Biomedical subjects

M G Thomas

Publications and source records attributed to M G Thomas.

At least 19 recordsLinked to original sources

PubMed2006

Validation of commercial DNA tests for quantitative beef quality traits.

Associations between 3 commercially available genetic marker panels (GeneSTAR Quality Grade, GeneSTAR Tenderness, and Igenity Tender-GENE) and quantitative beef traits were validated by the US National Beef Cattle Evaluation Consortium. Validation was interpreted to be the independent confirmation of the associations between genetic tests and phenotypes, as claimed by the commercial genotyping companies. Validation of the quality grade test (GeneSTAR Quality Grade) was carried out on 400 Charolais x Angus crossbred cattle, and validation of the tenderness tests (GeneSTAR Tenderness and Igenity Tender-GENE) was carried out on over 1,000 Bos taurus and Bos indicus cattle. The GeneSTAR Quality Grade marker panel is composed of 2 markers (TG5, a SNP upstream from the start of the first exon of thyroglobulin, and QG2, an anonymous SNP) and is being marketed as a test associated with marbling and quality grade. In this validation study, the genotype results from this test were not associated with marbling score; however, the association of substituting favorable alleles of the marker panel with increased quality grade (percentage of cattle grading Choice or Prime) approached significance (P < or = 0.06), mainly due to the effect of 1 of the 2 markers. The GeneSTAR Tenderness and Igenity TenderGENE marker panels are being marketed as tests associated with meat tenderness, as assessed by Warner-Bratzler shear force. These marker panels share 2 common mu-calpain SNP, but each has a different calpastatin SNP. In both panels, there were highly significant (P < 0.001) associations of the calpastatin marker and the mu-calpain haplotype with tenderness. The genotypic effects of the 2 tenderness panels were similar to each other, with a 1 kg difference in Warner-Bratzler shear force being observed between the most and least tender genotypes. Unbiased and independent validation studies are important to help build confidence in marker technology and also as a potential source of data required to enable the integration of marker data into genetic evaluations. As DNA tests associated with more beef production traits enter the marketplace, it will become increasingly important, and likely more difficult, to find independent populations with suitable phenotypes for validation studies.

Alleles↗

PubMed2006

Evaluation of DNA polymorphisms involving growth hormone relative to growth and carcass characteristics in Brahman steers.

Associations of DNA polymorphisms in growth hormone (GH) relative to growth and carcass characteristics in growing Brahman steers (N = 324 from 68 sires) were evaluated. Polymorphisms were an Msp-I RFLP and a leucine/valine SNP in the GH gene as well as a Hinf-I RFLP and a histidine/arginine SNP in transcriptional regulators of the GH gene, Pit-1 and Prop-1. Genotypic frequencies of the GH SNP, Pit-1 RFLP, and Prop-1 SNP were greater than 88% for one of the bi-allelic homozygous genotypes. Genotypic frequencies for the GH Msp-I RFLP genotypes were more evenly distributed with frequencies of 0.43, 0.42, and 0.15 for the genotypes of +/+, +/-, and -/-, respectively. Mixed model analyses of growth and carcass traits with genotype and contemporary group serving as fixed effects and sire fitted as a random effect suggested that sire was a significant source of variation (P < 0.05) in average daily gain, carcass yield, and marbling score. However, measures of growth and carcass traits were similar across GH Msp-I genotypes as steers were slaughtered when fat thickness was estimated to be approximately 1.0 cm. These polymorphisms within the GH gene and/or its transcriptional regulators do not appear to be informative predictors of growth and carcass characteristics in Brahman steers. This is partly due to the high level of homozygosity of genotypes. These findings do not eliminate the potential importance of these polymorphisms as predictors of growth and carcass traits in Bos taurus or Bos taurus x Bos indicus composite cattle.

Amino Acids, Essential↗

PubMed2006

The routine use of intra-operative ultrasound in patients with colorectal cancer improves the detection of hepatic metastases.

