, F245A-L246A, and L61A-K62A displayed diminished affinity for the D1 catalytic subunit. N42A-Y43A was uniquely defective in its ability to activate cap methylation by the catalytic subunit. Our results suggest that the methyltransferase activation function of D12, though clearly dependent on the physical interaction with D1, also requires constituents of D12 that are engaged specifically in catalysis.

Alanine↗

Immune related genetic polymorphisms and schizophrenia among the Chinese.

Genetic association studies were conducted among two independent cohorts of Chinese ethnicity. The samples consisted of cases and unrelated controls, ascertained from Guangzhou, China, and Singapore. The studies were prompted by our earlier report of an association between schizophrenia and HLA DQB1 alleles (HLA DQB1*0602 and HLA DQB1*0303) in the Singapore sample. Polymorphisms of HLA DQB1 and flanking markers on chromosome 6p21.3 were investigated in the first part of the study. A significant negative association with HLA DQB1*0402 was detected in the Guangzhou sample (Odds ratio, OR 0.26, 95% confidence intervals, CI 0.1, 0.6; p < 0.02, corrected for multiple comparisons). Additional analysis of the Guangzhou and Singapore samples revealed associations at three other anonymous markers flanking HLA DQB1. In the second part of the study, three polymorphisms at the Interleukin-1 gene cluster (IL-1, chromosome 2q13-q21) were investigated in both cohorts, since associations with schizophrenia have been reported in another sample. Persuasive evidence for an association at IL-1 was not detected in either sample. Our results suggest a susceptibility locus for schizophrenia in the HLA region among the Chinese, but further clarification is necessary.

Adult↗

Role of ureogenesis in the mud-dwelled Singhi catfish (Heteropneustes fossilis) under condition of water shortage.

The air-breathing Singhi catfish Heteropneustes fossilis was kept inside moist peat for 1 month mimicking their normal habitat in summer and the role of ureogenesis for their survival in a water-restricted condition was studied. The ammonia excretion rate by the mud-dwelled fish increased transiently between 6 and 12 h of re-immersion in water to approximately between eight and 10-fold, followed by a sharp decrease almost to the normal level at the later part of re-immersion. The urea-N excretion by the mud-dwelled fish increased to approximately 11-fold within 0-3 h of re-immersion, followed by a gradual decrease from 9 h onwards. The rate of urea-N excretion by the mud-dwelled fish, however, remained significantly higher (approx. threefold more) than the control fish even after 36-48 h of re-immersion. Although there was a significant increase of both ammonia and urea levels in the plasma and other tissues (except ammonia in the brain), the level of accumulation of urea was higher than ammonia in the mud-dwelled fish as indicated by the decrease in the ratio of ammonia: urea level in different tissues including the plasma. The activities (units/g tissue and /mg protein) of glutamine synthetase and three enzymes of the urea cycle, carbamyl phosphate synthetase, argininosuccinate synthetase and argininosuccinate lyase increased significantly in most of the tissues (except the brain) of the mud-dwelled fish as compared to the control fish. Higher accumulation of ammonia in vivo in the mud-dwelled Singhi catfish is suggested to be one of the major factors contributing to stimulation of ureogenesis. Due to this physiological adaptive strategy of ureogenesis, possibly along with other physiological adaptation(s), this air-breathing amphibious Singhi catfish is able to survive inside the moist peat for months in a water-restricted condition.

Ammonia↗

NO nerves in trematodes, too! NADPH-diaphorase activity in adult Fasciolopsis buski.

