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Biomedical subjects

H Maruyama

Publications and source records attributed to H Maruyama.

At least 55 records · Page 3Linked to original sources
PubMed2001

Magnetic circular dichroism of 3d5/2 --> 2p3/2 resonant inelastic X-ray scattering at the Ho L(III)-edge in Ho3Fe5O12.

Magnetic Circular Dichroism (MCD) of Resonant Inelastic X-ray Scattering (RIXS) of 3d(5/2) --> 2p(3/2) decay (Ho Lalpha1) was measured at the Ho L(III)-edge in Ho3Fe5O12. The MCD-RIXS, in which the intermediate state has the 2p4f(n+1) configuration due to the quadrupolar transition of 2p --> 4f, was also observed at the pre-edge region of the Ho L(III)-edge. The obvious superposition of two peaks, which comes from the high-energy off-resonant Raman scattering and the fluorescence, could be found in both the RIXS and the MCD-RIXS when the energy of the incoming X-ray was 7eV higher than the white line. The dependence of the integration of the MCD-RIXS spectra on the incident x-ray energy could roughly reproduce the MCD of X-ray absorption spectra (XAS).

Journal Article↗
PubMed2001

Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy.

Distinguishing corticobasal degeneration (CBD) from progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biological marker to discriminative these two diseases has been a subject of clinical interest. In the present study, we assessed tau protein levels in cerebrospinal fluids by sandwich ELISA to distinguish CBD from PSP. The subjects consisted of 27 cases of CBD, 30 cases of PSP, and 36 healthy controls (CTL). The tau values in CBD were significantly higher than those in PSP (P<0.001) and those in CTL (P<0.001). The assay of CSF tau provided diagnostic sensitivity of 81.5% and specificity of 80.0% between CBD and PSP according to receiver-operating characteristic (ROC) curve analysis. When values were compared separately with respect to stage of the disease, differences in the values for moderate CBD vs. moderate PSP had the greatest significance (P<0.001 sensitivity 92.3%, specificity 100.0%), followed by cases of mild CBD and PSP (P<0.005, sensitivity 100.0%, specificity 87.5%). The values in severe CBD and PSP were not significantly different (P=0.07, sensitivity 100%, specificity 75.0%). Using data obtained from a larger number of disease cases, we confirmed our previous findings that tau protein levels in cerebrospinal fluids in patients with CBD are significantly higher than those in patients with PSP. Because tau protein levels in cerebrospinal fluids are significantly higher in early CBD cases than in early PSP cases, measurement of tau protein levels in cerberospinal fluids may be useful for the differential diagnosis of early CBD from early PSP.

Aged↗
PubMed2001

Citrullinemia type II in a 64-year-old man with fluctuating serum citrulline levels.

We describe a 64-year-old man with 'citrullinemia type II' whose serum citrulline levels fluctuated between normal and abnormally high during episodic manifesting periods. Elevations of the serum threonine/serine ratio and pancreatic secretory trypsin inhibitor level are very useful diagnostic markers. Our patient's cerebrospinal fluid citrulline level was also elevated, and T1-weighted magnetic resonance images revealed high-intensity signals at the bilateral internal capsule and the cerebral peduncles. Single-photon emission computed tomography of his brain showed reduced bilateral temporal lobar blood flow. Even if the serum citrulline level is within the normal range, citrullinemia should be considered in adult patients without primary liver dysfunction who show episodic consciousness disturbance, psychotic symptoms or both.

Ammonia↗
PubMed2001

Primary non-Hodgkin's lymphoma of the uterine cervix.

We present a patient with primary malignant lymphoma of the uterine cervix, which is extremely rare. She had a complete remission with a combination of chemotherapy and radiotherapy. Measurement of the serum soluble interleukin-2 receptor level was a useful index of the effectiveness of treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Synaptic exocytosis and nervous system development impaired in Caenorhabditis elegans unc-13 mutants.

