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Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

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

The genetic background modifies the effects of the obesity mutation, 'fatty', on apolipoprotein gene regulation in rat liver.

BACKGROUND: Obesity is associated with disorders of plasma lipid transport in many, but not in all obese subjects. The effects of obesity on the regulation of genes involved in plasma lipid transport may depend on specific mutations causing or contributing to obesity and/or on interactions of a specific obesity mutation with the genetic background. The 'fatty' (Glu269Pro) leptin receptor mutation causes severe obesity associated with hypertriglyceridaemia and altered hepatic apolipoprotein gene regulation in Zucker fatty rats. OBJECTIVE: To determine whether the effects of the obesity mutation 'fatty' on apolipoprotein gene regulation in rat liver depend on the genetic background. METHODS: We studied hepatic apolipoprotein (apo) A-IV, A-I, and C-III gene expression in obese rats carrying the 'fatty' mutation on the background of the Zucker or Wistar strain. RESULTS: Basal apoA-IV gene expression was increased in fatty rats of both strains, whereas apoA-I and apoC-III gene expression differed between Wistar and Zucker fatty rats: apoA-I gene transcription was reduced to half and apoC-III mRNA was increased two-fold in Wistar fatty, but not in Zucker fatty rats vs lean controls. A fish oil diet suppressed apoA-IV, but not apoA-I gene transcription in Wistar fatty rats, whereas in Zucker fatty rats apoA-IV transcription was unaffected, but apoA-I transcription was suppressed. CONCLUSIONS: Interactions of the 'fatty' leptin receptor mutation with the genetic background significantly affect the basal and diet-induced regulation of the apoA-IV, C-III and A-I genes in rat liver. The genetic background may therefore be a major determinant of the consequences of a specific obesity mutation for plasma lipid transport.

Animals↗
PubMed2000

A randomised placebo controlled trial of the effects of tibolone on blood pressure and lipids in hypertensive women.

The effects of hormone replacement therapy in hypertensive women are controversial. This randomised placebo controlled trial assessed the effect of tibolone 2.5 mg on blood pressure and fasting plasma lipids in 29 hypertensive postmenopausal women over 6 months using a 2:1 randomisation to tibolone. The primary clinical end-point was mean office blood pressure. At 6 months systolic blood pressure declined by 5.30 +/- 2.87% vs 4.94 +/- 3.37% whilst diastolic blood pressure declined 5.38 +/- 2.65% vs 0.85 +/- 3.69% on tibolone and placebo respectively. These differences were not statistically significant. Triglycerides decreased by 33.3 +/- 6.1% vs 7.6 +/- 7.9% (P < 0.01) and high-density lipoprotein (HDL)-cholesterol by 21.7 +/- 3.8% vs 2.4 +/- 2.6% (P < 0.01) with tibolone as opposed to placebo. No significant differences were observed in total cholesterol, low-density lipoprotein (LDL)-cholesterol and lipoprotein (a). Fibrinogen levels were reduced by 13.6 +/- 6.8% on tibolone compared to a 19.3 +/- 15.4% rise (P < 0.05) on placebo. This study suggests that tibolone has no deleterious effect on blood pressure in women with hypertension but has contrasting effects on biochemical risk factors. Large-scale studies are required to determine the overall effect of tibolone on cardiovascular morbidity and mortality.

Antihypertensive Agents↗
PubMed2000

Investigation of the haem-nicotinate interaction in leghaemoglobin. Role of hydrogen bonding.

