Biomedical subjects

T Ansari

Publications and source records attributed to T Ansari.

At least 19 recordsLinked to original sources

PubMed2006

Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction.

OBJECTIVE: To evaluate placental morphology in pregnancies complicated by early- and late-onset pre-eclampsia (PET) with and without fetal growth restriction (FGR) using stereological techniques. DESIGN: A total of 69 pregnant women were studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by both PET and FUR; the remaining 16 were from gestational-age-matched controls. Each group was further classified into early onset (<34 weeks) and late onsets (>34 weeks) based on gestational ages. SETTING: NPIMR at Northwick Park and St Marks Hospital. POPULATION: placentae from pregnant women. METHODS: Formalin-fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained with haematoxylin. MAIN OUTCOME MEASURES: Volumes, surface areas, lengths, diameters and shape factors of the villous tissues and fetal vasculature in the intermediate and terminal villi of all the groups studied. RESULTS: Terminal villi volume and surface area were compromised in early-onset PET cases, late-onset PET had no impact on peripheral villi or vasculature features. The morphology of the vascular and villous subcomponents in the intermediate and terminal villi was significantly influenced by late-onset FGR, whereas early-onset FGR caused a reduction in placental weight. Length estimates were not influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was significantly reduced in late-onset FGR. CONCLUSIONS: Isolated early-onset PET was associated with abnormal placental morphology, but placentas from late-onset PET were morphologically similar to placentas from gestational-age-matched controls, confirming the existence of two subsets of this condition and supporting the hypothesis that late-onset PET is a maternal disorder and not a placental disease.

Adult↗

PubMed2006

Prolonged maintenance of neointestine using subcutaneously implanted tubular scaffolds in a rat model.

Tissue-engineered small intestine offers a possible alternative to long-term parenteral nutrition or intestinal transplantation in patients with short bowel syndrome. The aim of this study was to investigate the prolonged development of neointestine grown on subcutaneously implanted scaffolds. Tubular polylactide-coglycolide (PLGA) scaffolds were implanted into adult Lewis rats. Four weeks after scaffold implantation, a suspension of organoid units was delivered to the lumen of each scaffold. Organoid units were manufactured from small intestine harvested from neonatal Lewis rats by partial digestion using collagenase and dispase. Scaffolds were removed at 4, 8, and 12 weeks after organoid unit implantation, processed to paraffin, and sectioned. Hematoxylin and eosin staining demonstrated well-developed and well-differentiated intestinal mucosa and a vascularised submucosa within the scaffolds at 4, 8, and 12 weeks. Appearances were similar to native small intestine. Immunohistochemistry performed using primary antibody against proliferating cell nuclear antigen, a marker for cellular proliferation, demonstrated positively staining cells within the mucosa and submucosa at all time points. In the mucosal layer these positively staining cells were found primarily in the crypts. These findings show that neointestinal mucosa can be maintained for at least 12 weeks on a subcutaneous PLGA scaffold, and the presence of actively proliferating cells at 12 weeks suggests potential for further development beyond this.

Animals↗

PubMed2005

Reviewing the use of carbon monoxide-releasing molecules (CO-RMs) in biology: implications in endotoxin-mediated vascular dysfunction.

The inducible stress protein heme oxygenase-1 (HO-1) has been linked to tissue and organ protection against the deleterious actions of many pathological conditions, including endotoxin challenge. Similar protection can be achieved by the main products of heme oxygenase activity, namely bilirubin and carbon monoxide (CO). Since the identification of novel chemical compounds that liberate CO in biological systems (CO-releasing molecules or CO-RMs), our group and others have had access to a convenient and simple pharmacological tool that enables to study the role of CO in physiological functions. This article will review the scientific literature published to date on CO-RMs, with emphasis on the in vitro, ex vivo and in vivo experimental models employed to determine the contribution of CO to cellular mechanisms. In addition, we will report on the effect of heme oxygenase-related substances, such as bilirubin, CORM-3 and hemin, in a model of endotoxin-induced hypotension. Among the three different approaches examined, CORM-3 proved the most effective agent in reducing the fall in blood pressure caused by endotoxin. Furthermore, heme oxygenase-related substances affected the endotoxin-stimulated induction and distribution of hepatic HO-1 and inducible nitric oxide synthase (iNOS). Thus, it emerges that CO-RMs could exert important biological actions in the context of endotoxic-mediated dysfunction.