C. elegans mutants defective in unc-13 exhibited severe behavioral abnormalities including paralyzed locomotion and slow pharyngeal pumping and irregular defecation cycle. Consistent with the phenotypes, the mutants accumulated abnormally high levels of the neurotransmitter acetylcholine and were resistant to acetylcholinesterase inhibitors. The unc-13 gene was expressed in most, if not all, neurons when analyzed by using chimeric constructs consisting of the unc-13 promoter and green fluorescence protein or beta-galactosidase reporter gene. While Ca(2+)-regulated acetylcholine release is lacking, the mutants were still able to release acetylcholine in vivo and in vitro at similar levels to that mediated by the regulated mechanism. Double mutants defective in both unc-13 and other genes involved in synaptic transmission showed the Unc-13 phenotype, rather than other mutant phenotypes, in terms of locomotion as well as of acetylcholine accumulation. Furthermore, electron microscopic reconstruction of the mutant nervous system uncovered that a majority of neurons developed and connected as those in the wild type except for subtle abnormalities including inappropriate connections through gap junctions and morphological alterations of neurons. These results demonstrate that the unc-13 gene product plays an essential role at a late stage in Ca(2+)-regulated synaptic exocytosis. Neurotransmitters released through the Ca(2+)-regulated mechanism are required for, but do not play major roles in the nervous system development. The large amount of Ca(2+)-independent neurotransmitter release observed in the unc-13 mutants suggests that there may be a distinct mechanism from evoked or spontaneous release in neurotransmission.

Acetylcholine↗
PubMed2001

Multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis with a TSC2 gene.

A 45-year-old woman with a long-standing diagnosis of tuberous sclerosis (TSC) is presented. She has multifocal micronodular pneumocyte hyperplasia (MMPH) and lymphangioleiomyomatosis (LAM) of the lung, together with the detection of TSC2 gene mutation. During surgery for spontaneous pneumothorax, an open-lung biopsy was performed. Micronodules were well defined, measuring approximately 4 mm in diameter. These MMPHs were histologically composed of papillary proliferation of Type II pneumocytes, with positive immunoreactivity of keratin and surfactant apoprotein. The cystlike spaces, with dilatation and destruction of air spaces, were diffusely formed, and the walls were composed of the spindle cells. Such LAM showed positive immunoreactivity for HMB-45 (a monoclonal antibody specific for human melanoma) and tuberin (the gene product of TSC2). On germline mutation analysis using leukocytes of the present patient, a TSC2 gene mutation was confirmed as a deletion of G (or g) on Exon 9 by polymerase chain reaction-single-strand conformational polymorphism. However, no mutation was detected in her son. With microdissection analysis using paraffin-embedding lung tissues, LOH of the TSC2 gene preliminarily was detected in a LAM lesion but not in MMPH. It is suggested that MMPH, in addition to LAM, could be another pulmonary lesion in TSC patients and that the detection of TSC2 and/or TSC1 gene could essentially be useful for the pathogenesis of MMPH and LAM in TSC patients.

Adult↗
PubMed2001

Long-term production of erythropoietin after electroporation-mediated transfer of plasmid DNA into the muscles of normal and uremic rats.

The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major side-effect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats.

Animals↗
PubMed2001

Skin-targeted gene transfer using in vivo electroporation.

The skin is an important target for gene transfer because of its easy accessibility. Using plasmid DNA expressing rat erythropoietin (pCAGGS-Epo) as the vector, we previously demonstrated long-term Epo delivery in rats by muscle-targeted gene transfer using in vivo electroporation. Here we examined whether this electroporation approach could be applied to gene delivery in rat skin. To optimize gene transfer, we tested the efficiency of skin-targeted Epo gene transfer with three types of electrodes at three different electrode voltages. Each rat was injected intradermally with a total of 800 microg of pCAGGS-Epo, in the abdominal area. Plate-and-fork-type electrodes were effective for Epo delivery by skin-targeted gene transfer at low voltages (12 approximately 24 V). The vector-derived Epo mRNA was expressed only at the DNA injection site. The Epo gene was expressed in a dose-dependent manner, the expression persisted for 7 weeks, and hematocrit levels were increased for 11 weeks. Skin injection with pCAGGS-lacZ showed lacZ gene expression in the epidermis on day 1 after injection and in the subcutaneous muscle layer on day 7. Slight skin damage due to the gene transfer procedure was evident on day 1, but absent by day 7. These results demonstrate that skin-targeted pCAGGS-Epo transfer by in vivo electroporation at low voltage is a useful procedure for the short-term delivery of Epo.

Animals↗
PubMed2001

Hemodynamics in the left gastric vein after endoscopic ligation of esophageal varices combined with sclerotherapy.

