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Background Basal cell carcinomas (BCCs) with high-risk features are preferably treated by Mohs micrographic surgery. Studies have shown clinicopathologic characteristics that may predict more stages required for clearance. However, few studies have correlated such factors with the number of millimeters removed per stage. Objective To determine margins necessary for BCC clearance according to tumor features, especially for tumors less than 6 mm, and to suggest initial margins for Mohs micrographic surgery and margins for wide local excision. Methods Retrospective analysis of 295 consecutive Mohs micrographic surgeries for primary BCCs. Variables analyzed included patient age, sex, immunostatus, lesion size, location, histologic subtype, borders, stage number, and millimeters excised per stage. Results BCCs less than 6 mm had a clearance rate of 96% with 3-mm margins. In adjusted multivariable analysis, superficial, micronodular, infiltrative, and morpheaform subtypes were associated with larger margins, whereas clinically well-defined tumors were associated with smaller margins. Limitations Because of the limited sample of certain subtypes, a 3-mm margin is better suited for nodular tumors. Conclusion These data help guide initial Mohs micrographic surgery and wide local excision margins required for tumor clearance according to tumor features. Nodular BCCs less than 6 mm may be cleared with 3-mm margins instead of the current 4-mm margin recommendation.

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

A free-living, young adult, male Japanese raccoon dog (Nyctereutes procyonoides viverrinus) was rescued in Gifu, Japan in March 2009. The animal was weak and emaciated with neurological signs that included head tilt, tremor and tic. The brain showed no gross abnormality at necropsy, but microscopically there was severe meningoencephalitis associated with protozoa, which were morphologically consistent with the asexual developmental stage of Sarcocystis spp. The protozoa were immunohistochemically negative for Toxoplasma gondii and Neospora caninum, but reacted weakly with antiserum specific for Sarcocystis cruzi. Analysis of the partial 18S rRNA gene sequence revealed that the protozoa were most closely related to an unidentified Sarcocystis species that was isolated from the white-fronted goose (Anser albifrons).

Multiple coalescing granulomatous foci were detected in the pulmonary hilar and mediastinal lymph nodes and lung of a slaughtered pig aged 6 months. Haemolytic, Gram-negative bacilli were isolated from the lymph nodes. The isolate (strain TO17214) strongly cross-reacted with sera against Actinobacillus pleuropneumoniae serotype 12 in slide agglutination tests. Comparative 16S rDNA gene sequencing analysis identified strain TO17214 as Actinobacillus porcitonsillarum. Histologically, extensive inflammation took the form of large granulomas consisting of epithelioid cells and multinucleated giant cells in the lymph nodes and lung, and Gram-negative bacilli were discernible in the centres of the lesions. Immunohistochemically, the organisms cross-reacted with polyclonal antibodies against A. pleuropneumoniae serotypes 12 and 2. The results indicated that A. porcitonsillarum, previously considered non-pathogenic, can induce multifocal granulomatous lymphadenitis accompanied by pneumonia in the growing-finishing pig.

The Achilles tendon (AT) consists of fascicles that originate from the medial head of the gastrocnemius (MG), lateral head of the gastrocnemius (LG), and soleus muscle (Sol). These fascicles are reported to have a twisted structure. However, there is no consensus as to the degree of torsion. The purpose of this study was to investigate the twisted structure of the AT at the level of fascicles that originate from the MG, LG, and Sol, and elucidate the morphological characteristics. Gross anatomical study of 60 Japanese cadavers (111 legs) was used. The AT fascicles originated from the MG, LG, and Sol were fused while twisting among themselves. There were three classification types depending on the degree of torsion. Further fine separation of each fascicle revealed MG ran fairly parallel in all types, whereas LG and Sol, particularly of the extreme type, were inserted onto the calcaneal tuberosity with strong torsion. In addition, the sites of Sol torsion were 3-5 cm proximal to the calcaneal insertion of the AT. These findings provide promising basic data to elucidate the functional role of the twisted structure and mechanisms for the occurrence of AT injury and other conditions.

Large abdominal wall defects may require a prosthesis for closure. The aim of our study was to identify the best material for abdominoplasty in pediatric patients. One hundred twenty-eight Wistar KY strain male rats (3 weeks old) were used. All animals underwent celiotomy via a midline skin incision. They were divided into seven groups as follows: the animals in groups 1 through 6 underwent full-thickness abdominal wall excision 3 cm in diameter. The animals in group 1 underwent primary closure. In groups 2 through 6 the defect was closed with prosthetic material. In Group 7, a sham operation was performed. Daily weights were measured. The animals were killed after 3 and 9 weeks. Adhesion scores were assigned for each group. Vicryl mesh resulted in the fewest adhesions and had no effect on weight gain in the developing rats.

