Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques

We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.     

Oxalate:OH exchange across rat renal cortical brush border membrane

We demonstrated the presence of oxalate:OH exchange in rat renal brush border membrane. Transient concentrative uptake of oxalate ("overshoot") was observed in the presence of an inside alkaline (pH = 8.5 inside, 6.5 outside) pH gradient, but this pH gradient-stimulated oxalate uptake was abolished by 1 mM DIDS, indicating that DIDS-sensitive and -insensitive oxalate uptake mechanisms were present. The DIDS-sensitive oxalate uptake was temperature-dependent and saturable with a Km of 0.0365 mM and a Vmax of 1.38 nmol.30 second-1.mg protein-1. In addition, oxalate was transported into the osmotically active internal space. In the presence of the pH gradient, a change in transmembrane potential had no effect on pH gradient-stimulated oxalate uptake. Oxalate was exchanged for OH and this exchange was sensitive to inhibition by DIDS. Inhibition by DIDS, furosemide and probenecid facilitated the distinction of oxalate:OH exchange from formate:Cl and oxalate:Cl exchange. In preparation of our brush border membrane vesicles, no apparent SO4:HCO3 exchange was present. These data indicate that oxalate:OH exchange occurs on the brush border membrane.     

Clinical and long-term follow-up study in patients with spontaneous subarachnoid haemorrhage of unknown aetiology

Summary Clinical characteristics and the outcomes of 50 patients with confirmed subarachnoid haemorrhage (SAH) of unknown aetiology were evaluated. Twenty-nine of these patients were interviewed with a mean follow-up of 7.7 years. Seven patients experienced early rebleeding during hospitalization, and one patient experienced late rebleeding during the follow-up period.On admission to the hospital the consciousness level was clear in 43 of the patients, drowsy in 6, and semicomatose in only 1. Of 10 patients who underwent computerized tomography (CT) within 3 days after SAH, 6 showed no abnormal CT findings and 3 had mild subarachnoid blood. Another patient showed severe SAH. Neurological deficit due to symptomatic vasospasm persisted in only 1 case.Two patients died after re-bleeding during hospitalization, and two others died during the follow-up, thereby representing an overall mortality rate of 8%. Of the latter cases, one died of an unrelated disease, and the other died suddenly from an unknown cause. The remaining forty-six patients (92%) had a good outcome. These results confirm previously reported clinical characteristics, namely that the symptoms of the majority of such cases are mild, the incidence of symptomatic vasospasm is rare, the risk of late re-bleeding is very low (less than 1% per year), and the prognosis is good. The CT findings suggest that some of these features resulted from only mild SAH. Thus, SAH of unknown aetiology seems to be a disease entity with a good prognosis.     

Studies on function of the upper urinary tract. XXIX. Canine ureteral electromyogram isolated from "so-called Pacemaker"

Many workers have reported that ureteral peristaltic movement is controlled by the "so-called Pacemaker". But, in our recent studies, it was revealed that the existence of pacemaker is not always necessary for the peristaltic movement. In this study, we made isolated and non-isolated prototype models, using 18 mongrel dogs, to explore the influential factors on ureteral peristaltic discharge. Bilateral kidney and ureter were exposed transperitoneally. Unilateral upper urinary tract was prepared to preserve the pacemaker without renal blood supply, and contralateral one was prepared not to preserve the pacemaker by cutting at the proximal portion of the ureter. Vesico-ureteral reflux (VUR) was caused on these two models. A luminal pressure and ureteral electromyogram was recorded. In the result, there is spontaneous peristaltic discharges of the ureter which had the tendency to increase peristaltic frequency according to the increase of the luminal pressure. It was suggested that adequate expanding stimulation is the factor of peristaltic discharge to increase, and the peristaltic discharge under this condition propagates from upper to lower portion of the ureter.     

MTT assay using fresh surgical specimens with reference to the transfer system and reproducibility in "test center" method

A chemosensitivity test (MTT assay) was conducted using 59 fresh surgical specimens collected from Keio University, Kitasato Institute Hospital and 14 affiliated hospitals, in order to assess the specimen transfer system and the reproducibility of the assay results obtained at Keio University and Kitasato Institute Hospital. Although the optical density yielded by the tumor cells in a number of 5 x 10(4)/well and the number of evaluable cases were significantly reduced through the transfer, the chemosensitivity pattern of the specimen was identical before and after the transfer. Fifty seven of 59 cases were evaluable and the concordant rate of the assay results between the two institutes was 80.6% (108/134) among each case-drug combination. Since the transfer system of the specimen was established and the reproducibility of the assay results in two institutes was confirmed, the "test center" method of the MTT assay appears to be possible by collecting the surgical specimens from the affiliated hospitals.     

Characterization of connectin-like proteins of obliquely striated muscle of a polychaete (Annelida)

Summary In obliquely striated muscle of polychaete, Neanthes sp., three kinds of connectin (titin)-like high molecular weight proteins, 4000 kDa, 1200 kDa and 700 kDa, were detected by SDS gel electrophoresis and immunoblots using antibodies to vertebrate skeletal muscle connectin and antiserum to the protein in question. The 700 kDa protein was isolated and characterized as a sheet-rich filament 170 nm long and 4 nm wide. Using polyclonal antibodies to the 700 kDa protein, the binding of the immunogold to the thick filament was only demonstrated in high ionic strength relaxing solution which solubilized some myosin. This observation suggested that the 700 kDa protein was localized below the layers of myosin in the thick filament and this localization is different from that of twitchin of C. elegans bodywall muscle that is on the surface of thick filament. The 4000 kDa protein was identified as a very thin filament linking the thick filament to the dense body. The very thin filaments were visualized in gelsolin-treated actin filament-free fibres. The 1200 kDa protein was located in the periphery of the dense body. A model of the elastic filament in polychaete bodywall muscle is presented.     

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial. Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women’s coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.     

Clinical experience with video-assisted thoracic sympathectomy through the retrosternal pulmonary junction

A new technique of video-assisted thoracic sympathectomy through retrosternal pulmonary junction can be done safely using a scope guide and a flexible scope. Bilateral thoracic sympathectomy was performed, employing a single skin incision, in 18 patients with palmar hyperhidrosis. The advantages include minimal neuralgia and superior cosmesis.     

Postoperative mediastinitis after the coronary artery bypass grafting using internal thoracic artery graft

It has been pointed out in general that the resistance against infection is decreased in the diabetic patients. This problem is very important in patients undergoing major surgery. In cardiovascular surgery, the median wound infection may result in life threatening sequelae. We have used the internal thoracic artery as the appropriate graft for its excellent long-term patency. In this series of the diabetic patients who underwent coronary artery bypass grafting with bilateral internal thoracic artery grafts, the incidence of postoperative mediastinitis was significantly higher than other cases. Therefore the use of bilateral internal thoracic artery grafts should be avoided, if possible in the diabetic patients.