BACKGROUND AND METHODS: We examined the changes in portal hemodynamics after endoscopic variceal ligation (EVL) combined with endoscopic injection sclerotherapy (EIS) in relation to post-treatment relapse. The present study included 93 patients who underwent EVL-EIS combination therapy. Portal hemodynamics were examined by Doppler ultrasonography and percutaneous transhepatic portography (PTP). RESULTS: Therapy with EVL-EIS resulted in the complete disappearance of varices in 89 of 93 patients. Cumulative relapse-free rates (Kaplan-Meier method) were 75.8 and 50.2%, respectively, 1 and 3-5 years after treatment. At the end of treatment, the flow in the left gastric vein was examined by Doppler ultrasonography. In 50 of 63 patients, the flow remained hepatofugal. In 23 of these patients, PTP was performed at the end of treatment; selective left gastric venography did not reveal any palisade zone vessels or varices. However, fine blood vessels were seen around the lower esophagus in nine patients, only the paraesophageal vein was found in 10 patients and these two findings were present in four patients, indicating that collateral blood flow remained in the lower esophagus in 13 of 23 patients. These findings suggest that frequent relapse of varices results from insufficient blockage of blood flow from the left gastric vein to the lower esophagus. However, in patients with a patent paraesophageal vein, long-term effects obtained by EVL-EIS combination therapy were satisfactory. CONCLUSIONS: The pattern of the development of collateral left gastric veins represents important hemodynamic changes that predict the long-term prognosis of patients after treatment.

Adult↗
PubMed2001

Pathogenesis of multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis and association with tuberous sclerosis genes TSC1 and TSC2.

Tuberous sclerosis (TSC) is a rare, genetically determined disorder / familial tumor syndrome, currently diagnosed using specific clinical criteria proposed by Gomez, including the presence of multiorgan hamartomas. Pulmonary involvement in TSC is well known as pulmonary lymphangioleiomyomatosis (LAM), which has an incidence of 1-2.3% in TSC patients. LAM has immunohistochemical expression of both smooth-muscle actin and a monoclonal antibody specific for human melanoma, HMB-45. It has recently been reported that multifocal micronodular pneumocyte hyperplasia (MMPH) associated with TSC should be considered as a distinct type of lung lesion, whether it occurs with or without LAM. Two predisposing genes have been found in families affected by TSC; approximately half of the families show linkage to TSC1 at 9q34.3, and the other half show linkage to TSC2 at 16p13.3. TSC genes are considered to be tumor suppressor genes, and mutations in them may lead to abnormal differentiation and proliferation of cells. Tuberin, the TSC2 gene product, has recently been found to be expressed in LAM and MMPH. In this article we discuss the histogenesis and genetic abnormalities of neoplastic lesions associated with TSC, and we review the current understanding of the pathogenesis of pulmonary hamartomatous lesions such as LAM and MMPH in TSC.

Adolescent↗
PubMed2001

Osteoclastogenesis and osteoclast activation in dialysis-related amyloid osteopathy.

Dialysis-related amyloid osteopathy (DRAO) is characterized by local osteoarticular lytic lesions, which sometimes cause a pathological fracture and reduce the quality of life in affected patients. In DRAO, active osteoclastic bone resorption is found at the bone surface facing the invaded synovial tissue and/or intervertebral disc, whereas reactive bone formation is absent. The eroded bone surface is covered with osteoclasts, suggesting the local promotion of osteoclastogenesis and osteoclast activation around DRAO. Inflammatory cells infiltrating the synovial tissue are likely to promote inflammatory osteolysis. Three possible pathways can be considered for the osteoclastogenesis and/or osteoclast activation in inflammatory osteolysis in DRAO: (1) indirect action of the inflammatory cytokines through the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin ligand (RANKL/OPGL) expression in osteoblasts, (2) direct action of inflammatory cytokines, and (3) RANKL/OPGL expression in inflammatory cells. To apply antiosteoclastic agents as another therapy for DRAO, we have to clarify the roles of those pathways in local osteoclastogenesis and/or osteoclast activation.

Amyloidosis↗
PubMed2001

Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and beta3-adrenergic receptor gene Trp64Arg polymorphism on insulin resistance and fasting plasma glucose in young to older Japanese men.

The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the beta(3)-adrenergic receptor (beta3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the beta3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of beta3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in beta3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P =.010). In the older hyperglycemic group, the beta3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the beta3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype.

Adult↗
PubMed2001

Reduction of circulating beta2-microglobulin level for the treatment of dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is a common complication associated with long-term haemodialysis therapy. The elimination of beta2-microglobulin (beta2m), the major constituent of the amyloid fibrils in DRA, from circulation has been expected to bring some clinical benefit. Recently, a direct haemoperfusion method using selective beta2m absorption column to eliminate circulating beta2m has been introduced into clinical practice. According to a recently performed, prospective, multicentre study, joint pain, stiffness and daily activities were significantly improved in patients with established DRA after the introduction of selective beta2m absorption therapy. Meanwhile, although osteoarticular lesions progressed in the control group, there was no significant progression in the selective beta2m absorption therapy group. The absorptive affinity of the column for beta2m is not quite specific and therefore some other unknown uraemic toxins might be removed also. However, the improvement of joint pain and the ability to undertake daily activities showed reversed correlations against plasma beta2m clearance. Symptoms associated with the increased amount of extracorporeal circulation and increased economical burden are areas of concern for this therapy. In conclusion, selective beta2m absorption therapy was suggested to have the potential to ameliorate established DRA symptoms and simultaneously prevent its local development. The mechanism by which DRA symptoms are ameliorated remains obscure.