Active sliding between doublet microtubules of sea urchin sperm axonemes that were demembranated with Triton X-100 in the presence or absence of calcium was induced with ATP and elastase at various concentrations of Ca2+ to examine the effects of Ca2+ on the direction of the power stroke of the dynein arms. Dark-field light microscopy of microtubule sliding revealed that the sliding from the axonemes demembranated with Triton and millimolar calcium and disintegrated with ATP and elastase showed various patterns of sliding disintegration, including loops of doublet microtubules formed near the head or the basal body. These loops were often thicker than the remaining axonemal bundle. In contrast, only thinner loops were found from the axonemes demembranated with Triton in the absence of calcium and disintegrated with ATP and elastase at high Ca2+ concentrations. Electron microscopic examination of the direction of microtubule sliding showed that the doublet microtubules in the axonemes demembranated in the presence of millimolar calcium moved toward the base of the axonemes by the dynein arms on the adjacent doublet microtubule as well as by their own dynein arms. Doublet microtubules in the axonemes demembranated in the absence of calcium moved toward the base of the axonemes only by their own dynein arms. Similar observations have been obtained from the axonemes from which the outer dynein arms were selectively extracted. From these observations, we can conclude that the dynein arms generate force in both directions and this feature of the dynein arms arises from at least the inner dynein arms.

To determine the relationship between maximum power relative to body weight (Pmax-rel) and the aging process, and to indicate the target values of improvement of motor function in Japanese individuals.In 410 physically active Japanese subjects (7-79 years) with no impairment of daily activities were performed counter-movement jumps. We evaluated the correlation between age and Pmax-rel, mean Pmax-rel by age group, and the percentage Esslinger Fitness Index score relative to 100% for same-age Europeans (%EFI), by gender.Age and Pmax-rel were correlated in both males aged18 andor=18 years old (both p0.01) and females aged18 andor=18 years old (both p0.01). Pmax-rel declined gradually with age, reaching 53.5% of the peak in subjects in their 70s. There was no significant difference in %EFI scores in most age groups.Similar to Europeans, Pmax-rel in Japanese individuals is closely correlated with age, declining to 53% of the peak in subjects in their 70s. Thus, Pmax-rel and the %EFI appear to be suitable as normative indices applicable to different human populations for the assessment of physical function.

Background and purpose: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke. Methods: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study. Results: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907–8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes. Conclusions: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.

To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with localized scleroderma (LSc).Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 10 patients with generalized morphea, 10 with linear scleroderma, 10 with morphea, and 10 normal controls.The serum MMP-13 levels in patients with LSc were lower than those in normal controls, but there was no significant difference (64.9 +/- 19.9 versus 73.2 +/- 11.5, p = 0.058). Serum MMP-13 levels in patients with generalized morphea were significantly lower than those in normal controls (54.0 +/- 18.7 versus 73.2 +/- 11.5 ng/ml; p0.01). Serum levels of MMP-13 were comparable among normal controls, the patients with linear scleroderma, and those with morphea. The prevalence of muscle involvement was significantly greater in the LSc patients with decreased MMP-13 levels compared with those with normal MMP-13 levels (50% versus 8%, p0.05). Serum MMP-13 levels were significantly inversely correlated with the number of linear lesions (r = 0.366, p0.05) and the number of involved body areas (r = 0.552, p0.005) in patients with LSc, while there was no significant correlation between serum MMP-13 levels and the number of plaque lesions. Furthermore, there was significant inverse correlation between serum MMP-13 levels and the number of involved body areas in patients with generalized morphea (r = 0.631, p0.05).The serum MMP-13 levels may reflect the disease severity in patients with LSc, especially generalized morphea, the severest form of this disorder.

Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are benign and intermediate malignant fibrotic dermal tumours, respectively. The contribution of transforming growth factor (TGF)-beta has been implicated in the progression of sclerosis in fibrotic diseases.To investigate the expression of TGF-beta receptors in these fibrotic tumours.We examined the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical analysis. We also examined the expression of TGF-beta1 and collagen type I using immunohistochemical analysis.We detected strong expression of TGFbeta-RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in vascular endothelial cells, smooth muscle cells and neural tissues, and weak expression in fibroblasts in normal skin sections. The expression levels of TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in comparison with normal dermal sections using in situ hybridization and immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their expression was found to be homogeneous in each DFSP tumour cell. The staining for TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF, and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal skin or tumour cells in the central part of DFSP. Type I collagen expression was found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP.These results suggest the possibility that TGF-beta signalling may contribute to the fibrosis around DF, and that TGF-beta receptors may play important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and TGFbeta-RII may be helpful in distinguishing these diseases.

Alpha-fetoprotein (AFP) is an important tumor marker for yolk sac tumor and hepatoblastoma in childhood. We have been using the graph of the normal range of serum AFP made by Tsuchida et al, when we evaluate the serum AFP levels in early infancy. We measured the serum AFP levels by an immunoradiometric assay in 163 normal infants under 2 years of age, in order to make a more precise graph. Our normal range was a little wider than that of Tsuchida et al. According to our graph, false-positive cases would be fewer. Referring to the half-lives of serum AFP levels in normal infancy is also useful, when it is difficult to evaluate the AFP level.