The free radical nitric oxide (NO) is a unique molecule with an avidity to react with other molecules and is known to function as a neuronal messenger. This nitrergic transmitter with diverse functions in signal transduction, being a gas, is not stored in synaptic vesicles but is generated in various neuronal cells by a family of nitric oxide synthases (NOSs). The NADPH-d histochemical reaction is regarded as a selective marker for NOS in the neuronal tissue. With histochemical detection of NADPH-d, the presence of NOS is demonstrated in the digenetic trematode, Fasciolopsis buski. Strong NADPH-d staining was observed in the neuronal cell bodies in the two cerebral ganglia, the brain commissure and the nerve fibers in the main nerve cords. NADPH-d staining was also detectable in the innervation of the pharynx, the cirrus sac and the ventral sucker besides being observable sporadically in the nerve tributaries in the general parenchyma. NO released by the whole worm kept in PBS at 37 degrees C could also be measured biochemically. The NOS activity was assayed in the whole worm homogenate and also in the tissue homogenate containing only the anterior pre-acetabular part of the parasite body. The presence of NOS in this digenean parasite confirms that a nitrergic innervation occurs in the trematode group also as in other groups of exclusively parasitic helminths and that NO represents an old signal molecule in evolutionary scale.

Animals↗

Variations in the promoter region of the apolipoprotein A-1 gene influence plasma lipoprotein(a) levels in Asian Indian neonates from Singapore.

We studied the influence of two DNA polymorphisms (-75 bp G/A and +83 bp C/T) in the promoter region of the apolipoprotein A-1 (apoA1) gene on cord plasma level of lipoprotein(a) [Lp(a)] in 1076 newborns of both genders from the three major ethnic groups in Singapore-Chinese, Malays, and Asian Indians. The frequency of the A: allele at -75 bp in the Indians was significantly lower than the Chinese and Malays. There was no linkage disequilibrium between the two sites studied. Both polymorphic sites were not significantly associated with any lipid factors except for Lp(a) levels in the Asian Indians. The AA and CC homozygotes were significantly associated with lower Lp(a) levels. These associations were specific only to the male Indian neonates. The genetic variations at the -75 and +83 bp explained 6.9% and 7.2%, respectively, of the total variability of plasma Lp(a) levels at birth in the Asian Indians. The Lp(a) levels were also significantly different between composite genotypes in the order GG/TT > GA/CT > GG/CT > GA/CC > GG/CC > AA/CC. The effects of the two polymorphisms seem to be additive as the composite genotypes were able to explain 14% of the Lp(a) variance, equivalent to the sum of the two constituent sites. Our results showed that there is significant ethnic- and gender-specific influence of the apoA1 gene on plasma Lp(a) levels at birth that is inherent and independent of known gene-environment interactions.

Apolipoprotein A-I↗

Lactase haplotype diversity in the Old World.

Lactase persistence, the genetic trait in which intestinal lactase activity persists at childhood levels into adulthood, varies in frequency in different human populations, being most frequent in northern Europeans and certain African and Arabian nomadic tribes, who have a history of drinking fresh milk. Selection is likely to have played an important role in establishing these different frequencies since the development of agricultural pastoralism approximately 9,000 years ago. We have previously shown that the element responsible for the lactase persistence/nonpersistence polymorphism in humans is cis-acting to the lactase gene and that lactase persistence is associated, in Europeans, with the most common 70-kb lactase haplotype, A. We report here a study of the 11-site haplotype in 1,338 chromosomes from 11 populations that differ in lactase persistence frequency. Our data show that haplotype diversity was generated both by point mutations and recombinations. The four globally common haplotypes (A, B, C, and U) are not closely related and have different distributions; the A haplotype is at high frequencies only in northern Europeans, where lactase persistence is common; and the U haplotype is virtually absent from Indo-European populations. Much more diversity is seen in sub-Saharan Africans than in non-Africans, consistent with an "Out of Africa" model for peopling of the Old World. Analysis of recent recombinant haplotypes by allele-specific PCR, along with deduction of the root haplotype from chimpanzee sequence, allowed construction of a haplotype network that assisted in evaluation of the relative roles of drift and selection in establishing the haplotype frequencies in the different populations. We suggest that genetic drift was important in shaping the general pattern of non-African haplotype diversity, with recent directional selection in northern Europeans for the haplotype associated with lactase persistence.

Africa South of the Sahara↗