PubMed Health⌕ Search

Biomedical subjects

D Hinds

Publications and source records attributed to D Hinds.

At least 19 recordsLinked to original sources
PubMed1999

Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.

Chromosomal region 15q11-q13 has been implicated to harbor a susceptibility gene or genes underlying autism. Evidence has been derived from the existence of cytogenetic anomalies in this region associated with autism, and the report of linkage in a modest collection of multiplex families. Most recently, linkage disequilibrium with the marker GABRB3-155CA2 in the candidate locus GABRB3, located in this region, has been reported. We searched for linkage using eight microsatellite markers located in this region of chromosome 15 in 147 affected sib-pairs from 139 multiplex autism families. We also tested for linkage disequilibrium in the same set of families with the same markers. We found no evidence for excess allele sharing (linkage) for the markers in this region. Also, we found no evidence of linkage disequilibrium, including for the locus GABRB3-155CA2. Thus, it appears that the role of this region of chromosome 15 is minor, at best, in the majority of individuals with autism.

Adolescent↗
PubMed1999

Sib-pair analysis of the collaborative study on the genetics of alcoholism data set.

Nonparametric sib-pair analysis was performed on the Collaborative Study on the Genetics of Alcoholism data set. Concordant and discordant pair groups were examined using the ASPEX package of programs. Allele sharing and multipoint lod scores for six comparison groups were obtained. Sharing and lod score patterns were not consistent with a simple genetic interpretation.

Alcoholism↗
PubMed1999

Exclusion of linkage to the HLA region in ninety multiplex sibships with autism.

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.

Adolescent↗
PubMed1999

A genomic screen of autism: evidence for a multilocus etiology.

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

Adolescent↗
PubMed1996

A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

Chromosomes, Human, Pair 2↗
PubMed1996

A full genome search in multiple sclerosis.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

Chromosome Mapping↗
PubMed1996

Attitudes of patients to medical student participation: general practice consultations on the Cambridge Community-Based Clinical Course.

The clinical medical students on the Cambridge Community-Based Clinical Course (CCBCC) derive part of their training by taking part in consultations between patients and their general practitioners. Patients' attitudes to this arrangement and their support for student training in a general practice setting are an important factor in the development of community-based education. A postal questionnaire seeking information from patients achieved an 84% response rate. Both the numerical results and the patients' comments are presented. Patients proved generally supportive of the community-based course and some identified positive benefits to themselves from this provision. The large majority of patients did not mind the presence of medical students during consultations, although there are some areas in which patients are less willing to involve students.

Attitude↗
PubMed1995

Long-term community-based attachments: the Cambridge course.

This paper reports on the establishment of the Cambridge Community-based Clinical Course and places on record details of the organization, goals and teaching arrangements of the course. It also identifies the main questions which are being addressed in the course and which must be answered before it will be clear whether such attachments are generally viable.

Community Medicine↗
PubMed1994

Corticotropin-releasing factor mRNA increases in the inferior olivary complex during harmaline-induced tremor.

This study reports that corticotropin-releasing factor (CRF) expression within the inferior olivary complex (IOC) of the cat is increased 8 h after administration of the tremor-inducing beta-carboline harmaline. Following harmaline treatment, hybridization of an oligodeoxynucleotide complementary to CRF mRNA increased significantly in the dorsal accessory olive, subnuclei A and C of the medial accessory olive and the dorsal cap of Kooy, a subnucleus thought previously to be unresponsive physiologically to harmaline. At this early time point, greater increases in CRF mRNA hybridization were present in the caudal than the rostral IOC. These results support published reports that harmaline-mediated effects are more profound within the caudal than the rostral IOC, but also suggest that harmaline mediates cellular responses in inferior olivary neurons which are not related to activation of rhythmic firing.

Animals↗
PubMed1986

Ultrastructural analysis of major basement membrane types in rhesus monkey Macaca mulatta acellular renal cortex.

Increasing interest in animal models of human nephropathies have led to a number of renal studies in nonhuman primates. In the current investigation, sequential detergent extraction of cellular elements was carried out on renal cortical tissue blocks from rhesus monkey in an effort to demonstrate clearly the morphological features of major basement membrane (BM) types and their associated extracellular matrix (ECM). LM and TEM views of acellular tissue blocks demonstrate planar arrangements of ECM components, while SEM studies provide striking three-dimensional images of their surface characteristics. All major BM types maintain their in vivo histoarchitectures despite the absence of cells. We propose that the intrinsic structural rigidity of tubular (TBM), Bowman's capsule (BCBM) and peritubular capillary BM (PTCBM) may be related to to their close external association with collagenous fibrils, while glomerular BM (GBM) may be internally supported by a network of mesangial matrix (MM) plates and trabeculae which extend onto internal surfaces of peripheral GBM loops. Thicknesses of rhesus monkey renal BMs show that they are similar to those seen in the laboratory rat and, in general, BCBM greater than TBM greater than GBM greater than PTCBM. We conclude that rhesus monkey renal BMs closely resemble those described by us in the human [J. Ultrastruct. Res. 82: 96-110, 1983] and that this species offers an attractive model for studies of renal diseases of BM origin-notably diabetes mellitus.