In this study the hemodynamic status and treatment modality of aggressive dural arteriovenous fistulas (dAVFs) was evaluated. Of 145 intracranial dAVFs treated in our clinic, there were 38 aggressive lesions presenting with hemorrhage, infarction, seizures, and symptoms of increased intracranial pressure. They included 3 (5% of all cavernous sinus lesions) cavernous sinus, 24 (44%) transverse-sigmoid and superior sagittal sinus, and 11 (46%) direct cortical types of dAVFs. Of these 38 aggressive lesions, retrograde leptomeningeal venous drainage was disclosed in 35 lesions, and retrograde sinus drainage in 3. Eighteen cases were treated only with endovascular procedures, 7 with surgical interventions, and 13 with combined endovascular and surgical procedures. Angiographic results were complete obliteration in 66% of the cases, subtotal and partial obliteration in 34%. Clinical outcome was GR (good recovery) in 58% of cases, MD (moderate disability) in 18%, SD (severe disability) in 13%, VS (vegetative state) in 8%, and D (death) (due to acute cardiac infarction) in 3%. Symptomatic procedural complication occurred in 3 cases. In conclusion, aggressive dural AVF resulted from retrograde leptomeningeal venous drainage. Combined surgical and endovascular treatment played the leading part in the management of this aggressive type of lesion.

Recently the patient of the atherosclerotic disease associated with malignant disease has been increased. A 75-year-old man was referred to our section with an infrarenal abdominal aortic aneurysm (AAA) and a gastric cancer (GC). Preoperative coronary angiogram revealed the significant stenoses of the right coronary and the left anterior descending coronary artery. We selected the staged operation of off-pump coronary artery bypass grafting (CABG) [OPCAB] and the concomitant surgery for the AAA and the GC. Operative invasion could decrease with the surgical procedure of the OPCAB and the concomitant surgery compared to the conventional CABG or the separate operation. We used the aortic connector system during OPCAB to prevent such the serious complications of the aortic dissection or the systemic embolism due to the calcified ascending aorta.

In rodents, ACTH induces steroidogenesis in the adrenal cortex and also lipolysis in adipose tissues via the sole specific receptor for ACTH. Up-regulation of the ACTH receptor (ACTH-R) mRNA by ACTH was found to be evident in adrenocortical cells. However, a role of in vivo ACTH on ACTH-R mRNA expression in the adrenal cortex is not well understood. In addition, so far less attention has been also paid to the regulation of ACTH-R expression in adipose tissues. We investigated the effects of hypophysectomy and in vivo administration of ACTH or dexamethasone on the level of ACTH-R mRNA in the adrenal gland and adipose tissues of mice.ACTH mRNA in the adrenal glands and epididymal adipose tissues of mice sacrificed 10 days after hypophysectomy or sham operation, and 24 hours after ACTH-Z (2 IU i.m.) or physiological saline solution (PSS) injection, and also 3-days after dexamethasone (300 microg/day i.m.) or PSS administration was analysed by Northern blot, and intensities of autoradiographic bands were quantified.In the adrenal gland, in vivo administration of ACTH-Z significantly increased the level of ACTH-R mRNA to 342% of control values, but in vivo administration of dexamethasone or hypophysectomy induced no significant alteration of ACTH-R mRNA. In adipose tissues, these conditions did not significantly alter the level of ACTH-R mRNA.Low circulating ACTH may not be a substantial factor for ACTH-R gene expression in the adrenal gland, but a high level of in vivo ACTH dose up-regulated the expression. A different regulation of ACTH-R gene expression exists in the adrenal cortex and adipose tissues of mice.

We aimed to determine if successful or failed eradication of Helicobacter pylori with triple therapy causes any difference in gastric mucosal histology. Japanese H. pylori-positive patients with a healed peptic ulcer received high ( n = 112) or low ( n = 113) doses of triple therapy (omeprazole, amoxicillin and clarithromycin) for 1 week. Biopsies from the greater curvature of the central antrum and upper corpus were taken 6 weeks and 30 weeks after treatment completion, and gastric mucosal histology compared between successful ( n = 171) and failed (n = 34) eradication groups. Morphological variables of gastritis were graded according to the updated Sydney System. Successful eradication therapy was defined as improvement in inflammation, neutrophil activity and atrophy; failed eradication therapy as improvement in inflammation and neutrophil activity only. Gastric mucosal atrophy gradually improved (in addition to improvements in inflammation and neutrophil activity) with successful eradication of H. pylori infection. Conclusions: Improvements in atrophy, inflammation and neutrophil activity were confirmed histopathologically following successful H. pylori eradication therapy, but improvements in inflammation and neutrophil activity were also seen after failed eradication therapy. No improvement in metaplasia was observed, irrespective of the success or failure of treatment. Since atrophy is known to be involved in the aetiology of gastric cancer, H. pylori eradication might prevent development of gastric cancer.

Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitors of metalloproteinases-1 (TIMP-1) are involved in tissue inflammation and fibrotic processes. We previously reported an elevated serum TIMP-1 level in patients with systemic sclerosis (SSc). We measured serum TIMP-1 and active MMP-9 levels in 62 patients with SSc, 10 patients with rheumatoid arthritis (RA) and 15 normal controls using a modified enzyme-linked immunosorbent assay. The active MMP-9 level in the serum of the patients with RA or SSc was not significantly different from that of controls. Serum MMP-9 activity in patients with diffuse cutaneous SSc was significantly decreased compared with that of limited cutaneous SSc or normal controls. The MMP-9 activity and modified-Rodnan total skin thickness score in patients with SSc were negatively correlated. Serum MMP-9 activity and TIMP-1 level in patients with SSc were not correlated. Serum MMP-9 activity might be a useful indicator of disease activity, especially skin severity, in SSc patients.

