Repair of the UL21 locus in pseudorabies virus Bartha enhances the kinetics of retrograde, transneuronal infection in vitro and in vivo.

The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the U(L)21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha U(L)21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.

Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis.

The simultaneous occurrence of PSC and autoimmune CAH in a patient with ulcerative colitis is described. Although each disease is a well documented complication of UC, their combination has never been reported. The diagnosis of PSC was based on typical findings on ERCP and liver biopsy and that of CAH was based on typical findings on liver biopsy supported by HLA typings and a remarkable response to a combination of glucocorticoids and azathioprine. The difficulties in establishing the diagnosis and the management of such patients are discussed.

Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease.

Autoimmune chronic active liver disease (ACALD), a major indication for liver transplantation, is associated strongly with antigenic determinants HLA-B8 and DR3. A retrospective analysis of 43 patients who underwent OLTx for putative ACALD and who, as well as their tissue organ donors, were typed, was performed. Disease recurrence and graft rejection episodes were determined by chart review and histopathological review of all material available. Disease recurrence was histologically documented in 11 (25.6%) of these 43 cases. Graft rejection episodes occurred in 24 (55.8%). All recurrences were in recipients of HLA-DR3-negative grafts. Nine of the recurrences were in HLA-DR3-positive recipients (odds ratio: 6.14, P less than 0.03). Two of 11 cases of disease recurrence were in recipients who were HLA-DR3-negative. Nine of these 11 had received HLA-DR3-negative grafts. Rejection occurred in 13 HLA-B8-positive recipients, 12 of whom received HLA-B8-negative grafts. Eleven HLA-B8-negative recipients experienced at least one rejection episode and 9 of these had received HLA-B8-negative grafts. Based upon these data we conclude: 1) that recurrence of putative ACALD is more likely to occur in HLA-DR3-positive recipients of HLA-DR3-negative grafts; (2) that recurrences were not seen in recipients of HLA-DR3-positive grafts; (3) that HLA-B8 status does not affect disease recurrence; and (4) that neither the HLA-B8 nor the DR3 status of the graft or recipient has an effect on the observed frequency of rejection.

Reversal of andro-genetic alopecia in a male. A spironolactone effect?

This 73-year-old white male has been bald since the age of 28. He developed nonA-nonB-induced liver cirrhosis and had been treated with spironolactone for the last 6 years. For the last 3 months, his hair had started to regrow over the scalp. This might be related to the antiandrogenic effect of spironolactone.

Microcirculatory stasis precedes tissue necrosis in ethanol-induced gastric mucosal injury in the rat.

The relation of blood flow stasis to the development of unequivocal histologic necrosis (loss of parietal cells from the column of contiguous cells) in ethanol-induced gastric mucosal injury was studied in anesthetized rats. The most rapid vascular change that occurred when the gastric mucosa was exposed to 100% ethanol was a severe segmental constriction of the large submucosal venules. At 22 sec, the average venular diameter was 52.2 +/- 6.0% of the original one. This was followed by complete superficial mucosal blood flow stasis at 49 +/- 4 sec and appearance of histologic evidence of necrosis in one of seven rats at 2.5 min, four of six rats at 10 min, and seven of seven rats at 60 min. We conclude that in ethanol-induced gastric mucosal injury, submucosal venular constriction occurs first, followed by cessation of mucosal blood flow to be followed later on with histologic evidence of necrosis.