Absorption↗
PubMed2001

Vaccination with calpain induces a Th1-biased protective immune response against Schistosoma japonicum.

A large subunit of calpain, a calcium-activated neutral proteinase, from Schistosoma japonicum was cloned and expressed in Escherichia coli. When BALB/c mice were immunized with purified recombinant calpain (r-calpain) emulsified in complete Freund's adjuvant, a significant reduction in the number of recovered worms and also in egg production per female worm was observed (P<0.01). Spleen cells of the immunized mice showed enhanced production of gamma interferon (IFN-gamma) by activated CD4(+) T cells. Considering our observation of elevated expression of inducible nitric oxide synthase mRNA in immunized mice, r-calpain-induced IFN-gamma seemed to upregulate the production of nitric oxide by macrophages and subsequently mediated the killing of schistosomulae in the lung. On the other hand, spleen cells of immunized mice showed only faint interleukin-4 production in response to r-calpain in vitro, suggesting that immunization with r-calpain alters the Th1-Th2 balance in murine hosts even during a Th2-promoting S. japonicum infection. Furthermore, histopathological study of the livers of immunized mice showed that granulomas formed around eggs were diminished in both size and number. Egg production by female worms was clearly decreased in immunized mice, suggesting that r-calpain also has antifecundity effects. Taken together, these results point to S. japonicum calpain as a potential vaccine candidate for both worm killing and disease prevention, possibly through the induction of a strong Th1-dominant environment in immunized mice.

Animals↗
PubMed2001

Overexpression of activin A in stage IV colorectal cancer.

BACKGROUND AND AIMS: Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-beta) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII). METHODS: Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin betaA and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin betaA localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation. RESULTS: Inhibin betaA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin betaB and inhibin alpha were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin betaA mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin betaA mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers. CONCLUSIONS: Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.

Activins↗
PubMed2001

Hemorrhagic gastric carcinoma in an acromegalic patient.

A rare case of hemorrhagic gastric carcinoma in an acromegalic patient is reported. A 79-year-old Japanese man was referred to our hospital with diagnoses of upper gastrointestinal hemorrhage and angina pectoris. This patient showed typical clinical features of acromegaly, with increased serum growth hormone (GH) and insulin-like growth factor I (IGF-I) level. A high titer of serum anti-Helicobacter pylori (H. pylori) IgG was also observed. After percutaneous transluminal coronary angioplasty treatment for stenosis of the right coronary artery, the patient underwent distal gastrectomy. Gastric cancer was Type 2 macroscopically and was diagnosed histologically as a papillary and well to moderately differentiated tubular adenocarcinoma. Reverse transcription-polymerase chain reaction analysis estimated that the amount of IGF-I receptor mRNA expression in the gastric cancer tissue was 1.6 times higher than that in the adjacent atrophic mucosa, whereas the amount of IGF-I mRNA expression in the cancer tissue was only half that in the atrophic mucosa. Both the stimulatory effects of GH and/or IGF-I on cell proliferation and H. pylori infection in gastric tumorigenesis may have been responsible for the development and growth of gastric carcinoma in this patient.

Acromegaly↗
PubMed2001

Wide-spread distribution of sentinel lymph nodes in esophageal cancer.

Sentinel lymph nodes are the first draining nodes that contain tumor cells. Identification of sentinel nodes may help to determine the suitable extent of lymphadenectoy. To assess the location of sentinel lymph nodes, a series of 41 patients with single and two metastatic lymph nodes who underwent esophagectomy and 3-field lymphadenectomy between 1991 and 1999 were investigated retrospectively. Only 29 (47.5%) of 61 metastatic nodes showed correspondence between the tumor site and the regional metastatic lymph nodes by routine histologic examination. In the patients with tumors in the upper and middle thoracic esophagus, metastatic lymph nodes were distributed in the cervix, mediastinum and abdomen. Although sentinel nodes were limited to the regional and adjusting compartments in 82%, nodes were found beyond the adjusting compartments in 18%. The sentinel nodes were broadly distributed depending on the location of the tumor in esophageal cancer.

Adult↗