The purpose of this study was to define: the profile of patients with mitral valve dysfunction (stenosis and/or insufficiency) who were assisted at the University Outpatients' Clinic, the knowledge that these patients had concerning their disorder and the main difficulties and limitations resulting from it. The necessary data were obtained by interviewing 29 patients from November 1997 to February 1998. An analysis was conducted through the Content Analysis Technique. The results obtained helped to understand the problem under the individual's and his family's viewpoint, which helped to elaborate a nursing care program with an educational focus.

This study aimed at characterizing the profile of outpatients with aortic valve dysfunction, identifying their knowledge about the disease, their major limitations during everyday activities and their means of coping with their predicament. The data obtained by semi-structured interviews with 12 patients and analyzed by quantitative and qualitative methods enabled to identify how the patients perceive the illness and the treatment as well as the implications to their everyday activities, that is, they allowed to capture reality from the subject's perspective, which is the knowledge for the elaboration of an educational proposal.

We reported a case with dural arteriovenous fistula (dAVF) of the anterior cranial fossa associated with occlusion of the left cervical internal carotid artery. A 73-year-old man was admitted with total aphasia and right hemiparesis. Computed tomography showed an ischemic lesion of the left cerebral hemisphere and old infarction of the left occipital lobe. Angiography revealed occlusion of the left cervical internal carotid artery and dAVF of the anterior cranial fossa, fed by the left middle meningeal and the right anterior ethmoidal artery. Follow-up angiography revealed spontaneous recanalization and severe arteriosclerosis of the left internal carotid artery. After marked improvement of neurological deficits, the patient underwent surgical clipping of the draining veins to occlude the dAVF of the anterior cranial fossa. We speculated that marked development of the collateral circulation from the external carotid system might result in the occurrence of dAVF of the anterior cranial fossa.

We describe 2 patients with myositis and interstitial lung disease with the autoantibody to Wa antigen, a 48-kDa transfer RNA-related protein. In contrast to the previous description of anti-Wa antibody, our patients lacked systemic sclerosis-related features, but had clinical features consistent with those associated with antibodies to aminoacyl-transfer RNA synthetases. The difference in clinical presentation between our patients and patients with systemic sclerosis may be explained by recognition of different epitopes on the Wa antigen.

The interaction of various amyloid precursors and apolipoprotein E (apoE) is important for Congophilic amyloid formation. As for cerebral amyloidoses, although the correlation between amyloid beta protein (Abeta) and apoE in Alzheimer's disease (AD) has been clarified, the interaction of prion protein isoform (PrPsc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrPsc plaques, but to clarify the participation of apoE in the early stage of PDs, apoE deposition in immature lesions without Congophilic amyloid in PDs needs to be examined. In the present study two squirrel monkeys were inoculated with mouse PrPsc derived from sheep scrapie, and showed signs of severe spongiform degeneration. These lesions were immunohistochemically characterized as patchy perivacuolar and diffuse synaptic lesions without Congophilic amyloid. The central portion of the assemblies involving a few patchy perivacuolar lesions was detected by methenamine silver staining and appeared as a plaque-like lesion. ApoE was colocalized in all the plaque-like lesions and in half of the patchy perivacuolar lesions, but not in any diffuse synaptic lesions. These immunohistochemical characteristics indicated that apoE colocalization occurred in moderate mature lesions in PDs, and apoE might play an important role in the aggregation of PrPsc after a conformational change from cellular PrP isoform to PrPsc.

It has been found that brain atrophy develops more rapidly in patients with end-stage renal failure after initiation of dialysis therapy. The present study was designed to analyze the relationship between brain atrophy and asymptomatic ischemic brain lesions.Magnetic resonance imaging (MRI) was performed for the evaluation of brain atrophy and ischemic lesions. Brain atrophy was assessed by the ventricular-brain ratio (VBR), calculated as the ratio of the ventricular area to the whole brain area on the maximum MRI slice. The severity of periventricular hyperintensity (PVH) and the number of lacunae were also regarded as ischemic brain lesions. Fifty-five patients undergoing maintenance hemodialysis (HD) without clinically overt neurological signs and symptoms, with a mean age of 52 +/- 11 (SD) years and a mean HD duration of 7 +/- 6 (SD) years were subjected. VBR and its relationship to ischemic brain lesion data were compared to those in 35 non-HD patients (controls), with a mean age of 42 +/- 14 (SD) years.The VBR, the number of lacunae and the severity of PVH tended to increase with age in HD. The VBRs at all age groups were significantly higher in HD than in controls (7.0 vs 3.7% at the 4th decade, p0.05; 8.4 vs 5. 9% at the 5th decade, p0.05; 9.6 vs 5.4% at the 6th decade, p0.05; and 11.6 vs 6.3% at the 7th decade, p0.05). HD patients had significantly higher number of lacunae and had more advanced PVH than did controls. Both the number of lacunae and the severity of PVH were significantly correlated to VBR in HD.In conclusion, the rapid progression of brain atrophy was related to the asymptomatic ischemic brain lesions in our HD patients. Such data indicated that cerebral ischemia might be a causative mechanism of brain atrophy in chronic hemodialysis patients.

