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Background: Neutropenia is a common adverse reaction of chemotherapy. We assessed whether chemotherapy-induced neutropenia could be a predictor of survival for patients with non-small-cell lung cancer (NSCLC). Methods: A total of 387 chemotherapy-naïve patients who received chemotherapy (vinorelbine and gemcitabine followed by docetaxel, or paclitaxel and carboplatin) in a randomised controlled trial were evaluated. The proportional-hazards regression model was used to examine the effects of chemotherapy-induced neutropenia and tumour response on overall survival. Landmark analysis was used to lessen the bias of more severe neutropenia resulting from more treatment cycles allowed by longer survival, whereby patients who died within 126 days of starting chemotherapy were excluded. Results: The adjusted hazard ratios for patients with grade-1 to 2 neutropenia or grade-3 to 4 neutropenia compared with no neutropenia were 0.59 (95% confidence interval (CI), 0.36–0.97) and 0.71 (95% CI, 0.49–1.03), respectively. The hazard ratios did not differ significantly between the patients who developed neutropenia with stable disease (SD), and those who lacked neutropenia with partial response (PR). Conclusion: Chemotherapy-induced neutropenia is a predictor of better survival for patients with advanced NSCLC. Prospective randomised trials of early-dose increases guided by chemotherapy-induced toxicities are warranted.

There is little information on the molecular mechanisms in FK506-mediated neuroprotection. In the present study, we investigated the protective effect of FK506, an immunosuppressant and neuroprotectant, on trimethyltin (TMT)-induced neurotoxicity in the rat hippocampus. Histologically, TMT-induced neuronal damage was partially prevented by FK506 in the hippocampal CA1 region, but not in CA3. FK506 treatment significantly reduced the number of apoptotic cells in CA1, but not in CA3, and also prevented induction of cognitive deficits by TMT. Microarray analysis of the rat hippocampus detected 14 genes with TMT-induced alteration of mRNA expression that was rescued by FK506 treatment. Subsequent quantitative RT-PCR analysis confirmed elevated mRNA levels for four inflammatory genes, glutathione S-transferase, lysozyme, matrix Gla protein, and osteopontin after TMT treatment. Upregulation of these genes was reversed by FK506 treatment at 5 days postgavage. Immunohistochemistry revealed that FK506 reduced osteopontin (OPN) induction by TMT in the periarterial area at 5 days postgavage. Our data suggest that inflammatory gene expression is involved in TMT-induced damage to the hippocampal CA1 region, resulting in apoptosis, and that this process is initiated by periarterial OPN activation, and can be alleviated by FK506.

Previously we have shown that both CD4+ T cells and CD8+ T cells produce histamine when activated with Con A. The aim of this study was to examine whether cytokine production by these cells is regulated by autosecretion of histamine.CD4+ and CD8+ T cells were separated from spleen cells of C57BL/6 mice and mice lacking the H1 receptor (H1R) or H2R, using anti-CD4+- and anti-CD8+-coupled magnetic beads, respectively.Depletion of the H1R resulted in decreases in the release of IL-2 and IL-10 from both CD4+ and CD8+ cells and increases in the release of IL-4 from CD4+ T cells and IFN-gamma from CD8+ cells. Mice lacking the H2R showed up-regulation of IFN-gamma secretion from CD8+ cells and of IL-4 from CD4+ and CD8+ T cells. Release of IL-2 and IL-10 from CD4+ as well as CD8+ cells was down-regulated in these mice. Both CD4+ and CD8+ T cell fractions synthesized histamine, which was enhanced in the H1R-deficient CD8+ T cells. Treatment of the cells with alpha-fluoromethyl-histidine, a specific inhibitor of HDC, or histaminase increased IFN-gamma from CD8+ cells, whereas it had no appreciable effect on IL-4 secretion from CD4+ cells.These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.

Cdc25B and cdc25A phosphates are prominent stimulators of cell cycle progression and recent studies have also suggested their oncogenic roles. To elucidate the role of these proteins in thyroid neoplasms, we immunohistochemically investigated their expression, and neither protein was expressed in normal follicular cells. Cdc25B was frequently overexpressed in follicular adenoma and minimally invasive follicular carcinoma, but the incidence was significantly lower in widely invasive follicular carcinoma. Furthermore, the cdc25B expression level significantly decreased with the dedifferentiation of thyroid carcinoma. Cdc25A overexpression was observed in high incidences in all types of thyroid neoplasms. These results suggest that cdc25B and cdc25A play oncogenic roles in thyroid follicules and that cdc25B works predominantly in the early phase of the progression of thyroid carcinoma, whereas cdc25A plays a fundamental role in the development of thyroid neoplasms. British Journal of Cancer (2002) 86, 1909–1913. doi:10.1038/sj.bjc.6600364 www.bjcancer.com © 2002 Cancer Research UK

Objectives: Previously, we have shown that mouse T lymphocytes produce de novo histamine in response to mitogens. The aim of this study was to examine which subsets of T cells produce histamine and to clarify the regulatory mechanisms of the reaction.¶Materials: CD4+ and CD8+ T lymphocytes were separated from spleen cells of mast cell-deficient WBB6/F1 (W/Wv) mice using anti-CD4- and anti-CD8-coupled magnetic beads, respectively.¶Results: Both CD4+ T cells and CD8+ T cells released histamine when treated with Con A as a function of incubation time. Since histamine bound to each cell fraction was negligible before and after the treatment, it is highly likely that this indicates de novo synthesis of histamine by these cells. Granulocyte/macrophage colony-stimulating factor (GM-CSF) or IL-3 strongly enhanced the Con A-induced histamine formation. IL-1-α also potentiated the Con A-dependent histamine production. Dexamethasone, but not progesterone, significantly inhibited the Con A-dependent as well as Con A-independent histamine synthesis. Both GM-CSF and IL-3 caused a marked accumulation of histidine decarboxylase (HDC, EC 4.11.22) mRNAs in the cells.¶Conclusions: These results suggest that GM-CSF and IL-3 enhance histamine synthesis in CD4+ T cells and CD8+ T cells.

