Functional evaluation of lung by Xe-133 lung ventilation scintigraphy before and after lung volume reduction surgery (LVRS) in patients with pulmonary emphysema

We evaluated the respiratory functions of patients with pulmonary emphysema who underwent lung volume reduction surgery (LVRS) by the mean transit time (MTT) with Xe-133 lung ventilation scintigraphy, forced expiration volume in 1 sec (FEV1.0), residual volume (RV), distance walked in 6 min (6-min walk), and the Hugh-Jones classification (H-J classification) before and after LVRS. In 69 patients with pulmonary emphysema (62 men, 7 women; age range, 47-75 years; mean age, 65.4 years +/- 6.1, preoperative H-J classification, III (two were II)-V) who underwent LVRS, all preoperative and postoperative parameters (MTT 3 weeks after LVRS and the others 3 months after LVRS) were judged statistically by the Wilcoxon signed-ranks test and Odds ratio. Every postoperative parameter was improved with a significant difference (P < 0.05) compared to preoperative parameters. MTT at 3 weeks after LVRS was not associated with %FEV1.0 and the H-J classification at 3 months after LVRS, but was associated with RV and a 6-min walk at 3 months after LVRS. MTT was useful for the clinical evalution of aerobic capability after LVRS.     

Strain combination-dependent genesis of necrotizing arteritis in anti-ICAM-1 antibody-perfused renal allografts in the rat

Rat kidneys were perfused with anti-intercellular adhesion molecule-1 (anti-ICAM-1) monoclonal antibody prior to allo-transplantation. In the two strain combinations examined, LEJ-to-WKAH transplants resulted in accelerated graft loss, and no prolongation of graft survival. The accelerated graft logs was the resut of frequent occurrence of necrotizing arterttis wlthln the grafts. In contrast, TO-to-WKAH transplants resulted in no change In graft survival and no arteritis. Necratidng vasculitis in the LEJ-to-WKAH grafts was characterlzed by flbrinoid necrosis, collection of cellular infiltrates and serum macromolecular protein entrapment. The F(ab')² form of anti-ICAM-1 antlbody partially preserved the antibody's capacity to accelerate graft loss. Therefore, although endothelial injury by Fc-mediated cytotoxicity may be involved in vascular damage, other mechanisms also come into play. The amount and distribution pattern of ICAM-1 antigen were identical in both TO and LEJ strains. Intravenous anti-CAM-1 antibody administration combined with lipopolysaccharide, Poly(1)-Poly(C), warm ischemia to the kidney, or subcutaneous immunization with allogeneic spleen cells, but without renal transplantation, did not generate necrotizing vasculitis or proteinuria. These observations plus our previous data on the rat liver transplantation model clearly show that graft perfusion with anti-ICAM-1 monoclonal antibody invokes extensive vascular damage within allografts by Fc-mediated and Fc-independent mechanisms, depending on the donor-to-host combination.     

Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients

A few studies have reported a correlation between magnesium and co-morbidity and mortality in end-stage renal disease. We investigated the prognostic value of serum magnesium concentration for mortality in 515 patients on maintenance hemodialysis (60 +/- 12 years, 306 males and 209 females; 24% diabetics). The patients underwent follow-up for 51 +/- 17 (mean +/- SD) months, and the relationship between the baseline magnesium concentration (mean of four months) and outcomes was analyzed statistically. During the follow-up period, there were 103 all-cause deaths, including 63 non-cardiovascular deaths. Kaplan-Meier analysis revealed that mortality was significantly higher in the lower magnesium group (< 2.77 mg/dL, i.e. < 1.14 mmol/L, n = 261), compared to that in the higher magnesium group (> or = 2.77 mg/dL, n = 254) (p < 0.001). Multivariate Cox proportional hazard analysis demonstrated that serum magnesium was a significant predictor for mortality (HR [per 1 mg/dL increase], 0.485 [95% CI, 0.241-0.975], p = 0.0424), particularly for non-cardiovascular mortality (HR 0.318 [95% CI, 0.132 to 0.769], p = 0.0110), after adjustment for other confounders, such as age, gender, hemodialysis duration, and the presence of diabetes. In conclusion, it is demonstrated that lower serum magnesium level is a significant predictor for mortality in hemodialysis patients, particularly for non-cardiovascular mortality, although the mechanisms remain to be explored in future studies. Factors affecting serum magnesium concentrations should be investigated in terms of better survival, including dietary magnesium intake. Further extensive studies may be also needed for possible reconsideration of the current dialysate magnesium concentration (1.0 mEq/L, i.e. 0.50 mmol/L used in most countries), one of the strong contributors to the serum magnesium concentrations of dialysis patients.     

Association between HLA and Japanese patients with rheumatoid arthritis

Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis.     