KL-6 is a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. Circulating KL-6 has been shown to be a sensitive marker of the disease activity of interstitial lung diseases. We determined the serum levels of KL-6 in patients with systemic sclerosis (SSc) and investigated whether these levels would serve as a useful marker of pulmonary fibrosis (PF) in patients with SSc.The serum KL-6 levels were determined using a specific ELISA in 91 patients with SSc, and in 38 healthy controls.The serum levels of KL-6 were significantly higher in patients with SSc than in healthy controls (923+/-860 vs. 382+/-55 U/ml; p0.0001). The serum KL-6 levels of the patients with diffuse cutaneous SSc (dSSc) tended to be higher than those with limited cutaneous SSc (ISSc) (1054+/-1000 vs. 800+/-694 U/ml), but there was no significant difference between these 2 groups. The serum KL-6 levels in the patients with PF were significantly elevated compared to those without PF (1283+/-1056 vs. 520+/-148 U/ml; p0.0001). Moreover, DLCO and VC were also significantly decreased in the patients with elevated KL-6 levels compared to those with normal levels (62+/-22% vs. 72+/-17%, p0.05; 87 +/-20% vs. 100+/-18%, p0.01, respectively).Serum KL-6 level may be a useful serum marker for evaluating pulmonary fibrosis in patients with SSc.

To determine serum soluble CD30 (sCD30) levels in patients with localized scleroderma.Serum soluble CD30 levels were assayed by a sensitive ELISA in 55 patients with localized scleroderma, in 15 with systemic sclerosis (SSc), and in 20 healthy controls.Serum levels of sCD30 were significantly higher in patients with localized scleroderma than in healthy controls. Serum levels of sCD30 were correlated with the number of sclerotic lesions, the number of involved areas, levels of anti-histone antibody IgM, and levels of interleukin 6. sCD30 levels in sera from patients with SSc were also significantly higher than in healthy controls.These results suggest possible involvement of Th2 cells in the immunopathogenesis in localized scleroderma, and serum sCD30 levels may be helpful in following the outcome of the disease.

Outer arm dynein was purified from sperm flagella of a sea anemone, Anthopleura midori, and its biochemical and biophysical properties were characterized. The dynein, obtained at a 20S ATPase peak by sucrose density gradient centrifugation, consisted of two heavy chains, three intermediate chains, and seven light chains. The specific ATPase activity of dynein was 1.3 micromol Pi/mg/min. Four polypeptides (296, 296, 225, and 206 kDa) were formed by UV cleavage at 365 nm of dynein in the presence of vanadate and ATP. In addition, negatively stained images of dynein molecules and the hook-shaped image of the outer arm of the flagella indicated that sea anemone outer arm dynein is two-headed. In contrast to protist dyneins, which are three-headed, outer arm dyneins of flagella and cilia in multicellular animals are two-headed molecules corresponding to the two heavy chains. Phylogenetic considerations were made concerning the diversity of outer arm dyneins.

An 82-year-old man presented with a huge hypogastric tumor. A pelvic computed tomographic scan and magnetic resonance imaging revealed a multiple cystic mass 14 x 10 x 15 cm in diameter. The prostate specific antigen (PSA) value was elevated to 903 ng/ml. Histological examination of the needle biopsy specimens of the prostate revealed moderately differentiated adenocarcinoma. Bone scintigraphy showed a hot area in part of the costa. No other abnormalities were found. The tumor origin was suspected to be the prostate, but the possibility that it was another organ could not be denied completely since the tumor was located in the anterior portion above the bladder. Treatment with luteinizing hormone-releasing hormone agonist and diethylstilbestrol was initiated considering the patient's age. The PSA value returned to normal and the tumor size was reduced markedly after 28 weeks of therapy. Thirty-seven case of prostatic cancer with cystic formation in the Japanese literature are reviewed.

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine which has been reported to be important in the pathogenesis of rheumatoid arthritis (RA). In this study, the serum level of VEGF was measured using enzyme-linked immunosorbent assay in 17 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic lupus erythematosus, 49 patients with polymyositis/dermatomyositis (PM/DM), 40 patients with systemic sclerosis (SSc), 11 patients with RA and 20 control subjects. The VEGF level was 184 +/- 62 pg/mL (mean +/- SD) in the serum of normal individuals. The mean VEGF levels in the patients with PM/DM or RA were significantly higher than in the normal controls. In 21 of the 49 patients with PM/DM and nine of the 11 patients with RA, the serum VEGF level was considered to be elevated. In patients with SSc, those with diffuse cutaneous SSc showed elevated VEGF levels in comparison with normal controls. An elevated serum VEGF level was correlated with the frequency of lung fibrosis and reduced vital capacity in the patients with SSc.

We treated a man with giant cell granulomatous hypophysitis with pituitary enlargement, as seen on magnetic resonance imaging. Endocrinological examination revealed panhypopituitarism and diabetes insipidus. Microscopic examination of the specimen obtained by transsphenoidal pituitary biopsy revealed a granulomatous lesion, composed of epitheliod cells, Langhans' multinucleated giant cells, lymphocytes and other chronic inflammatory cells. On whole body gallium-67 scintigraphy, there was extensive uptake in the pituitary gland. Gallium-67 scintigraphy may greatly aid in the diagnosis of granulomatous hypophysitis.