The aim of this study was to examine the roles of various cytokines in histamine synthesis by macrophages in bone marrow. Pure (> 99% nonspecific esterase-, CD14-, and Mac-1-positive) macrophage populations were obtained after long term culture of bone marrow cells (bone marrow-derived macrophages). Culture of the cells in the presence of Escherichia coli LPS caused a slight, but dose-dependent, increase in histidine decarboxylase-associated histamine synthesis with a concomitant increase in the expression of CD14, a LPS receptor, as well as the Mac-1 Ag on their surface. Granulocyte/macrophage CSF (GM-CSF) or IL-3 strongly enhanced LPS-induced histamine formation and expression of CD14 on bone marrow-derived macrophages, without affecting the expression of Mac-1 Ag. GM-CSF and IL-3 also caused a marked accumulation of both histidine decarboxylase and IL-6 mRNAs in the cells. Macrophage CSF and IL-1-alpha also potentiated LPS-dependent histamine formation when it was stimulated with GM-CSF or IL-3. In contrast to these cytokines, IFN-gamma suppressed LPS-induced histamine production regardless of whether it was stimulated by GM-CSF or IL-3, and inhibited CD14 expression. Neither IL-6 nor granulocyte CSF had any appreciable effect on LPS-induced histamine production even in combination with GM-CSF or IL-3. These results suggest that GM-CSF and IL-3 enhance LPS-induced histamine production in bone marrow-derived macrophages and that macrophage CSF and IL-1 alpha augment the actions of GM-CSF and IL-3. Possible implication of CD14 molecule in the reactions is discussed.

Streptococcus mutans, a major pathogen of dental caries, is occasionally isolated from the blood of patients with infective endocarditis. Bacterial attachment of exposed collagen tissue in the impaired endothelium is an important step in the onset of infective endocarditis. In our previous studies, some S. mutans strains were shown to possess collagen-binding activities and most of them had an approximately 120-kDa cell-surface collagen-binding protein called Cnm. However, several strains without Cnm proteins show collagen-binding properties. In the present study, another collagen-binding protein, Cbm, was characterized and its coding gene cbm was sequenced in these strains. The amino acid alignment in the putative collagen-binding domain of Cbm was shown to have approximately 80% identity and 90% similarity to the comparable region of Cnm. Cbm-deficient isogenic mutant strains constructed by insertional inactivation of the cbm gene, lacked collagen-binding properties, which were recovered in the complemented mutant. Analyses of a large number of clinical isolates from Japan, Thailand and Finland revealed that cbm-positive strains were present in all of these countries and that cnm-positive and cbm-positive strains were detected in the oral cavity of approximately 10 and 2% of systemically healthy subjects, respectively. In addition, cnm-positive strains were predominantly identified in the serotype f group, whereas cbm-positive strains were frequently detected in serotype k. These results suggest that Cbm as well as Cnm are major cell surface proteins of S. mutans associated with binding to type I collagen and predominantly identified in serotype k strains.

A 55-year-old man underwent rectal amputation for rectal cancer in August 2005. A tiny thin-walled cavity lesion in his left S1+2 was found on computed tomography (CT) of the chest in November 2008. The cavity lesion in the left S1+2 gradually increased in size over 3 months and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) showed FDG accumulation at the lesion. Videoassisted thoracoscopic (VATS) wedge resection was performed to make a definite diagnosis in March 2009. The pathological findings revealed a metastatic lung tumor from the rectal cancer. It is necessary to consider the possibility of metastatic lung tumors in a case with the cavity lesions especially in patients with a history of colon cancer.

In order to clarify the mechanism of retinal tissue damage in diabetes mellitus, the effects of the inhibition of aldose reductase on the pathologic changes in the retina of streptozotocin-induced diabetic (STZ-diabetic) rats were examined histologically and histochemically. The STZ-diabetic animals were maintained with and without peroral administration of an aldose reductase inhibitor, SNK-860, and their retinas were examined microscopically after 12 months. Several abnormal changes observed; folding and edema in the retina, loss of pericytes in the retinal capillary walls, and thickening of basement membranes in the retinal capillaries, were significantly inhibited by SNK-860. Some of these changes were similar to those that had been previously noted in diabetic and galactosemic rats. These data suggest that the enhanced polyol metabolism may be involved in the diabetic changes of the retina.

The nuclear DNA contents of atypical mesothelial cells from five patients who had an eosinophilic pleural effusion (EPE) were studied by the use of DAPI (4',6-diamidino-2-phenylindole dihydrochloride) DNA staining. Analysis of the nuclear DNA content revealed a polyploid pattern, with a major peak in the tetraploid region. Using an immunocytochemical technique, the atypical mesothelial cells showed a positive reaction for cytokeratin. In contrast carcinoembryonic antigen (CEA) was always negative in these cells. It is suggested that the atypical mesothelial cells with EPE had a higher rate of proliferation than did the normal mesothelial cells.

A 74-year-old man was admitted to our hospital in order to treat a mediastinal mass and 2 ground-glass attenuations in the right upper lobe detected by chest X-ray and computed tomography (CT). Partial resection of right lung and thymectomy were performed. The mediastinal mass and 2 ground-glass attenuations in the right upper lobe proved to be thymoma and bronchioloalveolar carcinomas, respectively by pathology.

Porphyromonas gingivalis was recently shown to cause intimal hyperplasia in a mouse model by a novel cholesterol-independent mechanism, suggesting to be a pathogen-specific feature of cardiovascular diseases. The aim of this study was to characterize the clinical and histopathological features of aortic aneurysms in cardiovascular disease patients harboring oral P. gingivalis.Aortic aneurysm specimens were collected from 76 Japanese patients who underwent surgery, of whom dental plaque specimens were also collected from 31 patients. Bacterial DNA was extracted from each specimen to detect P. gingivalis by polymerase chain reaction. Histopathological analyses of the aortic aneurysm specimens, including immunohistochemical staining for embryonic myosin heavy chain isoform (SMemb) and S100 calcium-binding protein A9 (S100A9), were also performed.The number of aneurysms occurring in the distal aorta was significantly higher in subjects positive for P. gingivalis in dental plaque compared with those who were negative. The expressions of S100A9 and SMemb were also significantly greater in the subjects positive for P. gingivalis in dental plaque. On the other hand, there were no significant differences in adipocellular accumulation between the groups.These results suggest that aortic aneurysms in patients harboring oral P. gingivalis have greater expression of S100A9 and proliferative smooth muscle cells, which was different from the present patients without oral P. gingivalis.

