Balanced translocation 12/13 and situs abnormalities: homology of early pattern formation in man and lower organisms?

Studies in "lower" organisms have identified a set of homologous sequences expressed in oocytes and early embryos that is critical for pattern formation. Mutations in such genes may exhibit maternal effect--they cause abnormalities in the fetus only when present in the mother. We report on a mother and child with identical, apparently balanced translocations having the breakpoints 12q13.1 and 13p13. The fetus had multiple anomalies including bilateral trilobar lungs, complex heart defect, malrotation of the gut, and asplenia, while the mother was entirely normal. Several hypotheses are advanced to explain this variable expression including transection of a gene with maternal effect--lateral asymmetry in the fetus is influenced by the maternal genotype. This explanation would account for the higher transmission of congenital heart disease to offspring by affected females noted in several studies. The human counterparts of 2 loci (int-1 and HOX 3) involved in Drosophila early pattern formation are located near the translocation breakpoint 12q13.1. If one of these genes is responsible for situs abnormality, then university of positional code (but not of embryologic mechanism) is suggested for higher metazoans.

Evaluation of an enzyme-linked immunosorbent assay for prostatic acid phosphatase.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure prostatic acid phosphatase in human sera. The value of this method was tested on four groups: patients with non-prostatic disease, with prostatic hypertrophy, and with untreated and treated prostatic carcinoma. The results of ELISA were also compared with those of enzyme immunoassay (EIA) and the conventional, enzymatic method. The specificity of ELISA as calculated from the hypertrophy group, was 76% against 68% for EIA and 71% for the conventional method. The sensitivity of ELISA, calculated from the untreated carcinoma group, was 57% against 60% for EIA and 70% for the conventional method. ELISA did not prove better than EIA or the conventional method in quantifying prostatic acid phosphatase in patients' sera.

Quantification of cholesterol nucleation promoting activity in human gallbladder bile.

We have developed a simple method to quantitate cholesterol nucleation promoting activity in bile. The method makes use of the fact that gallbladder bile of cholesterol gallstone patients contains potent nucleation promoting activity. Gallbladder bile samples were serially diluted, routinely from 1/25 to 1/6,400. The diluted samples were mixed with a supersaturated model bile and the nucleation time (NT) of the mixtures was determined. The greatest dilution that resulted in a significant shortening of the NT was called the nucleation promoting activity titre (NPAT). The determination is independent of the original lipid content of the bile sample. The NPAT was measured in 14 gallbladder bile samples derived from patients with cholesterol gallstones and 9 controls. In all samples promoting activity was found. In the samples from the stone patients the NPAT was significantly elevated as compared to the patients without cholesterol stones (p = 0.01). Our results suggest that the cholesterol saturation index and the activity of cholesterol nucleation promoting factors are the most important factors in the pathogenesis of cholesterol gallstone disease. Assessment of the NPAT allows the differentiation of groups of patients with a normal cholesterol saturation index who are at risk for gallstone formation due to a high NPAT.

The Oxford-Manchester study of dialysis patients. Age, risk factors and treatment method in relation to quality of life.

A retrospective study of 159 patients who started Haemodialysis (HD) or Continuous Ambulatory Peritoneal Dialysis (CAPD), between 1981 and 1984 was carried out in two UK Renal Units. An extension of the study was carried out in one unit during 1985, gathering data on 30 patients aged greater than 65. The aim was to assess whether age, medical or social risk factors, or treatment method, affected perceived quality of life. Assessment was by standardised self-report questionnaire. The overall life satisfaction, measured on Cantril's ladder scale, showed no significant difference between dialysis patients and a normal population. On a quality of life semantic differential scale CAPD patients scored significantly better than HD patients. Satisfaction with sexual relationships showed marked deterioration in all age groups, but this did not seem to affect reported satisfaction with marriage. Those aged greater than 65 scored significantly better than younger patients on dialysis stress scales, and were generally more satisfied with life. When the study population was sub-divided into four groups, by age (less than or greater than 60) and presence or absence of additional factors, were seen to be those least satisfied with life on several different assessment scales.