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen

To examine early intercellular junction changes caused by treatmentwith 9, 10-dimethyl-l, 2-benzanthracene (DMBA), rat lingualepithelium was cultivated in isolation and observed by electrophysiological,freeze-fracture and whole-mount electron microscopy. Electrophysiologicalmeasurements showed a transient decrease in membrane potentialof -10.2 mV 6 h after the treatment. It returned to almost thesame level as that of the control group 1 day later. Six hoursafter treatment, input resistance decreased rapidly to 5.3 Mbut increased to 18.0 M 12 h after treatment. Transient reductionof input resistance and membrane potential occurred prior tothe decrease in the coupling ratio 6 h after treatment withDMBA. In freeze-fracture replicas, the number of gap junctionsdecreased by 45% of the control value 6 h after treatment withDMBA. At 12 h and thereafter, the number and area of gap junctionssubsequently decreased by 60–80% of the control value.Alterations in the number and area of desmosomes were similarto those of the gap junctions. The formation of epithelial cytoskeletons,partially devoid of the 2–4 and 5–8 nm filamentswas also observed. A decrease in the density of filament networksbeneath the plasma membranes was especially apparent. Treatmentwith a carcinogen brought about morphological cellular changesas early as 6 h after treatment, and such early changes mighttrigger metabolic cellular abnormalities. Affected cells appearto move away from normal cells in a process of repeated destructionand revision of intercellular junctions, and cytoskeletons.     

Ser203 as well as Ser204 and Ser207 in fifth transmembrane domain of the human beta2-adrenoceptor contributes to agonist binding and receptor activation.

We examined the contribution of Ser203 of the human beta2-adrenoceptor (beta2-AR) to the interaction with isoprenaline. The affinity of (-)-isoprenaline was reduced by substitution of an alanine for Ser203, as well as for Ser204 and Ser207. An (-)-isoprenaline derivative with only one hydroxyl group, at the meta-position, showed reduced affinity for wild-type beta2-AR and S207A-beta2-AR and even lower affinities for S203A-beta2-AR and S204A-beta2-AR. By contrast, an (-)-isoprenaline derivative with only a para-hydroxyl group showed reduced affinity for wild-type beta2-AR but the serine to alanine mutations did not cause further decreases. The EC50 value for cyclic AMP generation in response to (-)-isoprenaline was increased, by about 120 fold, for each alanine-substituted beta2-AR mutant. These results suggest that Ser203 of the human beta2-AR is important for both ligand binding and receptor activation.     

Oxygen uptake and carbon dioxide elimination during epinephrine-induced arrhythmias in humans

Key words  cardiac arrhythmias - oxygen uptake - carbon dioxide elimination     

Thrombin inhibitor ameliorates secondary damage in rat brain injury: suppression of inflammatory cells and vimentin-positive astrocytes

The effects of the thrombin inhibitor argatroban on the number of inflammatory cells and reactive astrocytes were investigated in a rat brain injury model. Gelatin sponge soaked with thrombin inhibitor (treatment group) or saline (control group) was placed in the brain defect to assess the infiltration of inflammatory cells by hematoxylin-eosin and immunohistochemical staining. Expression of polymorphonuclear leukocytes (PMNs) and monocyte/macrophage (Mo/Mo) cells, and vimentin (VIM)-positive astrocytes and glial fibrillary acidic protein (GFAP)-positive astrocytes were compared between groups. In the treatment group, infiltration of both PMNs and Mo/Mo cells, and the number of VIM-positive astrocytes were significantly reduced, but the number of GFAP-positive astrocytes was not different from the control group. Thrombin inhibitor suppresses the infiltration of inflammatory cells and excessive gliosis caused by VIM-positive astrocytes, but not expression of GFAP-positive astrocytes, suggesting minimization of secondary brain damage and promotion of the conditions required for neural regeneration.     

Three-Dimensional Evaluation of Innominate Bone Rotation in Female Patients with Developmental Dysplasia of the Hip

BackgroundPatients with developmental dysplasia of the hip (DDH) are known to have abnormal pelvic morphologies; however, rotation of innominate bone features remains unclear. Thus, we investigated innominate bone rotation in patients with DDH by measuring the associated angles and distances using three-dimensional (3D) computed tomography.MethodsWe defined four straight lines in pelvic 3D models: from the anterior superior iliac spine to the posterior superior iliac spine, from the anterior inferior iliac spine to the posterior inferior iliac spine, from the pubic tubercle to the ischial spine, and from the pubic tubercle to the ischial tuberosity. Similarly, we measured the angles formed by these lines using the vertical axis of the anterior pelvic plane on the horizontal plane and the horizontal axis on the sagittal plane. Additionally, we measured the distances between the femoral head centers and the acetabular centers in the coronal plane.ResultsThe difference in internal rotation angle between the superior and inferior parts of the iliac bone was significantly lower, by approximately 1.7°, in the DDH group than in the control group (p = 0.007); the difference between the inferior and superior parts of the ischiopubic bone was significantly higher, by approximately 1.5°, in the DDH group (p < 0.001). In the sagittal plane, the sum of the superior aspect of the iliac bone and the inferior aspect of the ischium was significantly lower in the DDH group (p = 0.001) than in the control group. The distances between the femoral heads and the acetabula were significantly greater in the DDH group than in the control group (p = 0.03, p < 0.01, respectively).ConclusionsPatients with DDH had a more internally rotated ilium and ischiopubic bone than normal individuals; however, it should be emphasized that internal rotation was reduced near the acetabulum, and the acetabulum was shifted laterally. Similarly, it was shown that patients with DDH had different rotations of the ilium and ischiopubic bone in the sagittal plane.