Desmoplastic malignant melanoma (DMM) consists of amelanotic spindle-shaped melanoma cells and is accompanied by desmoplasia with fibrous stromata. It has a strong tendency for local infiltrative growth and recurrence and a propensity for neurotropism. It is not yet known which cytokine is responsible for the desmoplasia in DMM. In the present study, we investigated the roles of several fibrogenic cytokines and cytokine receptors in DMM: basic fibroblast growth factor (bFGF), connective tissue growth factor (CTGF), transforming growth factor-beta, platelet-derived growth factor (PDGF) and PDGF receptors. Immunostaining and in situ hybridization were conducted in four cases of DMM and four cases of amelanotic malignant melanoma (AMM) as negative controls for desmoplasia. PDGF-beta receptor, bFGF and CTGF were intensely expressed in the DMM specimens in comparison with the AMM specimens. The reaction of PDGF-B ligand and CTGF to PDGF-beta receptor, in addition to the expression of bFGF, may contribute to the desmoplasia in DMM.

We compared clinical findings in 12 cases of systemic lupus erythematosus (SLE) in boys with those in 49 cases in girls. The age at which SLE developed in boys was consistent with that of infantile SLE and there was no age specificity. Momy cases in boys were diagnosed earlier as compared with cases in girls. Symptoms of infantile SLE, such as fever, arthalgia, butterfly rash, and urinary abnormalities, did not differ between boys and girls. However, a higher percentage of boys (58.3%) had central nervous system complications at onset than did girls (30.6%). Platelet counts tended to be higher in boys than in girls, a finding that suggests SLE tends to be more severe in boys than in girls. The incidence in the appiarance of LE cells, anti-Sm antibodies and immune complexes was higher in boys than in girls. Type IV or V renal pathologic changes (World Health Organization Histologic Classification) were present in 70% of boys. Our findings suggest that SLE in boys is more severe than that in girls and is more likely to be associated with central nervous system complications and severe renal complications.

The soluble form of the vascular cell adhesion molecule-1 (VCAM-1) is detectable in human sera and is elevated in diabetic patients, with unknown clinical significance. In the present study, the relationship between serum soluble VCAM-1 and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was evaluated in 95 Japanese patients with Type 2 diabetes mellitus (DM). Serum soluble VCAM-1 concentration was higher in patients with more advanced stages of retinopathy as well as nephropathy. There was a significant correlation between soluble VCAM-1 and log10 (urinary albumin excretion) in 69 patients with normal serum creatinine levels (r = 0.51, p < 0.0001) and a significant correlation between soluble VCAM-1 and log10 (serum creatinine) in all the patients (r = 0.83, p < 0.0001). Soluble VCAM-1 concentration was also elevated in patients with neuropathy. There was a significant correlation between soluble VCAM-1 concentration and the number of microvascular complications (r = 0.59, p < 0.0001). However, multivariate regression analysis revealed that only diabetic nephropathy, was associated with the soluble VCAM-1 concentration. The elevation of circulating VCAM-1 level in diabetic nephropathy may result from underlying systemic endothelial dysfunction, increased VCAM-1 production in damaged renal tubular or glomerular epithelial cells and/or decreased renal clearance of this molecule, depending on the stage of nephropathy.

A 56-year-old male had suffered from hepatocellular carcinoma treated by operation, PHoT and TAE since 1994. In December 1995, he had multiple metastases of lung in addition to recurrence of primary hepatic lesions. We discontinued treatment of TAE and decided to administer UFT (400 mg/day) orally as an outpatient. After seven months, the primary hepatic lesions were decreased in size, and metastatic lesions of lung were completely eliminated with reduction of AFP level. Generally, hepatocellular carcinoma with metastasis is refractory to treatment. However, this result suggests that UFT is one of the effective treatments for such advanced cases as having lung metastasis.

A 76-year-old man was admitted to our hospital with a diffuse reticulo-nodular shadow on chest X-ray. He had no symptoms. Transbronchial lung biopsy specimens revealed alveolitis and small numbers of lymphocytes. Bronchoalveolar lavage fluid (BALF) analysis revealed an increased number of eosinophils. Few eosinophils were seen in the alveolar lumen on biopsy. The patient had no symptoms, and was discharged without therapy. He was followed as an outpatient. Dyspnea on effort gradually developed June 1995. The diffuse infiltrative shadows on chest CT worsened and the patient was again admitted. Laboratory data revealed an elevation of serum LDH. Tumor markers were negative. Desquamative interstitial pneumonia (DIP) was diagnosed on open lung biopsy. Corticosteroid therapy (1 mg/kg/day) was administered. After treatment with corticosteroid, chest CT findings and pulmonary function tests improved remarkably. DIP is less common in Japan than elsewhere. The characteristic findings of BALF taken from patients with DIP are still inperfectly characterized. Our patient exhibited an increased number of eosinophils. To the best of our knowledge, BALF findings were reported for six cases of DIP in Japan. In five out of the seven cases (including our case), BALF findings demonstrated an increased number of eosinophils. This finding may be one of the characteristic features in patients with DIP.

