Application of HUMF13A01 (AAAG)n STR polymorphism to the genetic diagnosis of coagulation factor XIII deficiency

Deficiency of the A subunit of coagulation factor XIII causes a severe bleeding disorder requiring life long replacement therapy. The mutations causing A subunit deficiency appear to be very heterogeneous, and it is impractical to identify each mutation before genetic counselling or prenatal diagnosis can be attempted. In this study we have shown that a highly polymorphic short tandem repeat element, HUMF13A01 (AAAG)n that occurs in the 5' flanking sequence of the factor XIII A subunit gene, can be used to follow the segregation of deficiency causing mutations. We studied 6 families with factor XIII A subunit deficiency from 5 different ethnic groups. All parents were heterozygous for the repetitive element and therefore all the families were informative. The linked polymorphism was used to carry out the first prenatal diagnosis of factor XIII A subunit deficiency. The analysis of this polymorphism by the polymerase chain reaction is rapid, reliable, requires little DNA and is ideal for the genetic analysis of factor XIII A subunit deficiency.     

Modulation of embryonic glutathione peroxidase activity and phenytoin teratogenicity by dietary deprivation of selenium in CD-1 mice

Selenium (Se)-dependent and -independent glutathione (GSH) peroxidases detoxify H2O2 and lipid hydroperoxides, which may mediate the teratogenicity of phenytoin and related xenobiotics. To test this hypothesis, CD-1 mice were placed on Se-deficient diets for 15, 25 or 40 days and bred so that the day of analysis corresponded to gestational day 11. In Se-replete control animals, embryonic peroxidase activities were only 5% of activities in maternal liver (P < .05). After 15 days of Se deprivation, maternal activities for H2O2 (reflecting Se-dependent peroxidase) and cumene hydroperoxide (CmOOH) (reflecting both Se-dependent and -independent peroxidases) were reduced to 20% (P < .05) and 35% of controls, respectively. At this time, the incidence of fetal cleft palates initiated by phenytoin (55 mg/kg intraperitoneally on gestational days 11, 12 and 13) was doubled, from 12% to 25% (P < .05). Selenite rescue (Na2SeO3, 350 micrograms/kg intraperitoneally on day 9) restored maternal and embryonic peroxidase activities and completely inhibited phenytoin-initiated postpartum lethality and fetal resorptions in animals that had been Se depleted for 15 days. After 40 days of Se deprivation, maternal and embryonic peroxidase/H2O2 activities were reduced to < 1% and 27% of Se-replete controls, respectively. In contrast, maternal peroxidase/CmOOH activity was increased to 70% of controls, reflecting induction of Se-independent peroxidase, compared with that with 15 days' depletion. Phenytoin-initiated cleft palates with 40 days' depletion appeared to be reduced (16%) compared with Se-replete controls (24%) (P < .07). In 40-day Se-depleted animals given selenite rescue, the 10% incidence of cleft palates was significantly lower than that in the 40-day Se-replete group (24%) but not the Se-depleted group (16%). This is the first demonstration of reduced Se-dependent GSH peroxidase activities in embryonic tissues with dietary Se-deprivation. The results implicate reactive oxygen species and lipid hydroperoxides in the mechanism of phenytoin teratogenicity and suggest that GSH peroxidases are important embryoprotective enzymes.     

Active surveillance of health and safety in microbiology laboratories

In microbiology laboratories highly infectious material is handled alongside complex and potentially dangerous equipment, and staff are therefore at risk of infections and accidents. Acts of parliament and regulations exist to protect staff in the workplace, including those exposed to biological agents. The current monitoring of health and safety in laboratories seeks to ensure that employers and employees comply with existing regulations, but this form of passive surveillance is of limited value because it does not highlight shortcomings in techniques, equipment, premises, or personnel. We propose a scheme for the surveillance of health and safety in microbiology laboratories that will actively seek information about laboratory incidents and practices, in order to enable appropriate preventive measures to be instituted.     

The classification of diseases of the temporomandibular joint

There were 2040 patients with temporomandibular joint (TMJ) diseases in the investigation including clinical, physiological, X-ray methods of research, contrast arthrotomography, computer arthrotomography and magnetic resonance tomography. The changes of structure in different lesions were estimated. The result of received data was elaboration of classification of TMJ internal derangements with estimation of clinical forms in according with structural changes and characteristics of syndromes.     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

The high-temperature oxidation of Ni-20%Cr alloys containing various oxide dispersions

The oxidation behavior of Ni-20%Cr alloys containing approximately 3 vol.% Y₂O₃, ThO₂, and A1₂O₃ as dispersed particles has been examined in the temperature range 900 to 1200° C in slowly flowing oxygen at 100 Torr. The results show that the oxidation behavior of the Y₂O₃-, ThO₂-, Al₂O₃-, and Ce0₂-containing alloys is very similar and that some anomalies in the behavior of the ThO₂-containing alloy might be explained by the slower rate of chromium diffusion in this coarse-grained alloy. Two Al₂O₃-containing alloys were studied. One with a relatively coarse dispersoid size behaved in a manner analogous to a dispersion-free Ni-30% Cr alloy at 1100°C. The other alloy contained a dispersion of fine Al₂O₃ particles and behaved exactly like the Y₂O₃-containing alloy at 1000 and 1100°C, but at 1200° C oxidized at a faster rate. It has been shown that the adherent scales on dispersion-containing alloys have a stabilized fine grain size, whereas the nonadherent scales on dispersion-free alloys undergo grain growth.This work has been supported by the Naval Air Systems Command under Contract No. N00019-72-C-0190.