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Biomedical subjects

M Maruyama

Publications and source records attributed to M Maruyama.

At least 91 records · Page 5Linked to original sources
PubMed2000

Synthesis of a model compound related to an anti-ulcer pectic polysaccharide.

A stereocontrolled synthesis of the model compound for an anti-ulcer active polysaccharide (Bupleuran 2IIc) is described. Glycosidation of the disaccharide acceptor, 2-O-acetyl-3-O-benzyl-4-O-(p-methoxybenzyl)-alpha-L-rhamnopyranosyl-(1-- >4)-2,3,6-tri-O-benzyl-alpha-D-galactopyranosyl trichloroacetimidate, with the disaccharide receptor, allyl 3,4-di-O-benzyl-alpha-L-rhamnopyranosyl-(1-->4)-2,3,6-tri-O-benzyl-beta- D-galactopyranoside, using silver triflate (AgOTf) as a promoter gave the desired tetrasaccharide derivative, which was transformed into the acidic tetrasaccharide, corresponding to a segment of the rhamnogalacturonan (Bupleuran 2IIc) polysaccharide, propyl alpha-L-Rha-(1-->4)-alpha-D-GalA-(1-->2)-alpha-L-Rha-(1-->4)-beta-D-GalA , via removal of the corresponding ether and ester protecting groups, followed by oxidation.

Anti-Ulcer Agents↗
PubMed2000

p62 functions as a p38 MAP kinase regulator.

By screening a HeLa cDNA library to isolate genes encoding p38-regulating proteins, we have isolated two independent clones which encode the binding proteins to p38. We have found that both of these cDNA clones encode p62, first identified as a phosphorylation independent p56(lck) SH2 domain binding protein. Recent studies also indicate that p62 interacts with atypical PKCs to anchor them to intracellular membranes and with RIP to mediate signals to NF-kappaB through atypical PKCs. Moreover, p62 is shown to be involved in the transcriptional regulation via SV40 enhancer and to serve as a coactivator of an orphan nuclear hormone receptor. A coimmunoprecipitation assay shows its enhanced association in HeLa cells after stimulations such as sorbitol and anisomycin. An indirect immunofluorescence study indicates that p62 colocalizes with p38 in the nucleus in response to the stimulation. And in vitro kinase assays using MBP, but not ATF-2, as a substrate show that p62 enhances p38 activities in a dose-dependent manner. Together, these results demonstrate that p62 plays roles not only as an anchor but also as a regulator for the p38 kinase activity.

Adaptor Proteins, Signal Transducing↗
PubMed2000

An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene.

We report the neuropathologic and genetic features of a 70-year-old man with autosomal-recessive juvenile parkinsonism (AR-JP). At the age of 32 years, he developed a dystonic gait, followed by hand tremor, rigidity, bradykinesia, and impaired postural reflex. Levodopa was effective in ameliorating these symptoms. Pathologic examination of autopsy specimens from this patient revealed loss of pigmented neurons and gliosis in the substantia nigra pars compacta (SNPC), being most pronounced in the medial and ventrolateral regions, and locus ceruleus (LC). The melanin content of the remaining SNPC neurons was low. This feature was less marked in the LC. There were no Lewy bodies, as confirmed by immunostaining for alpha-synuclein. An additional, significant finding in this patient was neuronal loss and fibrillary gliosis in the substantia nigra pars reticulata; this feature has not been reported previously in AR-JP. Gene analysis revealed that this autopsied patient and his siblings had the parkin gene mutation (homozygous exon 4 deletion) that is responsible for the disease.

Aged↗
PubMed2000

Radiographic diagnosis of early colorectal cancer, with special reference to the superficial type of invasive carcinoma.

The possibility of radiographically diagnosing carcinoma with submucosal involvement (invasive carcinoma) is discussed based on 119 invasive carcinomas of the large bowel that had been treated surgically and colonoscopically over a period of 9 years (1989-1997) at the Cancer Institute Hospital in Tokyo. Of these lesions, 38 were superficial-type invasive carcinoma, accounting for 31.9% (38/119) of all invasive colorectal carcinomas, including 36 lesions (94.7%, 36/38) of types IIa and IIa + IIc and 2 lesions (5.3%, 2/38) of type IIc + IIa. No pure type IIc was seen. The radiographic images obtained were correlated with macroscopic findings and analyzed in terms of visualization of the lesion's contour, central depression, converging folds, and basal indentation. A definitive diagnosis of superficial invasive carcinoma can be made radiographically if a lesion measures 10 mm and reveals moderate to severe basal indentation in a complete or nearly complete profile radiographic image. Attention should be paid to the presence of superficial-type advanced carcinomas measuring 10 mm or less, which is not infrequently experienced in Japan. Polypoid invasive carcinoma can be definitively diagnosed in the same way with much more certainty than can the superficial type because few polypoid advanced carcinomas are less than 20 mm. The size and the radiographic sign of the basal indentation are the most important indicators for the diagnosis of invasive carcinoma.