INTRODUCTION: Up to one fifth of patients with carcinoma of the colon have occult liver metastases at the time of presentation. Intra-operative hepatic ultrasonography might improve disease staging. We report the use of intra-operative ultrasonography (IOUS) in routine clinical practice over a five-year period. METHOD: Seventy-six patients with colorectal carcinoma (F 21, M 55) of median age 67 years (range 43-89 years) for whom full data were available had IOUS at the time of colonic resection. All patients had had a computerized tomography (CT), magnetic resonance imaging (MRI) or ultrasonography (USS). RESULTS: Of 76 patients, 10 had a Dukes A, 32 had a Dukes B and 34 a Dukes C carcinoma. In 20 patients IOUS detected lesions not seen on pre-operative scanning including 11 metastases (one suitable for resection), seven benign hepatic cysts and two were benign hepatic nodules. Forty-nine patients have remained free of disease and 25 have died with systemic disease (mean survival 10 months, range 2-24 months). In the seven patients diagnosed as having hepatic cysts at IOUS two have died of systemic disease. The remaining patients (n=12) who died with systemic disease had a negative IOUS. CONCLUSION: IOUS increases diagnostic yield but a significant proportion of patients with occult hepatic metastases are not detected. IOUS improves disease staging in some patients refining the indications for adjuvant therapy and enhancing the estimate of prognosis and improving decision-making.

Adult↗

PubMed2006

Population structure in the Mediterranean basin: a Y chromosome perspective.

The Mediterranean region has been characterised by a number of pre-historical and historical demographic events whose legacy on the current genetic landscape is still a matter of debate. In order to investigate the degree of population structure across the Mediterranean, we have investigated Y chromosome variation in a large dataset of Mediterranean populations, 11 of which are first described here. Our analyses identify four main clusters in the Mediterranean that can be labelled as North Africa, Arab, Central-East and West Mediterranean. In particular, Near Eastern samples tend to separate according to the presence of Arab Y chromosome lineages, suggesting that the Arab expansion played a major role in shaping the current genetic structuring within the Fertile Crescent.

Chromosomes, Human, Y↗

PubMed2005

Multiple display of a protein domain on a bacterial polymeric scaffold.

The multiple display of protein domains on polymeric scaffolds is an emerging technology for many applications. BLS is a highly immunogenic protein that has an oligomeric structure formed by a 17.2 kDa subunit arranged as a dimer of pentamers. Here we describe the production as well as the structural, functional, and immunological properties of a 9 kDa double-stranded RNA-binding domain (RBD3) fused to the structure of BLS. We demonstrate that the BLS and RBD3 modules are stably and independently folded in the structure of the chimera and form a decameric structure of 255 kDa as the native BLS oligomers. The polymeric display of RBD3 in the structure of BLS increases the dsRNA binding strength of this domain both in vitro and in vivo, and also enhances its immunogenicity to the point that it breaks the tolerance of mice to the RBD3 self-antigen. Our results underscore the BLS display strategy as a powerful tool for biotechnological and therapeutic applications.

Animals↗

PubMed2005

The phylogenetic position of the 'giant deer' Megaloceros giganteus.

The giant deer, or 'Irish elk', has featured extensively in debates on adaptation, sexual selection, and extinction. Its huge antlers--the largest of any deer species, living or extinct--formed a focus of much past work. Yet the phylogenetic position of the giant deer has remained an enigma. On the basis of its flattened antlers, the species was previously regarded as closely related to the living fallow deer. Recent morphological studies, however, have challenged that view and placed the giant deer closer to the living red deer or wapiti. Here we present a new phylogenetic analysis encompassing morphological and DNA sequence evidence, and find that both sets of data independently support a sister-group relationship of giant and fallow deer. Our results include the successful extraction and sequencing of DNA from this extinct species, and highlight the value of a joint molecular and morphological approach.

Animals↗

PubMed2005

Single-fiber electromyography correlates more closely with incontinence scores than pudendal nerve terminal motor latency.

