Interaction of suriclone with central type benzodiazepine receptors in living baboons

The interaction of suriclone and two of its main metabolites with central type benzodiazepine receptors, which had been labeled in vivo with the radioligand [11C]RO 15-1788, was investigated in living baboons. The concentration of radioligand bound to the receptors, as measured in brain transverse sections by positron emission tomography, decreased rapidly after the i.v. administration of suriclone at doses known to induce pharmacological effects. The rate and extent to which [11C]RO 15-1788 binding was displaced increased with increasing doses of suriclone. The half-inhibitory dose (ID50) was determined to be 0.08 mg/kg in vivo. The rapid inhibitory effect of suriclone on the in vivo binding of [11C]RO 15-1788 in the brain seems to reflect its ability to act at the GABA-benzodiazepine receptor complex, at or near to the benzodiazepine binding site, to induce its pharmacological activity. The i.v. injection of the demethylated metabolite of suriclone, RP 35,489, only caused a slight displacement of [11C]RO 15-1788 binding even at a dose of 2 mg/kg. Thus, suriclone appears to be more potent than RP 35,489 to displace the benzodiazepine 11C antagonist in vivo. The sulfoxide metabolite, RP 46,166, did not significantly change the kinetics of [11C]RO 15-1788 binding in the brain. The slight effects produced by high doses of RP 35,489 and RP 46,166 on [11C]RO 15-1788 binding in the brain suggest that these metabolites are probably not responsible for the expression of biological activity of suriclone mediated by benzodiazepine receptors.     

Successful mitral valve repair for active infective endocarditis accompanied by anorexia nervosa

Infective endocarditis of the mitral area accompanied by anorexia nervosa is extremely rare. A 34-year-old Japanese woman presented with high fever and a heart murmur that had developed over the previous 2-month period. Echocardiography revealed mitral regurgitation and vegetation attached to the anterior mitral leaflet, which had markedly prolapsed to the left atrium. We removed the vegetation with a small part of the anterior mitral leaflet and successfully repaired the mitral valve. The patient showed good recovery, and the mitral regurgitation and left ventricular chamber size had satisfactorily decreased at 2 months after the operation.     

Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats

Liver transplantation, which serves as treatment of familial amyloidotic polyneuropathy (FAP), and domino liver transplantation, which utilizes resected livers from patients with FAP for treatment of liver diseases, may induce changes in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels decreased by 77%; at day 3, they returned to preoperative levels. Except for slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels remained unchanged. Thus, partial hepatectomy did not influence serum TTR concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h after the experiment started; however, after day 3, a rebound phenomenon occurred until day 7. Tacrolimus may facilitate serum TTR degradation, although production of TTR in the liver also increased. This finding -- that TTR, the source of FAP-inducing amyloid, did not increase after transplantation -- may help post-transplantation treatment of patients who have FAP and other liver diseases.     

Ross procedure in an infant weighing 4.5 kg

A 6 month-old male infant (weight: 4.5 kg) with congenital aortic stenosis underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The right ventricular outflow tract (RVOT) was reconstructed with a polytetrafluoroethylene (PTFE)-valved equine pericardial conduit. At the age of 5, re-RVOT reconstruction with an equine pericardial patch bearing a PTFE monocusp was required because of severe pulmonary stenosis resistant to 2 attempts of percutaneous transluminal pulmonary valvotomy. Currently, at the age of 8, the degree of aortic regurgitation is trivial and the pulmonary autograft is free of functional deterioration despite somatic growth.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.     

Acute effect of flunarizine on amygdaloid kindling in cats

Flunarizine (Flu), a difluoro derivative of cinnarizine, is well known as a calcium channel blocker. Recently, many authors have reported an antiepileptic effect of this drug in experimental models of epilepsy and in the clinical use. In the present study, acute effect of Flu was examined in the amygdaloid kindled cats, and add-on effects of Flu with valproic acid (VA) was also studied. Twenty three cats were used in this study. Amygdaloid kindling was established as previously reported. A strength of stimulations for kindling was at 300 microA. Same strength was used after completion of kindling. In this "high intensity" kindling, daily stimulation invariably induced initial amygdalo-hippocampal seizures followed by secondarily generalized seizures after completion of kindling. In addition, one amygdaloid stimulation was given daily for 5 days after completion of kindling in order to make it certain to induce secondarily generalized seizures. Drugs were injected on the 6th day intraperitoneally one or two hours before the stimulation daily given for 5 days after completion of kindling (GS 6) or after 4 days clearance period of previous administration of the drug. Pretreatment with Flu (high doses: 30 or 50 mg/kg, i.p.) abolished the secondary generalization after the GS 6. With this high doses of Flu animals died of side effect within 3 days after intraperitoneal administration. With lower doses of Flu less than 3 mg/kg, i.p. of Flu no side effect was encountered but antiepileptic effect was not obtained as well. Then add-on trials of Flu were performed with valproic acid (VA). The most effective combination was 100 mg/kg, i.p. of VA with 3 mg/kg, i.p. of Flu. With this combination, secondary generalization was suppressed at a ratio of 54.5% The results confirmed antiepileptic effect of Flu and add-on effect of Flu to VA.(ABSTRACT TRUNCATED AT 250 WORDS)     

