High-Temperature Short-Time Heat Inactivation of HIV and Other Viruses in Human Blood Plasma

An ultra-short-time heating system was used to process blood plasma spiked with various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus). Virus reduction and recovery of plasma proteins were measured at various temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s resulted in a high level of virus kill, including greater than or equal to 4.4 log10 HIV, while maintaining protein structure and activity essentially intact.     

Adenocarcinoma in an ileal conduit: a late recurrence of urethral adenocarcinoma

We report a case of recurrent adenocarcinoma in an ileal loop 13 years after cystectomy for adenocarcinoma of the urethra. The method of diagnosis is discussed.     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Pyeloureterostomy or ureteroneocystostomy in renal transplantation?

A retrospective comparison of pyeloureterostomy and external ureteroneocystostomy as methods of reconstructing the urinary tract in 128 renal transplants is presented. There was one urological complication in 52 pyeloureterostomies (1.9%) compared with 4 in the 76 ureteroneocystostomies (5.3%). 6/0 Polydioxanone (PDS) is preferred to Prolene for the anastomosis because of possible calculus formation on the latter. Wound sepsis is commoner in pyeloureterostomies undergoing concomitant nephrectomy, despite prophylactic antibiotics, though this is not statistically significant and the overall sepsis rate is higher for ureteroneocystostomy. Nephrectomy was avoided in 17 selected cases by simply ligating the recipient ureter where the pre-transplant urine output was low. Two of these patients developed hydronephrosis in the isolated kidney and required later nephrectomy.     

Hemorrhagic and nonhemorrhagic brain lesions: evaluation with 0.35-T fast MR imaging

Two fast magnetic resonance (MR) imaging techniques, advanced Fourier and partial-flip imaging, were used at 0.35 T to examine 21 patients with suspected intracranial lesions; the results were quantitatively compared with a conventional spin-echo study. Both of the fast MR techniques yielded a fourfold reduction in imaging time per section. The advanced Fourier sequence showed contrast that was identical to the conventional spin-echo study with signal-to-noise ratios of 58% and 57% for the first and second echoes, respectively. The partial-flip sequence showed a contrast of 109% and 57% for lesions versus substantia alba, and 107% and 78% for substantia grisea versus substantia alba relative to the first and second echoes of the conventional spin-echo study. The partial-flip sequence was particularly sensitive to magnetic susceptibility; this produced artifacts that may undermine the usefulness of partial flip for routine screening in certain parts of the brain. However, this susceptibility significantly improved the detection of intracranial hemorrhage when compared with the spin-echo sequence, particularly when combined with phase mapping of the partial-flip study.     

The effect of temperature change upon transmitter release, facilitation and post-tetanic potentiation

1. End-plate potentials (e.p.p.s) and miniature end-plate potentials (m.e.p.p.s) were intracellularly recorded from rat diaphragm phrenic nerve preparations in vitro at temperatures between 7 degrees and 40 degrees C.2. The quantal content of e.p.p.s and the frequency of m.e.p.p.s showed broadly similar relationships with temperature, with maxima about 20 degrees and above 39 degrees C.3. Analysis of the change in e.p.p. quantal content showed that the maximum about 20 degrees C was accompanied by a similar maximum of p, the probability of release of quanta. The maximum above 39 degrees C was associated with a rise in n, a presynaptic store of material needed for release.4. The rate at which transmitter could be mobilized was linear in an Arrhenius plot with an apparent activation energy of 25 kcal deg(-1).5. Facilitation and post-tetanic potentiation (PTP) were shown to be entirely attributable to changes in p.6. It is suggested that facilitation and PTP have a common basis and that the (temperature-dependent) rate of Ca removal from intracellular sites at which it exerts its action is as important a determinant of the magnitude of quantal release as is the amount of Ca combining with these sites.     

On the mechanism by which calcium and magnesium affect the release of transmitter by nerve impulses

1. The relationship between the quantal content of end-plate potentials (e.p.p.s) and the bathing [Ca] and [Mg] was determined at neuromuscular junctions in the rat diaphragm in vitro.2. E.p.p.s were recorded intracellularly from preparations exposed to solutions with [Ca] between 0.05 and 10 mM and [Mg] between 0.1 and 12.5 mM. The quantal content of e.p.p.s was increased by raising the [Ca] over this range and decreased by raising the [Mg]. There appeared to be competition of Mg with Ca at three sites in the nerve terminal membrane.3. A kinetic scheme based on competition of Ca and Mg at three sites could quantitatively explain the effects of Ca and Mg upon the quantal content of e.p.p.s and also the effects of these ions upon miniature end-plate potential frequency.     

Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.