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M Hoff

Publications and source records attributed to M Hoff.

At least 19 recordsLinked to original sources
PubMed1997

Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus.

Inheritance of a defect in a neuronal mechanism that regulates response to auditory stimuli was studied in nine families with multiple cases of schizophrenia. The defect, a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, is associated with attentional disturbances in schizophrenia. Decreased P50 inhibition occurs not only in most schizophrenics, but also in many of their nonschizophrenic relatives, in a distribution consistent with inherited vulnerability for the illness. Neurobiological investigations in both humans and animal models indicated that decreased function of the alpha 7-nicotinic cholinergic receptor could underlie the physiological defect. In the present study, a genome-wide linkage analysis, assuming autosomal dominant transmission, showed that the defect is linked [maximum logarithm of the odds (lod) score = 5.3 with zero recombination] to a dinucleotide polymorphism at chromosome 15q13-14, the site of the alpha 7-nicotinic receptor. Despite many schizophrenics' extremely heavy nicotine use, nicotinic receptors were not previously thought to be involved in schizophrenia. The linkage data thus provide unique new evidence that the alpha 7-nicotinic receptor gene may be responsible for the inheritance of a pathophysiological aspect of the illness.

Auditory Perception↗
PubMed1997

Experience with a high speed biopsy gun in breast cancer diagnosis.

Pre-operative determination of histology and receptor status is important in optimizing the management of breast cancer. The purpose of our study was to evaluate the high speed biopsy gun in 109 patients with palpable breast tumours. High speed biopsies were performed using the system BIP High Speed Multi 22 with 16-gauge-needles at a speed of 30 m/s. All biopsies could be used for frozen sections and for determination of receptor status. In 81 patients (74.3%) malignant breast tumours were diagnosed, and three patients (2.8%) had highly suspicious lesions. The oestrogen receptor status was negative in 32%, progesterone receptor status negative in 41%. In one patient (0.9%) a high grade non-Hodgkin's lymphoma of B-cell-type was diagnosed. In 21.1% benign tumours were found. In one patient a malignant tumour was missed at biopsy (0.9% false-negative). It was concluded that high speed biopsy is a reliable and simple method for preoperative sampling of breast lesions.

Biopsy, Needle↗
PubMed1997

Urinary iodine excretion during normal pregnancy in healthy women living in the southwest of France: correlation with maternal thyroid parameters.

A prospective study was undertaken to evaluate urinary iodine excretion and changes of maternal thyroid function during pregnancy in healthy women living in the southwest of France. The cohort included a total of 347 pregnant women (mean age 28.0+/-0.5 years). Iodine concentration in a random urine sample and thyroid tests (free thyroxine [FT4], free triiodothyronine [FT3], thyrotropin (TSH), thyroxine-binding globulin [TBG], and thyroglobulin [Tg]) were measured at initial presentation (before 12 weeks of gestation), and during the ninth month of pregnancy. A thyroid ultrasound was performed 1 to 5 days after delivery in 246 mothers. Mean urinary iodine levels were low during the first trimester (6.9+/-0.4 microg/dL), as well as during the ninth month of pregnancy (8.6+/-0.6 microg/dL). During pregnancy, FT4 and T3 concentrations decreased (p < .001), and TSH and Tg concentrations increased (p < .001). Thyroid hypertrophy (thyroid volume greater than 18 mL) was present in 15.4% of women whose first trimester urinary iodine concentration was less than 5 microg/dL, but was present in only 3.5% of women whose urinary iodine concentration was greater than 10 microg/dL. A goiter (thyroid volume greater than 22 mL) was present in 11% of the mothers. In conclusion, this prospective study shows that urinary iodine excretion is low in pregnant women living in the southwest of France. This low iodine intake is associated with reduced circulating thyroid hormone levels and growth of the thyroid gland. These data point to the need of an increased iodine supply in these pregnant women to reduce the potential consequences of low iodine intake on maternal thyroid economy.

Adolescent↗
PubMed1996

Analysis of chromosome 18 DNA markers in multiplex pedigrees with manic depression.

Six pedigrees segregating manic-depressive illness (MDI) were analyzed for linkage to 21 highly polymorphic microsatellite DNA markers on chromosome 18. These markers span almost the entire length of the chromosome, and gaps between markers are less than 20 cM. In particular, we analyzed several markers localizing to the pericentromeric region of chromosome 18 which generated lod scores suggestive of linkage in an independent study. Lod score analysis was performed and results were examined by family. One region produced positive lod scores, though at 18q23 and not in the pericentromeric region. We additionally used two nonparametric methods because the true mode of transmission of MDI is unknown; results were again somewhat suggestive for markers in the region of 18q23 but not in the pericentromeric region.

