Synthetic/secreting and apoptotic phenotypes in renal biopsy tissues from hypertensive nephrosclerosis patients.

The major glomerular abnormalities in hypertensive nephrosclerosis are described as glomerular obsolescence (GO), glomerulosclerosis (GS), and glomerular collapse (GC). However, glomerular cellular changes caused by hypertensive insults have not been well analyzed. Using an immunoenzyme method, we examined eleven biopsy samples from patients with hypertensive nephrosclerosis for two synthetic and secreting phenotypes, a-smooth muscle actin (alpha-SMA) and collagen type III (Col. III), and two apoptotic phenotypes, pro-apoptotic molecule Bax and anti-apoptotic molecule BcI-2. Together with the glomerular and vascular changes and interstitial fibrosis (IF) area, the results were scored quantitatively and semi-quantitatively and compared to the clinical findings, which included systolic blood pressure (SBP), mean arterial pressure (MAP), serum creatinine levels (sCr) and creatinine clearance (Ccr), using univariate and multivariate analyses. As a result, GS was frequently observed in the mild-to-moderate hypertensive group (140 < or = SBP<180 mmHg), whereas GC was positively correlated with SBP. Furthermore, there was a positive correlation of GS with mesangial alpha-SMA and Col. III, suggesting that GS was the reflection of these synthetic and secreting phenotypic changes in mesangial cells. Endothelial Bax was positively correlated with Ccr (p<0.01); in contrast, podocytic Bax was positively correlated with sCr (p<0.05) and showed a tendency to correlate with MAP (p=0.054). In conclusion, these findings support the view that mesangial synthetic and secreting phenotypic changes may be a reflection of cellular activation caused by mild-to-moderate hypertension and that apoptotic phenotypic expression in podocytes, rather than endothelial cells, may be related to the development of a severe form of hypertensive nephrosclerosis.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA: Implication for L‐DOPA‐induced dyskinesia in Parkinson's disease

The medial globus pallidus plays a crucial role in generation of L‐DOPA‐induced dyskinesia in patients with Parkinson's disease. The 6‐hydroxydopamine‐lesioned rat exhibiting behavioral sensitization to L‐DOPA is one useful animal model for examining L‐DOPA‐induced dyskinesia. To determine neuropathological abnormality responsible for behavioral sensitization, the medial globus pallidus and the substantia nigra reticulata in 6‐hydroxydopamine‐lesioned rats treated with L‐DOPA were examined. Intermittent L‐DOPA treatment induced hypertrophy of the lesioned‐side of medial globus pallidus and substantia nigra reticulata of 6‐hydroxydopamine‐lesioned rats with behavioral sensitization to L‐DOPA. Additionally, coadministration of a 5‐HT_1A receptor agonist, 8‐hydroxy‐2(di‐n‐propylamino)tetralin with L‐DOPA, alleviated the hypertrophy with improvement of the behavioral sensitization. These results suggest that hypertrophy of the medial globus pallidus and substantia nigra reticulata is associated with induction of behavioral sensitization to L‐DOPA in 6‐hydroxydopamine‐lesioned rats. Therefore, neuropathological changes corresponding to hypertrophy might underlie L‐DOPA‐induced dyskinesia in patients with Parkinson's disease.     

Upper thoracic myelopathy caused by vertebral collapse and subluxation in rheumatoid arthritis: report of two cases

We report two cases of rheumatoid arthritis (RA) with upper thoracic myelopathy and a review of the literature. Clinical data of a 47-year-old woman (case 1) and a 54-year-old woman (case 2) are described. Case 1 showed a transverse-type myelopathy at the T2 segment level of the spinal cord and case 2 had the same type of myelopathy at the T4 segment level. Case 1 had anterior vertebral subluxation of C7 due to marked vertebral collapse and Case 2 had subluxation of T2 with vertebral destruction. These two patients had the mutilating type of RA with multilevel spontaneous fusion in the cervical spine. The lesions in the thoracic spine might be caused by the severe destructive inflammation that is characteristic in mutilating disease. The vertebral collapse might lead to subluxation of the upper thoracic vertebra, resulting in spinal cord compression. Upper thoracic subluxation might be caused by vertebral collapse due to RA and the increased motion as a compensation for decreased mobility caused by spontaneous fusion in the cervical spine.     

Chemically induced forestomach papillomas in transgenic mice carry mutant human c-Ha-ras transgenes.

