Body fluid changes, thirst and drinking in man during free access to water

To investigate whether human thirst and drinking during ad lib access to water occur in response to body fluid deficits, we obtained blood samples and visual analog scale thirst ratings from five healthy, volunteer, young men at hourly intervals and when they were thirsty during a normal working day. Although there were significant increases in ratings of thirst, pleasantness of drinking water, mouth dryness and unpleasantness of the taste in the mouth when subjects were thirsty enough to drink compared with intervening intervals, there were no concomitant changes in body fluid variables (microhematocrit, plasma osmolality and plasma sodium, potassium, protein and angiotensin II concentrations). Subjects drank mainly in association with eating and were not overhydrated as indicated by constantly hypertonic urine and significant tubular reabsorption of free water over the experimental period. The results indicate that during free access to water humans become thirsty and drink before body fluid deficits develop, perhaps in response to subtle oropharyngeal cues, and so provide evidence for anticipatory thirst and drinking in man.     

Colchester revisited: a genetic study of mental defect.

This reanalysis of a classic survey leads to inferences about design of genetic studies, resolution of heterogeneity, and the role of autosomal and sex-linked genes in mental retardation, which is no longer refractory to segregation analysis. By discriminating between sociofamilial and biological types we estimate that at least 351 autosomal loci can produce mental retardation, with an inbred load of 0.83 detrimental equivalents and a mutation rate of 0.008 per gamete, or less than 2.4 X 10(-5) per locus. The distribution of probands was estimated as: 7 per cent medical, 60 per cent sociofamilial, and 33 per cent biological. Simple genetic mechanisms account for virtually all the biological category. Within the sociofamilial group cultural inheritance and polygenes could not be resolved.     

The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: A review (part 3)

Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part 1 of this series (Journal of Digital Imaging, 5:209–222, 1992) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. Part 2 discussed the application of CAID to SPECT perfusion studies (Journal of Digital Imaging, 6:1–15, 1993). This article reviews new variations of CAID programs for SPECT imaging and the application of expert systems and neural networks to CAID of nuclear medicine perfusion studies.     

Development of Coombs positive haemolytic anaemia in NZB mice injected with Freund's complete adjuvant

Intraperitoneal injection of young adult NZB mice with Freund's complete adjuvant emulsion, alone or incorporating BALB/c mouse erythrocytes, resulted in accelerated direct Coombs conversion and development of splenomegaly. Incorporation of adjuvant with NZB erythrocytes caused an accelerated reactivity in some animals, but in others resulted in a delayed Coombs conversion. In contrast, positive Coombs tests failed to develop at all in NZB mice injected with a Freund's complete adjuvant preparation containing ten times the usual amount of Mycobacterium. These observations might be explained in part by the relative influences of adjuvancy and of antigenic competition on the availability of precursor cells capable of responding to autoantigenic stimulation.     

Chromosome anomalies as predictors of recurrence risk for spontaneous abortion

Reproductive histories and chromosomes of spontaneous abortions were studied by segregation analysis in 1890 sibships ascertained through a cytogenetically studied abortion. Normal karyotypes are associated with recurrent abortion. Among abnormal karyotypes, trisomy has an elevated recurrence risk even after adjustment through a liability indicator for maternal age. Possible mechanisms and conflicting evidence in the literature on trisomy are discussed. None of these differences in recurrence risk is large enough to play a significant numerical role in genetic counseling.     

Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone.