The purpose of this study was to construct a method to predict CYP3A4 induction in the clinical setting from in vitro data using cryopreserved human hepatocytes. We recently developed an approach with in vitro assays of HepaRG cell lines for predicting CYP3A4 induction by using a novel value, termed the relative factor (RF), determined from the ratio of the concentration of an inducer to the reference standard. In this study, the applicability of the RF approach was expanded to cryopreserved human hepatocytes. Induction assays were performed in vitro using hepatocytes from four individual donors and eight typical inducers. The obtained RF values were related to the free plasma concentration of each inducer (expressed as Css,u/RF). A good relationship between the Css,u/RF values and the in vivo induction response was found for all donors. Inducers were classified by the Css,u/RF values into three categories for CYP3A4 induction risk (high, medium and low potency), and thereby the degree of CYP3A4 induction in vivo in humans could be predicted from the Css,u/RF values. The RF approach is applicable to human cryopreserved hepatocytes. Thus, a method to predict the potency of CYP3A4 inducers was constructed using cryopreserved human hepatocytes.

There is scant information available regarding the distribution of periodontal bacterial species in children and adolescents over an extended period. The purpose of this study was to compare bacterial profiles in the same individuals over a period of 7 years.Twenty-six children and adolescents from whom dental plaque and saliva specimens were obtained during both the first (1999-2000) and second (2006-2007) periods, were analyzed. Bacterial DNA was extracted from each specimen and the presence of 10 periodontal bacterial species was determined using a PCR method, with a focus on the red complex species of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia.Subjects with red complex species in saliva specimens obtained during the second collection possessed a significantly higher number of total bacterial species than those without. The detection rate of the red complex species in the second collection period samples was significantly greater in subjects who had two or more species detected in samples taken during the first collection compared with the other subjects.Subjects possessing red complex species may be at possible risk for infection with a high number of periodontal bacterial species during adolescent and younger adult years.

The contribution of the microsatellite polymorphisms of TNFa and TNFb, and the TNFB + 252 (TNFB) dimorphism to the pathogenesis of rheumatoid arthritis (RA) was studied among Japanese patients.The TNFa and TNFb microsatellite polymorphisms, and the TNFB dimorphism were determined in Japanese RA patients and normal subjects using electrophoresis followed by specific PCR amplification. HLA-DRB1*04 typing was carried out by the PCR-SSCP method.The allele frequency of TNFa11 showed a significant increase in RA with DRB1*0405 when compared to that in RA without DRB1*0405 (28.5% Vs 12.9%, respectively, p = 0.022). An association analysis indicated that TNFa11 was not primary, but secondary to the increase in HLA-DRB1*0405, because TNFa11 showed a strong positive association with HLA-DRB1*0405 in Japanese controls. The slight increase in the TNFb4 allele observed in RA with DRB1*0405 (50.0%) may be reflective of the increase in TNFa11 and DRB1*0405. In RA with DRB1*0405, the allele frequency of TNFB*2 significantly increased compared to that of normal controls (75.0% Vs 55.3%, respectively, p = 0.007) and compared to that of RA without DRB1*0405 (45.0%, p = 0.001). No significant positive association of TNFB*2 with HLA-DRB1*0405 or TNFa11 in Japanese controls might suggest that the increase in the TNFB*2 allele might not be secondary to the increase in DRB1*0405, and that TNFB*2 might contribute additively to DRB1*0405-positive RA in Japanese.TNFB*2 may contribute additively to Japanese RA with HLA-DRB1*0405, while TNFa11 and TNFb4 are not independent genetic markers of RA among Japanese.

We describe a patient who displayed impairment limited to skilled habitual right finger movements due to a traumatic hematoma in the most caudal part of the left superior frontal gyrus. A 44-year-old right-handed man without notable previous disease presented to our emergency room following a traffic accident. No aphasia or apraxia was observed during examinations. He performed intransitive and transitive gestures and sequential movements smoothly upon command. He could also understand easily the meaning of gestures performed by others. Brain MRI on the 7th day after the accident revealed a hematoma, which measured 15.3 × 17.7 × 17.5 mm, in the most caudal part of the left superior frontal gyrus adjacent to the prefrontal sulcus (figure). EEG showed no abnormalities. Figure. Brain MRI on the 7th day after the accident. The left side of the axial and coronal slices (left and middle) is the right side of the patient, and the left side of the sagittal slice (right) is the …

OBJECTIVE: To determine how polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles contributed to the pathogenesis of systemic lupus erythematosus (SLE) in Japanese patients. METHODS: TAP1 and TAP2 typing was carried out in 52 Japanese patients with SLE and 95 normal subjects by the PCR-RFLP (restriction fragment length polymorphism) method. HLA-DR typing and HLA-DRB1*15 genotyping were carried out by the PCR method and PCR-SSCP (single stranded DNA conformation polymorphism) method, respectively. RESULTS: No particular TAP 1 allele was associated with Japanese SLE or with immunological subgroup of SLE. TAP2H showed a tendency towards increased frequency in SLE (5.8% v 0% in control), but the corrected P value was not significant. No other particular association of TAP2 allele was observed. Furthermore, these was no evidence for linkage disequilibrium between any TAP1/TAP2 alleles and HLA-DRB1*1501--which is reported to be weakly but significantly association with Japanese SLE--in either the normal control or the SLE patient group. CONCLUSIONS: Neither the TAP1 nor the TAP2 gene appears to determine disease susceptibility to SLE in Japanese, and these results are in keeping with those reported in Caucasian SLE patients.

Probiotic bacteria such as lactobacilli and bifidobacteria are considered to be non-pathogenic and non-toxigenic on the basis of long years of safe usage. However, some species of lactobacilli are thought to be associated with the development of dental caries. The purpose of the present study was to examine the cariogenicity of the probiotic bacterium Lactobacillus salivarius in rats. Rats were divided into six groups, and infected with L. salivarius LS1952R and/or Streptococcus mutans MT8148R. L. salivarius LS1952R became established in the oral cavity of rats and induced significant level of dental caries even when infected for only 5 days from 18 to 22 days of age. In addition, the caries scores of rats superinfected with both Streptococcus mutans MT8148R and L. salivarius LS1952R from 18 days of age were significantly higher than those infected with either L. salivarius LS1952R or S. mutans MT8148R alone. Since strain LS1952R can adhere to saliva-coated hydroxyapatites, it is concluded that L. salivarius strain LS1952R possesses an inherent cariogenic activity following adherence to the tooth surface.