A strategic assessment of the contributions of two active-site hydrogen bonds in the binding of nicotinate to recombinant ferric soybean leghaemoglobin a (rLb) was carried out by mutagenic replacement of the hydrogen-bonding residues (H61A and Y30A variants) and by complementary chemical substitution of the carboxylate functionality on the nicotinate ligand. Dissociation constants, Kd (pH 5.5, mu = 0.10 M, 25.0 +/- 0.1 degrees C), for binding of nicotinate to ferric rLb, H61A and Y30A were 1.4 +/- 0.3 microM, 19 +/- 1 microM and 11 +/- 1 microM, respectively; dissociation constants for binding of nicotinamide were, respectively, 38 +/- 1 mM, 50 +/- 2 mM and 12 +/- 1 mM, and for binding of pyridine were 260 +/- 50 microM, 4.5 +/- 0.5 microM and 66 +/- 8 microM, respectively. Binding of cyanide and azide to the H61A and Y30A variants was unaffected by the mutations. The pH-dependence of nicotinate binding for rLb and Y30A was consistent with a single titration process (pKa values 6.9 +/- 0.1 and 6.7 +/- 0.2, respectively); binding of nicotinate to H61A was independent of pH. Reduction potentials for the rLb and rLb-nicotinate derivatives were 29 +/- 2 mV (pH 5.40, 25.0 degrees C, mu = 0.10 M) and - 65 +/- 2 mV (pH 5.42, 25.0 degrees C, mu = 0.10 M), respectively. The experiments provide a quantitative assessment of the role of individual hydrogen bonds in the binding process, together with a definitive determination of the pKa of His61 and unambiguous evidence that titration of His61 controls binding in the neutral to alkaline region.

Base Sequence↗
PubMed2000

Prevalence of HIV among pregnant women in Dundee 1988-1997: evidence to gauge the effectiveness of HIV prevention measures.

OBJECTIVES: During November 1988-July 1990, an HIV prevalence survey of pregnant women in Dundee, which used a combined voluntary diagnostic testing and voluntary unlinked anonymous approach, revealed a rate of 0.3%, the highest recorded prevalence among such a population in the U.K. at the time. To determine if, and why, any changes in HIV prevalence had occurred during the early to mid 1990s, further studies were conducted. METHODS: During January 1993-December 1997, antenatal patients of, and women undergoing therapeutic termination of pregnancy at, Ninewells Hospital, Dundee, were offered a diagnostic HIV antibody test. For those declining, residual sera from rubella specimens were tested for HIV antibodies using an unlinked anonymous approach which did not necessitate the securement of informed consent. Information about injecting drug use was obtained from all women and linked to their HIV test results. RESULTS: For all pregnant women, a significant decline in HIV prevalence (P<0.05) from 0.3% (19/6228) during 1988-1990 to 0.12% (22/17899) during 1993-1997 was observed. For those who injected drugs, prevalence decreased significantly (P<0.05) from 27.5% (11/40) to 7% (6/85), while among women who had never injected drugs prevalence decreased slightly, but not significantly (P>0.05), from 0.13% (8/6188) to 0.09% (16/17814).Prevalence in the non-injectors who reported no sexual intercourse with an injector was low at 0.04% (8/17682) during 1993-1997. No significant trends in HIV prevalence were seen over the 5 years up to 1997. CONCLUSION: The decline in HIV prevalence among pregnant women in Dundee during the early to mid-1990s can be explained predominantly by the control of HIV transmission among the city's injectors, and from them to the wider heterosexual population. It is likely that interventions designed to reduce needle/syringe sharing among injectors have been successful. It is imperative that the preventive effort is not allowed to be weakened.

Abortion, Induced↗
PubMed2000

Pattern of advancement in the zone of calcified cartilage detected in hand osteoarthritis.

OBJECTIVE: Using high definition macroradiography the pattern of advancement in the zone of calcified cartilage (termed a ZCC step) was detected in osteoarthritic hand joints of patients and compared to the joint space width (JSW) measurement. DESIGN: X5 macroradiographs were obtained of the osteoarthritic hands of 44 patients at baseline and at 18 months. The incidence of ZCC steps, identified as an advancement in the mineralized cartilage front into articular cartilage, was assessed at each articular surface. JSW was measured and was used to determine the difference in JSW between hands and groups of joints with and without ZCC steps at both X-ray visits. RESULTS: ZCC steps were found at the convex articular surfaces in only 42 (48%) hand joints in 28 (64%) patients. Here, ZCC steps were present in 36 joints in the non-dominant hand, compared with 30 joints in the dominant hand. In the former, they were present in 22 DIP, six PIP and eight MCP joints and in 12 DIP, eight PIP and 10 MCP joints in the dominant hand. By 18 months, new ZCC steps had formed in 15 hands with and 17 hands without previous ZCC steps. At both X-ray visits no statistically significant difference in JSW was found between the hands and joint groups with and without ZCC steps. CONCLUSION: In patients with ZCC steps, the pattern of distribution in the hand appeared to be related to that due to vascular changes, such as hyperlipidaemia, rather than to that associated with mechanical forces.