Animals↗

PubMed2005

Pre-eclampsia and fetal growth restriction: how morphometrically different is the placenta?

Both pre-eclampsia (PET) and fetal growth restriction (FGR) pose a heavy burden on fetal and maternal health and may disrupt pregnancy outcome. Using design based stereological techniques, placental vascular and villous morphology were assessed to determine the individual role played by both PET and FGR on placental growth during the third trimester. The following placentas delivered between 25 and 41 weeks of gestation were included into the study; controls (n=16), PET (n=20), FGR (n=17) and PET-FGR (n=16). Each placenta was uniformly randomly sampled and the sampled tissue processed to paraffin. Sections were stained with a CD34 antibody and the following morphometric parameters estimated: volumes, surface areas, length, diameters and the shape factor of the villous (terminal and intermediate) and vascular placental features. For stereologically estimated parameters pure PET had an effect on IVS and terminal villi volume only. FGR alone or when coexisting with PET contributed towards significant reductions in volumetric and surface area terminal villous and vascular features. FGR factors also contributed towards a significant reduction in the lengths of all parameters estimated and in the terminal villi diameter. Additionally, FGR was associated with a significant difference in shape factor indices for both intermediate and terminal villi. This study has shown that PET on its own has limited influence on the placental morphology studied, since the vascular features estimated do not differ stereologically from age matched normal controls. However, placental morphology is different between PET and PET-FGR and between PET-FGR and FGR. PET and FGR may have a cumulative effect on placental villous and vascular morphology as seen in the PET-FGR but there is no synergistic effect. These morphological abnormalities may have major physiological implications in terms of placental function and fetal growth.

Adult↗

PubMed2004

Analyses of the potential oxygen transfer capability in placentae from infants succumbing to sudden infant death syndrome.

BACKGROUND: Morphometric oxygen diffusive conductance (Dp) was estimated to assess the potential efficiency of oxygen transfer across the materno-fetal interface in placentae obtained from victims of sudden infant death syndrome (SIDS). STUDY DESIGN: SIDS placentae were retrieved from archived storage and classified into normal birth weight (NBW, n=16), or small for gestational age (SGA, n=9) and compared against control placentae (n=40) or SGA (n=24) placentae. A combination of stereological techniques and physiological constants were used to estimate total Dp. RESULTS: SIDS NBW cases showed a crucial reduction in fetal capillary surface area when compared with control placentae. SIDS SGA showed a number of deficiencies in basic volumetric and surface area parameters. Values for total and specific Dp in placentae in both SIDS groups were maintained at levels comparable with control and SGA cases, respectively. CONCLUSION: Since more reductions were observed in SIDS SGA group, this suggests that factors responsible for these reductions maybe associated with SGA rather than being SIDS-specific factors.

Adult↗

PubMed2003

Morphometric assessment of the oxygen diffusion conductance in placentae from pregnancies complicated by intra-uterine growth restriction.

