Immunoglobulin beta signaling regulates locus accessibility for ordered immunoglobulin gene rearrangements.

The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using mu heavy (H) chain membrane exon (microm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igbeta on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igbeta cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the kappaL chain germline transcription was found to be upregulated whereas the V(H) germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igbeta appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility.

Selective long-term elimination of natural killer cells in vivo by an anti-interleukin 2 receptor beta chain monoclonal antibody in mice.

The interleukin 2 receptor beta chain (IL-2R beta) is preferentially expressed in natural killer (NK) cells, but is not detected in a majority of resting T and B cells. We recently established a novel monoclonal antibody (mAb) to murine IL-2R beta and examined in vivo the effect of the mAb in mice. We found that intraperitoneal injection of the anti-IL-2R beta mAb into adult mice resulted in a selective in vivo elimination of splenic NK function in various mouse strains. The reduction of NK cell function is associated with complete disappearance of NK1.1+ cells in C57BL/6 mice. Other lymphocyte subsets in the thymus and spleen were uncompromised. T cell function was not affected by the mAb treatment as judged by allogeneic cytotoxic T cell induction. The single injection of anti-IL-2R beta mAb caused a long-term elimination of splenic NK cells, lasting for at least 5 wk. We also found that NK and/or NK precursor cells become susceptible to the mAb treatment only after birth, suggesting that functional maturation of NK cells in terms of IL-2R beta expression is a later event in the course of NK cell development. The use of the anti-IL-2R beta mAb will be useful in defining the physiological role of NK cells in host defense as well as dissecting their developmental pathway in vivo.

Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin-angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was <130 mm Hg before randomization for interventional studies or at baseline for prospective cohort studies. We identified nine eligible studies (486 patients): five randomized placebo-controlled trials; three randomized active drug-controlled trials; and one single-arm observational study. The mean differences in office SBP and diastolic BP (DBP) between the MRA and placebo groups were -9.4 (95% confidence interval (CI) -12.9 to -5.9) and -3.8 (95% CI, -5.5 to -2.2) mm Hg, respectively. Subgroup analysis results for study type, age, baseline office SBP and follow-up duration were similar to those of the main analysis. MRA mildly increased serum potassium (0.4 mEq l(-1); 95% CI, 0.3-0.5 mEq l(-1)). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

FK506 (tacrolimus) inhibits extravasation of lymphoid cells by abrogating VLA-4/VCAM-1 mediated transendothelial migration.

Extravasation is a critical process for the physiological lymphocyte traffic as well as the hematogenous spread of malignant hemopoietic cells. Here we report that abrogation of calcineurin activity leads to in vitro transendothelial migration and in vivo infiltration of human lymphoma Nalm-6 cells, which are associated with the abrogation of the VLA-4/VCAM-1 mediated pathway. Rapamycin, which can antagonize FK506 but not CsA to inhibit calcineurin, abrogates FK-506 mediated but not CsA mediated inhibition of in vitro transendothelial migration. FK506 may exert its potent immunosuppressive action partly by inhibiting VLA-4/VCAM-1 mediated transendothelial migration or insinuation of lymphoid cells to tissues.

A simplified method for the preparation of EAC14 intermediate cells using human serum treated with methylprednisolone.

The inhibitory effect of methylprednisolone 21-succinate ester (MPS) on the activities of complement components in human serum was studied by incubating human serum with various concentrations of MPS at 37 degrees C for 30 min and then measuring the residual activity of each component in human serum. The formation of EAC1 and EAC14 by C1 and C4 respectively, were only weakly inhibited by MPS at a final concentration of 10 mg/ml. In contrast, the same concentration of MPS completely inhibited the capacity of C2, C3, C5 and C6-9 to induce respective succeeding intermediates. On the basis of these findings a simplified method was devised for the preparation of EAC14 intermediates using human serum pretreated with MPS.

Generation and characterization of monoclonal antibodies against rabbit CD4, CD5 and CD11a antigens.

