Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

Two rare anomalies of the brachial plexus

Morphological variations of the brachial plexus and variants in the distribution of the anterior division of the middle trunk are relatively frequent. Two of the rarest anomalies occurred in the left brachial plexus of a 62-y-old Japanese male, 1 of 104 plexuses dissected between 1996 and 1997 at Kanazawa University Faculty of Medicine. The superior trunk of the brachial plexus was formed by the anterior primary division of C5 and C6 and a thin branch (0.5 mm in diameter) from C4, the middle trunk by the C7, and the inferior trunk by C8 and T1 (Fig.). We could not determine whether there was a branch derived from T2 to T1, since the subject had died of lung carcinoma. The entire anterior division of the middle trunk crossed the axillary artery and joined the medial root of the median nerve which was the continuation of the medial cord after the cord branched off the ulnar nerve. The lateral cord pierced coracobrachialis and divided into the musculocutaneous nerve and the lateral root of the median nerve just after emerging from the muscle, finally joining the medial root of the median nerve superficial to the brachial artery ∼115 mm distal to the lower border of latissimus dorsi to form the median nerve. The musculocutaneous nerve gave rise to the nerves to biceps brachii, brachialis, and the long head of biceps brachii and finally continued as the lateral cutaneous nerve of the forearm. The branch to coracobrachialis had already been cut and its course could not be traced.     

The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus

The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients.     

Signet-ring cell carcinoma of the prostate effectively treated with maximal androgen blockade

Primary signet-ring cell carcinoma (SRCC) of the prostate is very rare and has a poor prognosis, even when treated with aggressive therapy. We report herein a case of a 72-year-old man with prostatic SRCC. The patient had a tumor that extended directly to the rectum. Maximal androgen blockade was started and 20 months later, the patient was alive without evidence of recurrence. The present case of prostatic SRCC responded well to medical therapy, however, tumors can recur after a long period of time. Therefore, adjuvant therapy is recommended.     

Serum N-acetylglucosaminyltransferase III activities in hepatocellular carcinoma

N-Acetylglucosaminyltransferase III (GnT III) catalyses the addition of N-acetylglucosamine through a β 1–4 linkage to the mannose of the trimannosyl core, resulting in conversion of the concanavalin A (Con A)-reactive glycan into a non-reactive state. In this study, we measured GnT III activity to evaluate its diagnostic efficacy and its therapeutic effect on hepatocellular carcinoma (HCC). Concanavalin A-non-reactive fraction of serum transferrin (Tf) was also determined since the sugar chains of Tf are one of the possible candidates for the product of GnT III. Serum samples (159) were used from patients with HCC (89), liver cirrhosis (30), chronic hepatitis (19), alpha-fetoprotein (AFP) producing gastric carcinoma metastatic to the liver (five) and healthy controls (16). N-Acetyl-glucosaminyltransferase III activity was determined by high performance liquid chromatography. The reactivity of serum Tf to Con A was also analysed in 21 paired HCC samples before and after treatment by crossed immuno-affinoelectrophoresis. N-Acetylglucosaminyltransferase III activity from the HCC group (153 ± 72 pmol/mL/h) was significantly higher than that from liver cirrhosis (99 ± 67 pmol/mL per h), chronic hepatitis (84 ± 39pmol/mL per h) and the normal controls (62 ± 16pmol/mL per h). N-Acetylgiucosaminyltransferase III activity of 21 patients with HCC was significantly reduced after treatment such as transcatheter arterial chemoembolization and/or percutaneous ethanol infection therapy, (123 ± 77 to 100 ± 60pmol/mL per h). Commensurate decreases of AFP and des-γ-carboxy prothrombin with GnT III activity were also observed after treatment. The Con A-non-reactive fraction (n= 21; 6.4 ± 2.3%) in patients with HCC after treatment was significantly lower than before (8.2 ± 2.4%). The present study suggests that GnT III activity is a possible and in the diagnosis and evaluation of HCC, especially when other tumour markers are negative.     

Effects of glycyrrhizin on immune-mediated cytotoxicity

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-α is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4⁺ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-α-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-α-induced cytotoxicity in the TNF-α-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.     

HPLC-studies on nonmercapt-mercapt conversion of human serum albumin

Human mercaptalbumin (HMA) and nonmercaptalbumin (HNA) could be separated by high-performance liquid chromatography (HPLC) at neutral pH. Using HPLC, the present authors found the nonmercapt-mercapt conversion (HNA ← HMA) during hemodialysis and the mercapt-nonmercapt conversion (HMA ← HNA) after hemodialysis in chronic renal failure, indicating HMA as the covalent carrier protein for sulfur-containing amino acids.     

Fast-Slow Type of Atrioventricular Nodal Reentrant Tachycardia: Horizontal Dissociation of the AV Node During Tachycardia

Two patients with recurrent supraventricular tachycardia are presented. The tachycardia was initiated and terminated by atrial extrastimulation beyond the atrial relative refractory period and the atrial activation sequence during the tachycardia was low to high. The induction of tachycardia was dependent on a critical AH interval. In patient 1 who had ventriculoatrial conduction, the tachycardia was initiated by the premature ventricular stimulation followed by double atrial response. In patient 2 the ventriculoatrial conduction was not observed. In both patients, the unchanged atrial cycle length during the tachycardia with antegrade Wenckebach AH block was observed. When AH block occurred during tachycardia the first AH interval was shorter than the subsequent HA interval. In patient 2 verapamil (5 mg) prolonged the atrial cycle length during tachycardia and rapid intravenous injection of adenosine triphosphate (10 mg) terminated the tachycardia. Oral diltiazem (280 mg/day) suppressed the tachycardia in patient 1. These findings suggest that the mechanism of tachycardia may be fast-slow type of AV nodal reentry in the upper portion of the AV node and this type of arrhythmia has tendency to show incessant form.