The morphometric oxygen diffusive conductance (D(p)) of the placenta provides a measure of the efficiency of oxygen transfer between the mother and the developing fetus. Any change in the D(p)may point towards possible adaptation in the light of altered oxygen transfer. Placentae from normal (n=40) and small for gestational age SGA (n=24) pregnancies were analysed using stereological techniques. Each placenta was uniform randomly sampled and tissue samples processed to wax infiltration and embedding using conventional histological preparatory methods. A combination of stereological techniques and physiological constants were used to estimate the partial conductances across the five major tissue compartments involved in oxygen transfer. There was a significant reduction in both fetal birthweight and placental weight in the SGA group when compared with controls. A decrease in both chorionic (S(cv)) and fetal capillary (S(fc)) surface area was also observed in SGA placentae when compared with controls (P>0.001). Villous membrane harmonic thickness (T(vm)) was reduced in the SGA placentae (2.33 microm) when compared with controls (2.67 microm P=0.019). This resulted in a reduction in the minimum D(p)in SGA placentae when compared with controls (P=0.023). Adjusting for fetal weight resulted in no difference in the specific diffusive conductance. Changes in T(vm)in SGA placentae combined with changes in basic surface areas were insufficient to maintain overall D(p)values comparable with control placentae.

Adaptation, Physiological↗

PubMed2003

Elastase-induced changes in lung function: relationship to morphometry and effect of drugs.

Intratracheal administration of porcine pancreatic elastase (PPE) produced a dose related decline in lung function, as assessed by changes in dynamic lung compliance (C(dyn)) in New Zealand White rabbits. This occurred within 24 h of administration and persisted for 56 days (n=6). These lung function changes were accompanied by histological evidence of emphysema in the lungs and were not mimicked by intratracheal administration of the proteolytic enzyme trypsin. Neither the lung function nor the histological changes induced by elastase could be prevented or reversed by either the glucocorticosteroid, dexamethasone, or all trans retinoic acid (ATRA).Our data suggest that local administration of elastase to the lungs of rabbits may provide a convenient way to assess the effects of drugs on the changes induced by elastase in airways.

Animals↗

PubMed2003

Variation of CD8+ T-lymphocytes around the bronchial internal perimeter in chronic bronchitis.

The variation of CD8+ cells has been determined around the internal perimeter of intrapulmonary bronchi in smokers with chronic bronchitis (CB), and the amount of tissue required to confidently estimate the true mean has been calculated. Lung specimens were obtained from 10 smokers with CB. Paraffin sections of intrapulmonary bronchi were immunostained and CD8+ cells counted in the epithelium and subepithelium in up to 10 sequential 1-mm segments around the internal perimeter of each airway. The percentage of counts falling between +/-20% of the final mean was 43.0% for epithelium and 40.9% for subepithelium. In 90% of subjects, the cumulative mean was stable after examination of subepithelial tissue associated with 5 mm of reticular basement membrane. There is considerable variation in the counts of CD8+ cells between adjacent 1-mm airway mucosal segments in chronic bronchitis. In order to achieve a representative count and to maximise statistical power to detect differences between study populations, subepithelial tissue including a minimum of 5 mm of reticular basement membrane length should be examined.

Aged↗

PubMed2002

Quantitative neuropathological analysis of sudden infant death syndrome.

Detailed stereological analyses of specific regions of brains of children who had died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether global evidence of an underlying pathology exists, contributing to an increased susceptibility to SIDS. A significant reduction in the total number of neocortical neurones and neurone volume was observed in SIDS normal birth weight (NBW) infants in comparison to controls. A significant reduction in both volume and total neurone number were also noted in the dorsal motor nucleus of the vagus in SIDS NBW group when compared with controls. Anomalies in regions of the brain involved with cardiorespiratory control (brainstem) and arousal (brainstem and neocortex) may play a crucial role in the chain of events resulting in a SIDS event.

Brain Stem↗

PubMed2002

Prevalence and associated impairments of mild mental retardation in six- to ten-year old children in Pakistan: a prospective study.