Adult↗
PubMed1996

An analysis of the cost of clinical surveillance after primary therapy for women with early stage invasive breast cancer.

Routine surveillance for distant metastases in women with early stage breast cancer has limited clinical utility and can result in large medical care costs. In order to estimate breast cancer surveillance costs, we used the results of a survey administered to a random sample of physician members of the American Society of Clinical Oncology. The survey measured the frequency in which radiographic and laboratory tests are ordered for postmenopausal women with stage I or II breast cancer after the completion of surgery and radiation or adjuvant chemotherapy if indicated. There were 209 completed surveys representing a response rate of 48%. The volume of tests ordered was expressed in terms of Medicare's relative value units (RVUs) and 1993 cost equivalents. The mean total RVUs over 5 years post-diagnosis was 43.8 (interquartile range 30.1-54.2) which represents a cost of $1369 using the 1993 Medicare conversion factor of $31.249. A cumulative logistic regression model categorized RVUs according to intensity of care (minimal, average, and intensive). While medical oncologists compared to surgeons and radiation oncologists, and physicians practicing in the Northeast and Midwest, compared to those practicing in the South and West, were more likely to adopt an intensive practice style, these differences were not statistically significant (p = 0.1). None of the other provider characteristics evaluated, including gender, prior experience, and practice type, had a significant effect on physician practice in a multivariate model. The data showed a wide variation among providers in surveillance practice patterns that was largely unexplained by physician demographics. These results are consistent with the physician practice style hypothesis which suggests that wide variations in treatment patterns result from uncertainty regarding effectiveness of care.

Breast Neoplasms↗
PubMed1996

Anticipation in multiplex schizophrenia pedigrees.

Anticipation, a phenomenon in which the symptoms of an inherited disease become more severe and age of onset occurs earlier across generations, has become an issue of importance in schizophrenia. If anticipation is found in families manifesting the illness, a possible type of genetic mutation would be implicated for predisposition to schizophrenia, as anticipation is now known to result from expansion of unstable trinucleotide repeat sequences. Two recent studies have tested for evidence of this phenomenon in schizophrenia families and came to differing conclusions; it is possible that anticipation occurs only in a subset of families. Our sample shows significant decreases in age of onset and increases in severity across generations. To investigate possible ascertainment bias, we looked at early onset parents and found no consistent anticipation effects in this group. We did find some increase in anticipation for mother-child vs father-child pairs; this possible imprinting effect may indicate true anticipation, though the evidence is not strong in our small sample, and the most conservative interpretation of our results is that the differences are due to ascertainment bias.

Adult↗
PubMed1996

Identification of a nonsense mutation at the 5' end of the TSC2 gene in a family with a presumptive diagnosis of tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disease with a high mutation rate. It is clinically a very variable disorder and hamartomas can occur in many different organs. TSC shows genetic heterogeneity; one gene, TSC1, is on chromosome 9q34, and the second gene, TSC2, on chromosome 16p13.3. Clinical criteria for diagnosis have been established, but diagnosis of patients with minimal expression of the disease can be very difficult. In children the phenotype is often incomplete or not fully assessable. Hence mildly affected subjects, at risk for severely affected offspring, may remain undiagnosed. The detection of (small) mutations in the tuberous sclerosis gene located on chromosome 16 (TSC2) has recently become possible and may be helpful in the diagnosis of ambiguous cases. To our knowledge, this is the first report of a point mutation in the TSC2 gene in a familial case of tuberous sclerosis. A nonsense mutation was detected in a family in which the father had only minor signs hinting at tuberous sclerosis. The son had multiple cardiac tumours and white patches, but full clinical investigation was impossible in this child. This case illustrates that mutation analysis can contribute to a diagnosis of tuberous sclerosis in families with an incomplete phenotype.

Adult↗
PubMed1996

Serological markers of autoimmunity in renal transplant patients before and after alpha-interferon therapy for chronic hepatitis C.