We describe in this report the production and characterization of monoclonal antibodies (mAb) to the rabbit homologues of CD4, CD5 and CD11a antigens, and their use for phenotypic analysis of rabbit lymphoid cell lines. All the mAbs were produced by immunizing mice with rabbit thymocytes. mAb KEN-4 apparently identified rabbit CD4, precipitated two bands of 42 and 50 kDa under reducing and non-reducing conditions and markedly inhibited allo-MLR. The distribution of antigen-positive cells were restricted to the thymus and classical T-dependent areas in peripheral lymphoid tissues. mAb KEN-5 apparently identified rabbit CD5, precipitated a single polypeptide of 67 kDa similar to other anti-CD5 mAb in the human and mouse. The use of this mAb revealed that CD5+ B cells were infrequent in this species. mAb KEN-11 apparently identified rabbit CD11a and precipitated a heterodimer of 150/95 kDa by selectively recognizing the 150 kDa moiety. It blocked cation-dependent aggregation of phorbol ester-induced rabbit Con A blasts and also allo-MLR in a similar manner to other anti-CD11a mAb in various animal species. Phenotypic examination of HTLV-1 transformed rabbit lymphoid cell lines using these mAb clearly indicated that most of them were CD4+, CD5+ and CD11a+, and hence derived from CD4+ T cells. These mAb will be useful tools for the study of the cellular immune system in the rabbit.

Clinical application of transvenous mitral commissurotomy by a new balloon catheter.

A new balloon catheter was developed which allows mitral commissurotomy without thoracotomy. The procedure has been successful in five of the six patients with mitral stenosis so treated. In the remaining patient, the procedure could not be performed because of technical difficulties. The balloon is reinforced with a nylon micromesh and its shape changes in three stages, depending on the extent of inflation. It is inserted from the saphenous vein into the mitral orifice transseptally, fixed across the mitral orifice with partial inflation, and finally inflated to full its extent, separating the fused commissures by its expansile force. After the procedure, catheterization revealed a significant reduction in the mean diastolic pressure gradient across the mitral valve without resultant mitral regurgitation in each patient. Two-dimensional echocardiograms showed a marked to moderate degree of dilatation of the mitral orifice in each patient. All five patients are well with remarkable clinical improvements 2 to 16 months after the procedure.

A case of muscular hamartoma of the breast.

We describe a 74-year-old female presenting with a right breast mass. She had found the mass on self-examination. Physical examination revealed a 2.2 x 2.5 cm, firm, smooth, and mobile lump in the upper medial portion of the right breast. Mammography revealed a well marginated, oval-shaped, and isodense nodule. Calcification was not evident. On ultrasonography, the lesion was 17 x 18 x 9 mm and located 5 mm below the overlying skin. Excisional biopsy under local anesthesia was performed. The tumor was easily excised. Histopathologically, the lesion was composed of intersecting bundles of spindle-shaped smooth muscle cells, and involved peripheral ducts and fat tissue. Immunohistochemical staining showed positivity for alpha-smooth muscle actin (SMA), but was negative for S-100 protein, myoglobin, keratin, and vimentin. From these findings a muscular hamartoma of the breast, a rare subtype of hamartoma, was diagnosed.

Contractile responses of the basilar artery isolated from rabbits exposed to 8-day head-down tilt.

In the present study, the effects of head-down tilt (HDT) on contractile responses of basilar and popliteal arteries were investigated in vitro. The arteries were isolated from rabbits exposed to 8 d of 45 degrees HDT. Isometric tension and intracellular calcium were measured in an organ bath perfused with physiological salt solution. In the HDT rabbits, contractile response to norepinephrine (NE) was attenuated in the basilar artery, but not in the popliteal artery compared with control rabbits. HDT did not change the responses to either KCl or 5-hydroxytryptamine in both arteries. In the response of basilar artery to NE, the difference in both [Ca(2+)](i) transient and Ca sensitivity between control and HDT rabbits were statistically not significant. The response of the basilar artery to phenylephrine, a selective alpha(1)-adrenergic agonist, was also attenuated by HDT. Treatment with propranolol, a beta-adrenergic blockade, did not affect the response to NE in the basilar arteries isolated from control rabbits, but it significantly enhanced the response in the basilar arteries from HDT rabbits. These results suggest that exposure to 8-d HDT decreases a contractile response of the basilar artery to NE in rabbits. The reduction of NE-induced contraction is probably attributable to both decreased Ca transient and decreased Ca sensitivity, and decreased alpha(1)-adrenoceptor activity and increased beta-adrenoceptor activity seem to be involved in the mechanism.

Assessment of mutations of Ha- and Ki-ras oncogenes and the p53 suppressor gene in seven malignant mesothelioma patients exposed to asbestos--PCR-SSCP and sequencing analyses of paraffin-embedded primary tumors.

