Kinetics and viral protein specificity of the cytotoxic T lymphocyte response in healthy adults immunized with live attenuated varicella vaccine.

The cytotoxic T lymphocyte (CTL) response was evaluated in adults given live attenuated varicella vaccine, using target cells expressing varicella-zoster virus (VZV) immediate-early protein (IE62) or VZV glycoproteins gpI, gpIV, or gpV to determine viral protein specificity. The frequency of CTL that recognized IE62 was 1:171,000 +/- 46,000 SE in subjects tested 10 days to 8 weeks after the initial vaccine dose; the induction of CTL specific for gpI was equivalent. CTL recognition of VZV proteins was mediated by CD4+ or CD8+ cells. CTL recognition of IE62 and gpIV persisted in vaccinees (tested approximately 4 years later) and was comparable to that in the naturally immune. The mean frequency of CTL specific for gpV was lower (but not significantly) in vaccinees than in naturally immune subjects. Assay of responder cell frequencies showed persistence of equivalent numbers of T lymphocytes that recognized IE62 and gpI in vaccinees and naturally immune subjects. Immunization with this vaccine elicited memory T lymphocyte responses to VZV comparable to those induced by natural infection.     

Fos plays no role in apoptosis of epithelia in the mouse male accessory sex organs and uterus

Roles of Fos in apoptosis of epithelia in the mouse male accessory sex organs and uterus were investigated using Fos-deficient mice. Normal 30- and 50-day-old and Fos-deficient 50-day-old male and female mice were castrated, and testosterone propionate and estradiol-17 beta were daily injected into male and female mice, respectively, for 5 days. An apoptotic index (a percentage of apoptotic cells) in the epithelium was examined from the day following the last injection (day 1) to day 8. The body weights and the weights of the ventral prostate (VP), coagulating gland (C), seminal vesicle (SV) and epididymis (Ep) and uterus of 50-day-castrated Fos-deficient mice on day 1 suggested that the development of these mice corresponded to that of 30-day-castrated normal mice at the most. The extents of apoptosis estimated by an apoptotic index in the VP, C, SV, Ep and uterus in 50-day-castrated Fos-deficient mice were comparable to those in 30-day-castrated normal mice. The extents of apoptosis in the SV, Ep and uterus in 30-day-castrated normal and 50-day-castrated Fos-deficient mice were similar to those in 50-day-castrated normal mice, while the extents of apoptosis in the VP and C in the former two groups of mice were less than those in the latter mice. The present results show that Fos-deficiency does not affect apoptosis in the SV, EP and uterus. However, the extents of apoptosis in the VP and C were less in 50-day-castrated Fos-deficient mice than in 50-day-castrated normal mice. This seems to be due to the retarded development of 50-day-castrated Fos-deficient mice, but not to a role of Fos in apoptosis.     

Targeted disruption of p70s6k defines its role in protein synthesis and rapamycin sensitivity

Here, we disrupted the p70 S6 kinase (p70^s6k) gene in murine embryonic stem cells to determine the role of this kinase in cell growth, protein synthesis, and rapamycin sensitivity. p70^s6k−/− cells proliferated at a slower rate than parental cells, suggesting that p70^s6k has a positive influence on cell proliferation but is not essential. In addition, rapamycin inhibited proliferation of p70^s6k−/− cells, indicating that other events inhibited by the drug, independent of p70^s6k, also are important for both cell proliferation and the action of rapamycin. In p70^s6k−/− cells, which exhibited no ribosomal S6 phosphorylation, translation of mRNA encoding ribosomal proteins was not increased by serum nor specifically inhibited by rapamycin. In contrast, rapamycin inhibited phosphorylation of initiation factor 4E-binding protein 1 (4E-BP1), general mRNA translation, and overall protein synthesis in p70^s6k−/− cells, indicating that these events proceed independently of p70^s6k activity. This study localizes the function of p70^s6k to ribosomal biogenesis by regulating ribosomal protein synthesis at the level of mRNA translation.     