Calcinosis↗
PubMed2000

Use of a novel modified TSI for the evaluation of controlled-release aerosol formulations. I.

When considering the development of potential controlled-release pulmonary drug delivery systems, there is at present no standard method available for the assessment of in vitro drug release profiles necessary to understand how the drug might release following deposition in the lungs. For this purpose, the twin-stage impinger (TSI), apparatus A of the BP, has been redesigned and tested. This modified TSI was found capable of discriminating between drug release rates from conventional and different dry powder formulations consisting of model controlled-release excipients, providing information related to (a) drug diffusion properties of controlled-release dry powder blends with different excipient components and (b) the effect of varying drug concentration within a given formulation.

Administration, Inhalation↗
PubMed2000

Does the timing of hypertonic saline resuscitation affect its potential to prevent lung damage?

Hypertonic saline (HS) resuscitation has been reported to prevent lung damage by suppressing neutrophil activation in animal models. Data on the effectiveness of HS to prevent organ damage in the clinical setting are inconsistent. We investigated whether the timing of HS administration relative to neutrophil activation could affect its potential to block neutrophil responses. Different likely clinical circumstances were simulated in vitro by exposing human neutrophils to HS at different time points before and after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The in vivo effect of using HS as a secondary resuscitation fluid was determined with a mouse model of hemorrhage. BALB/c mice were hemorrhaged (40 +/- 5 mmHg) for 1 h and partially resuscitated with HS or Lactated Ringer's (LR) 20 min before completing resuscitation with LR or HS, respectively. Neutrophil activation parameters were determined 2 h after complete resuscitation and lung damage was assessed after 24 h. The length of exposure to physiologically relevant HS levels (20 mM) determined the suppressive effect on in vitro neutrophil superoxide formation. HS treatment caused a transient state of suppression during which neutrophil activation was suppressed; however, HS was unable to suppress cells that were stimulated with fMLP before HS was added. Accordingly, in vivo lung damage was greater in animals that received HS after they had been partially resuscitated with LR compared to mice that received HS before LR (P < 0.05). We conclude that timing of exposure to HS affects neutrophil responses in vitro and may reduce the potential of HS resuscitation to prevent lung injury in vivo.

Animals↗
PubMed2000

In vitro evaluation of two adhesive systems used with compomer filling materials.

AIM: To evaluate and compare the in-vitro shear bond strength, microleakage and dentine-restorative interface of a self-etching/self-priming dentine bonding agent with a three-component dentine-bonding agent. METHOD: For shear bond strength (SBS) testing 30 non-carious human molars were used of which 15 were tested with Non-Rinse Conditioner (NRC)/Prime&Bond NT (PBNT) and Dyract AP and 15 were tested with Scotchbond Multi-Purpose Plus (SBMP) and F2000. For the microleakage evaluation cavity preparations were made on the facial surfaces of 30 non-carious human premolars of which 15 were restored with NRC and PBNT with Dyract AP and 15 were restored with SBMP and F2000. The dentine-restorative interface was examined through a confocal scanning laser microscope (CSLM). RESULTS: The mean SBS of PBNT and SBMP were 12.8 and 18.1 MPa, respectively. The microleakage scores showed NRC/PBNT leaked on the dentine side in 13 of the 15 specimens examined. On the enamel side two of the 15 specimens showed microleakage. With SBMP no microleakage was observed on either enamel or dentine sides. The CSLM images show clear resin tag and hybrid layer formation for both the materials examined although SBMP showed better and deeper penetration into the dentine with longer resin tags. SBMP showed resin tags measuring about 150 mm while the hybrid layer measured about 5 mm. The length of the resin tags as well as the thickness of the hybrid layer for PBNT were 20 mm Pounds and 2 mm Pounds, respectively. CONCLUSIONS: The acid-etch technique of SBMP produced higher bond strength and no microleakage when compared with the self-etching/self-priming 'non-rinse technique' of NRC with PBNT. Thus it can only be speculated that SBMP should be the superior in the clinical situation.