To examine whether malignant mesothelioma due to asbestos has genetic alterations in the Ha- and Ki-ras oncogenes or in the p53 suppressor gene, we analyzed the point mutations of these genes in paraffin-embedded autopsy samples of the primary tumors of malignant mesothelioma in seven asbestos patients who died from malignant mesothelioma. The genetic analysis was conducted by the polymerase chain reaction-single strand comformation polymorphysms (PCR-SSCP) method in all patients, and through the sequencing of deoxyribonucleic acid (DNA) bases in one patient. No genetic alterations were found in exons 1 or 2 of Ha- and Ki-ras oncogenes, or in exons 5 to 9 of the p53 gene, in any of the patients. Further studies on a larger number of patients are required to reach a definite conclusion concerning the genetic effects of asbestos on malignant mesothelioma.

Increase in memory (CD4+CD29+ and CD4+CD45RO+) T and naive (CD4+CD45RA+) T-cell subpopulations in smokers.

To examine the effects of smoking on lymphocyte subpopulations, we measured the following cell subpopulations: CD4+ T-cell subpopulations (i.e., CD4+CD29+, CD4+ CD45RO+, and CD4+CD45RA+ cells); CD8+ T-cell subpopulations (i.e., CD8+CD11a+ and CD8+CD11b+ cells); and natural killer cell subpopulations (i.e., CD16+CD57-, CD16+CD57+, and CD16-CD57+ cells). We measured these subpopulations, together with total CD4+ T, total CD8+ T, total CD3+ T, B (CD19+), and total lymphocytes, in 10 male heavy smokers, 38 male light-to-moderate smokers, and 33 male nonsmokers. The mean ages were 30 y, 31 y, and 32 y, respectively, and ages did not vary significantly among the smokers. CD4+CD29+ and CD4+CD45RO+ (memory T) cells in heavy smokers were significantly more numerous than those in light-to-moderate smokers and nonsmokers. Also, these memory T-cell subpopulations were significantly more numerous in light-to-moderate smokers than in nonsmokers. The number of CD4+CD45RA+ (naive T) cells was significantly larger in heavy smokers than nonsmokers; numbers of CD4+CD45RO+ T and CD4+CD29+ T cells (memory T cells) were significantly correlated with daily cigarette consumption. Numbers of CD3+ T, CD4+ T, CD19+ B, and total lymphocytes in heavy smokers were significantly larger than in nonsmokers. There were significantly more CD3+ T, CD4+ T, and total lymphocytes in light-to-moderate smokers than in nonsmokers. The numbers of CD4+ T lymphocytes in heavy smokers were significantly larger than in light-to-moderate smokers. Perhaps CD4+ T cell subpopulations, especially memory T cells, are most susceptible to the effects of smoking on lymphocyte subpopulations.

[A case of tuberculous granulomatous mediastinitis and constrictive pericarditis simulating malignant mediastinal tumor].

A case is 40-year-old man. He presented anterior chest pain. Pericardial effusion was pointed out and a tuberculin skin test was positive. Tuberculous pericarditis was highly suspected, so INH and RFP were medicated. After 6-month medication pericardial effusion decreased, but right pleural effusion appeared on chest X-ray. Chest CT revealed a thickening of pericardium extend to anterior mediastinal mass. Echocardiogram revealed a pressure gradient in right ventricle, which was compressed by the thickened pericardium. We underwent median sternotomy in order to rule out neoplastic diseases. Intraoperative pathologic diagnosis was granulomatous mediastinitis and pericarditis, so we resected granuloma as much as possible to decompress the heart. Although Mycobacterium tuberculosis was not found in the resected granuloma, it was most probable pathogen. He received additional antituberculous chemotherapy for 6 months.

Inverted left atrial appendage.

An unexpected left atrial mass was found during postoperative echocardiography in a 17-years old man following aortic valve replacement, suggesting thrombus, vegetation and neoplasm. Reoperation showed that the mass to be an inverted left atrial appendage. Left ventricular venting may cause such inversion. To prevent this complication, we suggest the use of careful monitoring and intraoperative transesophageal echocardiography.

[Simultaneous operation of intra-descending aorta bypass grafting and brachiocephalic artery reconstruction in a patient of aortitis syndrome].

A 42-year-old woman underwent concomitant intra-descending aorta bypass grafting and brachiocephalic artery reconstruction successfully. She was diagnosed as aortitis syndrome with brachiocephalic artery obstruction, severe stenosis of descending aorta and stenosis of right upper renal artery. Chief complaint was chest oppressive feeling, but none of brain nor upper extremity ischemia. Catheterization showed 100 mmHg pressure gradient across stenosis of descending aorta and 100 mmHg pressure gradient between ascending aorta and right brachial artery. In order to relieve hypertension and prevent right head and upper extremity ischemia, concomitant vascular reconstruction was performed using woven Dacron prostheses. Hypertension had subsided postoperatively, and she was relieved from any symptom.