Erythropoietin production in virulent malaria.

Erythropoietin, the hormone responsible for stimulating erythrocyte production, was shown to increase significantly in the serum of mice during virulent malaria infection. Although erythropoiesis was enhanced, it did not keep pace with the rate of erythocyte destruction; hence all Plasmodium berghei-infected mice quickly succumbed to the deleterious consequences of severe uncompensated hemolytic anemia. Since this apparently inadequate rate of erythropoiesis is not attributed to impaired erythropoietin generation, mechanisms relating to (i) hemopoietic stem-cell resistance to endogenous erythropoietin, (ii) deficits in numbers of hemopoietic stem cells, and/or (iii) ineffective erythropoiesis are of interest.

Zambian women's attitudes toward mass nevirapine therapy to prevent perinatal transmission of HIV.

Use of mass nevirapine therapy--universal provision of the drug without HIV testing--for prevention of perinatal HIV in high prevalence settings with extreme resource constraints is a controversial strategy. A quarter of pregnant Zambian women surveyed would prefer to receive nevirapine through a non-testing mass strategy, and most would support mass therapy as a policy if it would make the drug available to a larger proportion of the at-risk population.

Molybdenum cofactor deficiency.

We describe a new case of molybdenum cofactor deficiency, an underrecognized inborn error of metabolism that results in neonatal seizures and neurologic abnormalities. Characteristic biochemical defects in affected individuals include hypouricemia, elevated urine sulfate (detectable by dipstick), and elevated S-sulfocysteine (detectable by anion exchange chromatography). This disorder should be considered in the differential diagnosis of neonatal seizures.

Cholesterol nucleation-influencing activity in T-tube bile.

Nucleation-influencing activity was determined in T-tube bile samples derived from patients with obstructive jaundice. Since native T-tube bile samples do not nucleate, nucleation-influencing activity was determined by measuring the influence of T-tube bile on the nucleation time of model bile. In the assay, T-tube bile was mixed with model bile, and the nucleation time of this mixture was compared with the nucleation time of a model bile supplemented with the same amount of lipid as present in the bile sample. The results were expressed as ratio of the nucleation time of the mixture and the nucleation time of the control (NTm/NTc). There was a significant difference (p less than 0.01) between bile samples from patients with cholesterol gallstones and samples from patients with biliary obstruction due to other causes. More than 80% of the 33 samples from eight patients with stones were nucleation-promoting (NTm/NTc less than or equal to 0.6). Of the 40 bile samples from patients without stones, 7 were nucleation-promoting, 25 had no effect (NTm/NTc = 0.8 to 1.2) and 8 bile samples were nucleation-inhibiting (NTm/NTc greater than or equal to 1.4). There was no correlation between the lipid or protein content of a T-tube bile sample and its nucleation-influencing activity. The presence of both nucleation-promoting and nucleation-inhibiting activity in the same T-tube bile was demonstrated by chromatography on concanavalin A-Sepharose. More than 75% of the biliary protein did not bind to the column. This fraction showed nucleation-inhibiting activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Splenic mediated erythrocyte cytotoxicity in malaria.

Cell-mediated cytotoxicity in virulent rodent malaria has been demonstrated in vitro, whereby splenic cells effected specific lysis of 51Cr-labelled erythrocytes from parasitized animals. More than one cellular cytolytic effector system appeared to be operative in the mouse. One effector system involved splenic macrophages, from normal or immune animals, which were increasingly cytotoxic to target cells in the presence of antibody. A second effector system involved nylonpurified immune spleen cells which were significantly more cytotoxic than similary prepared normal spleen cells in the presence of immune serum. Although antibody alone was not cytolytic, the data strengthen the concept that immune spleen cells and antibody can interact in a co-operative fashion to mediate cytotoxic reactions in malaria.