Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Impact of hemochromatosis screening in patients with indeterminate results: the hemochromatosis and iron overload screening study.

PURPOSE: Assess the quality of life impact of receiving indeterminate test results for hemochromatosis, a disorder involving HFE genetic mutations and/or elevated serum transferrin saturation and ferritin. METHODS: The study sample was from the Hemochromatosis and Iron Overload Screening Study, a large observational study of hemochromatosis among primary care patients in the US and Canada using HFE genotype and serum transferrin saturation and ferritin screening. Study subjects included 2,304 patients found with hemochromatosis risk of uncertain clinical significance. Assessed was SF-36 general health and emotional well-being before screening and six weeks after participants received their test results. Health worries were assessed after screening. RESULTS: Of the study subjects, 1,268 participants (51.5%) completed both assessments. Compared to normal controls, those with HFE mutations or elevated serum transferrin saturation and ferritin levels of uncertain significance were more likely to report diminished general health and mental well-being, and more health worries. These effects were associated with participants' belief of having tested positive for hemochromatosis or iron overload. CONCLUSION: Notification of indeterminate results from screening may be associated with mild negative effects on well-being, and might be a potential participant risk in screening programs for disorders with uncertain genotype-phenotype.     

Anatomic and physiologic development of the photoreceptor of the kitten

Summary The postnatal development of the photoreceptor of the cat was studied using physiological and anatomical methods. The late receptor potential (LRP) was recorded in vitro and the threshold and maximum amplitude determined. The same specimens used in the electrophysiological studies were then prepared for microscopy, and rod cell outer and inner segment length and diameter, photoreceptor density, and inter-receptor distance were determined. A small LRP was first recorded at 9–10 days, but only at very high stimulus intensities. Thereafter, there was a rapid decrease in the threshold and an increase in the amplitude of the LRP. The threshold reached adult values at 17–18 days, while the amplitude of the LRP was adultlike at 23–26 days. Of the anatomical parameters examined, inter-receptor spacing and rod cell diameters seem to be most clearly associated, respectively, with the attainment of adult LRP threshold and amplitude. Outer segment length was adult-like at 35–43 days of age and thus postdated physiological maturity of the photoreceptor. These observations suggest that the surface area of the rod cell outer segment tips is more critical in the development of the adult LRP than is the number of discs in the outer segment. In addition, changes over time in the mean diameter and length of rod cell inner segments follows the pattern of ontogenetic changes in LRP amplitude. These findings imply a close relationship during ontogeny between the metabolic functions of the inner segment and phototransduction at the outer segment disc.This study was supported by the Florida Lions Eye Bank (GST) and by a grant, 2-RO1-EY00376-08, from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (DIH)Andrew Labbie and Joseph Muroff were participants in the Community Laboratory Research Programm sponsored by the Dade County Public School System, Miami, Florida     

Adjacent-2 disjunction of a maternal t(9;22) leading to duplication 9pter----q22 and deficiency of 22pter----q11.2

The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,-22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations.     

Spectral electroencephalographic correlates of iron status: Tired blood revisited

For some time, clinical reports have described impairment of affective and cognitive functions in iron deficient persons. Recent studies suggest that both brain biochemistry and cognitive performance capacity may be disrupted by inadequate intake of dietary iron, but the relationship of the possible neurophysiological effects to psychological ones is unclear. To examine the relationship of iron status to simultaneous measures of cortical activation and cognitive performance, 8 channels of electroencephalographic (EEG) data were recorded during a resting period and during the performance of several cognitive tasks in two groups of men. The EEG data were spectrally analyzed, and measures of total power and frequency of peak power in each of several bands of the power spectrum for each channel were used as predictors in multiple regression analyses with serum iron and serum ferritin as alternative criteria. Measures of power in the delta frequency in the resting period appeared relevant to iron status in both groups, perhaps indicating alertness or arousal level. Consistently in these regressions, the asymmetry of the EEG appeared relevant to iron and ferritin. These findings suggest that the combination of EEG and performance measures may help characterize the neuropsychological effects of trace element nutrition.     

Construction of an antigenic map for human B-cell precursors

The purpose of this study was to evaluate the binding of a panel of monoclonal antibodies to human pre-B cells present in fetal, pediatric, and adult bone marrow. The antibodies included BA-1, BA-2, BA-3 (anti-CALLA), anti-B1, L243 (anti-HLA-DR), and T101. Binding of the monoclonal antibodies to pre-B cells was evaluated at the single-cell level by double fluorochrome analysis. Percentages of BA-1+ and anti-B1+ pre-B cells were independent of age group. BA-1 bound to approximately 80% of fetal, pediatric, and adult bone marrow pre-B cells, whereas anti-B1 bound to approximately 50%. BA-2 bound to 55% of fetal pre-B cells, but this percentage decreased to 32% in pediatric and 16% in adult bone marrow. CALLA was expressed on less than 10% of fetal, pediatric, and adult bone marrow pre-B cells, and HLA-DR was expressed on greater than 95% of fetal, pediatric, and adult pre-B cells. Although T101 (an anti-T-cell monoclonal antibody) did not bind to pre-B cells, it did bind to approximately 25% of the sIgM+ cells in fetal bone marrow. These results suggest a predominant phenotype of L243 (anti-HLA-DR)+, BA-1+, BA-3 (anti-CALLA)-, T101- for the human pre-B cell while phenotypic heterogeneity exists for anti-B1 and BA-2.     

Carcinoma of the esophagus with adenoid cystic differentiation

Adenoid cystic carcinoma of the esophagus is a relatively rare lesion which characteristically exhibits a clinically aggressive behavior. In spite of this aggressive nature, it is most often referred to as a counterpart of the more common adenoid cystic carcinoma of salivary gland origin, a comparatively indolent tumor. In this report, the clinical and pathologic findings in a series of six cases of esophageal adenoid cystic carcinomas are contrasted with those of typical salivary gland lesions, and also compared to similar tumors exhibiting "adenoid cystic" differentiation arising in other extrasalivary gland sites. It is concluded that the esophageal tumors, as well as certain similar lesions arising in other extrasalivary gland sites, represent a class of poorly differentiated basaloid neoplasms distinct both clinically and morphologically from the common adenoid cystic carcinoma of salivary gland origin.     

Milk-Fat Intake and Differences in Abdominal Adiposity and BMI: Evidence Based on 13,544 Randomly-Selected Adults

The primary purpose of this investigation was to evaluate the relationship between milk-fat intake and obesity, particularly abdominal obesity, in 13,544 U.S. adults. A lesser objective was to measure the degree to which the association was influenced by multiple potential confounding variables. This cross-sectional study used data from the 2011–2016 National Health and Nutrition Examination Survey (NHANES). Quantity of milk-fat regularly consumed was the exposure variable. Sagittal abdominal diameter (SAD), a measure of abdominal obesity, and body mass index (BMI) were the outcome variables. Sagittal abdominal diameter is a strong predictor of visceral abdominal fat, when measured by computed tomography, and has been shown to predict cardiometabolic disorders better than BMI. After controlling for age, race, gender, physical activity, leisure computer use and gaming, alcohol habits, and cigarette use, significantly lower BMIs were associated with consistent non-fat and full-fat milk consumption (F = 4.1, p = 0.0063). A significantly lower SAD was associated only with regular consumption of non-fat milk (F = 5.0, p = 0.0019). No significant differences were detected between the other milk-fat groups or milk abstainers. In this nationally representative sample, only 19.6% of adults regularly consumed low-fat milk. In conclusion, consistent non-fat milk intake was predictive of lower levels of abdominal adiposity compared to consumption of higher levels of milk-fat.