BACKGROUND. Lymphomatoid papulosis is a benign cutaneous eruption that in 10 to 20 percent of patients is associated with the development of lymphoma. The atypical cells of lymphomatoid papulosis histologically resemble the malignant cells of cutaneous T-cell lymphoma or the Reed-Sternberg cells of Hodgkin's disease. We studied a patient in whom lymphomatoid papulosis developed in 1971, Hodgkin's disease in 1975, and cutaneous T-cell lymphoma in 1985, to determine whether these diseases are clonally related. METHODS. The T-cell-receptor alpha-chain gene was cloned and sequenced from a cell line derived from the advanced-stage cutaneous T-cell lymphoma, and the polymerase chain reaction was used to search for this rearrangement of the alpha-chain gene in tissues obtained earlier that were affected by Hodgkin's disease or lymphomatoid papulosis. RESULTS. The tumor-specific rearrangement of the alpha-chain gene was detected in the patient's earlier tissues affected by lymphomatoid papulosis and Hodgkin's disease, but not in control tissue, including uninvolved tissues from the staging laparotomy for Hodgkin's disease. Cytogenetic studies revealed a translocation, t(8;9)(p22;p24), in cutaneous T-cell lymphoma lines and in a dermatopathic lymph node removed two years before the clinical onset of the cutaneous T-cell lymphoma. Immunohistochemical findings were consistent with an activated T-cell phenotype for the atypical cells of lymphomatoid papulosis, the Reed-Sternberg cells of Hodgkin's disease, and the malignant cells of the T-cell lymphoma. CONCLUSIONS. Lymphomatoid papulosis, Hodgkin's disease, and cutaneous T-cell lymphoma can be derived from a single T-cell clone. A t(8;9) genetic translocation may be involved in the pathogenesis of lymphomatoid papulosis or its progression to malignant disease.     

Genetic and environmental determinants for lipoprotein concentrations in blood

Path and segregation analyses have been performed on cholesterol and triglyceride contents of serum as well as on very low, low and high density lipoproteins in 78 Swedish nuclear families. The effect of environmental variables like alcohol and smoking on the concentrations of the different lipoproteins has been studied. Genetic heritability was 0.16-0.68 for the cholesterol fractions and 0-0.56 for the triglyceride fractions. No major gene was evident for any of the variables studied.     

Relative contributions of balance and voluntary leg-coordination deficits to cerebellar gait ataxia

Different cerebellar regions participate in balance control and voluntary limb coordination, both of which might be important for normal bipedal walking. We wanted to determine the relative contributions of balance versus leg-coordination deficits to cerebellar gait ataxia in humans. We studied 20 subjects with cerebellar damage and 20 control subjects performing three tasks: a lateral weight-shifting task to measure balance, a visually guided stepping task to measure leg- coordination, and walking. We recorded three-dimensional joint position data during all tasks and center of pressure coordinates during weight-shifting. Each cerebellar subject was categorized as having no detectable deficits, a balance deficit only, a leg-placement deficit only, or both deficits. We then determined the walking abnormalities associated with each of these categories. Five of 10 measures of gait ataxia were abnormal in cerebellar subjects with a balance deficit, but only 1 was abnormal in cerebellar subjects with a leg-placement deficit. Furthermore, subjects with a balance deficit performed worse than subjects with a leg-placement deficit on 9 of the 10 gait measures. Finally, performance on the balance task, but not the leg-placement task, explained a significant proportion of the variance in walking speed for the entire cerebellar group. We conclude that balance deficits are more closely related to cerebellar gait ataxia than leg-placement deficits. Our findings are consistent with animal literature, which has suggested that cerebellar control of balance and gait are interrelated, and dissociable from cerebellar control of voluntary, visually guided limb movements.     

Allelic association with SNPs: metrics, populations, and the linkage disequilibrium map

Comparison of different metrics, using three large samples of haplotypes from different populations, demonstrates that rho is the most efficient measure of association between pairs of single nucleotide polymorphisms (SNPs). Pairwise data can be modeled, using composite likelihood, to describe the decline in linkage disequilibrium with distance (the Malecot model). The evidence from more isolated populations (Finland, Sardinia) suggests that linkage disequilibrium extends to 427-893 kb but, even in samples representative of large heterogeneous populations, such as CEPH, the extent is 385 kb or greater. This suggests that isolated populations are not essential for linkage disequilibrium mapping of common diseases with SNPs. The in parameter of the Malecot model (recombination and time), evaluated at each SNP, indicates regions of the genome with extensive and less extensive disequilibrium (low and high values of in respectively). When plotted against the physical map, the regions with extensive and less extensive linkage disequilibrium may correspond to recombination cold and hot spots. This is discussed in relation to the Xq25 cytogenetic band and the HFE gene region.