Differences in infectivity between endosymbiotic Chlorella variabilis cultivated outside host Paramecium bursaria for 50†years and those immediately isolated from host cells after one†year of reendosymbiosis.

Chlorella variabilis strain NC64A is an intracellular photobiont of the ciliate Paramecium bursaria. NC64A was isolated from P. bursaria nearly 50 years ago and was thereafter cultivated outside the host. This study was undertaken to detect changes in its infectivity to P. bursaria and its auxotrophy for growth outside the host induced during long-term cultivation. NC64A can grow in Modified Bold's Basal Medium but not in C medium, whereas another symbiotic Chlorella variabilis strain, 1N, that was recently isolated from the host grew in C medium but not in Modified Bold's Basal Medium. With regards infectivity, NC64A in the logarithmic phase of growth showed low infectivity to alga-removed P. bursaria cells, whereas those in the early stationary phase showed high infectivity of about 30%. Those in the decay phase of growth showed no infectivity. Results show that NC64A has infectivity, but the infection rate depends on their culture age in the growth curve. Furthermore, NC64A that had been re-infected to P. bursaria for more than one year and isolated from the host showed a nearly 100% infection rate, which indicates that NC64A can recover its infectivity by re-infection to P. bursaria.

Plasma thrombopoietin level and platelet indices in hemodialysis patients receiving recombinant human erythropoietin.

We focused on thrombocytopenia in hemodialysis patients (HD) receiving recombinant human erythropoietin (rHuEPO) and investigated thrombopoietin (TPO) level and platelet indices. We analyzed platelet parameters including mean platelet volume (MPV), platelet-crit (PCT), mean platelet component (MPC) concentration and platelet count (PLT) using ADVIA 2120 in 375 HD patients. This study included 25 HD patients undergoing treatment with rHuEPO at 9000 IU/week. These patients were divided into two groups by reference PLT of 130 x 10(9)/l [eight patients with low PLT (L-PLT group) and 17 patients with normal PLT (N-PLT group)], and TPO level and platelet indices in each group were compared with those in nine HD patients not receiving rHuEPO. In HD patients, the mean value of MPV was slightly higher and the mean values of PLT, PCT, and MPC were significantly lower than those in healthy controls. TPO levels were significantly higher in patients receiving rHuEPO than in patients not receiving rHuEPO. However, no significant difference was found between TPO levels in patients in the L-PLT group and patients in the N-PLT group. TPO levels were not correlated with PLT in these patients and that MPC levels decreased remarkably regardless of PLT.

Axillary apocrine carcinoma with Paget's disease and apocrine naevus.

Apocrine carcinoma is a rare malignant sweat-gland neoplasm with apocrine differentiation. There have been some reported cases of apocrine carcinoma with apocrine naevus. We report a case of a 78-year-old man with a painless tumour of the left axilla. Positron emission tomography (PET) showed slight fluorodeoxyglucose (FDG) uptake in both axillae. The patient underwent radical excision of the left axilla with left axillary lymph-node resection. The resected specimen showed apocrine adenocarcinoma with extramammary Paget's disease and apocrine naevus. Two years later, the patient noted enlargement of the right axilla, and PET showed increased FDG uptake. On resection of this enlarging right axilla, an apocrine naevus was found. FDG-PET is a useful method for detecting precancerous lesions, allowing monitoring of abnormal foci that are not suspicious for cancer and have no clinically apparent cause for concern.

Touch imprint cytology with cytokeratin immunostaining versus Papanicolau staining for intraoperative evaluation of sentinel lymph node metastasis in clinically node-negative breast cancer.

AIM: This study investigated whether intraoperative assessment of SLN status in patients with clinically node-negative breast cancer was improved using touch imprint immunohistochemistry. MATERIAL AND METHODS: Each SLN was cut into slices 2mm thick and evaluated intraoperatively by touch imprint cytology with Papanicolaou staining until the end of 2005, or by a combination of Papanicolaou staining and immunostaining with an anti-cytokeratin antibody from early 2006. RESULTS: When intraoperative cytology of SLN in 85 patients who were clinically node-negative was evaluated with Papanicolaou staining, 81 patients were diagnosed as negative and four were positive. Intraoperative cytology with Papanicolaou staining had a sensitivity of 30%, specificity of 99%, false-negative rate of 70%, false-positive rate of 1.3%, and accuracy of 90.6%. When intraoperative cytology was done with immunohistochemistry plus Papanicolaou staining for SLN evaluation, 92 patients were diagnosed as negative and 17 patients were positive. Intraoperative cytology with immunohistochemistry had a sensitivity of 79%, specificity of 98%, false-negative rate of 21%, false-positive rate of 2.2%, and accuracy of 94.5%. Compared with intraoperative cytology using Papanicolaou staining alone, the combination of immunohistochemistry and Papanicolaou staining achieved a significant increase in sensitivity and a significant decrease in the false-negative rate. CONCLUSION: Intraoperative SLN evaluation by imprint cytology with immunohistochemistry achieves a more accurate diagnosis of metastasis than imprint cytology alone. This combined method is considered useful for deciding whether to perform axillary lymph node dissection.