UNLABELLED: The aim of this study was to find the prevalence of mild mental retardation (MMR) in 6-10-y-old children in a prospectively followed cohort in Pakistan from four areas with different socioeconomic conditions. Retarded children were identified by a two-step method, comprising a household screening with the Ten Questions Screening in 649 families followed by clinical investigation and psychometric testing (WISC-R and Griffiths) of the 132 children found by the screening. The overall prevalence of MMR among 6-10-y-old children was 6.2%. The distribution of MMR was uneven, with 1.2% among children from the upper-middle class, 4.8% in the village, 6.1% in the urban slum and 10.5% in the poor periurban slum area. Additional impairments were found in 75% of the children with MMR, of which speech impairment was the most common. CONCLUSION: The prevalence of MMR was found to be higher in a developing country than in developed countries. It also seemed to be related to poor socioeconomic conditions, as the prevalence in the upper-middle class was comparable to figures from developed countries, while the prevalence in children from poor population groups was much higher.

Child↗

PubMed2001

Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells.

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV(1)% of predicted of 43-77% and FEV(1)/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA(+) cells. The highest number of IL-4 mRNA(+) cells were in the submucosal glands of the CB group with normal lung function (216/mm(2)), significantly higher than the values in either the AS (63/mm(2)) or the CB+COPD (87/mm(2)) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA(+) cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8(+) and IL-4 or IL-5 mRNA(+) cells. Of 1328 IL-4(+) and 1404 CD8(+) cells counted none was double labeled. Of 727 IL-5(+) and 1569 CD8(+) cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-alpha(+) cells were also CD8(+) and 15% of CD8(+) cells were TNF-alpha positive. Thus, cells other than the CD8(+) phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.

Aged↗

PubMed2001

Estimation of mean nuclear volume of neocortical neurons in sudden infant death syndrome cases using the nucleator estimator technique.

At present, no information is available with regards to either neocortical neuronal mean nuclear volume or maturation (functional or morphological) in abnormal paediatric brains. Using the nucleator estimator technique, the mean neocortical nuclear volume was estimated in sudden infant death syndrome (SIDS) cases [10 normal birth weight (NBW) and 10 low birth weight (LBW) cases classified by birth weight for gestational age] and compared to 10 NBW control cases. Both the control and SIDS LBW cases showed an increase in mean nuclear volume with age; the SIDS NBW cases showed no increase. At 8 months, the SIDS NBW cases showed a reduced mean nuclear volume (p = 0.02) when compared to controls. The SIDS LBW cases showed no statistically significant difference (p = 0.10) when compared with controls. A deficiency in mean neuronal nuclear volume may represent a deficiency in neuronal function.

Birth Weight↗

PubMed2001

Organogenesis of lung and kidney in Thoroughbreds and ponies.

Equine lung and kidney organogenesis has not previously been examined with the use of unbiased stereological techniques. The present study examined healthy (control) pony and Thoroughbred lungs and kidneys to establish baseline data of organ development from before birth until maturity at age 3-18 years. Whole left lungs and kidneys were collected from 45 equine postmortem examinations (34 Thoroughbred, 11 pony). Stereological techniques were used to estimate whole kidney, cortex and medulla volume, total glomerular number and volume-weighted mean glomerular volume, lung volume, total terminal bronchiolar duct ending number and total gas exchange surface area. Lungs were demonstrated to be more developed at birth in ponies compared with Thoroughbreds. Thoroughbreds showed continued lung development after birth, a unique micromorphogenic postnatal development. Kidneys were developed equally in ponies and Thoroughbreds. This study has provided data on the baseline development of the equiune lung and kidney which can be used in further studies to examine whether the development of these organs is affected by specific illnesses.

Animals↗

PubMed1999

Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis: a quantitative study of open lung biopsies.