The patient was complicated by type C hepatitis considered dur to blood preparations during the treatment of acute lymphoblastic leukemia. On administration of Sho-saiko-to, the white blood cell count decreased. When the drug was administered again, interstitial pneumonia developed concurrently. The case is a 7-year-old boy. He is the youngest to suffer interstitial pneumonia due to Sho-saiko-to in Japan, showing the possibility that interstitial pneumonia occurs even in childhood. A study of the IgG subclass at the time of the development of interstitial pneumonia in the affected child showed an imbalance of the subclass, with an increase in the percentage of IgG1 and IgG3, and a decreased in the percentage of IgG2 and IgG4. With improvement in the symptoms thereafter, however, the IgG subclass normalized. Thus it is possible that the IgG subclass is concerned with the development of interstitial pneumonia in this case. So, making careful observations is needed in administering Sho saiko-to to children with type C hepatitis who use various immunosuppressants.

1. The effects of the vasoconstrictor angiotensin II (Ang II) on whole-cell ATP-sensitive K+ currents (IK,ATP) of smooth muscle cells isolated enzymatically from rat mesenteric arteries were investigated using the patch clamp technique. 2. Ang II, at a physiological concentration (100 nM), reduced IK,ATP activated by 0.1 mM internal ATP and 10 microM levcromakalim by 36.4 +/- 2.3%. 3. The protein kinase C (PKC) activator 1-oleoyl-2-acetyl-sn-glycerol (OAG, 1 microM) reduced IK,ATP by 44.1 +/- 2.7%. GDP beta S (1 mM), included in the pipette solution, abolished the inhibition by Ang II, while that by OAG was unaffected. 4. Pretreatment with the PKC inhibitors staurosporine (100 nM) or calphostin C (500 nM) prevented the Ang II-induced inhibition of IK,ATP. 5. Ang II inhibition was unaffected by cell dialysis with PKA inhibitor peptide (5 microM), and the PKA inhibitor Rp-cAMPS (100 microM) did not reduce IK,ATP. 6. Our results suggest that Ang II modulates KATP channels through activation of PKC but not through inhibition of PKA.

A 25-year-old man was admitted to the hospital because of uncontrollable coughing and sputum production. He had been suffering from coughing and sputum production since he was 7 years old. He was given a diagnosis of bronchiectasis and persistent airway infection with Pseudomonas aeruginosa when he was 16 years old. One year of treatment with erythromycin and another year of treatment with roxithromycin were not effective. After he was referred to our hospital in 1993, he was given clarithromycin together with tosufloxacin for two years as an outpatient. The treatment was not very effective, but some prophylactic effect was seen with regard to prevention of acute exacerbations of Pseudomonas aeruginosa airway infection. Examination after admission revealed a high level of serum IgE (3703 U/ml), a strong skin reaction to aspergillus allergen, and marked central bronchiectasis in both upper lobes. He had no history of eosinophilia or of attacks of dyspnea. Our diagnosis was acute exacerbation of long-standing allergic bronchopulmonary aspergillosis and chronic airway infection. Treatment with oral prednisolone (30 mg per day) together with intravenous cefsulodin for three weeks resulted in marked relief symptoms and improvement in pulmonary function. The delay in correct diagnosis seems to have been caused by the lack of an obvious episode of asthma, and by the fact that the chronic productive coughing was thought to have been due to bronchiectasis, and to chronic bacterial infection. The characteristic bronchiectasis of this patient prompted us to examine the allergic reaction to aspergillus and let us to the correct diagnosis.

A case of right hydronephrosis as a complication of appendicitis is reported. The patient was a 63-year-old male, whose chief complaints were pollakisuria and dysuria. Roentgenographic examination revealed right hydronephrosis due to stenosis of right lower ureter and intrapelvic tumor at the right side. Exploration revealed an abscess in the pelvic cavity, and pathologic examination disclosed periappendiceal perforation and an old inflamed appendix. A review of the literature revealed that it is difficult to diagnose the appendicitis without typical symptoms.

We encountered seven children with hemophagocytic syndrome complicated with collagen diseases of whom five were JRA and two SLE, HPS was seen as one of initial symptoms in 6 cases excluding one case of JRA. Hematologically, cytopenia in 2 cell lines (RBC and platelets) was seen in most cases. Active hemophagocytosis by matured large histiocytes was observed in all cases. All patients had moderately to extremely high serum ferritin levels and LDH levels. Although both lives did not correlated with prognosis in HPS with collagen disease, the higher serum total cholesterol/serum triglyceride ratio, the worse was the prognosis. Those findings suggested that HPS in collagen diseases may be a different entity from other types of HPS.

