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M Hoff

Publications and source records attributed to M Hoff.

At least 55 records · Page 3Linked to original sources
PubMed1994

Schizophrenia and glutamate receptor genes.

Nine multiplex schizophrenia families were genotyped with polymorphisms for the GLUR5 and NMDAR1 glutamate receptor subunit genes. Using the lod score technique, evidence of linkage was not found assuming either dominant or recessive transmission. Similarly, the non-parametric sib pair test did not yield significant evidence of linkage.

Genetic Linkage↗
PubMed1994

Analysis of GABAA receptor subunit genes in multiplex pedigrees with manic depression.

The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of manic depression. Tests of this hypothesis can now be carried out due to the recent characterization of simple sequence repeat polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1, beta 3 and gamma 2 subunit genes. Using both parametric and non-parametric methods, we tested for linkage between manic depression and these polymorphisms in six multi-generational pedigrees. No evidence of linkage was found.

Adolescent↗
PubMed1994

Linkage analysis between schizophrenia and a microsatellite polymorphism for the D5 dopamine receptor gene.

Using 23 multiplex pedigrees we tested for linkage between schizophrenia and a microsatellite polymorphism for the D5 dopamine receptor gene (DRD5). Assuming autosomal dominant inheritance and a maximum penetrance of 0.6, an overall lod score of -4.54 was derived at 0% recombination. For recessive transmission the summary lod score was -8.37 at 0% recombination. These data suggest that mutations of the D5 dopamine receptor gene are unlikely to be of major etiological importance in the pathogeneses of schizophrenia in the families studied. However, our study does not exclude the D5 dopamine receptor gene as a candidate gene for schizophrenia because some of our families were not informative for linkage and because of the likelihood of genetic heterogeneity.

Adolescent↗
PubMed1993

Use of a neurophysiological trait in linkage analysis of schizophrenia.

Traditional diagnostic techniques may not provide all the information necessary to reveal the genetic causes of schizophrenia through linkage analysis. Use of neurophysiological indicator variables that are associated with the disease may increase the probability of detecting linkage. Such variables not only produce simpler phenotypes for analysis, but they also may be more proximal to the gene products involved in neurological dysfunctions underlying schizophrenia. We have used a previously characterized neurophysiological variable, the P50 evoked-auditory response, to search for chromosomal regions that may be of interest in the study of schizophrenia. Although our scan of over 300 markers did not show strong evidence for linkage to P50 in nine families, this exploratory analysis has revealed several chromosomal regions that may deserve further study.

Adolescent↗
PubMed1993

C to T nucleotide substitution in codon 713 of amyloid precursor protein gene not found in 86 unrelated schizophrenics from multiplex families.

Jones et al. Nature Genet 1:306-309, [1992] recently detected a C to T nucleotide transition (codon 713) in a highly conserved region of the beta-amyloid precursor gene in a single case of schizophrenia. Although the sequence variant may be a natural polymorphism, it is crucial to determine whether the mutation might be present in a small subset of schizophrenics. We isolated DNA from 86 unrelated chronic schizophrenics who had a first degree relative with chronic schizophrenia or chronic schizoaffective disorder. After PCR amplification of exon 17, we were unable to detect the presence of the codon 713 variant in these schizophrenic cases, as well as in 156 controls. Unless additional cases are found with the codon 713 mutation, it is unlikely that the sequence variant is pathogenic for schizophrenia.

Amyloid beta-Protein Precursor↗
PubMed1993

An evaluation of clinical follow-up in women with early stage breast cancer among physician members of the American Society of Clinical Oncology.

Routine clinical follow-up for distant metastatic disease among women with early stage breast cancer is of uncertain clinical benefit. In order to evaluate current practice patterns, we administered a mailed survey to a stratified random sample of physician members of the American Society of Clinical Oncology (ASCO) (N = 435). The survey assessed the frequency and motivation for ordering follow-up medical tests in asymptomatic postmenopausal women with stage I or II breast cancer. The response rate was 55%, distributed as 39% radiation oncologists, 32% medical oncologists, and 29% surgeons. In the first year after treatment, physicians performed, on average, one physical examination every 3 months, one blood panel (CBC, alkaline phosphatase and liver function tests) every 4 months, and one chest radiograph every 9 months. In addition, 38% of the respondents ordered CEA and 21% ordered CA 15-3 levels, 28% ordered bone scans, and less than 4% ordered CT scans, bone surveys, or bone marrow biopsies in the first year after treatment. A logistic regression analysis controlling for physician age, gender, sub-specialty, practice type, years of experience, number of breast cancer patients treated annually, geographic region, and community size, showed that surgeons were less likely to order blood tests (p < 0.001) and tumor markers (p < 0.0029) than medical oncologists in years 3 and 5 of follow-up. Compared to physicians practicing in the northeast, those from the midwest were less likely to order chest radiographs in year 3 of follow-up (p = 0.0028). Other provider characteristics had no significant effect on test ordering behavior. The results of this survey suggest that relatively uniform practice patterns in regard to the follow-up of postmenopausal women with early stage breast cancer exist among ASCO physicians.

Adult↗
PubMed1993

Linkage analysis of schizophrenia with five dopamine receptor genes in nine pedigrees.

