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Biomedical subjects

J Hewitt

Publications and source records attributed to J Hewitt.

At least 73 records · Page 4Linked to original sources
PubMed1988

A highly polymorphic locus very tightly linked to the Huntington's disease gene.

The genetic defect in Huntington's disease (HD), an inherited neuropsychiatric disorder of unknown etiology, has not been defined. The discovery of linkage between HD and the DNA marker D4S10(G8) raised the possibility of isolating the disease gene on the basis of its chromosomal location, in addition to providing a limited presymptomatic test for the late onset disorder. But it has been difficult to isolate other DNA markers nearer to the HD gene, and this has hampered attempts to identify the disease locus and limited the applicability and accuracy of predictive testing. Recently, several new DNA markers from the region of the genome near the HD gene have been isolated using a directed cloning strategy. We describe here the characterization of one of these new markers, D4S95, a highly polymorphic locus which displays no recombination with the HD gene in the families tested. The high degree of polymorphism at this locus and its proximity to the HD gene make it extremely useful for predictive testing and as a new starting point for attempts to clone the disease gene.

Alleles↗
PubMed1988

Presymptomatic neuropsychological impairment in Huntington's disease.

Ten asymptomatic individuals at risk for Huntington's disease (HD) were determined by the use of linked DNA probes to have a high (HD+ group) or low (HD- group) probability of having inherited the mutant gene. Neuropsychological examination, performed without knowledge of DNA results, revealed impairments in five of seven subjects in the HD+ group. Abnormalities were related to visuospatial abilities or to functions associated with the frontal lobes. All three subjects in the HD- group showed no neuropsychological impairment. Statistical analyses confirmed differences between the HD+ and HD- groups. Affected parents of subjects were at least 12 years older at symptom onset. These results demonstrate that clear neuropsychological impairment may be present in HD even when overt signs and symptoms are not expected for a number of years.

Adult↗
PubMed1988

Sink Metabolism in Tomato Fruit : II. Phloem Unloading and Sugar Uptake.

Analysis of [(3)H]-(fructosyl)-sucrose translocation in tomato (Lycopersicon esculentum Mill.) indicates that phloem unloading in the fruit occurs, at least in part, to the apoplast followed by extracellular hydrolysis. Apoplastic sucrose, glucose, and fructose concentrations were estimated as 1 to 7, 12 to 49, and 8 to 63 millimolar, respectively in the tomato fruit pericarp tissue. Hexose concentrations were at least four-fold greater than sucrose at all developmental stages. Short-term uptake of [(14)C]sucrose, -glucose, and -fructose in tomato pericarp disks showed first order kinetics over the physiologically relevant concentration range. The uptake rate of [(14)C]-(glucosyl)-1'-fluorosucrose was identical to the rate of [(14)C]sucrose uptake, suggesting sucrose may be taken up directly without prior extracellular hydrolysis. Short-term uptake of all three sugars was insensitive to 10 micromolar carbonyl cyanide m-chlorophenylhydrazone and to 10 micromolar p-chloromercuribenzene sulfonic acid. However, long-term accumulation of glucose was sensitive to carbonyl cyanide m-chlorophenylhydrazone. Together these results suggest that although sucrose is at least partially hydrolyzed in the apoplast, sucrose may enter the metabolic carbohydrate pool directly. In addition, sugar uptake across the plasma membrane does not appear to be energy dependent, suggesting that sugar accumulation in the tomato fruit is driven by subsequent intracellular metabolism and/or active uptake at the tonoplast.

Journal Article↗
PubMed1988

A polymorphic DNA marker that represents a conserved expressed sequence in the region of the Huntington disease gene.

A polymorphic marker (D4S62) that is genetically closely linked to D4S10 and is in the region of the gene for Huntington disease is described. A four-allele polymorphism is detected when HincII-digested DNA is hybridized with D4S62. D4S62 maps, by Southern blot analysis using somatic-cell hybrids, to 4p16.1 closer to the centromere than does D4S10. The use of the polymorphisms detected by D4S62 increases the informativeness of markers close to the gene for Huntington disease and will be useful for preclinical diagnosis. D4S62 detects transcripts of approximately 6,000 nucleotides in rat, mouse, and monkey liver and brain. This represents the first demonstration of conserved expressed sequences close to the gene for Huntington disease.