The roles of histamine formed by the macrophage - T lymphocyte system were evaluated in the regulation of lymphocyte proliferation using mice lacking histamine receptors.Mice deficient in histamine type 1 (H1R), type 2 (H2R) or both receptors were employed to estimate possible intervention of the receptors in the histamine-dependent lymphocyte proliferation.Histamine was produced de novo by spleen cells. Con A-dependent T cell proliferation decreased when histamine produced in the culture was degraded by the addition of histaminase. The H2R-deficient mice also showed a significant decrease in the Con A-dependent T cell proliferation, whereas it was not modulated in the H1R-deleted mice. Consistent with the reduction in T cell proliferation, there was a significant down-regulation of the production of IL-2, a T cell growth factor, in the H2R-deficient mice. Con A-dependent IL-2 synthesis was abrogated by the addition of histaminase.Con A-dependent T cell proliferation is (up)regulated by histamine produced de novo through the H2R, suggesting that histamine is a newly found regulator of T cell proliferation.

Previously, we isolated and characterized a new Streptococcus mutans strain (serotype k) from human blood and oral cavity samples, and found that the serological properties of serotype k strains were similar to those of a gluA-inactivated mutant strain of MT8148 (MT8148GD). MT8148GD showed significantly lower sucrose-dependent adhesion to glass surfaces, sucrose-independent adhesion to saliva-coated hydroxyapatite, dextran-binding activity, and cell-associated glucosyltransferase (GTF) activity than the parent strain. Further, Western blot analysis revealed reduced GTFB and GTFC expression in serotype k strains as compared to MT8148, though the caries-inducing activities of MT8148GD and a serotype k oral isolate in rats were similar to that of MT8148. We conclude that a glucose side-chain defect in the serotype-specific polysaccharide of S. mutans may be associated with its cariogenicity, though to a lesser extent than its other major surface proteins.

To evaluate left ventricular function during exercise after aortic annular enlargement 15 patients with either aortic (group I, n = 8) or aortomitral (group II, n = 7) annuloplasty for small aortic annuli and eight patients (group III) with standard valve replacement for aortic stenosis without small aortic annuli received gated cardiac pool imagining by technetium-99m-labelled red blood cells at rest and during exercise at a mean of 23 months after operation. Left ventricular ejection fraction, preload requitable stroke work and stroke power index (preload requitable stroke work/systolic ejection period) were measured. Compared with resting values, left ventricular performance and stroke work rate on exercise after aortic annular enlargements increased significantly, as did those after standard aortic valve replacement. These results suggest that aortic annular enlargement can be indicated for surgical treatment of valvular heart diseases associated with small aortic annuli.

For a pancreatic body or tail tumor, distal pancreatectomy with splenectomy (DPS) is a standard operation. Spleen-preserving distal pancreatectomy (SPDP) was introduced in order to preserve the organ and thus provide the patient with a better quality of life. Clinical data were compared between 38 Japanese patients with DPS and 9 with SPDP for benign tumors or tumor-like lesions at the body or tail of the pancreas at preoperative, early postoperative (3 months after operation), and late postoperative periods (6 months after operation). The preoperative findings were not different between the two groups except for the significantly higher serum amylase levels in the SPDP group. Operation time, operative blood loss, and length of postoperative hospital stay were not different between the two groups. Pancreatic fistula occurred in 3 (8%) of the 38 patients in the DPS group and in 1 (11%) of the 9 patients in the SPDP group, abdominal abscess in 5 (13%) of the 38 patients in the DPS group and none (0%) in the 9 patients in the SPDP group. At short-term, clinical findings were not different between the two groups except for a significantly greater platelet count in the DPS group than in the SPDP group (46.8 x 10(4)/microl versus 29.6 x 10(4)/microl, P = 0.0081). At long-term after the operation, clinical findings, including the platelet count, were not different between the two groups. Computed tomography revealed a pseudocyst in 9 (53%) of 17 patients examined in the DPS group and in 3 (75%) of 4 patients examined in the SPDP group at short-term after operation. All patients with pseudocysts were asymptomatic. Two asymptomatic patients (one in the DPS group and one in the SPDP group) first developed a pseudocyst at long-term after the operation. The alteration of glucose tolerance was similar between the two groups. Postoperative pancreatic exocrine function (the N-benzol-L-tyrosyl-p-aminobenzoic acid test) was not different between the two groups. These data suggest that SPDP with preservation of the splenic vessels can be satisfactorily performed without elongating operative time and postoperative hospital stay or increasing risk of postoperative complications, with the exception of increased platelet count in the DPS group at short-term after the operation. Thus, SPDP is worth considering as one of the options for the treatment of benign lesions of the body or tail of the pancreas.

In this report we describe the respiratory patterns of six patients with Leigh syndrome, including two individual cases with accompanying clinical phenotypes of Alpers disease and mitochondrial encephalopathy with ragged red fibers. In five cases where sleep apnea was monitored, each one showed isolated or post-sigh central apnea, hiccup, apneusis-like breathing and obstructive apnea in various combinations. The remaining patient with Alpers/Leigh overlap syndrome showed an apneusis-like pattern of dyspnea. The sleep structure was examined in three patients. Two patients with brainstem lesions showed a decrease in the deep sleep stages and an absence of REM sleep. Medullary lesions were found in four patients by magnetic resonance imaging or at autopsy and involved predominantly the dorsal respiratory group (DRG) of medullary neurons. The role of DRG lesions in the pathophysiology of respiratory symptoms in Leigh syndrome is discussed.

Four out of 522 streptococcal isolates from the peripheral blood of patients with bacteremia exhibited typical properties of Streptococcus mutans in terms of sucrose-dependent adhesion, expression of glucosyltransferases, fermentation profiles of sugars, the presence of surface protein antigen, and DNA-DNA hybridization. Two strains were determined as serotype f and e by immunodiffusion, whereas the other two isolates did not react with the specific antiserum to S. mutans serotype c. e. or f of the eight different serotypes of mutans streptococci. The latter two untypable isolates, however, expressed a new antigenic determinant that was different from serotype c/e/f specificity as revealed by immunodiffusion. Analysis of the cell wall polysaccharides revealed very low contents of glucose in the untypable isolates. Furthermore, Southern blot analysis demonstrated that the untypable strains lacked at least one gene corresponding to a glucose-adding enzyme. These results indicate that the serologically untypable nature is due to the loss of glucosidic residue from the serotype-specific polysaccharide antigens of S. mutans.