Skewed T cell receptor repertoire of Vdelta1(+) gammadelta T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein-Barr virus-infected B cells in clonal restriction.

The proliferation of Vdelta1(+) gammadelta T lymphocytes has been described in various infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV) and malaria. However, the antigen specificity and functions of the human Vdelta1(+) T cells remain obscure. We sought to explore the biological role for this T cell subset by investigating the reconstitution of T cell receptor (TCR) repertoires of Vdelta1(+) gammadelta T lymphocytes after human allogeneic haematopoietic stem cell transplantation (HSCT). We observed skewed TCR repertoires of the Vdelta1(+) T cells in 27 of 44 post-transplant patients. Only one patient developed EBV-associated post-transplant lymphoproliferative disorder in the present patient cohort. The -WGI- amino acid motif was observed in CDR3 of clonally expanded Vdelta1(+) T cells in half the patients. A skew was also detected in certain healthy donors, and the Vdelta1(+) T cell clone derived from the donor mature T cell pool persisted in the recipient's blood even 10 years after transplant. This T cell clone expanded in vitro against stimulation with autologous EBV-lymphoblastoid cell lines (LCL), and the Vdelta1(+) T cell line expanded in vitro from the same patient showed cytotoxicity against autologous EBV-LCL. EBV-infected cells could also induce in vitro oligoclonal expansions of autologous Vdelta1(+) T cells from healthy EBV-seropositive individuals. These results suggest that human Vdelta1(+) T cells have a TCR repertoire against EBV-infected B cells and may play a role in protecting recipients of allogeneic HSCT from EBV-associated disease.

Focal segmental glomerulosclerosis associated with polycythemia vera: report of a case and review of the literature.

A 69-year-old female with a 3-year history of polycythemia vera (PV) developed nephrotic syndrome. A renal biopsy showed focal and segmental glomerulosclerosis (FSGS). The patient was treated with prednisolone and myelosuppressive agents. Thereafter, parallel improvement of the two conditions was observed. After 4-year treatment, proteinuria disappeared. To our knowledge, there are five reported cases of FSGS associated with PV. Among them, three patients suffered from progressive azotemia. We suggest that steroid therapy with myelosuppressive agents can resolve the renal lesion in patients with PV.

Esophageal cancer after distal gastrectomy.

The effect of gastrectomy on the subsequent development of esophageal cancer was investigated. Duodenogastroesophageal reflux is thought to be common in patients after distal gastrectomy, but whether this contributes to the development of esophageal cancer in such patients is controversial. We retrospectively evaluated 153 patients who underwent subtotal esophagectomy for thoracic esophageal cancer between January 2002 and July 2005. They were divided into two groups, according to whether or not they had previously undergone a gastrectomy: group 1, comprising 14 patients who had undergone gastrectomy and group 2, comprising 139 patients who had not. Clinical profiles of the patients were obtained from the medical records and the whole resected esophagus was histopathologically examined. The interval between gastrectomy and esophagectomy in group 1 was significantly shorter in the patients who had undergone gastrectomy for gastric cancer (10.5 +/- 4.2 years) than in those who had undergone gastrectomy for a peptic ulcer (28.9 +/- 3.0 years). The interval was also somehow shorter in the patients for whom anastomosis had been performed by Billroth I (21.3 +/- 5.6 years) compared with Billroth II (29.7 +/- 3.2 years), although the difference did not reach its statistical significance (P = 0.11). Moreover, the proportion of lower third tumors in patients after gastrectomy was significantly higher compared with that of the patients with intact stomach. These findings suggest that a history of gastrectomy is associated with more lower-third squamous cell esophageal carcinoma.

