Biomedical subjects
D Hughes
Publications and source records attributed to D Hughes.
Confirmation and refinement of the localisation of the c-MEL locus on chromosome 19 by physical and genetic mapping.
The human gene locus c-MEL was identified following transfection of genomic DNA from the human melanoma cell line NK14; it has previously been assigned to chromosome 19 (p13.2-q13.2) by analysis of somatic cell hybrids. We have further refined the position of this gene to the proximal region of 19p (cen-p13.2), using cell hybrids containing only fragments of human chromosome 19. We have confirmed this physical localisation by linkage analysis with a recently described restriction fragment length polymorphism for the c-MEL gene, and mapped the locus within the region of the low density lipoprotein receptor gene (LDLR) (Lod 4.43, theta = 0.10) and the anonymous marker D19S11 (13.1.25) (Lod 9.33, theta = 0). This gene thus maps to a region of chromosome 19 involved in karyotypic abnormalities in a variety of malignancies including melanomas and leukaemias.
Osseous repair with Le Fort I osteotomy.
The effectiveness of rigid and semirigid fixation at various distances between Le Fort I osteotomy segments after different healing periods was evaluated in 16 Macaca fasicularis monkeys. The histologic findings revealed better healing with semirigid fixation.
Magnetic resonance imaging of the knee.
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Papillary and follicular thyroid carcinomas show a different pattern of ras oncogene mutation.
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Paper and people: the work of the casualty reception clerk.
This paper examines the exercise of discretion by casualty reception staff, focussing on the problems of accountability that arise when their judgements help shape the process of patient categorization that culminates in clinical diagnosis. Rules and guidelines which ostensibly relate to bureaucratic objectives, are applied in ways which reflect situational exigencies of reception work, and values embedded in organisational culture. But reception staff are reluctant to acknowledge the importance of their decisions, and, particularly where judgements relate to patient condition, present rule-use as a straightforward and certain activity in which interpretation plays little part.
An overview of maternal and infant health services in rural America.
Economically disadvantaged rural families, like their urban counterparts, face significant difficulties obtaining adequate maternity and infant health care resulting, in part, from an unequal distribution of resources as well as economic and racial barriers to health care nationwide. Rural women and infants must contend with additional access problems that reflect the inherent constraints of rural existence as well as specific state policies that exacerbate the barriers associated with isolation. This article provides an overview of the availability and accessibility of maternal and infant health services in nonmetropolitan America and identifies policy reforms to improve access to care.
Genetic characterization of frameshift suppressors with new decoding properties.
Suppressor mutants that cause ribosomes to shift reading frame at specific and new sequences are described. Suppressors for trpE91, the only known suppressible -1 frameshift mutant, have been isolated in Escherichia coli and in Salmonella typhimurium. E. coli hopR acts on trpE91 within the 9-base-pair sequence GGA GUG UGA, is dominant, and is located at min 52 on the chromosome. Its Salmonella homolog maps at an equivalent position and arises as a rarer class in that organism as compared with E. coli. The Salmonella suppressor, hopE, believed to be in a duplicate copy of the same gene, maps at min 17. The +1 suppressor, sufT, acts at the nonmonotonous sequence CCGU, is dominant, and maps at min 59 on the Salmonella chromosome.
Suppression of a -1 frameshift mutation by a recessive tRNA suppressor which causes doublet decoding.
sufS was found to suppress the only known suppressible-1 frameshift mutation, trpE91, at a site identified as GGA and mapped within the single gene of the only tRNA that can decode GGA in Escherichia coli. It mapped to the same gene in Salmonella typhimurium. sufS alleles were recessive, and dominant alleles could not be isolated. This is in contrast to all other tRNA structural gene mutations identified thus far that cause frameshift suppression. The recessiveness implies that all sufS alleles are poor competitors against their wild-type tRNA(Gly2) counterparts. The base G immediately 5' of the GGA suppression site influenced the level but was not critical for suppression by sufS601. From this result, it is inferred that sufS601 causes frameshifting by doublet decoding.
Bush's budget and the babies. Broken promises for health care.
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Immunohistology or conventional histology for the diagnosis of renal allograft rejection?
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Activated ras oncogenes in human thyroid cancers.
Human thyroid epithelial (follicular) cells give rise to two malignant tumors--"follicular" carcinomas, which metastasize almost exclusively via the bloodstream, and "papillary" carcinomas, which metastasize predominantly via lymphatics (Williams, E. D. In: W. Duncan (ed.), Recent Results in Cancer Research: Thyroid Cancer, pp. 47-55. Berlin: Springer-Verlag, 1980). We have investigated whether this contrast in biological behavior might be associated with different patterns of oncogene activation. DNA transfection analysis of five follicular and ten papillary cancers indeed showed a statistically significant difference in the pattern of genes responsible, activated ras oncogenes being found in 80% of follicular tumors but only 20% of papillary tumors. In addition, in follicular cancers we have found activation of all three ras oncogenes (H-ras, K-ras, and N-ras), the first time that this has been demonstrated in a primary human tumor type (as opposed to cell lines). We suggest therefore that ras activation may be an important determinant of metastatic capability in these epithelial cancers.
