Down-regulation of inducible nitric oxide synthase (iNOS) in rat with congenital hydronephrosis

BACKGROUND: Most of our knowledge concerning obstructive uropathy has been derived mainly from surgically manipulated animal models, and the pathogenesis of congenital obstructive hydronephrosis is not fully elucidated. Nitric oxide (NO) acts as an important biological modulator with diverse physiological functions, which can be either toxic or protective depending on the situation. NO is synthesized from l-arginine by nitric oxide synthase, and in the kidney iNOS is expressed spontaneously. The aim of our study is to investigate the expression of iNOS protein and its relationship with tubulointerstitial fibrosis and tubular cell apoptosis in congenital hydronephrosis. METHODS: We conducted histological studies on 18 kidneys of six-week-old-rats from an inbred colony of congenital hydronephrosis with reference to the histological grading of the affected kidney, tubulointerstitial fibrosis, renal tubular atrophy, and tubular cell apoptosis. Renal transforming growth factor-beta1 (TGF-beta1) level was determined by a sandwich ELISA assay and the expression of iNOS was analyzed by western blotting. RESULTS: Most of the hydronephrotic kidneys were markedly enlarged with dilatation of the collecting system, parenchymal thinning, tubular atrophy, interstitial infiltration and fibrosis. Renal TGF-beta1 level was higher in hydronephrotic kidneys than normal control kidneys (364.81 +/- 52.60 vs. 221.19 +/- 22.53 pg/mg protein, P < 0.05). Tubular apoptotic score in hydronephrotic kidneys was also significantly higher than in the normal control kidneys (1.97 +/- 0.42 vs. 0.14 +/- 0.02/HPF, P < 0.01). The expression of iNOS protein was lower in the affected kidneys compared with the normal control kidneys (8.79 +/- 0.78 vs. 14.00 +/- 0.83 arbitrary unit, P < 0.01). There was a negative correlation between iNOS expression and histological grading in congenital hydronephrosis. The iNOS expression also correlated negatively with renal interstitial fibrosis, TGF-beta1 level and tubular cell apoptosis. CONCLUSION: Our study confirmed the down-regulation of iNOS expression in affected kidneys from rats with congenital hydronephrosis, in which the cytoprotective effect of NO may be lost or weakened.     

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.     

Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and BALB/cN mice

Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV 2) into BALB/cN and C57BL/6N mice was carried out to induce experimental myelitis. The myelitis was clearly observed in C57BL/6N mice following intraperitoneal inoculation. Within 24 hours before death, the mice showed urinary and rectal incontinence and paraplegia of the hind legs. Randomly distributed, severe necrosis was demonstrated in the spinal cord, mainly at the lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as the mice died shortly after their onset. Although spinal cord necrosis was more prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in the latter, and not in the former. Both strains of mouse showed marked nuclear pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was also detected in the necrotic spinal cord. In contrast, intracranial inoculation of the virus into both strains did not cause myelitis. Spinal cord necrosis was not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples. In the brain, however, the virus was demonstrated by both PCR and immunohistochemistry.     

SECONDARY AMYLOIDOSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS: DIAGNOSTIC AND PROGNOSTIC VALUE OF GASTRODUODENAL BIOPSY

Upper gastrointestinal endoscopy was performed in patients withrheumatoid arthritis (RA) during the period 1989–1991,and biopsy specimens were obtained from the stomach and fromthe duodenum for examining amyloid deposits. Among 407 patients,gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-twopatients were regarded as having slight amyloid deposits, while32 patients were categorized as having marked amyloid deposits.The incidence of clinical manifestations suggestive of systemicamyloidosis was more frequent in the marked deposits group thanin the slight deposits group (47% vs 14%, P < 0.05). Amongthe patients who died of manifestations associated with amyloidosis,the survival period following endoscopy was shorter in the markeddeposits group than in the slight deposits group. These findingssuggest that gastroduodenal biopsies may be useful for diagnosingsecondary amyloidosis and that the degree of amyloid depositsseems to be correlated with the clinical manifestations of RA. KEY WORDS: Rheumatoid arthritis, Complications, Secondary amyloidosis, Diagnosis, Endoscopy, Biopsy, Prognosis     

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.     