Adenoma↗
PubMed2000

Current progress and perspectives in immunoisolated islet transplantation.

This review summarizes the recent results of immunoioslated islet allo- and xenotransplants, especially in large animal species, and presents certain issues that would be important for the advancement of this technology toward clinical application. To date, the best results have been obtained with alginate microcapsules in both allo- and xenogeneic (porcine) islet transplantation in the spontaneously diabetic dogs and monkeys. Reversal of diabetes was also achieved in mice with cryopreserved, microencapsulated rat islets. However, results with these microcapsules have been highly variable and inconsistent from one laboratory to another. The causes of these discrepancies are multiple, but not totally understood. Immunoisolation devices have been investigated as an alternate approach to house a large number of islets in a space constructed by membranes of a defined pore size. Vascularized bioartificial devices were among the few cases that obtained long-term allo- and xenogeneic islet survival in totally pancreatectomized dogs. Thrombosis and associated problems were the major cause of failure with these devices. Diffusion chambers that have no vascular connection have been tested successfully in rodents, but no report has been available in large animal species. We have learned many important lessons and made considerable progress in islet immunoisolation. However, immunoisolated islet transplants have been only minimally successful in large animal models, and such technologies must be improved to achieve consistent success in large animal models prior to clinical trials. This will requires strict quality control of the islets, the membrane material, and the device construction. The membrane pore size that allows the permeation of molecules necessary for islet survival and function also permits the entry of cytokines, oxygen-radicals, and other small-size inflammatory products. Thus, the key to success appears to be to minimize inflammatory reactions generated by immuneisolation devices/capsules.

Alginates↗
PubMed2000

The likely transformation of papillary thyroid carcinoma into anaplastic carcinoma during postoperative radioactive iodine-131 therapy: report of a case.

We report herein a case of papillary carcinoma which appeared to transform into anaplastic carcinoma during postoperative radioactive iodine-131 (131I) therapy. A 67-year-old man who was diagnosed as having papillary thyroid carcinoma with bilateral neck lymph node involvement and multiple lung metastases underwent total thyroidectomy prior to 131I therapy. Immediately after a second course of 131I therapy, the patient complained of right neck pain and swelling, and a biopsy of the swollen neck lymph node was taken. Histologic examination of this biopsy specimen revealed anaplastic carcinoma. With p53 immunohistochemical staining, both the primary tumor and the biopsy specimen were positive. We speculate that first, some DNA damage in tumor cells was induced by the initial 131I therapy, but neither DNA repair nor cell apoptosis occurred because the p53 gene was already mutated; then further DNA damage was induced by the second 131I therapy, leading to anaplastic transformation.

Aged↗
PubMed2000

Solitary brain metastasis from papillary thyroid carcinoma in a patient with depression: report of a case.

Papillary carcinoma of the thyroid is a common thyroid malignancy with a relatively good prognosis. However, distant metastases may develop and become threatening, particularly to older patients, in a more aggressive manner. We report herein the clinical, radiological, and pathological findings of a patient with papillary thyroid carcinoma who had a solitary cerebral metastasis. The patient had been suffering from depression and had already undergone a hemithyroidectomy for primary thyroid carcinoma, and was known to have metastatic thyroid carcinoma of the lungs and bone. After the removal of the remnant thyroid gland prior to radioiodine (131I) therapy, he developed additional problems related to depression. Electroencephalography played an important role in identifying suspected brain metastasis and computed tomography demonstrated a space-occupying lesion in the left cerebral hemisphere. Consequently, an early removal of intracranial mass could be performed without any further life-threatening complications. Moreover, after removal of the brain mass the patient's depression improved immediately without the use of any antidepressants. This case report indicates the possibility that a patient's depression might be associated with brain metastasis from papillary thyroid carcinoma, and also suggests that an early diagnosis with the appropriate surgical management of a brain metastasis followed by radioiodine therapy could be valuable for achieving a prolonged disease-free period.