BACKGROUND: The investigation of fecal incontinence is important in deciding the most appropriate treatment. The presence of neuropathy has been shown to affect surgical outcomes adversely. Latency studies are of dubious value in assessing neuropathy; needle electromyography is the gold standard test. The relationship between these two tests and the symptoms of fecal incontinence has not been studied. METHOD: A cohort of 57 patients underwent neurologic and symptom assessment using latency studies, concentric and single-fiber electromyography, and symptom assessment using the Cleveland Clinic Scoring System. RESULTS: There was a significant correlation between left mean fiber density and Cleveland Clinic Scoring (correlation: 0.32, P = 0.02) but not between right or left latency studies. CONCLUSION: Single-fiber electromyography gave relevant results that could be obtained easily on modern equipment. Latency values were not reliable.

Adult↗

PubMed2005

Cannula-associated Staphylococcus aureus bacteraemia: outcome in relation to treatment.

BACKGROUND: Despite the frequency of cannula-associated Staphylococcus aureus bacteraemia (CASAB) there is uncertainty regarding the duration of treatment required. AIM: To determine the relationship between the duration and type of treatment for CASAB and subsequent relapse with deep-seated S. aureus infection. METHODS: We prospectively studied 276 patients with CASAB. Patients were followed for at least 8 weeks after completion of antibiotic treatment. Initial and subsequent isolates of S. aureus were compared using molecular methods to determine strain similarity. RESULTS: Initial mortality was 9% (26 of 276) and a complicating focus of infection presented during initial treatment in 6% (15 of 250) of the survivors. There were nine relapses of deep-seated infection from the strain causing the original infection. Relapses were equally common following peripheral CASAB and central CASAB. There was no relationship between the duration of treatment and the rate of relapse of deep-seated infection (P = 0.24). This observation held true regardless of whether the duration of treatment was analysed as < or = 7 versus > or = 8, < or =10 versus > or =11, or < or=14 versus > or =15 days (P = 0.62, 0.87 and 0.16, respectively). CONCLUSION: Episodes of peripheral CASAB pose an equal risk of relapse to central cannula-related episodes. Although further studies are needed to determine the optimal treatment of CASAB, our study strongly suggests that more than 14 days treatment is excessive for most patients who respond promptly to cannula removal and antibiotic treatment.

Adolescent↗

PubMed2005

The role of colonoscopic endoanal ultrasound scanning (EUS) in selecting patients suitable for resection by transanal endoscopic microsurgery (TEM).

OBJECTIVE: This study was performed to assess the accuracy of colonoscopic endoanal ultrasound scanning (EUS) in the selection of patients with rectal neoplasia suitable for local excision by transanal endoscopic microsurgery (TEM). Our policy is to offer TEM to patients with premalignant (T0) lesions or with T1 tumours that have early disease. PATIENTS AND METHODS: Data were collected prospectively on all patients undergoing EUS for the assessment of rectal neoplasia at our institution over a six-year period. A colonoscopic EUS probe was used to determine whether the tumour breached the muscularis propria (the interface between T1 and T2 disease). Subsequently patients underwent surgical resection, including TEM for those with T0/1 disease. The preoperative stage predicted by EUS (uT stage) was compared to the postoperative histopathological stage of the resected specimens (pT stage). RESULTS: One hundred and fifty-six EUS examinations were evaluated. Sixty-two patients went on to have TEM whilst the remaining 94 had another form of surgery. Of the 62 patients undergoing TEM, 3 were overstaged on EUS. No patients were understaged, giving an accuracy of 95%. Of the 94 patients undergoing an alternative procedure, 5 were overstaged on EUS as having T2 tumours when in fact their histology was T1. Accuracy of EUS at predicting more advanced disease fell to 89%, giving an overall accuracy of 92%. CONCLUSIONS: EUS is accurate at predicting T0/1 vs T2 disease in our institution, and we believe that it is a useful modality in assessing patient suitability for local excision.