Improvement of accessory symptoms of hypertension by TSUMURA Orengedokuto Extract, a four herbal drugs containing Kampo-Medicine Granules for ethical use: a double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was conducted to evaluate the efficacy, safety, and utility of TSUMURA Orengedokuto Extract Granules for Ethical Use (TJ-15) as a treatment for the accessory symptoms of hypertension. Two capsules of the study drug were administered orally 3 times daily (i.e., before meals) for 8 weeks. Among 265 patients enrolled in the study, 134 were assigned to the TJ-15 group and 131 were assigned to the placebo group, of whom 204 patients (103 in the TJ-15 group and 101 in the placebo group) were included in the efficacy and utility analyze and 251 patients (128 in the TJ-15 group and 123 in the placebo group) were included in the safety analysis. Efficacy was significantly higher in the TJ-15 group based on the total score for the accessory symptoms of hypertensions which was the primary efficacy endpoint (Wilcoxon's rank sum test, p=0.013). When each accessory symptom of hypertension was assessed separately, efficacy was higher for hot flushes and facial suffusion in the TJ-15 group (Wilcoxon's rank sum test, p=0.034, and 0.022, respectively). There were no significant differences between the TJ-15 and the placebo groups with respect to the decrease of blood pressure or the antihypertensive effect. There was also no significant difference between the two groups with regard to the overall safety rating. The utility rating was significantly higher in the TJ-15 group than in the placebo group (Wilcoxon's rank sum test, p=0.016). In conclusion, TJ-15 was superior to placebo with respect to efficacy, safety, and utility for the treatment of accessory symptoms of hypertension.

Review of combination of peritoneal dialysis and hemodialysis as a modality of treatment for end-stage renal disease.

Because the contribution of residual renal function (RRF) to total solute clearance is often significant in continuous ambulatory peritoneal dialysis (CAPD), loss of RRF over time can lead to inadequate dialysis if appropriate prescription management strategies are not pursued. Additionally, declines in ultrafiltration caused by increases in peritoneal permeability may limit continuation of CAPD therapy. Peritoneal dialysis and hemodialysis (PD + HD) combination therapy (complementary dialysis therapy) is an alternative method. This therapy allows the patient to maintain daily activities, as with CAPD, while undergoing once-a-week HD supplements for the insufficient removal of solutes and water. This therapy allows for the continuation of PD without shifting to total HD in PD patients who continue to have uremic symptoms even after individualization of the PD prescription. This treatment option is psychologically more acceptable to patients and may be expected to provide such accompanying beneficial effects as peritoneal resting, improvement of QOL and reduction in medical cost.

Helicobacter pylori infection in rheumatoid arthritis: effect of drugs on prevalence and correlation with gastroduodenal lesions.

OBJECTIVE: The aim of this study was to investigate the impact of Helicobacter pylori infection on clinical features in patients with rheumatoid arthritis (RA) under medication with non-steroidal anti-inflammatory drugs. METHODS: One hundred and eighty-four patients with RA were tested for the presence of H. pylori infection. Clinical features and gastroduodenal lesions were compared between H. pylori-positive and -negative patients. RESULTS: One hundred and thirteen patients were positive and 71 patients were negative for H. pylori. The age, severity of RA, prevalence of gastrointestinal symptoms and gastroduodenal lesions and the class of gastroprotective drugs were not different between the two groups. Reflux oesophagitis was less frequent and sulphasalazine was less frequently administered in the H. pylori-positive group. CONCLUSIONS: The severity of RA, prevalence of gastroduodenal lesions other than reflux oesophagitis and the application of gastroprotective drugs do not seem to depend upon H. pylori infection in RA patients. Sulphasalazine may be protective against H. pylori infection.

Primary biliary cirrhosis associated with ulcerative colitis.

A rare case of concurrent primary biliary cirrhosis and ulcerative colitis is described in a 61 year-old Japanese male. Primary biliary cirrhosis was diagnosed on the basis of characteristic histologic findings and a positive serum mitochondrial antibody test. Ulcerative colitis was diagnosed from typical findings on colonoscopy and the histologic features of a sigmoid colon biopsy specimen. This is the 12th report of a patient presenting with the combination of primary biliary cirrhosis and ulcerative colitis. The potential autoimmune relationships on the basis of these conditions are discussed.

Inhibition of Na+/H+ exchanger reduces infarct volume of focal cerebral ischemia in rats.

