Pathophysiologic concentrations of lysophosphoglycerides quantified by electron microscopic autoradiography

Lysophosphoglycerides accumulate in ischemic myocardium and appear to contribute to malignant dysrhythmia. Exposure of normoxic isolated Purkinje fibers or ventricular muscle strips to exogenous lysophosphatidyl choline (LPC) results in rapid, yet reversible, electrophysiologic derangements analogous to changes associated with ischemia in vivo. However, subcellular, local concentrations required for induction of electrophysiologic effects have not yet been elucidated unambiguously. The present study was designed to delineate the subcellular distribution and the sarcolemmal concentration of LPC by quantitative electron microscopic autoradiography after exposure of canine ventricular muscle strips to 3H-methyl LPC (200 microM) for 10 minutes. Tissue was processed for electron microscopy with a new procedure developed specifically to spatially fix choline phosphatides and render them insoluble in lipid solvents. Grain distributions were analyzed in the same group of cells that had been monitored electrophysiologically while superfused with LPC. LPC significantly decreased the resting membrane potential, action potential amplitude, duration, Vmax of phase 0, and conduction time. Grains were concentrated in the membranous organelles of cardiac myocytes. Myocyte sarcolemma exhibited the highest grain density (129 grains/100 micron2 versus a background of 0.27 grains/100 micron2). Calculations based on grain densities, emulsion sensitivity, exposure time, and specific activity indicated that the sarcolemma incorporated 5.4 X 10(6) LPC molecules/micron3 of membrane volume corresponding to approximately 1% of total sarcolemmal phospholipid. Since incorporation of only this small amount of lysophosphoglyceride into the sarcolemma was sufficient to elicit electrophysiologic disturbances, the observed accumulation of lysophosphoglycerides induced by ischemia appears to be sufficient to contribute to malignant dysrhythmia in vivo.     

Absence of simian virus 40 (SV40) DNA in lymphoma samples from Tasmania, Australia

AIMS: It has been postulated that the recent world-wide increase in the incidence of non-Hodgkin's lymphoma (NHL) may have been caused by human infection with simian virus 40 (SV40) (a lymphotropic monkey virus that was introduced to man from contaminated poliovirus vaccines between 1955 and 1963); therefore, we set out to determine the incidence of SV40 DNA positivity in lymphoma samples from patients in Tasmania, Australia. METHODS: One hundred lymph node samples, 50 from patients with lymphomas and 50 from controls, were tested using PCR amplification of three SV40-specific primer pairs followed by dot-blot hybridisation. RESULTS: All of the samples tested contained amplifiable DNA, but none contained amplifiable SV40 sequences with any of the primer sets used. CONCLUSIONS: Our results demonstrate absence of SV40 in the lymphoid tissues of our study population in Tasmania, Australia. SV40 does not explain the increasing incidence of NHL in our population.     

Thermoluminescent dosimetry of the SourceTech Medical model STM1251 125I seed

Many new models of 125I seeds are being introduced, mainly due to the increase in prostate seed implants. We have evaluated the SourceTech Medical (STM), model STM1251, 125I seed using thermoluminescent dosimeters (TLDs) in a solid water phantom. TLD cubes, LiF TLD-100, with dimension 1 mm on each edge, were irradiated at various distances, 1, 2, 3, and 5 cm, at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. Sensitivity calibration of the TLDs was achieved by irradiation to 10 cGy with 6 MV x rays from a clinical linear accelerator, Clinac 600C. Concurrent with the 125I seed exposures, several TLDs were also exposed to 10 cGy with the 600C as a control set. Dose rates per unit air kerma strength were determined based on the 1999 NIST traceable standard for the STM1251 seed. They are presented as a function of distance r and angle theta. The TG-43 parameters, including the dose rate constant, lambda, anisotropy function, F(r,theta), radial dose function, g(r), anisotropy factor, phian(r), and anisotropy constant, phi, were obtained for use in radiation treatment planning software. The value of lambda was determined as 1.07 +/- 5.5% cGy U(-1) h(-1), which is comparable to model 6702 and to the value determined using the point extrapolation method by Kirov and Williamson. We also find agreement between our TLD data and their Monte Carlo results for g(r), F(r,theta), phian(r), and phi. Additionally, agreement is found with the TLD data of Li and Williamson for lambda and g(r).     

Implementation of HaemScreen, a workplace-based genetic screening program for hemochromatosis

There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace.     

Morphological and immunohistological study of testicular lymphomas

We have studied normal testis, seminomas and malignant lymphomas of the testis using routine stains and a panel of antibodies directed against lymphoid and basement membrane antigens. The results show that normal testis contains, at most, a minor population of T-lymphocytes: seminomas contain mixed T- and B-cell populations with a predominance of B-lymphocytes; and most primary lymphomas are B-cell tumours of large centroblastic type. Solid testicular lymphomas presenting secondarily to acute lymphoblastic leukaemias showed intact seminiferous tubular basement membranes with predominantly interstitial lymphomatous infiltrates, whereas the tubules in primary cases were over-run by lymphoma cells and basement membranes were disrupted.     

Advancement to independent living: a model behavioral program for the intermediate care of adults with behavioral and emotional problems

This article describes and evaluates the treatment effectiveness of a behaviorally oriented intermediate day-care clinic for adults with psychiatric disturbances. The goals of the program included reducing the number of psychiatric hospital admissions and readmissions, providing a community-based controlled environment to assist patients in the modification of specific problem behavior, improving interpersonal relations with "significant others" in the natural environment, teaching patients how to use community resources, and preparing them for employment and/or continued outpatient treatment. The program was structured so that patients advance through a series of four achievement levels for a variety of extrinsic and intrinsic reinforcers. While in the program, patients were introduced to available community resources, and were gradually phased into follow-up services. Results showed that 79% of all patients thus far treated partially, if not completely, advanced through the levels. There was also a high probability that a patient would advance from any given level. Outside-clinic behavior showed sustained improvement, with the authors concluding that the day-care clinic offered promise for the future.     

The genetic basis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Familial clustering of cases suggests that genetic factors play an important part in its aetiology. A number of studies of families with several cases of PCOS have produced results suggesting an autosomal dominant trait. Detailed analysis of a large number of affected families has, however, cast some doubt about the mode of inheritance. An autosomal dominant trait remains possible but a more complex aetiology seems more likely. The results of our recent studies support the concept of an oligogenic disorder in which genes affecting metabolic pathways in glucose homeostasis and steroid biosynthesis are both involved. We review evidence for an important role for the insulin gene minisatellite in the aetiology of anovulatory PCOS and for the gene coding for P450 cholesterol side chain cleavage (CYP11a) in the mechanism of excessive androgen secretion in women with polycystic ovaries. We propose that the heterogeneity of clinical and biochemical features in PCOS can be explained by the interaction of a small number of key genes with environmental, particularly nutritional, factors.