Alleles↗
PubMed1987

First-trimester prenatal diagnosis for Huntington's disease with DNA probes.

Polymorphic DNA probes linked to the locus for Huntington disease (HD) were used for prenatal diagnosis of a 10-week fetus at 25% risk for the disease. The fetus proved to have a 48% risk of having inherited the HD mutation which was similar to that for the at-risk parent (50%). On this basis the parents elected to terminate the pregnancy. When appropriate family members are available and DNA studies are informative, prenatal diagnosis of HD with polymorphic DNA probes can determine the at-risk status of the fetus with 96% accuracy.

Adult↗
PubMed1987

Intravenous energy and amino acids in the preterm newborn infant: effects on metabolic rate and potential mechanisms of action.

The effects of intravenously administered amino acids and of varying amounts of energy on metabolic rate were studied and potential mechanisms examined in 19 healthy 4- to 6-day-old preterm (30 to 32 weeks gestation) infants. The infants were randomized to three groups. Group 1 (n = 6) received nonprotein energy 38 kcal/kg/d; group 2 (n = 5), 64 kcal/kg/d; and group 3 (n = 8), 64 kcal/kg/d plus 1 to 2 g/kg/d crystalline amino acids. Thirty-six hours after beginning the infusion, oxygen consumption (VO2) was measured by indirect calorimetry for 5 to 6 hours. Simultaneously, urine was collected for urinary norepinephrine excretion, which was determined using liquid chromatography with electrochemical detection. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were determined by radioimmunoassay. Group 1 had lower VO2 and urinary norepinephrine excretion than did groups 2 and 3, which did not differ. T4 and T3 were not different among the three groups. The demonstrated simultaneous changes in VO2 and norepinephrine excretion with varying energy intakes independent of age supports energy intake as a modulator of the sympathetic nervous system, which in turn controls metabolic rate. Moderate amounts of intravenously administered amino acids do not appear to play an active role in this process; nor do they alter T3 and T4 valves. When VO2 increased with increasing energy intake, T3 and T4 were unaffected, supporting a passive role for thyroid hormones in diet-induced thermogenesis.

Amino Acids↗
PubMed1987

The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease.

Twenty-three persons at risk for Huntington's disease (HD) have been studied using a polymorphic human linked DNA marker (D4S10) and positron emission tomography (PET). We determined the likelihood of inheritance of the gene for HD in 13 persons, using DNA polymorphism studies. Of these, eight persons had a greater than 90% probability of being presymptomatic heterozygotes for HD. Three of these eight subjects had caudate glucose utilization detected by PET that was more than 2 standard deviations (SD) below the age-matched control mean. Measurement of caudate glucose utilization in the other five presumed presymptomatic heterozygotes revealed results between 1 and 2 SD below the mean. Five persons had a less than 10% likelihood of having inherited the abnormal gene for HD. Of these, four had normal rates of glucose utilization in the caudate nuclei. However, one individual with DNA results indicating a low risk of developing HD had abnormally low measures of caudate glucose utilization. This suggests that a recombination had occurred between the linked marker and the gene in this person. These studies suggest that PET studies of caudate glucose utilization may help to confirm results of DNA studies in some persons, and may provide an opportunity to detect when DNA results may be incorrect due to recombination.

Brain↗
PubMed1987

DNA polymorphisms in and around the Apo-A1-CIII genes and genetic hyperlipidemias.

We have studied the frequency of DNA polymorphisms in and around the apolipoprotein A-1 (Apo-A1) and apolipoprotein CIII (Apo-CIII) gene loci in 53 persons of Caucasian descent with genetic hyperlipidemias. Three restriction-fragment-length polymorphisms (RFLPs) have previously been located 5' and 3' to the Apo-A1 gene and in the Apo-CIII gene and were detected after digestion with XmnI, PstI, and SstI, respectively, and hybridization with a 2.2-kb fragment of the Apo-A1 gene. These RFLPs are in linkage equilibrium. The rare variant sites for XmnI (X2) and SstI (S2) were more frequent in familial combined hyperlipidemia (FCH) than in controls and persons with other genetic hyperlipidemias. When considered as a haplotype, this difference was significant (P less than .03). The findings in this study suggest that the previously reported association between S2 and hypertriglyceridemia may be accounted for, in part, by inclusion of numerous patients with FCH. Our data provide further evidence that these RFLPs around and within the Apo-A1/Apo-CIII genes do not participate in unmasking clinical expression in persons with familial dysbetalipoproteinemia.