Compomers↗
PubMed2000

Neonatal hypoglycaemia in Nepal 1. Prevalence and risk factors.

AIMS: To measure the prevalence of hypoglycaemia among newborn infants in Nepal, where classic risk factors prevail, and to evaluate their importance. METHODS: A cross sectional study was done of 578 term newborn infants aged 0 to 48 hours on the postnatal wards of a government maternity hospital in Kathmandu, with unmatched case-control analysis of risk factors for moderate hypoglycaemia (less than 2.0 mmol /l). RESULTS: Two hundred and thirty eight (41%) newborn infants had mild (less than 2.6 mmol/l) and 66 (11%) moderate hypoglycaemia. Significant independent risk factors for moderate hypoglycaemia included postmaturity (OR 2.62), birthweight under 2.5 kg (OR 2.11), small head size (OR 0.59), infant haemoglobin >210 g/l (OR 2.77), and raised maternal thyroid stimulating hormone (TSH) (OR 3.08). Feeding delay increased the risk of hypoglycaemia at age 12-24 hours (OR 4.09). Disproportionality affected the risk of moderate hypoglycaemia: lower with increasing ponderal index (OR 0.29), higher as the head circumference to birthweight ratio increased (OR 1.41). Regression expressing blood glucose concentration as a continuous variable revealed associations with infant haemoglobin (negative) and maternal haemoglobin (positive), but no other textbook risk factors. CONCLUSIONS: Neonatal hypoglycaemia is more common in a developing country, but may not be a clinical problem unless all fuel availability is reduced. Some textbook risk factors, such as hypothermia, disappear after controlling for confounding variables. Early feeding could reduce moderate hypoglycaemia in the second 12 hours of life. The clinical significance of raised maternal TSH and maternal anaemia as prenatal risk factors requires further research.

Adolescent↗
PubMed2000

Neonatal hypoglycaemia in Nepal 2. Availability of alternative fuels.

AIMS: To study early neonatal metabolic adaptation in a hospital population of neonates in Nepal. METHODS: A cross sectional study was made of 578 neonates, 0 to 48 hours after birth, in the main maternity hospital in Kathmandu. The following clinical and nutritional variables were assessed: concentrations and age profiles of blood glucose, hydroxybutyrate, lactate, pyruvate, free fatty acids (FFA) and glycerol; associations between alternative fuel levels and hypoglycaemia; and regression of possible risk factors for ketone availability. RESULTS: Risk factors for impaired metabolic adaptation were common, especially low birthweight (32%), feeding delays, and cold stress. Blood glucose and ketones rose with age, but important age effects were also found for risk factors like hypothermia, thyroid hormone activities, and feeding practices. Alternative fuel concentrations, except FFA, were significantly reduced in infants with moderate hypoglycaemia during the first 48 hours after birth. Unlike earlier studies, small for gestational age (SGA) infants had significantly higher hydroxybutyrate:glucose ratios which suggested counter regulatory ketogenesis. Hypoglycaemic infants were not hyperinsulinaemic. Regression analysis showed risk factors for impaired counter regulation which included male and large infants, hypothermia, and poorer infant thyroid function. SGA infants and those whose mothers had received no antenatal care had increased counter regulation. CONCLUSIONS: Alternative fuels are important in the metabolic assessment of neonates, and they might provide effective cerebral metabolism even during moderate hypoglycaemia. Hypoglycaemic infants generally had lower concentrations of alternative fuels through either reduced availability or increased consumption. SGA and post term infants increased counter regulatory ketogenesis with early neonatal hypoglycaemia, but hypothermia, male gender, and low infant T4 were associated with impaired counter regulation after birth.

Age Factors↗
PubMed2000

Scanning the visual world: a study of patients with homonymous hemianopia.