Differences in the inflammatory response and prognosis of cryptogenic fibrosing alveolitis (CFA) and that associated with systemic sclerosis (FASSc) are beginning to emerge. It is hypothesized that these differences may be reflected in a distinct pattern of T-helper (Th)-1 and Th-2-type cytokines. Open lung biopsies were obtained from clinically well-documented cases of CFA and FASSc and, as a control, compared with grossly and histologically normal parenchyma obtained from smokers whose lungs were resected for cancer (n=5 in each group). In situ hybridization (ISH) was applied to the samples using anti-sense and sense 35S-labelled riboprobes to detect messenger ribonucleic acid (mRNA) for interleukins (IL)-2, IL-4, IL-5 and interferon (IFN)-gamma. Between 52-91% of cells expressing the cytokines studied were present in the alveolar interstitium rather than in lumenal cells or the alveolar epithelial lining. The highest values for all four cytokines were present in the patients with FASSc, i.e., 22-39 ISH positive cells x mm(-2) alveolar tissue compared with 1-19 cells x mm(-2) and 4-5 cell x mm(-2) in CFA and control subjects, respectively. Whereas the proportions of the four cytokines in FASSc were similar to the control subjects, IL-4 and IL-5 predominated significantly in CFA (p<0.001). For example, the ratio of IL-5 to IFN-gamma was 22:1 in CFA, significantly higher than in the cases with FASSc (2:1) or the control subjects (4:1) (p<0.05). In conclusion, cryptogenic fibrosing alveolitis is an inflammatory condition which is characterized, like asthma, by a predominance of gene expression for T-helper-2-type regulatory cytokines, whereas cryptogenic fibrosing alveolitis associated with systemic sclerosis appears to have a distinct mixed T-helper-1/T-helper-2 functional phenotype and a greater number of cells expressing each of these pro-inflammatory cytokines.

Adult↗

PubMed1999

Allergen-induced eosinophil cytolysis is a primary mechanism for granule protein release in human upper airways.

Cytotoxic eosinophil granule proteins are considered important in the pathogenesis of allergic airway diseases such as rhinitis and asthma. To explore the cellular mechanisms behind eosinophil granule release in human allergic airways, 16 symptom-free patients with seasonal allergic rhinitis were challenged daily with allergen during 1 wk. Nasal lavage samples and biopsies, obtained before and 24 h after the last allergen exposure, were processed for immunohistochemical and electron microscopic analysis. The allergen challenges produced nasal symptoms, marked tissue eosinophilia, and an increase in lavage fluid levels of eosinophil cationic protein (ECP). The nasal mucosa areas with intense extracellular immunoreactivity for ECP were associated with abundant free eosinophil granules. Electron microscopy confirmed the free granules and revealed that all mucosal eosinophils were involved in granule release, either by cytolysis (33%) or piecemeal degranulation (PMD) (67%). Resting or apoptotic eosinophils were not observed. Cytolytic eosinophils had less signs of intracellular granule release (p < 0. 001) and a higher content of intact granules (p < 0.001) compared with viable eosinophils in the same tissue. This study demonstrates eosinophil cytolysis (ECL) as a distinct mechanism for granule mediator release in human allergic airway mucosa. The nature and extent of the ECL and its product (i.e., protein-laden extracellular granules) indicate that allergen-induced cytolysis is a primary and major mechanism for the release of eosinophil proteins in human allergic airway inflammation in vivo.

Adolescent↗

PubMed1999

Shipboard impact of a probable Norwalk virus outbreak from coastal Japan.