Forestomach papillomas and skin papillomas were induced very efficiently by a single dose administration of the chemical carcinogen methylnitrosourea (MNU) in transgenic mice (rasH2 line) carrying human hybrid c-Ha-ras genes, which encode the prototype p21 gene product. The incidence of forestomach papillomas was dose dependent; when 50 mg/kg of MNU were administered i.p., all of the transgenic mice (56 of 56) developed forestomach papillomas within 12 weeks after administration, whereas 5 and 0.5 mg/kg of MNU induced papillomas in 2 of 19 and 1 of 19 mice, respectively. Nine of 56 transgenic mice (16%) also developed skin papillomas at sites wounded by bites or scratches. Only 1 of 77 nontransgenic littermates developed forestomach papillomas after administration of 50 mg/kg of MNU, and no skin papillomas appeared within 12 weeks after MNU administration. The transgenes (integrated copy number, 5-6) in the tumors developed in 55 of 56 affected transgenic mice (98%) contained at least 1 copy of the transgene that was activated by somatic point mutation at the 12th codon, from GGC (Gly) to GAC (Asp). Because somatic point mutations at the 12th or 61st codon of transgenes have never been detected in normal tissues of transgenic mice thus far examined, these mutational activations of transgenes are tumor-specific events. RNA expression of these activated transgenes was also detected. From these results, it is suggested that somatic mutational activation of the human c-Ha-ras transgene plays a causative role in the occurrence of forestomach and skin papillomas induced by MNU administration in these transgenic mice. This transgenic mouse provides a unique screening system for chemicals that induce or suppress papillomagenesis.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

Intracellular free magnesium of red blood cells in patients with renal disease.

While serum magnesium (Mg) level is increased in patients with end-stage renal disease (ESRD), it is decreased in renal transplant recipients (TR) receiving ciclosporin. This study was performed to examine the cation metabolism of red blood cells (RBC) in these patients. Intracellular free Mg was measured with 31P-nuclear magnetic resonance spectrometry, and ouabain-sensitive sodium (Na) efflux rate (Eos) was measured from the increase in RBC-Na concentration when RBC were incubated in the presence of ouabain. The ouabain-sensitive Na efflux rate constant (ERCos) was obtained by dividing Eos by RBC-Na concentration. RBC free Mg and ERCos were significantly higher in the TR group than in the ESRD group. There was a significant correlation between RBC free Mg and ERCos (r = 0.474, p less than 0.01). These results support the views that the regulation mechanism for intracellular free Mg is different from that for extracellular Mg in patients with renal disease, and intracellular free Mg modulates Na pump activity of RBC.     

Relationship between morphological and functional changes in the stomach with aging]

The authors investigated the relationship between morphological changes and functional changes of the stomach with ageing, especially in term of change of gastric emptying in 92 healthy subjects. We checked the difference in chronological age and the stomach age in these subjects (in order to assess these subjects). The morphological change was evaluated by extent of atrophic gastritis in endoscopical atrophic border and histological findings of biopsy specimens, and the functional change was evaluated by maximal acid output in gastric secretion. Atrophic gastritis was expanded and maximal acid output was significantly reduced with ageing. From these results we confirmed that there was no difference between the chronological age and the stomach age and the quality of these subjects was very good. Gastric emptying was investigated by the acetaminophen method. In spite of ageing, gastric emptying was almost constant in these healthy subjects.     

Absorption of tetrahydropyranyl adriamycin administered intravesically immediately after transurethral resection of bladder carcinoma

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.     

The role of magnetic resonance cholangiopancreatography (MRCP) after resection of the pancreas

Magnetic resonance cholangiopancreatography (MRCP) was performed in 35 patients to evaluate the feasibility of its use as a postsurgical imaging technique after resection of the pancreas. The surgical procedures performed were: pancreatoduodenectomy in 22 patients, segmental pancreatectomy in 1, distal pancreatectomy in 7, and pyroluspreserving pancreatoduodenectomy in 5. The pancreatic duct was shown in its entirety in 24 of the 35 patients (68.6%) and was partially visualized in 8 patients (22.9%), but the intrahepatic and extrahepatic bile ducts were visualized completely in all patients. Furthermore, MRCP was able to demonstrate lesions in 3 of 6 patients who had shown clinical evidence of recurrence. The visualization of the pancreatic and bile duct system was satisfactory despite anatomical changes brought about by resection of the pancreas. Thus, we conclude that MRCP is an appropriate follow-up screening test for patients with suspected abnormalities of the biliary and pancreatic duct system.