Causal organisms and their changes were evaluated in 158 cases of septicaemia admitted to Jikei University Hospital from 1975 to 1994. Eighty patients (50.6%) were aged less than 1 year, and 37 patients (23.4%) were newborns. The average mortality rate was 18.4%. The mortality rate between 1975 and 1984 was 26.8%, and that of the past 10 years (from 1985 to 1994) decreased to 13.7%. Staphylococcus aureus (29 cases, 19.4%) was the most common pathogens isolated, followed by Pseudomonas sp. (24 cases, 15.2%), Escherichia coli (19 cases, 12.0%), and Haemophilus influenzae (18 cases, 11.4%). H. influenzae, Acinetobacter sp., Streptococcus pneumoniae and Group B streptococcus (GBS) increased in the past 10 years (from 1985 to 1994), compared with the preceding 10 years (from 1975 to 1984). The mortality rate of Klebsiella sp. septicaemia (28.6%) was highest, followed by Pseudomonas sp. (25.0%), S. aureus (24.1%), S. pneumoniae (22.2%). H. influenzae and Acinetobacter sp. septicaemia were not fatal. E. coli and GBS were common among neonates and patients aged less than 1 year. H. influenzae septicaemia occurred mainly in patients with meningitis, in those younger than school age. Acinetobacter sp. was common among neonates and children with leukaemia Pseudomonas sp., Klebsiella sp., and Acinetobacter sp. were mainly detected in patients with underlying diseases. E. coli, H. influenzae, S. pneumoniae and GBS were mainly detected in patients without underlying diseases.

We encountered three cases of juvenile rheumatoid arthritis which showed a depressed serum complement level during the clinical course. Circulating immune complex and increased secondary fibrinolysis were detected in all cases. The laboratory data suggested the presence of vesculitis. Cutaneous vasculitis was observed by biopsy in 2 cases and abnormal respiratory function in one cases. These 3 cases were in contrast to other 95 JRA cases treated in our department who showed normal serum complement levels. Estimation of serum complement may, therefore be useful to predict the vascular complication and refractoriness to therapy in JRA.

We describe an 8-year-old boy with CVID and chronic CMV infection. Although at onset he was diagnosed as IgA deficiency, 4 years after his clinical manifestations because compatible to CVID. During his clinical course he had suffered from various disorders as follows; AIHA, interstitial pneumonia, hemophagocytic syndrome, chronic gastroenterocolitis and so forth. At the age of 8 the PCR of CMV-DNA of biopsy specimen from colon, lung and bone marrow were confirmed to be positive. Hematological examinations revealed abnormal cellular immunity such as decreased CD 4/8 ratio with increased HLA- DR+ CD 8+ T cell, decrease of absolute blood lymphocytes count and reduced response of lymphocytes to blastogenetic agents. These findings brought us to diagnose him as having CVID complicated with chronic CMV infection. This case gives us some impact to speculate what role CMV infection plays in CVID, Whose etiology is unknown.

Several clinical trials have demonstrated that cisplatin-based chemotherapy for primary intracranial germ-cell tumors is effective as a neoadjuvant chemotherapy. In this report, we describe a 6-year-old boy, Down syndrome and Hirschsprung's disease with intracranial pure yolk sac tumor treated by combined chemotherapy with cisplatin, vinblastine, bleomycin and cyclophosphamide (modified VAB-6 regimen). He had been admitted to our hospital because of intractable vomiting, and left facial nerve palsy since 1 month before. An MRI revealed an enlarged mass, 4cm in diameter, in the left cerebello-pontine angle with uniformal enhancement by Gd-DTPA, and bilateral ventricular dilatation. He was found to have increased serum alpha-fetoprotein level (AFP 11, 786ng/ml), but not human chorionic gonadotropin beta-subunit. After a partial resection of the tumor, diagnosed as pure yolk sac tumor, and ventriculo-peritoneal shunt, three courses of combined chemotherapy with cisplatin, bleomycin, vinblastine and cyclophosphamide (modified VAB-6 therapy) were carried out. The serum AFP level returned to normal, and the tumor mass entirely disappeared (a complete response) on MRI after the second course of chemotherapy. However, cisplatin-induced vomiting and mild neutropenia and renal tubular injury developed after the third course of chemotherapy. Irrespective of administration of recombinant human G-CSF and broad spectrum antibiotics, he suffered from pneumonia and died of septic shock and multiple organ failure. Autopsy showed microscopic residual tumors. The combination chemotherapy with cisplatin, bleomycin, vinblastine and cyclophosphamide is effective for initial treatment of childhood intracranial yolk sac tumor. It is necessary, however, to reevaluate the cisplatin dosage and treatment schedule in order to reduce such side effects as bone marrow suppression and renal damage.

The main cause of death in chronic hemodialysis patients is heart failure. We studied cardiac function prospectively in diabetic and non-diabetic patients who had recently been started on hemodialysis. We analyzed the mechanocardiograms and echocardiograms in addition to routine blood chemistry tests, chest X-rays, and electrocardiograms of ten hemodialysis patients at our hospital from 1989 to 1991. Ejection fraction (EF) and fractional shortening (FS) were not significantly different between diabetic patients and non-diabetic patients at the start of hemodialysis. After starting hemodialysis, EF and FS declined in diabetic patients. In contrast, non-diabetic patients did not show any changes in EF and FS during hemodialysis. The results demonstrated a poor prognosis in cardiac systolic function in hemodialysis patients with diabetes mellitus.

A 34-year-old male with intrathoracic lipoma arising from the chest wall is described. Although asymptomatic, the patient was pointed out an abnormal shadow on the chest X-ray film taken at the mass survey. No findings of CT suggested lipoma. The tumor, measuring 2.5 x 2.0 x 1.5 cm in diameter, was surgically removed, and the diagnosis of lipoma was confirmed postoperatively by histopathologic examination.