WIDESPREAD ECZEMA VACCINATUM ACQUIRED BY CONTACTS A Report of an Autopsy Case

A4-moth-old male infant predisposed to allergic dermatitis acquired widespread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease. ACTA PATH. JAP. 29 : 435–455, 1979.     

Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method, loop-mediated isothermal amplification

A novel nucleic acid amplification method, termed loop-mediated isothermal amplification (LAMP), which amplifies DNA with high specificity, efficiency, and rapidity under isothermal conditions, may be a valuable tool for the rapid detection of infectious agents. LAMP was developed for human herpesvirus 6 (HHV-6), and its reliability was evaluated in this study. Although LAMP products were detected in HHV-6 B and HHV-6 A DNA, they were not detected in HHV-7 and human cytomegalovirus DNA. The sensitivity of the original HHV-6 LAMP protocol was 50 copies/tube. In order to increase the method's sensitivity, HHV-6 LAMP was modified by increasing the primer concentration. As a result of the modification, sensitivity increased to 25 copies/tube. After these initial validation studies, 13 patients with fever were tested for HHV-6 by viral isolation, serological analysis, and HHV-6 LAMP. In three of the eight patients with primary HHV-6 infection, HHV-6 DNA was detected in whole blood by the original HHV-6 LAMP protocol in not only the acute phase but also the convalescent phase. HHV-6 DNA was detected by modified HHV-6 LAMP in all eight plasma samples collected in the acute phase; however, no HHV-6 DNA was detected in plasma samples collected in the convalescent phase. Although HHV-6 DNA was detected in both the acute and convalescent phases of whole-blood samples in patients with past HHV-6 infection, it was not detected in plasma samples that did not contain latent viral DNA. Thus, detection of HHV-6 DNA in plasma by using this modified HHV-6 LAMP protocol is appropriate for diagnosis of active HHV-6 infection.     

Dominant-Negative Rho, Rac, and Cdc42 Facilitate the Invasion Process of Vibrio parahaemolyticus into Caco-2 Cells

To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.     

Cytoarchitectonic subdivisions of the parabrachial nucleus in the Japanese monkey (Macacus fuscatus) with special reference to spinoparabrachial fiber terminals

The cytoarchitectonic subnuclear organization of the parabrachial nucleus (PB) surrounding the brachium conjunctivum (BC) in the monkey was examined using the Nissl method and the anterograde axonal flow method. PB of the monkey could be divided into the following subnuclei: the dorsal area (DPBM) along the medial surface of the medial three-fourths of BC in the caudal half of medial PB (PBM), the ventral area (VPBM) along the medial surface of the lateral one-fourth of BC in the rostral two-thirds of PB, the ventrolateral part of lateral PB (PBL) lateral to BC throughout PB (EL), the ventral part of the rostral half of PBL ventral to EL (EXL), the medial part of middle PBL along the dorsal surface of BC (VL), the dorsal and lateral marginal part of PBL in the rostral two-thirds of PB (DL), the cell cluster in the dorsomedial part of the rostral half of PBL between VL and DL (CL), the dorsocentral part appearing at the level of root exit of the trochlear nerve between DL and CL and extending to the rostral end of PBL (IL), the area between DL and IL in the rostral one-seventh of PBL (SL), and K?lliker-Fuse nucleus (KF) ventral to EL and BC in the middle one-third of PB and lateral to the lateral pontine tegmentum. After the injection of biotinylated dextran amine into the upper cervical segments, labeled fibers terminated in each subdivision of PB with different densities; most heavily in IL, more heavily in DL and KF, moderately in EL and VPBM, and scarcely in the rest of PB. The present study demonstrated for the first time the subdivisions of PB in the monkey, which were essentially common to those of the rat based on the cytoarchictecture of PB and spinal fiber terminals in it.