Adult↗

PubMed2005

Fast-track barium enema: meeting the two-week wait rule for patients with suspected colorectal cancer.

OBJECTIVES: To meet the introduction of the two-week wait (TWW) rule for patients with suspected colorectal cancer, a fast-track barium enema (FTBE) service was set up. This study was conducted to evaluate the success of this approach in preparation for meeting the forthcoming targets on waiting times to treatment from referral and diagnosis. METHODS: All patients were offered a double-contrast barium enema within two-weeks, except those with a palpable rectal mass. FTBE were double-reported by specialist gastrointestinal radiologists. Patients with a suspected malignancy were booked for an urgent staging CT and outpatient appointment, whilst the remaining patients were referred back to their general practitioner with a report. Prospective data were collected and two 16-month periods analysed. RESULTS: Three hundred and nine patients had a FTBE over the first 16-month period and 277 (89.6%) were seen within two-weeks. Mean times from initial referral to staging CT and first outpatient appointment were 30.7 and 36.0 days, respectively. Cancer was confirmed histologically in 32 (10.4%) patients. Of 267 patients without a malignancy, 46 (17.2%) were referred back to the colorectal outpatient or endoscopy service within 6-months. The number of referrals increased with time from a mean of 19.3 per month in the first period to 27.8 in the second, but the percentage with a suspected malignancy remained similar at 13.6% and 10.1%, respectively. CONCLUSION: FTBE diagnosed malignancy accurately and facilitated rapid staging. The TWW target was met in almost 90% of patients, whilst the impact on the colorectal outpatient and endoscopy service was minimized.

Aged↗

PubMed2005

Pulmonary staging in colorectal cancer--is computerised tomography the answer?

INTRODUCTION: Pulmonary staging in colorectal cancer (CRC) has traditionally been carried out by means of plain chest radiograph (CXR), although computerised tomography (CT) imaging of the chest is increasingly being performed for this purpose. The aim of this study was to assess the value of pre-operative thoracic CT for pulmonary staging in CRC. PATIENTS AND METHODS: Data were collected prospectively on all patients referred into hospital over a 20-month study period for double contrast barium enema evaluation of symptoms suggestive of an underlying CRC. Patients with a CRC went on to have a staging intravenous, contrast-enhanced CT of the chest, abdomen and pelvis prior to an out-patient appointment with a colorectal surgeon. The CXRs of those patients in whom a radiological abnormality was seen on thoracic CT were reviewed blindly by an independent consultant radiologist. RESULTS: A total of 403 barium enemas were performed, of which 38 demonstrated a CRC (9%). In those patients diagnosed with CRC, nine (24%) had an abnormality on thoracic CT. Four patients with positive thoracic CTs had chemotherapy and or radiotherapy with no surgery. One patient underwent colectomy, and 2 patients who had primary lung tumours as opposed to metastases also underwent colectomies. One patient received palliative care only. In addition, one of the patients underwent multiple, non-diagnostic thoracic investigations prior to a diagnosis of sarcoidosis being made and then proceeding to surgery. An independent consultant radiologist reviewed seven out of the nine CXRs of patients with an abnormality on thoracic CT without knowledge of the clinical diagnosis, and reported three of the CXRs to be normal. CONCLUSIONS: Thoracic CT appears to improve the accuracy of pulmonary staging in CRC allowing a more appropriate level of intervention. However, CT is likely to identify more benign radiological abnormalities than CXR alone, and investigations should not occur to the detriment of treating the primary tumour.

Aged↗

PubMed2004

Effect of increasing levels of undegradable intake protein on metabolic and endocrine factors in estrous cycling beef heifers.