Activation of Na+/H+ exchanger (NHE) may have an important role in ischemic cell death by means of intracellular overload of Na(+) and Ca(2+). Recent evidence has suggested that inhibitors of NHE have protective effects on myocardial ischemia both in vivo and in vitro. In this study, we tested the hypothesis that FR183998, an inhibitor of NHE, reduces infarct volume produced by focal cerebral ischemia in rats. We used 20 male spontaneously hypertensive rats. Either FR183998 (1 mg/kg; n=10), or vehicle (n=10) was given intravenously to the rats and the distal middle cerebral artery of each animal was occluded using a photothrombotic technique. We measured regional cerebral blood flow using laser-Doppler flowmetry throughout the experiments. After 3 days, infarct volume was measured in each animal group. To estimate the brain edema, we also calculated the cortical volume in both hemispheres. The infarct volume in the FR183998-treated group (82+/-8 mm(3), mean+/-S.E.M.) was significantly smaller than that in the control group (115+/-12 mm(3)) (P=0.034). The cortical volume of the occluded side in the FR183998-treated group (359+/-7 mm(3)) tended to be smaller than that in the control group (378+/-9 mm(3)) (P=0.116). The regional cerebral blood flow and physiological variables during ischemia were not significantly different between the two groups throughout the experiments. These results suggest that inhibition of NHE by FR183998 may have beneficial effects in reducing infarct volume and brain edema during cerebral ischemia. Thus, NHE may play an important role in the development of neuronal damage during acute cerebral ischemia.

Difference in degree of mucosal atrophy between elevated and depressed types of gastric epithelial tumors.

BACKGROUND: The significance of atrophy in the background mucosa and Helicobacter pylori infection in the morphogenesis of gastric epithelial tumors has not yet been investigated. METHODS: The degree of mucosal atrophy, as determined by a histological analysis and the serum pepsinogen (PG) levels, and H. pylori status were investigated in patients with elevated adenoma (EA group; n = 40), elevated early cancer of intestinal type (ECI group; n = 30), depressed early cancer of intestinal type (DCI group; n = 37) and depressed early cancer of diffuse type (DCD group; n = 33), and the findings were then compared to those in 91 controls. RESULTS: At all sites of the stomach, the histologic score of atrophy was higher in the EA group and in the ECI group than in the controls. In the DCI group, the histologic score of atrophy in the antrum was higher than in the controls, but no such difference in the score was found in the DCD group. The PG I/II ratios in the EA, ECI and DCI groups were significantly lower than in the controls, and the value was also different between the ECI and DCI groups. While H. pylori prevalence was higher in all groups than in the controls, a logistic regression analysis which included the grade of atrophy as a determinant revealed the infection to be an independent associated factor for the DCD group. CONCLUSIONS: The difference in the background mucosal atrophy seems to contribute to different macroscopic types in gastric epithelial tumors. This seems to be the case especially for cancer of intestinal type.

Magnesium decreases arterial pressure and inhibits cardiovascular responses induced by N-methyl-D-aspartate and metabotropic glutamate receptors stimulation in rostral ventrolateral medulla.

OBJECTIVE: Magnesium sulfate (MgSO4) is widely used for the treatment of eclampsia. However, effects of Mg2+ in central cardiovascular regulation remain unclear. In the present study, the role of Mg2+ on cardiovascular regulation in the rostral ventrolateral medulla (RVLM) of rats was examined. METHODS: Adult male Wistar rats were anesthetized with urethane, and artificially ventilated. The ventral surface of the medulla was exposed, and the RVLM was identified by microinjection (50 nl) of l-glutamate (l-Glu; 2 nmol). Then, MgSO4 (1, 3, 10 nmol, n = 7 for each dose) and magnesium chloride (MgCl2; 10 nmol, n = 7) were microinjected into the RVLM. l-Glu (2 nmol), N-methyl-D-aspartate (NMDA; 20 pmol), alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA; 5 pmol) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, metabotropic glutamate receptor agonist; 1 nmol] were also microinjected with or without pretreatment of MgSO4 (10 nmol; n = 7 for each drug). RESULTS: MgSO4 dose-dependently decreased mean arterial pressure (MAP) and heart rate (HR). The high dose of MgSO4 (10 nmol) significantly decreased MAP and HR (-25 +/- 4 mmHg and -43 +/- 6 bpm). Similarly, MgCl2 decreased MAP and HR (-27 +/- 4 mmHg and -30 +/- 6 bpm). The pressor response evoked by NMDA or (1S,3R)-ACPD was significantly attenuated by the pretreatment with MgSO4. In contrast, pressor response caused by l-Glu or AMPA was not affected by pretreatment with MgSO4. CONCLUSIONS: These results suggest that Mg2+ has an inhibitory role on the RVLM neurons, and inhibits cardiovascular responses induced by NMDA and metabotropic glutamate receptor agonists.

Tolerability and safety of a calcium channel blocker in comparison with a diuretic in the treatment of elderly patients with hypertension: secondary analysis of the NICS-EH.