Depressive symptoms and depressive diagnoses in a community population. Use of a new procedure for analysis of psychiatric classification.
A multivariate classification technique was used to examine whether depressive symptoms and symptoms frequently associated with depressive disorders would cluster into recognizable syndromes that parallel traditional DSM-III psychiatric diagnoses. An analysis was made of all respondents in the Epidemiologic Catchment Area (ECA) project of the Piedmont region of North Carolina who reported suffering from depressive symptoms (n = 406) at the second wave of the ECA study. The analysis identified five profiles of symptoms that adequately described the interrelationships of the symptoms as reported in the population. One profile included a set of symptoms nearly identical to the symptoms associated with the DSM-III classification of major depression. Other depressive syndromes emerged and included a premenstrual syndrome among younger women and a mixed anxiety/depression syndrome. The existence of these other depressive syndromes may explain the present discrepancy in the epidemiologic literature between a high prevalence of depressive symptoms and a low prevalence of traditional depressive diagnoses in community populations.
Cytoarchitecture of the fetal murine soleus muscle.
The organogenesis of the soleus muscle of the 129 ReJ mouse (a mixed muscle, which in the adult contains approximately equal numbers of slow-twitch oxidative and fast-twitch oxidative-glycolytic myofibers) was studied in spaced, serial transverse, and longitudinal sections of muscles of 14-, 16-, and 18-day in utero and 1- and 5-day postnatal mice. A discrete soleus muscle was distinguished by 14 days in utero. It consisted of groups of closely apposed primary myotubes displaying junctional complexes and a pleomorphic population of mononucleated cells. Between 14 and 16 days in utero there was little de novo myotube formation. At 16 days in utero, basal lamina surrounded groups of primary myotubes; and primitive motor endplates were found on these myotubes. At 18 days in utero, the basal-lamina-enclosed groups of primary myotubes were no longer present. At this stage, basal lamina surrounded clusters (consisting of one primary myotube and one or more secondary myotubes) or independent myotubes (single myotubes surrounded by their own basal lamina). Cluster formation and cluster dispersal occurred concurrently, beginning at 18 days in utero and extending until birth. At birth, there was still a substantial population of immature, secondary myotubes that interdigitated with larger, more mature primary myofibers. At this stage, intermuscular axons had begun to myelinate, and postsynaptic specialization of the motor endplates had begun. Cluster dispersal and myonuclear migration was completed during the first 5 days postnatally with the muscle taking on adult characteristics. Beginning at 16 days in utero and extending into the neonatal period, there was evidence of myotube death in the soleus muscle.
Morphometric analysis of the developing mouse soleus muscle.
The pattern of organogenesis of the soleus muscle of the 129 ReJ mouse was evaluated quantitatively using spaced, serial, ultrathin sections and computer-assisted morphometric analysis. Muscles from 14-, 16-, and 18-day in utero mice and muscles of 1- and 5-day-old mice were analyzed to determine age-related alterations in the maximal girth and length of the muscle, number of myotubes, cluster frequency, and the lengths and diameters of myotubes. Primary myotubes are found in the muscle at 14 days in utero. There is little de novo myotube formation between 14 and 16 days in utero, this interval being principally one of primary myotube growth and maturation. The interval between 16 and 18 days in utero is marked by extensive secondary myotube formation, with more myotubes being formed during this period than in any period studied. Morphometric data support the hypothesis that secondary generation myotubes use primary myotubes as a scaffold on which they are formed. Morphometric data also confirm the hypothesis that cluster formation and cluster dispersal occur concurrently during the prenatal period. Secondary myotubes continue to form until birth. At birth, the soleus muscle contains the adult number of myofibers. The first 5 days postnatally are marked by myofiber growth and maturation.
A survey of referred patients experiencing problems with complete dentures.
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Activation of Ha-ras in human chronic granulocytic and chronic myelomonocytic leukaemia.
DNAs from chronic granulocytic leukaemia (CGL) and chronic myelomonocytic leukaemia (CMML) were assayed for transforming genes by transfection into NIH 3T3 cells. Foci DNA was tagged with a geneticin-resistance cosmid, then followed through a drug selection and tumorigenicity assay. Activated Ha-ras genes, with point mutations at codon 12 (glycine to valine) were subsequently detected. The mutation was detected in the original samples by either MspI/HpaII digestion or polymerase chain reaction (PCR). Although mutations in the ras gene family may occur frequently in leukaemias, these are the first examples of Ha-ras mutations in CGL (blast crisis) and CMML.
Changes in memory following general or spinal anaesthesia for hip arthroplasty.
Patients scheduled for hip arthroplasty were anaesthetised using either general or spinal anaesthesia. Each patient's memory was tested for both recall and recognition by using lists of 10 words each of a different category. This testing for memory extended from the pre-operative visit to one week after operation. Memory was not tested on the day of operation. There was little overall change of memory after either spinal or general anaesthesia although there was an inexplicable but significant decrease in the ability to recognize words after spinal anaesthesia.