To determine the influence of three levels of undegradable intake protein (UIP) supplementation on metabolic and endocrine factors that influence reproduction, 23 yearling crossbred heifers (body condition score = 4.5 +/- 0.5; initial BW = 362 +/- 12 kg) were stratified by BW and assigned randomly to one of three supplements: 1) low UIP (1,135 g x heifer(-1) x d(-1); 30% CP, 115 g UIP, n = 7); 2) mid UIP (1,135 g x heifer(-1) x d(-1); 38% CP, 216 g UIP, n = 8); or 3) high UIP (1,135 g x heifer(-1) x d(-1); 46% CP, 321 g UIP, n = 8). Heifers were estrually synchronized before initiation of supplementation. Supplement was individually fed daily for 30 to 32 d, at which time heifers were slaughtered (d 12 to 14 of the estrous cycle) and tissues collected. Heifers were fed a basal diet of sudan grass hay (6.0% CP) ad libitum. On d 28 of supplementation (d 10 of the estrous cycle), no differences were observed (P > 0.10) in serum insulin or IGF-I among treatments. At slaughter (d 10 to 12 of the estrous cycle), treatments did not influence corpus luteum weight, cerebral spinal fluid leptin, or IGFBP; serum estradiol-17beta, progesterone, leptin, IGF-I, and IGFBP; or anterior pituitary content of IGFBP (P > 0.10). Follicular fluid IGFBP-2 and IGFBP-4 were greater in high-UIP heifers than low- or mid-UIP heifers on d 12 to 14 of the estrous cycle (P < 0.05). Basal serum LH concentrations and LH area under the curve (every 15 min for 240 min) did not differ (P > 0.10) following 28 d of supplementation (d 10 of the estrous cycle); however, basal serum FSH concentrations were greater (P = 0.06) in low- and mid- vs. high-UIP heifers (5.2 and 5.2 vs. 4.6 ng/mL, respectively), and FSH area under the curve was greater (P = 0.03) in low- vs. high-UIP heifers. At slaughter (d 12 to 14 of the estrous cycle), anterior pituitary LH and FSH content and steady-state mRNA encoding alpha, LHbeta, and GnRH receptor did not differ (P > 0.10) among treatments. However, FSHbeta mRNA was increased approximately twofold (P = 0.03) in mid vs. low UIP. In summary, low and mid levels of UIP supplements fed to estrous cycling beef heifers seemed to enhance pituitary expression and/or secretion of FSH relative to high levels of UIP. Moreover, high-UIP supplementation was associated with increased low-molecular-weight IGFBP compared with supplementation of low and mid levels of UIP. These data suggest that differing levels of UIP supplementation may alter pituitary and ovarian function, thereby influencing reproductive performance in beef heifers.

Animal Nutritional Physiological Phenomena↗

PubMed2003

Effect of neuropeptide Y on GnRH-induced LH release from bovine anterior pituitary cell cultures derived from heifers in a follicular, luteal or ovariectomized state.

Objectives were to determine if neuropeptide Y (NPY) had direct effects GnRH induced secretion of LH from the anterior pituitary gland, and if endogenous steroids modulated the effect of NPY. To accomplish these objectives, 15 Hereford heifers were assigned to one of three ovarian status groups: follicular, luteal, or ovariectomized. One animal from each of the three ovarian status groups was slaughtered on each of 5 days and anterior pituitary gland harvested. Anterior pituitary gland cells within ovarian status were equally distributed and randomly assigned to one of three cell culture treatments: no NPY or GnRH (control), 10 nM GnRH, or 100 nM NPY+10 nM GnRH. Anterior pituitary cell cultures were incubated with or without NPY for 4 h and further incubated for an additional 2 h with or without GnRH and supernatant collected for quantification of LH. Treatment of anterior pituitary cell cultures with GnRH or GnRH+NPY did not affect LH release in cultures obtained from follicular (S.E.=5%; P=0.58) or ovariectomized (S.E.=7%; P=0.22) heifers. Both GnRH and GnRH+NPY increased LH release from anterior pituitary cell cultures from heifers in the luteal phase (S.E.=14%; P < or = 0.05) compared to control cultures. Cultures from luteal phase heifers treated with GnRH did not differ from those treated with GnRH+NPY (P=0.34). These data provide evidence to suggest that effects of NPY on LH release may occur primarily at the level of the hypothalamus.