OBJECTIVES: This study examined the scanpaths of patients with homonymous hemianopia while viewing naturalistic pictures in their original and also spatially filtered forms. Features of their scanpaths with respect to various saccade and fixation parameters were examined to determine whether they develop compensatory eye movement strategies. The effects of various lesion parameters including location, size, and age on the evolution of such strategies were considered. METHODS: Eye movements of eight patients with homonymous hemianopia (four left, four right), but lacking neglect, were recorded while they viewed 22 images of real scenes, and they were compared with the eye movements of eight age matched controls. Subjects viewed each image for 3 seconds, initially in a spatially filtered form in which much of the semantic content had been removed, and then in their unfiltered, original form. RESULTS: Patients differed significantly from controls in various fixation and saccade parameters. For fixation parameters patients with hemianopia fixated different spatial positions from controls, made more fixations which were more widely distributed and of shorter duration than controls, and spent a greater proportion of their total fixation time in the area corresponding to their blind hemifield. They did not make significantly more refixations than controls. For saccade parameters patients made more saccades into their blind hemifield, these saccades having shorter latencies and shorter amplitudes than those made into their seeing field, and had longer scanpaths than control subjects. The amplitude of their first saccade was longer than that of controls although its direction did not correlate simply with the side of the field defect. Their mean saccade amplitude was similar to that of controls. Filtering out high spatial frequencies within images seemed to accentuate the described differences between eye movement characteristics of hemianopes and controls. Scanpath differences correlated with increasing age but not location or size of lesions causing the hemianopia. CONCLUSION: Various features of scanpaths produced by hemianopes were different from normal subjects. These differences correlated with lesion age and may reflect the evolution of a compensatory eye movement strategy.

Adult↗
PubMed2000

Hepatic malignancies: improved detection with pulse-inversion US in late phase of enhancement with SH U 508A-early experience.

Twenty consecutive patients with known liver malignancies underwent ultrasonography (US) in conventional B mode and in pulse-inversion mode in the late hepatic-specific parenchymal phase after intravenous administration of SH U 508A, a microbubble US contrast agent. Two experienced readers assessed subjective and objective conspicuity, number of lesions, and smallest lesion diameter in each mode. Subjective and objective conspicuity were improved with pulse-inversion mode, and smaller lesions were depicted with pulse-inversion mode than with conventional B mode, improving the detection of metastases less than 1 cm in size.

Adult↗
PubMed2000

Printing patterns of biospecifically-adsorbed protein.

The advancement of elastomeric patterning techniques in recent years has significantly enhanced our ability to spatially control biomaterial surface chemistry at the micrometre level. The application of this technology to the patterning of biomolecules onto solid surfaces has created many potential applications including the development of advanced biosensors, combinatorial library screening and the formation of tissue engineering templates. In this paper, we describe the direct patterning of protein by microcontact printing. An important consideration for the fabrication of protein micropatterns intended for these applications is the nature of the protein immobilization to a substrate. To date, the patterning of proteins by direct microcontact printing (microCP) has relied on the non-covalent adsorption to a substrate. Ideally, the proteins need to be firmly anchored onto a surface without adversely effecting their activity. Here, the high affinity avidin-biotin receptor-ligand interaction has been exploited to form arrays of avidin molecules onto a polymeric substrate expressing biotin moieties. This has created a generic technique by which any biotinylated species can be subsequently immobilized into defined patterns. Utilizing atomic force microscopy (AFM), the patterned surfaces have been characterized to molecular resolution. The micropatterned sample supported cell adhesion when biotin-(G)11-GRGDS was bound to the avidin bearing arrays.

3T3 Cells↗
PubMed2000

Botanical perspectives on health: of cystitis and cranberries.

With generalised increased use of antibiotics there has been the accompanying development of antibiotic resistance. It has been suggested that the therapy of uncomplicated cystitis is one area in which it is possible to reduce the usage of such compounds. Many women have long drunk cranberry juice--and it has become an 'old-wives' tale in the treatment of this infection. Perhaps it is now time for science to investigate further the benefits of the humble cranberry.

Beverages↗
PubMed2000

Moderately low vitamin B12 does not compromise transmethylation in adults on a free diet: implications for assessment of vitamin B12 status.