Field dependence and body balance.

This study reports four points about the portable Rod and Frame Test performance of 30 Japanese women in terms of body balance. The primary findings using a stabilometer are: (a) field dependence correlated negatively with increased sway path within 1 min. both while a dot pattern as a visual stimulus was stationary and while it was moving. (b) Field dependence correlated positively with the difference in sway path between the two following phases, in one of which the subjects watched the horizontal visual movement to the right and in the other movement to the left. (c) Motion aftereffect had no direct and immediate influence on sway path, but rather a latent and long-term effect. And on a pedograph which measures the distribution of foot pressure and the shape of the sole, (d) field dependence correlated negatively with anterior positions of the center of foot pressure and with the proportion of the front part to the rear of the sole. Over-all, field dependence measured by the Rod and Frame Test seems to be associated with body posture when dot patterns are viewed.

Influence of looking at hazard lights on car-driving performance.

The purpose of the present study was to determine what effect (if any) looking at an automobile's hazard lights has on the direction in which a car is driven. Eight Japanese drivers participated in this experiment. Analysis indicated that (a) at night drivers passed closer to a forward-facing stationary car than during the day and (b) when instructions were given to look at the hazard lights of a forward-facing stationary car, drivers passed closer than when no such instructions were given or when the hazard lights were off. The relationship between looking at the visible targets in a visually poor environment and the direction in which a car is driven was discussed.

[A case of successful reoperation for distal aortic arch pseudoaneurysm after replacement of descending aorta].

The patient was a 69-year-old man who had undergone replacement of descending aorta under close clump technique. Hoarseness occurred 8 years after the operation. Computed tomography and aortography revealed a saccular aneurysm of the distal aortic arch. During surgery, the pseudoaneurysm originated from a intimal defect close to the proximal anastomotic site of the graft. Total aortic arch replacement was successfully performed under retrograde and selective cerebral perfusion. The postoperative course has been uneventful.

[Analysis of T1N0M0 nonsmall cell lung cancer undergoing surgical resection without mediastinal lymph node dissection].

Eleven patients of T1N0M0 non-small cell lung cancer underwent relatively non-curative surgical resection without mediastinal lymph node dissection (the undissected group). The 5 year survival rate of this group was 70.7% and no significant difference in survival was found between the undissected group and the patients of T1N0M0 non-small cell lung cancer undergoing absolutely curative surgical resection (the dissected group). No patient died of pneumonia in the undissected group, while 4 aged patients in the dissected group died of pneumonia. This may suggest that mediastinal lymph node dissection is also injurious in distant period after surgery, especially in the aged patient. So "simple lobectomy" without mediastinal lymph node dissection may be considered as an elective procedure in the poor risk patient such as the aged, who has an early staged non-small cell lung cancer.

[Aortic valve replacement for aortic valve stenosis due to congenital bicuspid aortic valve with abnormal positioning of coronary orifice, pseudotendon, and persistent left superior vena cava, report of a case].

A patient was a 65-year-old female who had a complaint of palpitation was diagnosed aortic valve stenosis due to congenital bicuspid aortic valve with pseudotendon by the echocardiographic examination. We suspected left single coronary artery by the aortography and the coronary artery angiography. Aortic valve replacement and resection of pseudotendon was performed with Carbomedics supra-annular aortic valve (21 A). During surgery, persistent left superior vena cava was detected. High-posterior take-off right coronary artery was casually detected at aortic closure. Ventricular fibrillation due to insufficient supply of cardioplegic solution at right coronary area frequently occurred after cardio-pulmonary bypass and percutaneous cardiopulmonary support was required. The patient was discharged 32 days after the operation. Preoperative and intraoperative evaluation was important in the case of aortic valvular disease.

[A case of traumatic intrapulmonary foreign body].

A case of 60-year-old man with traumatic intrapulmonary foreign body that was not inhaled, but through the chest wall was described. In July 1992 a grass cutter was working in a forestry with a circular saw when he was struck into the right lung. He had a sharp pain in the anterior chest. No abnormality was seen in front of his neck and the chest wall. The next month he developed a cough with bloody sputum. The chest X-ray showed a metallic foreign body at the right side of manubrium. Computed tomogram showed a steel wire fragment lodging beside the innominate artery and vein and in the right lung. Median sternotomy was performed and a foreign body was successfully removed with partial resection of upper lobe.