Animals↗

PubMed2003

Comparison of ultrasound and manometric sphincter length and incontinence scores.

PURPOSE: Fecal incontinence can be assessed by a wide variety of means that vary in their clinical relevance. This study assesses the correlation between two methods of recording sphincter length and incontinence scores. METHODS: A retrospective review of results from 1999 to 2001 of 137 patients with fecal incontinence was undertaken on patients who had both ultrasound and manometric assessment. Incontinence scores, ultrasonic sphincter length, and manometrically derived sphincter length were recorded. The data were analyzed using the Spearman rank correlation coefficient (r(s)) for nonparametric data. RESULTS: There was negative correlation between incontinence scores and manometric sphincter length (r(s) = -0.27; P = 0.002) but not with ultrasonic length (r(s) = -0.08; P = 0.38). There was correlation between manometric and ultrasonic lengths (r(s) = 0.21; P = 0.02). In males, all three correlated but none of the values were significant (n = 12). Internal and external sphincter defects had no effect on correlation coefficients. CONCLUSION: Given that all measurements include a degree of subjectivity, manometry more closely correlates with the fecal incontinence scores than ultrasound measurements. There seems to be little benefit in measuring the sphincter length with ultrasound. Manometric sphincter length measurement seems to have a role in assessing patients with fecal incontinence.

Anal Canal↗

PubMed2003

Luteinizing hormone and growth hormone secretion in ewes infused intracerebroventricularly with neuropeptide Y.

Neuropeptide Y (NPY) provides an important hypothalamic link between nutritional status and neuroendocrine mechanisms regulating growth and reproduction. The objective of the following series of experiments was to determine the effects of single or continuous administration of NPY on secretion of luteinizing hormone (LH) and (or) growth hormone (GH). In experiment 1, four ovariectomized (OVX) ewes and four OVX + estrogen-treated ewes each received, in a 4 x 4 Latin Square arrangement of treatments, a single injection of 0, 0.5, 5, or 50 microg NPY via an intracerebroventricular (i.c.v.) cannulae to determine the effects on secretion of GH. NPY significantly elevated serum GH at the 50 microg dose regardless of estrogen exposure (P = 0.003). In experiment 2, eight OVX ewes were infused i.c.v. with NPY or saline (n = 4/trmt) continuously for 20 h in a linearly increasing dose, ending at 50 microg/h NPY. Blood samples were collected via jugular cannulae every 10 min during hour -4-0 (interval 1, pre-treatment), hour 6-10 (interval 2) and hour 16-20 (interval 3) relative to the initiation of infusion (0 h). Mean LH and LH pulse frequency were lower in NPY- versus saline-infused ewes during intervals 2 and 3 (P < 0.01), but NPY had no discernable effect on serum GH (P > 0.10). In experiment 3, four OVX ewes were continuously infused with NPY as in experiment 2, except that the maximum 50 microg/h dose was achieved after only 10 h of infusion. Blood samples were collected every 10 min, beginning 4 h before and continuing until 4h after the NPY infusion. Mean serum LH changed significantly over time (P = 0.0001), decreasing below pre-treatment levels by hour 3 of NPY infusion (P < 0.01), and returning to pre-treatment concentrations following the end of infusion (P > 0.15). Serum GH also changed significantly over time (P < 0.001). Mean GH levels tended to be greater than pre-treatment levels by hour 2 of infusion (P < 0.08), but thereafter returned to basal levels. Serum GH also increased following the end of NPY infusion (P < 0.03). From these data we conclude that NPY exerts a persistent inhibitory effect on secretion of LH, and may stimulate the secretion of GH during the initiation and cessation of infusion of NPY. These observations support a role for NPY in mediating the effects of undernutrition on both LH and GH, and also provide evidence for potential mechanisms by which leptin, acting through NPY, may stimulate the secretion of GH.