Norwalk virus has been implicated in shipboard diarrheal disease outbreaks throughout Asia. A large outbreak of suspected Norwalk virus was investigated on a U.S. Naval aircraft carrier following the clinical recognition of 450 cases of gastroenteritis over a 2-week period (September 14-28, 1997) during coastal exercises. A random sampling of 44 cases from 450 personnel who sought medical attention was compared with 19 controls. Junior enlisted sailors and marines comprised 97% of all cases. There was no evidence of shipboard geographic clustering of cases. Furthermore, no single food type was associated with illness on the basis of comparative analysis (cases versus controls). Principal case signs and symptoms reported included watery stools (89%), nausea (82%), and vomiting (77%). Anecdotal reports indicated > 50% of the cases received rehydration therapy. An absence of fever was also noted in 32% of the cases and only 5% had blood in their stools. The mean duration of illness was 37 hr, with a range of 3-96 hr. Laboratory findings based on reverse transcription-polymerase chain reaction and Southern hybridization methods showed that 21 (72%) of 29 patients had evidence of the UK2 prototype of the Norwalk virus. A cross-sectional study of 131 crew members from the ships population (n = 4,200) showed an attack rate of 44%. Attack rate is a variant of an incident rate applied to a narrowly defined population observed for a limited period of time, such as during an outbreak. The numerator is people who get sick and the denominator is people (population) at risk. An extrapolation of these findings suggests as many as 1,806 sailors may have been affected during the outbreak, of which only 26% (of the 57 outbreak related cases) where identified from sick call records. There was no difference in the mean ages between outbreak and non-outbreak affected crewmen, or geographic clustering based on berthing or work spaces. Outbreak-related cases reported signs and symptoms of watery-stools (79%), nausea (65%), and vomiting (47%). The mean duration of illness was 28 hr, ranging from 2 to 96 hr. Thirty-one percent of outbreak affected cases reported a sick call visit. Loss of work was reported by 39% of the outbreak affected population. This report documents the epidemic potential of Norwalk virus and the associated impact on fleet operational readiness. Additionally, that this outbreak occurred against a background of 3 other consecutive gastroenteritis outbreaks onboard the same ship (March 1997, February/March 1998, and June 1998), all sharing the same clinical and epidemiologic profiles, suggests possible shipboard persistence of Norwalk virus over time, despite periodic ship-wide disinfection efforts.

Adult↗

PubMed1998

Management of undiagnosed persistent pleural effusions.

Difficult to diagnose pleural effusions are not uncommonly encountered in clinical practice. We define these effusions as those that remain undiagnosed after initial thoracentesis and repeat thoracentesis with pleural biopsy. Tuberculosis and malignancy are often found to be the underlying causes when a diagnosis is ultimately made, but other causes, including pulmonary embolism and intra-abdominal conditions, need to be considered as potential causes of the difficult to diagnose effusions. In selected cases, presumptive treatment of tuberculosis is indicated whereas in others, a decision must be made either to obtain a definitive diagnosis by invasive surgical procedures or to follow the patient with careful observation and watchful waiting.

Biopsy, Needle↗

PubMed1998

Priming and induction of eosinophil trafficking in guinea-pig cutaneous inflammation by tumour necrosis factor alpha.

Tissue eosinophilia is a hallmark of allergic and parasitic diseases. Priming mechanisms may play an important role in mediating the process of eosinophil accumulation in these conditions. We have previously shown that blockade of tumour necrosis factor alpha (TNFalpha) inhibited the capacity of lipopolysaccharide to prime skin sites for chemoattractant-induced eosinophil recruitment. The present study was carried out to investigate the capacity of TNFalpha to prime an inflammatory site for enhanced eosinophil accumulation. Initial experiments investigated the capacity of TNFalpha itself to induce eosinophil accumulation. Intradermal injection of murine TNFalpha (10-300 ng per site) in the guinea-pig induced significant accumulation of 111In-eosinophils. Kinetic studies showed the response to be delayed in onset and inhibited by cycloheximide, consistent with a dependency on protein synthesis. Trafficking of 111In-eosinophils to sites treated for 2 h with TNFalpha (10-100 ng per site) was inhibited by monoclonal antibodies (mAbs) against beta2 or alpha4 integrins. Intradermal injection of a low dose (3 ng) of TNFalpha (which by itself had no significant effect on eosinophil trafficking) prior to chemoattractants or antigen in sensitized skin sites, induced significant priming of eosinophil accumulation. Recruitment of both 111In-eosinophils and endogenous eosinophils was enhanced. Trafficking to TNFalpha-primed responses was dependent on protein synthesis and beta2 integrins. In contrast, the alpha4 integrin mAb failed to inhibit the TNFalpha primed response. Thus, TNFalpha can induce and also prime eosinophil recruitment in guinea-pig skin. Our results provide further evidence that this cytokine may be an important mediator of allergic- or parasite-induced eosinophilic inflammation.

Animals↗