Chronic hepatitis C is the major cause of chronic liver disease after successful cadaveric renal transplantation. The aims of this prospective, open study were to assess in such a population, firstly the prevalence of different organ-specific and nonspecific antibodies and related disorders, and secondly their outcome after inteferon-alpha therapy as well as the incidence of new immunologic disorders under and after this therapy. In 15 cadaveric renal transplant patients (10 men, 5 women, ages 29-65 years) with chronic hepatitis C and histological features of chronic active hepatitis, undergoing chronic immunosuppression (ciclosporine A with or without steroid and azathioprine) and treated with recombinant alpha 2b-interferon (IFN alpha) (mean duration 142 +/- 35 days), we assessed before and after this therapy the serum levels of cryoglobulinemia, rheumatoid factors (RF), thyroid-stimulating hormone (TSH), free thyroxine (fT4), and antinuclear (ANA), antismooth muscle (ASMA), antimitochondrial (AMA), anti-LKM1, antimicrosomal thyroid (MCA), antithyroglobulin (TGA) autoantibodies. At the start of IFN alpha therapy, 14 of 15 patients had detectable autoantibodies (RF: 9; ANA > 1/50: 8; ASMA > 1/50: 4; other autoantibodies: 0); 1 had cryoglobulinemia. At the end of therapy the cryoglobulinemia had disappeared, the preexisting autoantibodies remained present in all patients but 2; 3 patients had developed MCA without evidence of clinical or biological thyroid abnormalities and 3 others had developed either RF (1) or ANA (1) or ASMA (1), without any related symptoms. One patient developed transient type II diabetes mellitus without anti-Langerhans beta-cell antibodies. Finally, the occurrence of autoantibodies in our patients was associated either with HLA DR3 or DR4 or DR7 phenotypes. We found that the prevalence of extrahepatic immunologic abnormalities was high in renal transplant patients with chronic hepatitis C and no exacerbation was observed during of after IFN alpha therapy. The most frequent autoantibody appearing after IFN alpha therapy was MCA although without thyroid abnormalities.

Adult↗
PubMed1995

Search for a gene predisposing to manic-depression on chromosome 21.

Six kindreds containing multiple cases of Manic-depressive illness (MDI) were genotyped with seven highly polymorphic microsatellite loci used in the construction of an index map for chromosome 21. The kindreds were also genotyped with a microsatellite polymorphism for PFKL, a chromosome 21 locus that has shown suggestive linkage to MDI in one pedigree [Straub et al., 1993: The American Society of Human Genetics]. Evidence of linkage was not found assuming either autosomal dominant or recessive inheritance. The nonparametric affected sib pair test did not yield significant evidence of linkage.

Biomarkers↗
PubMed1995

Mutation scan of the D1 dopamine receptor gene in 22 cases of bipolar I disorder.

In a previous study [Coon et al., Am J Hum Genet 52:1234-1249, 1993], we found suggestive evidence of linkage between manic-depressive illness (MDI) in eight multiplex pedigrees and D5S62, a DNA marker mapping to the telomeric region of 5q. As the D1 dopamine receptor gene (DRD1) maps to this region and as alterations in dopaminergic neurotransmission have been indirectly implicated in the pathogenesis of MDI, we directly searched for mutations in the coding region of the DRD1 gene in 22 unrelated cases of bipolar I (BPI) disorder derived from multiplex families. Using single strand conformation polymorphism (SSCP) analysis, we did not observe any abnormal SSCP variants in the BPI cases that differed from controls.

Adult↗
PubMed1995

Effect of age and race on the survival of men with prostate cancer in the Metropolitan Detroit tricounty area, 1973 to 1987.

OBJECTIVES: Reports have demonstrated that African Americans diagnosed with prostate cancer have a poor survival compared with whites. We examined the impact of age, race, and stage of disease on survival for men diagnosed with prostate cancer. METHODS: A retrospective analysis was made of men diagnosed with prostate cancer utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database. A total of 12,907 men (9339 white, 3568 black) diagnosed from January 1, 1973 through December 31, 1987 were included in the study. For each stage of disease, survival experience was examined using Kaplan-Meier and life table methods, followed by analysis using Cox's proportional hazard model. RESULTS: African-American men have a poorer survival than whites for all stages of prostate cancer when the cancer is diagnosed at younger ages. These differences in survival were not demonstrated for men diagnosed with prostate cancer after age 70. CONCLUSIONS: Age and race should be taken into account when assessing the survival of patients with prostate cancer.

Adenocarcinoma↗
PubMed1995

Schizophrenia and GABAA receptor subunit genes.

Alterations in gamma-aminobutyric acid (GABA) neurotransmission have been indirectly implicated in the pathogenesis of schizophrenia. Using nine multiplex pedigrees, we tested for linkage between schizophrenia and simple sequence repeat polymorphisms for the GABAA receptor alpha 1, alpha 2, alpha 4, alpha 5, alpha 6, beta 1 and beta 3 subunit genes. Evidence of linkage was not found when assuming either autosomal dominant or autosomal recessive inheritance. The non-parametric sib pair test also did not reveal significant evidence of deviation from expected segregation ratios.

Genes, Dominant↗
PubMed1995

Search for a schizophrenia susceptibility gene on chromosome 18.

Nine multiplex schizophrenia families were genotyped with 15 microsatellite markers mapping to the short and long arm of chromosome 18. Assuming either autosomal dominant or recessive inheritance evidence of linkage was not found. In addition, the non-parametric sib pair test did not reveal significant evidence of linkage.

Chromosome Mapping↗
PubMed1994

Search for a schizophrenia susceptibility locus on human chromosome 22.