A randomized prospective controlled study, the National Interventional Cooperative Study in Elderly Hypertensives (NICS-EH), previously demonstrated that the preventive effect of the long-acting calcium channel blocker nicardipine on the cardiovascular endpoint was similar to that of the diuretic, trichlormethiazide. The present report is a sub-analysis in which we compare the tolerability and safety of the calcium channel blocker with that of a diuretic in the long-term treatment of elderly hypertensives. A total of 429 elderly patients with hypertension were assigned to the nicardipine group or the diuretic group by the double-dummy method and were followed up for 5 years. Two hundred four patients in the nicardipine group and 210 patients in the diuretic group were analyzed. The incidences of fatal and nonfatal cardiovascular (CV) events in the two groups were comparable, and there was no significant difference in the cumulative event-free rate. However, the total incidence of adverse reactions, including non-CV events and unfavorable BP changes, was 31 cases (15.2%) in the nicardipine group, which was significantly lower than the 47 cases (22.4%) in the diuretic group (log-rank: p=0.026, G. Wilcoxon: p=0.01). The total number of medical endpoints, including CV events, the withdrawal of the patient from the study, was 52 (25.5%) in the nicardipine group, which was significantly lower than the 65 (31.0%) in the diuretic group (log-rank: p=0.078, G. Wilcoxon: p=0.044). It was concluded that sustained-release nicardipine is better tolerated, as it exhibits a lower incidence of medical-related withdrawals such as adverse drug reactions, non-cardiovascular events and unfavorable BP responses during the treatment.

Trends in the pathophysiological characteristics of malignant hypertension.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

Alteration of regional cerebral metabolism in patients with cirrhosis in positron emission tomography.

To evaluate the alteration of cerebral blood flow and oxygen metabolism in cirrhosis, we measured regional cerebral blood flow (rCBF), cerebral metabolic rate for oxygen (rCMRO2), and oxygen extraction fraction (rOEF) in twelve patients with cirrhosis (six with a history of hepatic encephalopathy and six without) and six age-matched controls using positron emission tomography. Regional CBF in whole brain was not different in cirrhotic patients from that in controls. In six cirrhotic patients with a history of hepatic encephalopathy, rCMRO2 was significantly lower in the frontal, temporal, parietal and occipital cortices, hippocampus, thalamus, cerebellum and brain stem, than that in each region of controls. On the other hand, rCMRO2 in six cirrhotic patients without a history of hepatic encephalopathy did not differ from the controls in all regions except for the frontal cortex. Regional OEF in cirrhotic patients without a history of hepatic encephalopathy was higher in the hippocampus and striatum than that in each region of controls. Among twelve cirrhotic patients, rCMRO2 in the occipital cortex and striatum correlated directly with plasma leucine levels, and rCMRO2 in the striatum directly correlated with plasma valine levels. Regional CMRO2 in the frontal cortex, temporal cortex, parietal cortex, white matter as well as brain stem correlated inversely with plasma phenylalanine levels, and rCMRO2 in the occipital cortex correlated inversely with plasma tyrosine levels. Brain oxygen metabolism is impaired in cirrhotic patients with a history of hepatic encephalopathy, but preserved in those without a history or in the early stage of cirrhosis. Reduced oxygen metabolism is related with altered amino acid metabolism.

Bradykinin mediates the acute effect of an angiotensin-converting enzyme inhibitor on cerebral autoregulation in rats.

BACKGROUND AND PURPOSE: In patients with stroke and long-standing hypertension, the autoregulation curve of cerebral blood flow (CBF) shifts toward higher blood pressure levels. Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and shift the autoregulation curve back to normal in hypertensive patients. ACE inhibitors have 2 major pharmacological properties: they inhibit both the production of angiotensin II and the breakdown of kinins. Hence, we investigated whether the effect of an ACE inhibitor on the lower limit of CBF autoregulation is mediated by the potentiation of bradykinin-mediated vasodilatation. METHODS: In 28 male Sprague-Dawley rats, CBF was measured by laser-Doppler flowmetry during stepwise controlled hypotension. The lower limit of CBF autoregulation was defined as the mean arterial pressure at which CBF decreased by 20% of the baseline value. The rats were treated with an ACE inhibitor, captopril, in the captopril group; a bradykinin BK2-receptor antagonist, Hoe140, in the Hoe140 group; and both agents in the captopril+Hoe140 group. Other rats served as a control group. The lower limits of CBF autoregulation were compared among the 4 groups. RESULTS: In the captopril group, the lower limit of CBF autoregulation was 43+/-8 mm Hg (mean+/-SD), which was significantly lower than that in the control group (57+/-14 mm Hg). Inhibition of bradykinin abolished the effect of captopril on the lower limit of CBF autoregulation. Hoe140 alone had no significant effect on the lower limit of CBF autoregulation. CONCLUSIONS: These results suggest that the shift of the lower limit of CBF autoregulation by captopril is mediated, at least in part, by bradykinin.