Successful Coil Embolization of a Ruptured Basilar Artery Aneurysm in a Child with Leukemia: A Case Report

Ruptured intracranial aneurysms are rare in the pediatric population compared to adults. This has incited considerable discussion on how to treat children with this condition. Here, we report a child with a ruptured saccular basilar artery aneurysm that was successfully treated with coil embolization. A 12-year-old boy with acute lymphoblastic leukemia and accompanying abdominal candidiasis after chemotherapy suddenly complained of a severe headache and suffered consciousness disturbance moments later. Computed tomography scans and cerebral angiography demonstrated acute hydrocephalus and subarachnoid hemorrhage caused by saccular basilar artery aneurysm rupture. External ventricular drainage was performed immediately. Because the patient was in severe condition and did not show remarkable signs of central nervous system infection in cerebrospinal fluid studies, we applied endovascular treatment for the ruptured saccular basilar artery aneurysm, which was successfully occluded with coils. The patient recovered without new neurological deficits after ventriculoperitoneal shunting. Recent reports indicate that both endovascular and microsurgical techniques can be used to effectively treat ruptured cerebral aneurysms in pediatric patients. A minimally invasive endovascular treatment was effective in the present case, but long-term follow-up will be necessary to confirm the efficiency of endovascular treatment for children with ruptured saccular basilar artery aneurysms.     

Comparison of Gas-less laparoscopy-assisted surgery, hand-assisted laparoscopic surgery and pure laparoscopic surgery for radical nephrectomy

BACKGROUND: We report our experience with Gas-less laparoscopy-assisted surgery (Gas-less LAS), hand-assisted laparoscopic surgery (HALS) and pure laparoscopic surgery (LS) for renal carcinoma and compare the characteristics and usefulness of these methods. METHODS: Seventeen, 14 and 16 patients were subjected to Gas-less LAS, HALS and LS, respectively. The study started with Gas-less LAS and then gradually shifted to HALS and LS. We evaluated the operative and postoperative parameters for each group. The learning curve effect was evaluated based on data from the first 10 cases of each group, which were operated on by the same surgeon and operation team. RESULTS: The learning curve of operation times in the LS group demonstrated that the operation time for this procedure is acceptable even in early-stage cases. Differences in mean operative time between the three surgical groups, excluding the conversion cases, were not statistically significant; however, there was a significant difference in blood loss volume between the groups (P 相似文献   

Assessment of body composition measured by bioelectrical impedance in children

Bioelectorical impedance methods have been found to be a valid and reliable way of estimating per cent body fat (%BF) in adults. We applied them to healthy children and compared them with conventional anthropometry methods. One thousand two hundred and sixteen children participated in this study. Impedance and skinfold thickness were measured, and %BF was estimated using these values. Bodyweight and height were measured, and per cent obesity (%OB) and body mass index (BMI) were obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6 ± 4.0% in the junior male group, 14.2±2.8% in the junior female group, 7.9±4.7% in the senior male group and 16.1 ±2.9% in the senior female group. The % BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi correlated strongly with variables from conventional methods. It was concluded that it is a reliable way of assessing lipid storage in children.     

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.     

Injection Sclerotherapy for Recurrent Esophageal Varices after Surgical Procedures

Abstract: Thirteen patients, who had recurrent esophageal varices after esophageal transection or esophagoproximal gastrectomy were treated by endoscopic injection sclerotherapy. Four patients successfully underwent emergency sclerotherapy to control active variceal hemorrhaging. Three of these patients and the remaining nine patients (including six rebleeding patients who were conservatively treated) underwent elective sclerotherapy. None of the patients had variceal rebleeding in the follow-up study with sclerotherapies. Only one patient with recurrent varices did not undergo any additional sclerotherapy following emergency treatment. In this study, no deaths occured nor any major complications. Minor complications such as low grade fever and chest pain were observed, but they were transient and disappeared within 2 or 3 days without specific treatments. It is concluded that endoscopic injection sclerotherapy is considered to be the most effective procedure for recurrent varice following surgery.