Alterations in dopamine neurotransmission have been strongly implicated in the pathogenesis of schizophrenia for nearly 2 decades. Recently, the genes for five dopamine receptors have been cloned and characterized, and genetic and physical map information has become available. Using these five loci as candidate genes, we have tested for genetic linkage to schizophrenia in nine multigenerational families which include multiple affected individuals. In addition to testing conservative disease models, we have used a neurophysiological indicator variable, the P50 auditory evoked response. Deficits in gating of the P50 response have been shown to segregate with schizophrenia in this sample and may identify carriers of gene(s) predisposing for schizophrenia. Linkage results were consistently negative, indicating that a defect at any of the actual receptor sites is unlikely to be a major contributor to schizophrenia in the nine families studied.

Adolescent↗
PubMed1993

A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance.

Manic-depressive illness (MDI), also known as "bipolar affective disorder," is a common and devastating neuropsychiatric illness. Although pivotal biochemical alterations underlying the disease are unknown, results of family, twin, and adoption studies consistently implicate genetic transmission in the pathogenesis of MDI. In order to carry out linkage analysis, we ascertained eight moderately sized pedigrees containing multiple cases of the disease. For a four-allele marker mapping 5 cM from the disease gene, the pedigree sample has > 97% power to detect a dominant allele under genetic homogeneity and has > 73% power under 20% heterogeneity. To date, the eight pedigrees have been genotyped with 328 polymorphic DNA loci throughout the genome. When autosomal dominant inheritance was assumed, 273 DNA markers gave lod scores < -2.0 at recombination fraction (theta) = .0, 174 DNA loci produced lod scores < -2.0 at theta = .05, and 4 DNA marker loci yielded lod scores > 1 (chromosome 5--D5S39, D5S43, and D5S62; chromosome 11--D11S85). Of the markers giving lod scores > 1, only D5S62 continued to show evidence for linkage when the affected-pedigree-member method was used. The D5S62 locus maps to distal 5q, a region containing neurotransmitter-receptor genes for dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid. Although additional work in this region may be warranted, our linkage results should be interpreted as preliminary data, as 68 unaffected individuals are not past the age of risk.

Adult↗
PubMed1992

Tyrosine hydroxylase gene not linked to manic-depression in seven of eight pedigrees.

We ascertained 8 multigenerational pedigrees afflicted with multiple cases of bipolar and recurrent major depressive disorder. Alterations in dopaminergic and noradrenergic neurotransmission have been implicated in the pathogenesis of this disease, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of these two catecholamines. As TH mutations could underlie susceptibility to manic-depression, we carried out a linkage analysis between this disease in 8 families and two RFLP probes that map to the TH gene region on the short arm of chromosome 11. Evidence of linkage was not found in 7 of 8 kindreds.

Bipolar Disorder↗
PubMed1992

Linkage analysis of the D1 dopamine receptor gene and manic depression in six families.

Disturbances in dopaminergic activity may play an important role in the pathogenesis of manic depression. The effects of dopamine are mediated by at least five G protein coupled receptors, D1, D2, D3, D4 and D5. Recently, three separate research groups have cloned and characterized the D1 dopamine receptor, which localizes to 5q35.1. We undertook a linkage analysis between the D1 receptor polymorphisms and manic depression in six families in which segregation of the disease was consistent with autosomal dominant inheritance. A highly polymorphic flanking DNA marker, CRI-L1200, was also analyzed as the D1 gene RFLPs were relatively uninformative in our families. Multipoint analyses of manic depression and these DNA markers resulted in lod scores of less than -3.0 at the D1 locus, indicating that the D1 dopamine receptor gene does not confer an inherited susceptibility to manic-depressive illness in the families studied.

Bipolar Disorder↗
PubMed1990

Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy.

Thyroid function and lipid tests were measured in 29 premenopausal women with subclinical hypothyroidism. This group was compared with 41 euthyroid women matched for age and metabolic parameters. In basal condition there was no difference in thyroid hormone levels between the two groups except for TSH concentration (P less than 0.01). Total cholesterol, triglycerides and apolipoprotein (apo A1, A2, B) of women with subclinical hypothyroidism were not different from controls. HDL cholesterol was significantly decreased in subclinical hypothyroidism compared to the controls (P less than 0.01). With thyroxine therapy, normalization of serum TSH was associated with (1) no significant change in total cholesterol and triglycerides, (2) an increase of HDL cholesterol (P less than 0.01) and apoprotein A1 (P less than 0.05) levels. Total cholesterol/HDL cholesterol ratio was increased in subclinical hypothyroidism (P less than 0.01). During L-thyroxine therapy this ratio returned to normal value. Decreased HDL cholesterol concentration might cause coronary heart disease reported in women with subclinical hypothyroidism.

Adult↗
PubMed1990

[Detection of respiratory allergies using the Phadiatop test in children 1 to 6 years of age].

Phadiatop, a new test for detecting hypersensitivity to airborne allergens, was used in 83 children aged 9 months to 6 years with recurrent respiratory manifestations, i.e. recurrent expiratory obstruction and/or recurrent respiratory infections. A good correlation was found between this test and both the prick tests (95%) and the specific IgE assays (91% for RASTS of classes greater than or equal to 1, and 95% for RASTS of classes greater than or equal to 2). However, the correlation was less strong with the total IgE level (68%). The overall correlation with the specialist's prediction based on history and physical evaluation was excellent (94%). In this study, Phadiatop was found to have a 90% sensitivity and a 98% specificity. Furthermore, this test costs 40% less than the often used strategy combining skin tests and determinations of total and specific IgE levels. In the age group studied, Phadiatop is most useful above the age of two, since in younger patients true respiratory allergies are fairly infrequent in recurrent ENT and lower respiratory tract infections, whereas infections are far more common.

Child↗