Animals↗

PubMed2003

Body composition, leptin, and the leptin receptor and their relationship to the growth hormone (GH) axis in growing wethers treated with zeranol.

Age-related changes in body composition, leptin, and hypothalamic-pituitary expression of the leptin receptor and associative relationships of these factors to constituents of the growth hormone (GH) axis were evaluated. Seventy wethers were randomly assigned at birth to one of four treatment groups: control; treatment 1 implanted with the estrogenic compound zeranol (12 mg, Ralgro on days 0, 45, and 90; treatment 2 received zeranol on days 45 and 90; and treatment 3 received zeranol on day 90. Serum and tissues were collected from wethers (n > or = 5) from each group on days 28, 73, 118, and 135. Percent body fat and leptin increased linearly (P < 0.01) with age, but were not influenced (P > or = 0.14) by zeranol. The leptin receptor in the pituitary appeared to be differentially (P = 0.097) expressed across days 73-135, but no differences (P > or = 0.43) were detected in expression of this receptor in the hypothalamus among treatments and ages. Leptin and % body fat were negatively correlated (r > or = -0.52, P < 0.05) to mRNA levels of factors involved in pituitary synthesis and secretion of GH. Serum leptin increased with age as did percent body fat, but zeranol did not influence body composition, serum leptin, or expression of the leptin receptor in the hypothalamus or pituitary; however, the leptin receptor appeared to be differentially expressed among the hypothalamus and pituitary with level of body fat and leptin being inversely associated to transcriptional-factors involved in somatotrope synthesis and secretion of GH.

Adipose Tissue↗

PubMed2003

Role of the IGF-II receptor in mediating acute, non-genomic effects of retinoids and IGF-II on keratinocyte cell death.

In this study, we have examined the effects of retinoic acid (RA) on the human immortalized keratinocyte cell line (HaCaT). A significant twofold (P < 0.01) increase in apoptotic cell death compared with the control was found within 24 h of treatment with 10-5 M of RA. Apoptosis was confirmed by flow cytometry. Cycloheximide did not inhibit this acute RA-induced apoptosis. Interestingly, insulin-like growth factor-II (IGF-II, 50 ng/ml) was able to significantly (67.3%; P < 0.05) reduce RA effects, whereas IGF-I (50 ng/ml) and insulin (75 ng/ml) were without effect. Furthermore, analogues of IGF-II [leu27 IGF-II and Des(1-6) IGF-II], with altered affinities for the IGF-I receptor and IGF-binding proteins (IGFBPs), but retained affinities for the IGF-II receptor, also completely inhibited (100%; P < 0.01) RA-induced apoptosis, while an IGF-I receptor antagonist did not reduce the survival effects of IGF-II. Insulin pretreatment negates the survival effect of IGF-II. In contrast, mannose 6 phosphate (M6P) did not alter RA or IGF-II actions. These results indicate that rapid induction of cell death by RA is independent of production or secretion of new proteins. The inhibition of RA action by IGF-II was independent of its ability to signal through the IGF-I receptor or to interact with IGFBPs.

Apoptosis↗

PubMed2003

An analysis of consanguinity and social structure within the UK Asian population using microsatellite data.

We analysed microsatellite genotypes sampled from the Pakistani and Indian communities in Nottingham, UK, to investigate the genetic consequences of substructuring mediated by traditional marriage customs. The application of a recently developed likelihood approach identified significant levels of population substructure within the Pakistani community as a whole, as well as within the finer divisions of castes and biradheri. In addition, high levels of cryptic or unacknowledged consanguinity were detected within subgroups of this community, including biradheri. The Indian sample showed no significant evidence of either substructure or consanguinity. We demonstrate that estimates of disease gene frequencies can be inaccurate unless they are made jointly with estimates of population substructure and consanguinity ((theta congruent to FST) and C). The magnitude of these estimates also highlights the importance of accounting for the finer scale of social structuring when making decisions regarding the risk of recessive disorders in offspring.

Analysis of Variance↗