With the concept of less invasive surgery, PpPD (pylorus-preserving pancreatoduodenectomy) has taken the place of conventional Whipple pancreatoduodenectomy (Whipple) as a standard operation for pancreatic head carcinoma. The aim of this paper is to compare early and late postoperative results of PpPD and Whipple for pancreatic head carcinoma.Postoperative clinical follow-up data and outcome of 50 Japanese patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with or without pylorus preservation were reviewed to scrutinize the demerits and merits of the pylorus preservation.Preoperative and postoperative serum chemistry was not different between the two groups. Mean operation time of the Whipple group was 517 minutes, which was significantly shorter than 624 minutes of the PpPD group (P = 0.0006). Cumulative stage was not different between the two groups. Cumulative curability of the PpPD group was superior to the Whipple group; of the 27 patients with Whipple, A in 4, B in 5 and C in 18, while of the 23 patients with PpPD, A in 12, B in 2 and C in 9 (P = 0.0182). Gastric tube was removed on POD 6.0 in the Whipple group, while on POD 39 in the PpPD group (P0.0001). Oral intake was started on POD 14.0 in the Whipple group, while on POD 28.3 in the PpPD group (P = 0.0018). Discharge was on POD 57.8 in the Whipple group, while POD 86.9 in the PpPD group (P = 0.0023). At the time of discharge and postoperative 6, 12, and 18 months, body weight loss from the preoperative level was 1kg smaller in the PpPD group than in the Whipple group. 1-year and 3-year survival rates of the Whipple group was 53.8% and 15.8%, while 62.8% and 19.6% of the PpPD group, showing no significant difference.These data show that delayed gastric emptying is evident in the PpPD group, resulting in longer hospital stay, while long-term body weight loss is smaller in this group. The clinical outcome is similar between the two groups. PpPD can be accepted as a standard operation for pancreatic head carcinoma.

We examined the indication of upper mediastinal lymphadenectomy for a squamous cell carcinoma of the lower thoracic oesophagus.49 patients underwent a curative oesophagectomy with upper mediastinal lymphadenectomy for a squamous cell carcinoma of the lower thoracic oesophagus. Node status and clinicopathological characteristics of these patients were reviewed retrospectively.16 (94.1%) of 17 patients with superficial tumours had no positive node in the upper mediastinum. Nine (29.0%) of 31 patients with transmural tumours had positive nodes in the upper mediastinum (P = 0.04). Ten (20.4%) of 49 patients had many positive nodes in the upper mediastinum. Of these 10 patients, 6 patients had 5 or more positive nodes in all. The 5-year survival rate for patients with 5 or more positive nodes was 7.7%, which was significantly poorer than patients with 4 or fewer positive nodes.Upper mediastinal lymphadenectomy is unnecessary in most of the superficial squamous carcinomas of the lower thoracic oesophagus.

The choice of a valve substitute in elderly patients remains controversial. Moreover, the combined use of the maze procedure in elderly patients raises further discussion. We report a case of bioprosthetic aortic valve replacement concomitant with the maze procedure in a 74-year-old man. With symptom of orthopnea and short of breath, he was diagnosed as aortic stenosis and regurgitation with atrial fibrillation. We performed the bioprosthesis aortic valve replacement and the maze procedure in this patient. He was extubated next day and discharged on the fifteenth day after the operation without any complications. Postoperatively he gained a sinus regular rhythm and A wave of transmitral flow was detected by Doppler echocardiography. Now, he enjoys his better quality of life without any drugs including warfarin. Although combined aortic valve replacement and maze procedure are more invasive for elderly patients, these procedures provides better quality of life after the operation.

Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathyBALB/c mice were immunized with carboxy-methylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 +/- 12.0 vs. 61.1 +/- 13.2 years, NS: HbA1c 69 +/- 1.5 vs. 5.2 +/- 0.4%, P0.0001).A monoclonal antibody against CMV-Hb beta-chain NH2-terminal and an assay method for measurement for CNMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 +/- 6.9 vs. 12.7 +/- 0.9 pmol CMV/mg Hb, P0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed.We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.

A 45-year-old man was admitted with a severe dry cough and fever. He had been given 100 mg/day of minocycline and other drugs for 9 days to treat hematopyuria. Chest X-ray film showed multiple nodular shadows with diffuse reticular shadows. After all the drugs were discontinued, the fever and the shadows improved, but the severe dry cough persisted. The day 4 bronchofiberscopic findings included multiple white plaques in the tracheobronchial mucosa. Punch biopsy specimens obtained from the white plaques revealed severe eosinophil infiltration, and the eosinophil count in the bronchoalveolar lavage fluid had increased (differential count 23%). After three days of 125 mg/day of methylprednisolone sodium succinate injection therapy, the severe cough, the X-ray shadows and the white plaques disappeared. With a positive result in the lymphocyte migration inhibition test, the patient's condition was diagnosed as minocycline-induced eosinophilic pneumonia.

Less invasive pancreatic head resection, such as pylorus preserving pancreatoduodenectomy (PPPD) and duodenum preserving pancreatic head resection (DPPHR) has been introduced for the treatment of pancreatoduodenal lesions, especially for benign conditions, in consideration of postoperative quality of life. Surgical stress and exocrine and endocrine function of the residual pancreas were examined in 44 patients with PPPD, 10 with conventional pancreatoduodenectomy (PD) and six with DPPHR. Clinical findings including serum levels of C reactive protein (CRP), fasting blood sugar, a 120-min value of the 75-g oral glucose tolerance test (OGTT), N-benzol-L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value (a pancreatic exocrine function test), and volume of postoperative pancreatic juice drainage were compared among the three different variants of pancreatectomy. Operation time and operative blood loss in PD were largest of the three, followed by PPPD and DPPHR. Postoperative elevation of serum CRP on postoperative day (POD) 2 or 3 was similar among the three different types of operation. Fasting blood sugar concentrations were not different among the three groups at short- and long-term after the operation, while the 120-min value of the GTT showed a marked elevation at long-term only after PPPD. The volume of pancreatic juice drainage increased up to POD 4 and became constant thereafter. The total amount of pancreatic juice drainage from POD 4 to 13 was smallest in PD (637 ml) followed by PPPD (1,255 ml) and DPPHR (1,431 ml). The BT-PABA value declined after PD (-20.3%, P = 0.0437) and PPPD (-20.2%, P = 0.0239) at short term, but not after DPPHR (8.2%). These findings suggest that the early impairment of the pancreatic exocrine function after PD and PPPD but not after DPPHR may indicate that the invasiveness of pancreatic head resection to the pancreatic functions is greater in PD and PPPD than in DPPHR.

