Age at time of hepatitis Be antibody seroconversion in childhood chronic hepatitis B infection and mutant viral strain detection rates.

BACKGROUND: Investigations of adult patients have demonstrated that with seroconversion, changes occur from wild-type strains of the infecting virus to mutant strains. However, to date, there have been few reports and insufficient investigation of this issue in children. METHODS: The presence or absence of nucleotide base and amino acid sequence mutations in a portion of the X region containing the core promoter region, the pre-C region, and the C region of HBV genomic DNA were investigated using a polymerase chain reaction-direct sequencing method on serum samples collected from 14 children who were hepatitis Be antibody (HBeAb)-positive carriers. Samples from three children who were HBe antigen (HBeAg)-positive carriers served as the control subjects. RESULTS: When patients were grouped based on whether they had had documented seroconversion before age 6 or at age 6 or older, differences in mutant viral detection rates involving the core promoter region and the pre-C region were apparent. Specifically, a mutant strain showing a G-to-A substitution at nucleotide 83 in the pre-C region, or a mutant strain showing an A-to-T substitution at nucleotide 1762 and a G-to-A substitution at nucleotide 1764, was detected in only two of eight cases (25%) from the HBeAb-positive carriers with documented seroconversion before age 6. In contrast, these findings were present in six of six patients (100%) with documented seroconversion at age 6 or older. CONCLUSIONS: The results of the present study suggest that the mechanism of onset of HBeAb seroconversion differs between children aged less than 6 years and those who are aged 6 or more.     

Oxatomide inhibits the release of bronchoconstrictor arachidonic acid metabolites (iLTC4 and PGD2) from rat mast cells and guinea-pig lung

The effect of oxatomide, an orally active antiallergic drug, on immunoreactive LTC4 (iLTC4) production has been studied in rat peritoneal exudate cells (PEC) and guinea-pig lung fragments using the calcium ionophore A23187 and specific antigen in vitro. Oxatomide (10(-5) M) inhibited iLTC4 release by 70% with A23187 from rat PEC, and by 48% with antigen from guinea-pig lung. Oxatomide is supposed to affect the biosynthesis pathway of leukotrienes, because oxatomide inhibits 5-lipoxygenase from guinea-pig peritoneal leukocytes with an IC50 17 microM. Oxatomide also depressed the release of PGD2 from rat peritoneal mast cells stimulated by A23187 (IC50 4.2 microM). The effects of oxatomide on iLTC4 and PGD2 release were more potent than other antiallergic drugs (DSCG, ketotifen, tranilast).     

Autonomic regulation of tight junctional permeability in the rat submandibular gland

The permeability of tight junctions to tracers having different molecular weights was investigated in the submandibular gland of rats stimulated parasympathetically, sympathetically, or both. Lactoperoxidase (82,000 daltons), horseradish peroxidase (40,000 daltons), and microperoxidase (1,630 daltons) were used as the tracers. The tracers were administered by close arterial infusion via the glandular artery, and their secretion into the saliva was quantified biochemically, and their secretory routes within the gland were determined histochemically at the electron microscopic level. Microperoxidase and horseradish peroxidase passed into the saliva by electrical stimulation of either the chorda or superior cervical ganglion, and the combined stimulation of both caused a larger output of both tracers. No output of lactoperoxidase into the saliva occurred with any type of nerve stimulation. Electron microscopic histochemical observations showed that molecules of molecular weight equal to or lower than that of horseradish peroxidase entered the lumen through the tight junctions between adjacent acinar cells following combined stimulations of chorda and superior cervical ganglion. These findings indicate that electrical stimulation of parasympathetic and sympathetic nerves causes an increase in tight junctional permeability of acinar cells to microperoxidase and horseradish peroxidase. Although the combined stimulation of parasympathetic and sympathetic nerves resulted in increased junctional permeability to these tracers, the junctions remained impermeable to larger molecules, i.e., lactoperoxidase.     

Localization of alpha 1-adrenoceptors in hypertrophic prostate]

In order to determine the localization of alpha 1-adrenoceptors in human hypertrophied prostates, in vitro autoradiography was performed on the frozen specimens from 13 enucleated hypertrophied prostates with [125I]-HEAT (iodo-2-[beta-(4-hydroxyphenyl)-ethylaminomethyl] tetralone) and [3H]-prazosin. In vitro autoradiograms showed macroscopically the specific binding site on the areas seemed to the nodular area for [125I]-HEAT, but not so clear specific binding sites for [3H]-prazosin. Microscopic autoradiograms seemed to show binding sites located mainly on the interstitial beneath the gland, and partly on the basement membrane and epithelium of the prostatic gland. Further studies are needed to show clearer specific binding sites of alpha 1-adrenoceptors.     