We used 10 highly informative DNA polymorphic markers and genetic linkage analysis to examine whether a gene locus predisposing to schizophrenia is located on chromosome 22, in 105 families with schizophrenia and schizoaffective disorder. The LOD score method, including analysis for heterogeneity, provided no conclusive evidence of linkage under a dominant, recessive, or penetrance free model of inheritance. Affected sib-pair analysis was inconclusive. Affected pedigree member analysis gave only suggestive evidence for linkage. Multipoint APM analysis, using 4 adjacent loci including D22S281 and IL2RB, a region of interest from the APM analysis, gave non-significant results for the three different weighting functions.

Chromosome Mapping↗
PubMed1994

Search for mutations in the beta 1 GABAA receptor subunit gene in patients with schizophrenia.

As alterations in GABAergic neurotransmission have been indirectly implicated in the pathogenetics of schizophrenia, GABAA receptor subunit genes are plausible candidate genes for the illness. We undertook a search for sequence variations in the coding region of beta 1 subunit gene by designing intron-based primers to amplify its 9 exons. Using single strand conformation polymorphism (SSCP) analysis, we found an exon 9 variant present in 3 of 86 unrelated schizophrenic cases derived from families having at least 2 first-degree relatives with schizophrenia. Direct sequencing of the SSCP variant revealed a C-->G nucleotide transversion at codon 396 predicting a histidine to glutamine substitution in the beta 1 peptide. The predicted amino acid substitution occurs at a highly conserved site, 9 residues from a cAMP-dependent serine phosphorylation consensus sequence. All known GABAA beta 1 subunit genes including human, bovine, and rat, code for histidine at position 396. Although the variant cosegregated with disease in a family with 2 affected sibs, it was only transmitted to 2 of 3 affected sibs in a multiplex family. The variant was not found in an additional sample comprising 155 unrelated schizophrenics and the sequence variant was present at a low frequency (approximately 1.1%) in control groups. Although these results indicate that the sequence variant is likely to be a natural polymorphism, it is possible that the variant may be a predisposing allele in rare instances. It is also possible that the variant may change the function or regulation of the GABAA receptor complex and it may be of pharmacogenetic relevance.

Adolescent↗
PubMed1994

Genomic scan for genes predisposing to schizophrenia.

We initiated a genome-wide search for genes predisposing to schizophrenia by ascertaining 9 families, each containing three to five cases of schizophrenia. The 9 pedigrees were initially genotyped with 329 polymorphic DNA loci distributed throughout the genome. Assuming either autosomal dominant or recessive inheritance, 254 DNA loci yielded lod scores less than -2.0 at theta = 0.0, 101 DNA markers gave lod scores less than -2.0 at theta = 0.05, while 5 DNA loci produced maximum lod scores greater than 1: D4S35, D14S17, D15S1, D22S84, and D22S55. Of the DNA markers yielding lod scores greater than 1, D4S35 and D22S55 also were suggestive of linkage when the Affected-Pedigree-Member method was used. The families were then genotyped with four highly polymorphic simple sequence repeat markers; possible linkage diminished with DNA markers mapping nearby D4S35, while suggestive evidence of linkage remained with loci in the region of D22S55. Although follow-up investigation of these chromosomal regions may be warranted, our linkage results should be viewed as preliminary observations, as 35 unaffected persons are not past the age of risk.

Adolescent↗
PubMed1994

Analysis of chromosome 22 markers in nine schizophrenia pedigrees.

Previous results of a genome-wide survey for schizophrenia susceptibility genes in nine multiplex families indicated a possible region of linkage on chromosome 22. We therefore tested for linkage using ten highly polymorphic chromosome 22 DNA markers. Lod score analyses were suggestive of linkage for several markers on the distal end of the chromosome; however, no lod score exceeded 3 assuming either autosomal dominant or autosomal recessive transmission. The highest lod score was 2.09 (theta = 0.10) for marker D22S276 under autosomal recessive inheritance. Based on simulation analyses, this result is unlikely to represent a false positive. Analyses using information from affected individuals only resulted in reduced lod scores, with a maximum of 1.40 (theta = 0.05) for D22S276 assuming autosomal recessive inheritance. Two nonparametric methods, sib pair analysis and the Affected-Pedigree-Member method, also yielded suggestive but inconclusive findings; results were positive, but strict thresholds of significance were not met. Additionally, we tested one candidate gene, the Arylsulfatase A gene, located in the region of 22q13.31-qter. Results were again inconclusive, though the DNA marker available for this gene was a 2-allele RFLP with heterozygosity of 0.5, and therefore not maximally informative. Further investigation of this chromosomal region and this and other candidate genes may be warranted.

Adolescent↗