In this prospective study, we evaluated contamination of surgical fields in open heart operations by salvaged blood culture used in autologous transfusions device (Cell Saver 5, Heamonetics Corp., Braintree, MA, USA). And also, we prospectively investigated an efficacy of pre- and intra-operative prophylactic antibiotics administrations (cefazolin). Thirty patients undergone open heart surgeries with median sternotomy enrolled in this study. The patients were divided into two groups, group A (n = 15); without prophylactic antibiotics administration, group B (n = 15); with pre- and intra-operative prophylactic antibiotics administrations. Blood samples were drawn through the right atrium after the discontinuation of CPB and from salvaged blood bags. Bacterial growth was detected in 80.0% of salvaged blood samples in group A, 86.7% in group B (p = 0.62). Whereas no bacterial growth detection in blood samples though the right atrium. Quantitative estimates of contaminations showed 1.06 +/- 1.41, 0.90 +/- 1.24 cfu/ml, respectively (p = 0.22). Although bacterial growth rate were not statistically significant difference between groups, detective rate of Staphylococci was remarkably decreased (p = 0.005) in group B. Pre- and intra-operative prophylactic antibiotics administrations were effective for Staphylococci, but not whole microorganisms. In conclusion, salvaged blood used in autologous transfusions was highly contaminated and it suggests that surgical fields were not clear. Prophylactic antibiotics administrations were effective especially for Staphylococci.

The patient was a 53-year-old man whose chief complaint was a dry cough and hemoptysis. Chest X-ray films and computed tomographic scans revealed a hazy shadow with unclear margins in the left middle lobe. A diagnosis of inflammatory pseudotumor was made because transbronchial lung biopsy specimens showed proliferation of plasma cells and lymphocytes. Initially, in response to steroid therapy, his clinical condition and pulmonary infiltration improved, but about 30 days after the start of steroid therapy, hemoptysis occurred and the shadow increased, and therefore left segmentectomy was performed. Histology revealed not only proliferation of acute and chronic inflammatory cells but also changes in the vessels. These pathologic findings were considered to be related to the infiltration shadows and the hemoptysis.

We evaluated the postoperative adjuvant chemotherapy by UFT using the primary tumor amputation-pulmonary metastasis model. When Lewis lung carcinoma (LLC) primary tumors on the hind foot pad grew palpable, they were amputated on two different days. In experiment (A) (earlier amputation model), micrometastases were detected on the day of amputation only by the histopathological examination. In the experiment (B) (later amputation model), nodules could be determined even by necropsy. Long-term (60-day) consecutive administration of UFT (22 mg/kg/day), which produced no body weight loss, markedly prolonged the survival period in experiment (A) (ILS: over 118%), 1 of the 15 mice being cured. UFT had a relatively weak but significant effect (67% of ILS) in schedule (B). Using the same model, we examined the inhibitory effect of UFT (2-week administration) on the number of metastatic nodules. A significant decrease of metastatic nodules was observed by UFT with both amputation schedules, but its effect was superior with schedule (A). In the same model using Colon 26 PMF-15, UFT markedly prolonged the survival period of mice (150% of ILS) and significantly decreased the metastatic nodules (86% inhibition). The dose of UFT used was relatively low, and did not significantly inhibit the growth of large tumors. However, the sensitivity to the micrometastases was high. These findings suggest that the postoperative adjuvant chemotherapy by the long-term consecutive administration of UFT would be effective for clinical cancer especially in curatively resected cases.

To establish a suitable method for measurement of nuclear DNA content in breast tissues from frozen storage after frozen section diagnosis.For fundamental research, rat liver samples preserved in a deep freezer were used. Four protocols were used (1. fixation with 70% ethanol followed by naked nuclei preparation; 2. fixation with 10% neutral buffered formalin followed by naked nuclei preparation; 3. preparation for naked nuclei prior to fixation with 70% ethanol; and 4. preparation for naked nuclei prior to fixation with 70% neutral buffered formalin). For clinical research, 13 separate fresh frozen breast tissue samples were analyzed after frozen section diagnosis. One contained a malignant phyllodes tumor (MPT) consisting of 2 components, benign epithelial cells and malignant stromal cells; 3 were benign tumors containing fibroadenoma; and 9 cases were carcinomas, consisting of 5 scirrhous, 3 papillotubular and 1 mucinous.Protocols 1, 2 and 3 were not suitable methods for our purpose because remaining cytoplasm or cohesive nuclei were observed. In protocol 4 the cytoplasm was completely undetectable, and nuclei were suitably separated for nuclear DNA content measurement. Benign epithelial cell component nuclei presented a diploid pattern, and the malignant stromal cell component nuclei indicated a euploid pattern in MPT. All 3 cases of benign constituents in fibroadenoma showed a diploid pattern, as did the 3 carcinoma cases (1 mucinous, 1 scirrhous and 1 papillary). Four scirrhous and 2 papillary carcinomas showed an aneuploid pattern.Our findings show that it is possible to measure nuclear DNA content of human frozen storage tissues after frozen section diagnosis.

A 86-year-patient who had acute myocardial infarction and critical cardiogenic shock was diagnosed to have the left main trunk (LMT) and triple vessel disease. Emergent coronary artery bypass grafting to the left anterior descending artery was performed using saphenous vein graft without cardiopulmonary bypass through median sternotomy. On the 41st postoperative day, catheter intervention was performed to the remaining lesions by stenting of LMT and percutaneous transluminal coronary angioplasty to the right coronary artery lesions. Tl scintigraphy showed remarkable reduction of myocardial ischemia. Hybrid therapy is the effective new strategy for critical cases which cannot be successfully and securely treated by medical or surgical approach alone.

Ionic mechanisms and signal transduction underlying noradrenaline (NA)-induced depolarization in single smooth muscle cells of guinea-pig vas deferens were studied. NA caused depolarization followed by action potentials through activation of 1-adrenoceptors. In the presence of nifedipine, no action potential was generated, and the magnitude of the depolarization depended on the concentration of NA (0.1-100 micrometer). NA, through 1-adrenoceptor activation, reduced the magnitude of membrane currents in response to voltage ramp pulses from -90 to -30 mV in a concentration-dependent manner. The reversal potential of the current inhibited by NA changed proportionally to the change in the equilibrium potential of K+, suggesting that NA inhibited K+ channel activity. Treatment of cells with GDPS, an inhibitor of G proteins, or bisindolylmaleimide (BIM), a selective protein kinase C (PKC) inhibitor, prevented the NA inhibition of the currents. Application of 12-O-tetradecanoylphorbol 13-acetate (TPA), an activator of PKC, mimicked the effect of NA. It is suggested that in the smooth muscle of guinea-pig vas deferens, activation of 1-adrenoceptors and the subsequent activation of PKC led to inhibition of K+ currents, which is responsible for the depolarization induced by NA.