Clinical effects and toxicity of chemotherapy with cisplatin for head and neck cancer--the multi-institutional joint research in Tokai district]

We investigated the clinical effects and toxicity of chemotherapy with Cisplatin (CDDP) for head and neck cancer as the third joint research project of the Tokai Meeting for Head and Neck Tumors. The cases were examined at the cooperating institutions from September 1986 to March 1988. The subjects were 93 cases consisting of 66 patients (intravenous infusion: 47 cases; intraarterial infusion: 19 cases) of PP therapy (CDDP + PEP), 16 cases of PF therapy (CDDP + 5-FU) and 11 cases of PPV therapy (CDDP + PEP + VCR). The regimens of PP therapy were: CDDP 50-100 mg/body x 1 day, PEP 5 mg/body x 5 days (i.v.), and CDDP 10-20 mg/body x 5 days, PEP 5-10 mg/body x 5 days (i.a.). In the regimen of PF therapy, CDDP 80-100 mg/body x 1 day and 5-FU 750-1,000 mg/body x 5 days were administered. In the regimen of PPV therapy, CDDP 80-100 mg/body x 1 day, PEP 5 mg/body x 5 days and VCR 1 mg/body x 1 day were administered. As a rule, two courses of each of the regimens were performed. The total dose of CDDP in intraarterial infusion of PP therapy was significantly less than in intravenous infusion. The major results were as follows: 1) Total response rate was 57.0% on the average, and this was not significantly different among the regimens. 2) The response rate of intraarterial infusion of PP therapy was as high as that for intravenous infusion in spite of the lower CDDP dose. 3) The response rate of oral cavity was significantly higher than that of nasal cavity and paranasal sinuses. 4) In the squamous cell carcinoma, the response rate of the well differentiated type was significantly higher than that of the poorly differentiated type. 5) The leukocyte counts significantly decreased with the intravenous infusion of PP therapy, PF therapy and PPV therapy. 6) The platelet counts significantly decreased with PPV therapy. 7) There were no significant changes with time with Ccr and PaO2 of PP therapy. 8) The frequency of toxicities such as nausea and vomiting was high in the intravenous infusion of PP therapy, PF therapy and PPV therapy. However, the frequency of toxicity was low in the intraarterial infusion of PP therapy.     

Effect of vitamin K2 on osteoblast apoptosis: vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine

Vitamin K2 is used for the treatment of osteoporosis, but the precise mode of action is still not clear. We investigated the effects of vitamin K2 on apoptosis of human osteoblasts. Human osteoblastic cell line MG63 cells and human primary osteoblast-like cells obtained from bone fragments in corrective surgery were used as human osteoblasts. Cells were cultured with or without various concentrations of vitamin K2 and tumor necrosis factor-alpha (TNF-alpha). We then determined the proliferative response, expression of Fas and Bcl-2-related proteins, and Fas-mediated apoptosis of these cells induced by anti-Fas immunoglobulin M (IgM). In addition, the effect of vitamin K2 in osteoblast apoptosis induced by Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or staurosporine was also examined. Human osteoblasts did not show spontaneous apoptosis in culture, even in the presence of vitamin K2 or TNF-alpha. Furthermore, proliferation of the cells was not influenced by vitamin K2 or TNF-alpha. Fas was functionally expressed on human osteoblasts, and the treatment with TNF-alpha significantly enhanced both Fas expression and Fas-mediated apoptosis of osteoblasts. The addition of vitamin K2 to the culture resulted in a dose-dependent inhibition of functional Fas expression on osteoblasts, in the presence or absence of TNF-alpha. Treatment of human osteoblasts with vitamin K2 clearly suppressed Bax expression of the cells, although the expression of Bcl-2 was not influenced by vitamin K2. Fas ligand (FasL) cDNA transformants were cytotoxic against osteoblasts, and the cytotoxicity was increased when osteoblasts were treated with TNF-alpha. The addition of vitamin K2 to osteoblasts significantly decreased the cytotoxic effects of FasL cDNA transformants. Furthermore, apoptosis of human osteoblasts induced by LLL-CHO, etoposide, or staurosporine was also clearly suppressed in vitamin K2-treated osteoblasts. Our results suggest that vitamin K2 inhibits apoptotic cell death of osteoblasts and maintains the number of osteoblasts. These actions may explain the therapeutic efficacy of vitamin K2 in osteoporosis.     

Secondary hypertension

In patients with hypertension and chronic renal parenchymal disease, BP should be controlled to 130/85 mmHg or lower (125/75 mmHg) in patients with proteinuria in excess of 1 g/day. Reducing dietary sodium (< 7 g/day) and protein (< 0.6-0.7 g/kg) helps control high BP and renal function in patients with renal insufficiency. As first antihypertensive drug, ACE inhibitors or long-acting Ca antagonists are recommended. In patients with renovascular hypertension, angioplasty is the first choice increasingly to be accompanied by stenting, and surgical revascularization is the next choice. As antihypertensive drugs, beta blockers, ACE inhibitors, and AII-receptor blockers are recommended. Hypertension accompanied by endocrine disease with adenoma or tumor is almost cured or improved by surgical removal. Spironolactone and Ca antagonists are used in patients with idiopathic aldosteronism (bilateral hyperplasia). Alpha and beta blockers are used in patients with pheochromocytoma during preoperative period.     

Capsular polysaccharide antibodies after pneumococcal polysaccharide vaccination in patients with chronic respiratory disease]

We investigated the antibody response to a 23-valent pneumococcal polysaccharide vaccine (23PSV), in 151 patients (average age: 70 years old) with chronic respiratory disease. Serotype-specific IgG antibodies to 4 pneumococcal capsular polysaccharides (6B, 14, 19F, and 23F) were analyzed by ELISA before, and one month after, 23PSV vaccination in all patients. Patients showed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (5.5 times-20.9 times). Even patients aged over 80, patients with respiratory failure, and patients receiving corticosteroid therapy developed a significant immunologic response to 23PSV. Local pain or induration occurred in 9.1-14.3% and fatigue or chills occurred in 0.7-6.5% of patients. All adverse reactions disappeared in 2 or 3 days and there was no severe adverse events. Further studies are needed to confirm the exact protective antibody level and to examine the decline of antibody level after vaccination.