Lower reference limits for vitamin B12 are often defined solely in relation to haematological criteria. This may be misleading and there is evidence indicating that biochemical anomalies should also be considered. In 50 patients we measured creatine, as the major product of B12-mediated remethylation, to see if this helps the definition of the B12 reference interval and to investigate the possible effect of low B12 on essential transmethylation. Vitamin B12 values were grouped into six fractiles covering the range 50-500 ng/L; the corresponding creatine results were assessed by analysis of variance giving F = 0.94 and a significance of 0.466. Although no correlation between B12 and creatine was found, and therefore no obvious effect on transmethylation of low B12 concentration, this must be interpreted with respect to methionine availability. Other factors indicate that biochemical perturbations should be taken into account when defining vitamin B12 reference intervals.

Analysis of Variance↗
PubMed2000

Baculovirus-mediated gene transfer into pancreatic islet cells.

Baculovirus transduction is a gene transfer method that uses a moth cell virus for mammalian cells in culture, which results in a high-level prolonged expression. Here we demonstrate that recombinant baculoviruses can serve as efficient gene transfer vehicles for delivering foreign genes driven by mammalian promoters into human and mouse pancreatic islet cells. Existing methods, such as various transfection and electroporation techniques, either suffer from low efficiency or cause extensive membrane damage. Viral vectors have emerged as an important tool for gene delivery and expression in mammalian cells but suffer from several drawbacks, such as lengthy construction time and expression of viral genes. The baculovirus Autographa californica multiple nuclear polyhedrosis virus is widely used as a vector for expression of foreign genes in insect cells and, more recently, in some mammalian cells. Using several green fluorescent protein- and LacZ-expressing constructs in a cytomegalovirus promoter cassette, we obtained efficient gene expression in primary human and mouse islet cells. There was no impairment of glucose-stimulated intracellular free calcium responses after baculovirus infection. The safety and the relative ease of construction and propagation of the virus makes the baculovirus system a useful tool for facilitating the transfer of foreign genes.

Animals↗
PubMed1999

Ectopic expression of protein kinase CbetaII, -delta, and -epsilon, but not -betaI or -zeta, provide for insulin stimulation of glucose uptake in NIH-3T3 cells.

Insulin regulates a diverse array of signaling pathways involved in the control of growth, differentiation, proliferation, and metabolism. Insulin increases in glucose uptake via a protein kinase C-dependent pathway in target tissues such as fat and muscle are well documented. Insulin-regulated events, however, occur in all cells. The utilization of glucose as a preferred energy source is a ubiquitous event in eukaryotic cells. In NIH-3T3 fibroblasts, insulin treatment increased levels of the cPKC and nPKC activator, diacylglycerol. Insulin-responsive 2-[(3)H]deoxyglucose uptake was stimulated in a dose-dependent manner. The overexpression of protein kinase C (PKC)betaI, -betaII, -delta, -epsilon, and -zeta was used to investigate the specificity of PKC isozymes for insulin-sensitive glucose uptake. The stable overexpression of PKCbetaII, -delta, and -epsilon resulted in increases in insulin-stimulated 2-[(3)H]deoxyglucose uptake compared to vector control cells, while basal 2-deoxyglucose uptake levels were not elevated. Overexpression of PKCbetaI and PKCzeta isozymes had no further effect on basal or insulin-stimulated 2-deoxyglucose uptake. The PKC-specific inhibitor, CGP41251, blocked insulin effects on 2-deoxyglucose uptake but not its effects on tyrosine phosphorylation of cellular substrates. Insulin-stimulated 3-O-methylglucose uptake was also greater in cells overexpressing PKCbetaII, -delta, and -epsilon, compared to control cells. The increased responsiveness was not accompanied by conversion of 3T3 cells to the adipocyte phenotype or the increased expression of insulin receptors or glucose transporters (GLUT1-type). Insulin-stimulated recruitment of GLUT1 to plasma membranes of cells overexpressing PKCbetaII, -delta, and -epsilon, was greater than that in control cells. The data suggest that more than one PKC isozyme is involved in insulin signaling pathways in fibroblasts, resulting in increased GLUT1 transporter recruitment to cell membranes.

3-O-Methylglucose↗