A 48-year-old man consulted us with the chief complaints of right flank mass. On examination, there was a soft bulge on the right superior lumbar area. Since computed tomographic scanning showed subcutaneous fatty tissue, we suspected a superior lumbar hernia. The diagnosis was confirmed by magnetic resonance imaging (MRI) that revealed a lumbar muscle defect and prolapsed fatty tissue around the kidney. During the operation, a small hernia hiatus, 2 cm in width, opened in the superior lumbar triangle. The herniated fatty tissue was excised, and the defect of fascia was closed by overlapping the adjacent fascial structure. No signs of recurrence were found at 3 months postoperatively. The usefulness of MRI for the diagnosis is discussed and previous literature is reviewed.

Significance of three-field lymhpadenectomy for carcinoma of the thoracic esophagus was examined retrospectively based on depth of tumor infiltration, lymph nodal involvements and long-term survival.One hundred and fifty-two consecutive patients who underwent curative esophagectomy for thoracic carcinoma invading to submucosa (pT1) or deeper layers of the esophageal wall from 1983 to 1996 were examined. Sixty-six patients underwent three-field lymphadenectomy (3F) and 86 underwent two-field lymphadenectomy (2F). Survival curves were compared between 3F and 2F after stratifications according to depth of tumor infiltration, the number of positive nodes (0, 1 to 4, 5 or more), and positive intrathoracic recurrent nerve-chain nodes.Overall 5-year survival rate for 3F was 43.8%, while it was 30.2% for 2F (p = 0.07). In 41 patients with pT1 cancers, the 5-year survival rate for 3F was 55.7%, while it was 41.4% for 2F (p = NS). In patients with cancers invading to muscularis propria (pT2), the 5-year survival rate for 3F was 49.4%, while it was 30.7% for 2F (p = 0.06). In patients with tumors invading to adventitia, there was no significant difference. In patients with one to four positive nodes, the 5-year survival rates for 3F was 50.1%, while it was 24.1% for 2F (p = 0.01). There was no significant difference in the subgroups with no positive nodes and five or more. In subgroups with positive recurrent nerve-chain nodes, the 5-year survival rate for 3F was 27.9%, while it was 0% for 2F (p = 0.01).Significance of three-field lymphadenectomy was found in patients with one to four positive nodes or positive intrathoracic recurrent nerve-chain nodes.

We undertook a retrospective study of elderly patients with stage III non-small cell lung cancer who had been treated solely with radiotherapy during the period 1986 to 1995. Our study was designed to assess the influence of age on survival and malnutrition in patients aged 75 years or older (elderly group) and patients aged 74 years or younger (younger group). Radiotherapy alone resulted in a median survival period of 11.5 months in the younger group and 6.3 months in the elderly group (p = 0.0043). With the Cox multivariate model, good performance status, age less than 75 years, and good response were significant favorable independent predictors. Furthermore, the elderly group patients more frequently died of respiratory infections and had lower prognostic nutritional indexes than the younger group patients before and after radiotherapy. These findings suggested elderly patients with stage III non-small cell lung cancer who had been treated with radiotherapy alone had a poor prognosis and that malnutrition caused by radiotherapy was a factor contributing to the risk of death from respiratory infection in such patients.

Malaria is relatively rare in Japan. Of 13 patients referred to our laboratory for malarial screening in the past 4 years, malarial parasites were detected in 8. Conventional screening procedures commonly detect hepatic dysfunction, thrombocytopenia, elevated LDH activity, and increased CRP levels in malaria patients. More notably, the 8 malaria patients identified by our laboratory also demonstrated reactive lymphocytosis. In the absence of additional clinical information, reactive lymphocytosis alone may be enough to warrant laboratory blood smear tests on the suspicion of malaria. Conventional microscopic methods have often proved inconclusive in identifying malarial parasite species or detecting mixed infections. However, by combining the methods of DNA analysis with those of microscopy, we were able to conclusively diagnose all cases of suspected malaria. As a test of their skills, 9 laboratory technicians relatively inexperienced with malarial parasites were asked to screen 6 samples: 3 containing malarial parasites, and 3 that were malaria-free. Although none of the technicians were able to accurately identify the samples without additional clinical information, 4 accurately identified all malarial samples when that information was provided. Experience is a crucial determinant of ability to detect malarial parasites by microscopic methods alone. Nonetheless, the findings of our study suggested the diagnostic accuracy of laboratory screening procedures for malaria can be significantly improved if combined with minimal clinical data and the techniques of DNA analysis.

Atrial fibrillation (AF) is a relatively common complication in elderly patients with an atrial septal defect (ASD). However, use of the simultaneous maze procedure for AF associated with ASD remains controversial. We examined the efficacy and risk of the use of the maze procedure in these patients.Between March 1992 and April 1997, 26 patients underwent the maze procedure as a concomitant operation with ASD closure (maze group). Kosakai's modified maze procedure was performed in 17 patients, the modified Cox maze II or III procedure was performed in 6, and the restrictive right-sided maze procedure was performed in 3. The mean +/- SD age at surgery was 58.2 +/- 9.1 years. The mean +/- SD duration of AF was 7.8 +/- 8.5 years. The mean +/- SD left atrial dimension was 47 +/- 9 mm, and 24 patients (92%) had a larger-than-normal (35 mm) left atrium. The mean +/- SD follow-up period was 2.7 +/- 1.7 years. There were no hospital or late deaths. There was no thromboembolic episode in the late follow-up period. Sinus rhythm was regained in all patients who underwent conventional the right- and left-sided maze procedure except for 1 patient. However, 3 patients who underwent the restrictive right-sided maze procedure showed a return to AF rhythm. The atrial A wave was detected with the use of pulsed Doppler study in all patients who had a restored sinus rhythm. During the same period, 45 patients who were40 years old and without AF underwent only ASD closure (control group). The incidence of reopening the chest for bleeding was significantly (P = 0.046) higher in the maze group (12%) than in the control group (0%). Paroxysmal AF more frequently (P = 0.023) occurred in the control group (18%) than in the maze group (0%).These results suggest that the standard maze procedure should be considered in patients with AF associated with ASD. The restrictive right-sided maze procedure was not reliable, probably due to preoperative enlargement of the left atrium.