Near-infrared spectrometry analysis of fat, neutral sterols, bile acids, and short-chain fatty acids in the feces of patients with pancreatic maldigestion and malabsorption

Summary Conclusion. Near-infrared spectrometry is a new, rapid, and accurate method for measuring fecal fat that does not require a great deal of chemical knowledge and that can be used by anyone. This method is considered indispensable for the diagnosis of pancreatic steatorrhea and treatment follow-up. Methods. Fecal fats (GLC method, van de Kamer method), neutral sterols (GLC method), bile acids (GLC method) and short-chain fatty acids (HPLC method) were assayed by the respective conventional methods in 120 subjects, including patients with pancreatic dysfunction, and the results were compared with the those obtained by near-infrared spectrometry. The correlations between fecal fat excretion measured by the GLC method (x) and van de Kamer method (x) and by near-infrared spectrometry (y) were expressed by y=1.10 x-0.16 (r=0.949, P<0.01) and y=0.750x+1.654 (r=0.930, p<0.01), respectively. Results. The sensitivity and specificity of near-infrared spectrometry for fecal fats were 94.9 and 98.2%, respectively, when compared with the GLC method, and 87.5 and 90.0%, respectively, when compared with the van de Kamer method. In contrast, near-infrared spectrometry was not nearly as accurate as the conventional methods for determining neutral sterols, bile acids, and short-chain fatty acids.     

Primary Sj?gren's syndrome with antibodies to HTLV-I: clinical and laboratory features.

The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was studied in patients with primary Sjögren''s syndrome. Thirteen of 36 serum samples were positive by enzyme linked immunosorbent assay (ELISA) and particle agglutination assay for antibodies to HTLV-I and were confirmed by western blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier state. These patients had a high occurrence of extraglandular manifestations such as uveitis, myopathy, and recurrent high fever compared with patients who did not have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased spontaneous proliferation of peripheral blood mononuclear cells compared with those without the antibodies. The proportions of activated and memory T cells (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers than in non-carriers. The presence of antibodies to HTLV-I in some patients with primary Sjögren''s syndrome suggests that HTLV-I may cause primary Sjögren''s syndrome or its extraglandular manifestations, or both.     

Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

A case of intractable hemoptysis originating from the branches of the right subclavian artery, successfully treated with arterial coil embolization]

A 30-year-old woman was admitted because of persistent and severe hemoptysis in November 2005. She had been given a diagnosis of interstitial pneumonia (IP) and pulmonary aspergilloma in 2001, and she was treated with oral prednisolone and itraconazole. However she had persistent and intractable hemoptysis. Multi-detector row computed tomography (MDCT) revealed that hemoptysis from the right upper lobe did not originate in bronchial arteries, but the abnormal branches of the right subclavian artery. Surgery was not performed because of her pulmonary function, but she was successfully treated by non-bronchial arterial coil embolization. At 10 months after the embolization, hemoptysis has not recurred. MDCT was very useful for diagnosing the cause of hemoptysis and selective nonbronchial arterial coil embolization might be helpful in treating intractable or refractory hemoptysis.     

The sera from GM1 ganglioside antibody positive patients with Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy blocks Na+ currents in rat single myelinated nerve fibers

OBJECTIVE: To determine the possible role of anti-GM1 ganglioside antisera from patients with Gullain-Barr*e syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) in the development of nerve dysfunction. METHODS: The effect of the anti-GM1 antibody positive antisera obtained from 4 GBS patients and 1 CIDP patient on membrane potential and ionic currents in rat single myelinated nerve fibers was investigated using the voltage clamp technique and compared with that of the anti-GM1 negative antisera obtained from 3 healthy controls and 2 GBS patients. RESULTS: In the presence of active complement, anti-GM1 positive antisera from 5 patients including 4 GBS patients and 1 CIDP patient significantly suppressed Na+ current more than anti-GM1 negative antisera. CONCLUSION: This study supports the notion that anti-GM1 antibody is one of the causative factors of conduction abnormality in GBS patients.