Animals↗
PubMed1984

Characterization of the Descemet's membrane/posterior collagenous layer isolated from Fuchs' endothelial dystrophy corneas.

The combined Descemet's membrane (DM) and posterior collagenous layer (PCL) of Fuchs' endothelial dystrophy corneas were isolated and characterized by biochemical and immunofluorescence methods. The amino acid composition of the Fuchs' DM-PCL was similar to age-matched normal Descemet's membranes (DM). As determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 125I two-dimensional peptide mapping, normal DM and Fuchs' DM-PCL contained the same collagen types [type IV and endothelial cell (EC) collagen], but a slight discrepancy was seen in the electrophoretic mobility of some collagen chains. Immunofluorescence staining localized fibrinogen/fibrin to Fuchs' DM-PCL but not to normal DM. These data suggest that the appearance of 110 nm banded material in sheets and fusiform bundles characteristic of Fuchs' PCL is not due to the presence of a new (abnormal) collagen type but may represent altered assembly of collagen molecules, and that the fibrinolytic system may play a role in the degenerative process of Fuchs' endothelial dystrophy.

Amino Acids↗
PubMed1983

A topographical (SEM) analysis of acellular glomerular mesangial matrix in situ.

Normal kidneys from human and New Zealand white rabbits were made acellular by vascular perfusion with detergents. Cortical regions were dissociated from the central renal mass and further minced to 2 mm3 and fixed for TEM and SEM analyses. In an effort to visualize the internal histoarchitecture of glomerular basement membranes (GBM) and associated mesangial matrix (MM), some of the fixed samples were cryofractured prior to preparation for SEM observations. By this technique, the in situ MM exhibits a lacy network of fenestrated plates (septa) that separate and support peripheral glomerular channels. It seems possible that these structures may be intrinsically rigid and that their shape-preserving properties may be transmitted to the entire GBM. The matrix is not restricted to centrolobular zones, but extends throughout the glomerulus via a loose inner (endothelial-mesangial) layer of GBM. This filamentous layer is similar to MM in texture and surface characteristics and is often thrown into folds or trabeculae. In contrast, the outer (epithelial) surface of GBMs is more compact and smoothly contoured. Our SEM and correlative TEM studies indicate that the inner layer is continuous with MM septa distally and extends proximally to the glomerular vascular pole via arteriolar BMs where it reaches the extraglomerular interstitium. This establishes an extracellular morphological pathway from centrolobular zones to the polar cushion.

Animals↗
PubMed1983

Effect of hypothermic perfusion on corneal endothelial morphology.

The effect of moderate in-vivo hypothermic perfusion on corneal endothelial integrity was studied in the cat. Eleven cats underwent in-vivo anterior chamber perfusion for 30 minutes with either normothermic (23 degrees C) or hypothermic (5 degrees C) perfusate. Corneas were then evaluated clinically (biomicroscopy), functionally (vital staining), and morphologically (scanning electron microscopy) for changes attributable to hypothermic perfusion. All 3 modes of evaluation suggested no difference in corneal endothelial integrity under the 2 experimental perfusion conditions. At the clinical and scanning electron microscope levels hypothermic perfusion does not show any effects on the corneal endothelium. Regional hypothermia is of theoretical and potential utility in procedures involving prolonged intraocular perfusion.

Animals↗
PubMed1981

Propionibacterium acnes infection following subdural tap.

The case of an infant who had subdural hematomas that became infected with Propionibacterium acnes is reported. This is the second reported case of intracranial Propionibacterium acnes infection resulting from diagnostic or therapeutic manipulation.

Bacterial Infections↗
PubMed1981

Morphological studies on 'adherent cells' in bone marrow cultures from humans, dogs, and mice.

Comparative morphological studies were conducted on adherent cells in bone marrow cultures obtained from humans, dogs, and mice. Scanning electron micrographs demonstrated that the adherent colonies are much more homogeneous in humans and dogs and appear larger and more flattened than in mice. In mice, many more rounded cells (macrophages) were seen intermixed with the flattened cells. Transmission electron microscopy demonstrated that the flattened type of cells are characterized by a large primitive nucleus and abundant cytoplasm exhibiting an extensive network of microtubules and submembranous microfilaments and the formation of endoplasmic reticulum-associated secretory bodies. Our results would favor a fibroblastic rather than epithelial nature of the flattened cell type.

Animals↗