To evaluate whether or not the combination of sagittal and coronal spin-echo (SE) T1 and sagittal gradient echo (GRE) T2* weighted imaging is adequate to diagnose internal derangement of the knee, a study was done in 300 knees of 293 consecutive patients who underwent both MR imaging of the knee and arthroscopy. In prospective analysis, the MR imaging had an accuracy, sensitivity and specificity of more than 90% in the evaluation of medial meniscus (MM) and of 97% in the evaluation of anterior cruciate ligament (ACL). In the evaluation of lateral meniscus (LM), accuracy was 83%, sensitivity 76%, and specificity 88%. In a review of false-negative MR diagnoses (n = 42) of menisci, the most significant lesion was not in the meniscus but in the ACL in 32 knees (76%). Conservative treatment was selected in 25 knees (60%), rather than partial meniscectomy (n = 13) or meniscoresis (n = 4). There were 21 false-positive MR diagnoses of menisci even in retrospective analysis, and 17 of them (81%) had findings of tear in the posterior zone, which is known to be a difficult area for arthroscopic examination. The results were similar to those of other authors' with SE T1 and/or proton density and T2 weighted images. The combination of sagittal and coronal SE T1 and sagittal GRE T2* weighted images could be sufficient as a routine MR protocol for diagnosing the internal derangement of the knee.

From April 1993 to May 1997, 21 patients underwent surgical treatment for prosthetic valve endocarditis (PVE). There were 13 males and eight females aged from 46 to 79 years old (mean 62 years). There were four cases of early PVE (onset of PVE within 60 days from previous valve replacement), and 17 cases of late PVE (after 60 days). The predominant organisms were Staphylococcus epidermidis (eight cases), Staphylococcus aureus (two cases), MRSA (one case), streptococcal species (three cases), Candida (two cases), Pseudomonas cepacia (one case) and Enterococcus (one case). The predominant organisms were identified in 16 of 20 cases by preoperative blood culture, and in 11 of 20 cases by intraoperative tissue culture, and in 19 cases in all. There were four cases of preoperative cerebral complications, and three cases resurged. The hospital mortality rate was 24% (five patients). Reoperation was required in four patients for recurrence of PVE. Autopsy was performed in four of five patients. Intramyocardial abscess was detected in three patients. Earlier diagnosis and earlier surgical treatment could prevent emboli due to vegetations, which might cause catastrophic results, and could achieve better outcomes. Identification of the predominant organisms, especially from operative tissue cultures, is required.

Crossline is a novel advanced glycation endproduct (AGE) which has both a crosslink and fluorescence similar to AGE-protein in vivo. To assess the association of AGEs to the development of diabetic retinopathy we developed a sensitive and specific enzyme-linked immunosorbent assay (ELISA) for crossline in blood samples and investigated the association of the development of retinopathy and erythrocyte membrane protein (EMP)-crossline concentrations in patients with Type 2 diabetes mellitus (Type 2 DM). Crossline formation in EMP exceeded that in haemoglobin and was detectable in normal EMP samples without pretreatment by this ELISA system. Mean (+/-SE) EMP crossline levels were elevated 1.6-fold in diabetic patients without retinopathy (7.6 +/- 0.5 pmol mg(-1), p0.005), 2.2-fold in diabetic patients with non-proliferative retinopathy (10.5 +/- 0.6 pmol mg(-1), p0.001) and 2.6-fold in diabetic patients with proliferative retinopathy (12.0 +/- 0.6 pmol mg(-1), p0.001) compared with healthy control subjects (4.7 +/- 0.5 pmol mg(-1)). Type 2 DM patients with retinopathy had significantly higher EMP-crossline levels than those without retinopathy (p0.005). Our data suggest that elevated EMP-crossline concentrations are associated with the presence of retinopathy in patients with Type 2 DM and EMP-crossline measured by our ELISA may provide a useful marker for assessing the role of glycation in the development of diabetic retinopathy.

We have carried out the maze procedure for atrial fibrillation (AF) as a combined operation with mitral valve surgery in a consecutive fashion until December 1994 (period 1). Therefore, the success rate in sinus rhythm conversion remained unsatisfactory. We have selected the patients according to arbitrarily decided new criteria since January 1995 (period 2), and examined the results prospectively.Between May 1992 and February 1997, we carried out the maze procedure in 220 patients as a combined operation with mitral valve surgery. During period 2, we carried out the maze procedure in 63 cases who satisfied all the new criteria (voltage of f-wave in V1 lead0.1 mV, cardiothoracic ratio (CTR)70%, LA dimension70 mm), and 37 patients out of these criteria. Success was defined as sinus rhythm restoration without sick sinus syndrome.There were 4 hospital deaths (1.8%) and 4 late deaths (1.8%). Success rate was significantly (P = 0.0089) higher in period 2 (82%) than in period 1 (65%). Success rate was significantly higher in patients within criteria than out of criteria both in period 1, period 2, and total (77 versus 48%, P = 0.018; 90 versus 66%, P = 0.004, and 83 versus 55%, P = 0.0001).The maze procedure is highly reliable when combined with mitral valve surgery if patients are selected properly.

The contribution of the polymorphism of complement C4A and C4B alleles to the pathogenesis of systemic sclerosis (SSc) was studied in Japanese patients.C4A and C4B typing was carried out in 44 SSc patients and in 83 normal subjects using electrophoresis followed by immunofixation and immunoblotting. HLA-DR typing and HLA DRB1*15 and *08 genotyping were carried out by the PCR method and the PCR-SSCP method, respectively.In SSc with diffuse scleroderma, the frequency of C4BQ0 was significantly increased (44.4%, p0.001, pc0.01). In SSc with antitopoisomerase I antibody (a-Scl-70) C4BQ0 was also increased (50.0%, p0.001, pc0.01). Association analysis indicated that the increase in C4BQ0 was not primary but reflected an increase in HLA-DRB1*1502. In contrast, C4A/Q0 was significantly increased in limited scleroderma (53.8%, p0.005, pc0.05) and SSc without a-SCL-70 (53.8%, p0.005, pc0.05).Diffuse scleroderma with SSC with a-Scl-70 have different genetical backgrounds from limited scleroderma and SSc without a-Scl-70, respectively, in Japanese patients. C4AQ0 were independent genetic markers for each clinical subgroup and for a a-Scl-70 positivity.

We report a pilot study of three oral doses of coenzyme Q10 (CoQ10) (200 mg administered two, three, or four times per day for 1 month) in 15 subjects with Parkinson's disease. Oral CoQ10 caused a substantial increase in the plasma CoQ10 level. It was well tolerated, but at the highest dose (200 mg four times per day) mild, transient changes in the urine were noted. CoQ10 did not change the mean score on the motor portion of the Unified Parkinson's Disease Rating Scale. There was a trend toward an increase in complex I activity in the subjects.

Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.