Adult↗
PubMed1987

Preconceptional sex selection.

The desire to control the sex of our offspring prior to conception has been present throughout man's history. In recent years the application of a more scientific approach to the problem has resulted in techniques capable of providing interested couples with an 80% chance of having either a boy or a girl according to their wishes. The medical, ethical, economic and sociological implications of these advances will require close attention in future years.

Diet↗
PubMed1986

Defective interhemispheric integration and anomalous language lateralization in children at risk for schizophrenia.

The present study was carried out to determine whether children at risk for schizophrenia might exhibit abnormalities in test performance indicative of defective interhemispheric integration and abnormal specialization of language function. Twenty-two high-risk and 22 matched normal children were administered two independent tests of speech comprehension, delivered under monaural and binaural listening conditions, and a standard verbal dichotic listening test. On both comprehension tests the high-risk children exhibited significantly poorer binaural, relative to monaural, recall. On the verbal dichotic test the normal group exhibited a significant right ear advantage whereas for the high-risk group there was no significant difference between right and left ear recall. These results were taken to indicate abnormalities of both interhemispheric integration and language specialization in the high-risk group. Analyses indicate that these two abnormalities may be related in a specific fashion. The implications of these results are discussed within a developmental framework.

Adolescent↗
PubMed1986

Histologic criteria for lichen sclerosus of the vulva.

Although lichen sclerosus was first described almost a century ago, a grading system was not devised, and the minimal histologic criteria required for diagnosis were not defined. The present study was based on the sequential sectioning of nine vulvectomy specimens removed for invasive carcinoma. Both epidermal and dermal changes were noted, but only the dermal ones were unique to the disease. Early changes included subtle densification of the basement membrane as well as hyalinization of the papillary dermis and superficial capillaries. Based on these findings, a grading system was developed.

Epithelium↗
PubMed1986

Subregional assignment of the linked marker G8 (D4S10) for Huntington disease to chromosome 4p16.1-16.3.

The linked DNA marker for Huntington disease has recently been mapped to the short arm of chromosome 4 by somatic cell hybridization studies. Southern blot analysis of DNA from patients with Wolf-Hirschhorn syndrome (WHS) has suggested that the linked marker maps within the terminal 4p16 band. We have now accomplished subregional assignment of G8 (D4S10) to 4p16.1-16.3 using in situ hybridization techniques on two patients with nonoverlapping interstitial deletions of 4p. The mapping of G8 (D4S10) to a region deleted in patients with WHS will allow the application of new strategies for detecting DNA sequences closer to the locus for Huntington disease.

Chromosome Banding↗
PubMed1986

Serum lipid response to oat product intake with a fat-modified diet.

Healthy adult volunteers (no. = 208), men and women aged 30 to 65 years, participated in a 12-week study on dietary fat modification plus oat product ingestion (60 gm/day) to test whether moderate daily intake of oat bran and oatmeal enhanced serum lipid response. During weeks 0 to 6, all participants followed the American Heart Association fat-modified eating style. At 6 weeks, participants were randomly assigned to one of three groups. All participants continued to follow the fat-modified eating pattern; groups 1 and 2 were asked during weeks 7 to 12 to consume two servings of either oat bran or oatmeal per day, for a total of 60 gm/day isocalorically substituted for other carbohydrates. Group 3 ingested no oat products. At baseline, the group mean cholesterol level was 208.4 mg/dl. After 6 weeks of dietary fat intervention, the level was 197.6--a fall of 10.8 mg/dl (5.2%). At 12 weeks, the mean serum cholesterol level fell further, by 5.6, 6.5, and 1.2 mg/dl for groups 1, 2, and 3, respectively. Group mean weight loss was small--1.9 lb during the first 6 weeks and 0.6 to 0.8 for the three groups during weeks 7 to 12. Reported oat product ingestion was 39 and 35 gm per person per day, respectively, for groups 1 and 2 (2.2 and 1.4 servings per person per day, respectively). Dietary fat composition remained similar among the three groups during weeks 7 to 12. Pooled results indicated that the addition of oat products at a moderate and practical level enhanced serum lipid response (p less than .05) to a fat-modified eating pattern among free-living adults.

Adult↗