Bone Neoplasms↗
PubMed2000

A new assay for thyroglobulin concentration in serum using monoclonal antibodies against synthetic peptides.

The concentration of thyroglobulin (Tg) measured by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) is greatly affected by the presence of anti-Tg autoantibodies in sera. We developed a new assay for detecting Tg in the presence of high concentrations of anti-Tg autoantibodies. A 48-kDa fragment was purified from Tg after treatment with V8 protease. This fragment did not appear to bind to two types of monoclonal antibodies (57Ab and 28D3) against a peptide in the C-terminus (amino acids 2735-2748) of Tg and intact Tg, respectively, by ELISA and Western blot analysis. In contrast, anti-Tg autoantibody or anti-Tg polyclonal antibody reacted well with this fragment. Our new ELISA used 57Ab as a solid phase antibody and 28D3 as a antibody conjugated to horseradish peroxidase. Buffer containing purified 48-kDa fragment was used to neutralize autoantibodies against Tg. With this assay, the recovery of Tg was 84.0-89.6% in normal healthy donors (n=5) in the presence of immunoglobulin G (IgG) purified from sera positive for anti-Tg autoantibody, and 76.2-104.4% in patient sera Grave's disease (n=15). Furthermore, the Tg concentrations in sera from patients with Grave's disease (n=20) ranged from 25 to 526 ng/ml, even though the Tg concentration, as measured by a commercial RIA did not exceed 55 ng/ml. There was good agreement between Tg concentrations measured by new Tg-ELISA and commercial Tg-RIA in sera that were negative for anti-Tg autoantibody. Overall, our new ELISA containing a Tg fragment to neutralize the presence of autoantibodies, showed good sensitivity and precision, and may be useful for routine use. Further investigations with the new assay should allow wider assessment of the prevalence and pattern of thyroid autoimmunity or thyroid neoplasms.

Amino Acid Sequence↗
PubMed2000

Development of an antibody against a 40,000 mol. wt brain injury-derived neurotrophic peptide-binding protein and identification of a 40,000 mol. wt brain injury-derived neurotrophic peptide-binding protein in hippocampal neurons.

Brain injury-derived neurotrophic peptide is a 13-amino acid peptide derived from a 15,000 mol. wt neurotrophic factor released from sites of mechanical injury in neonatal rat brain. This peptide promotes survival of septal cholinergic neurons and mesencephalic dopaminergic neurons, and protects hippocampal neurons from glutamate-induced neurotoxicity. In this study, we have developed a monoclonal antibody against a brain injury-derived neurotrophic peptide-binding protein by immunizing mice with septal synaptosomes from five-week-old rat brain. Monoclonal antibodies were screened for inhibition of the binding of a 125I-labeled analogue of brain injury-derived neurotrophic peptide to rat brain synaptosomes. The monoclonal antibody 6A22 suppressed the biological activity of brain injury-derived neurotrophic peptide and abolished the protective effect of the neurotrophic peptide against glutamate-induced neurotoxicity. This monoclonal antibody recognized a 40,000 mol. wt brain injury-derived neurotrophic peptide-binding protein, which was also identified by cross-linking experiments. Immunohistochemical studies showed that the 6A22 antibody bound to the cell surfaces of a subpopulation (about 60%) of hippocampal neurons in culture. These results are consistent with the possibility that the 40,000 mol. wt protein belongs to brain injury-derived neurotrophic peptide receptors.

Animals↗
PubMed2000

Autosomal recessive juvenile parkinsonism.

Autosomal recessive juvenile parkinsonism (AR-JP) is a hereditary neurodegenerative disorder characterized by levodopa-responsive parkinsonism with onset before age 40 years and a slowly progressive course. Families with this condition have been described predominantly in Japanese population, occasionally under different names including an autosomal recessive early-onset parkinsonism with diurnal fluctuation (AR-EPDF) or a familial form of juvenile parkinsonism. Recently, the causative gene for AR-JP was mapped on chromosome 6q25.2-q27, and subsequently a novel gene 'parkin' was identified by means of positional cloning. In this manuscript, we review the clinical, pathological and genetical aspects of AR-JP. It would not only promise to provide important insights into the molecular mechanisms of selective degeneration of dopaminergic neurons in AR-JP, but also bring insights into the mechanisms of degeneration of these neurons in Parkinson's disease.

Adolescent↗
PubMed2000

Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms.

Bradykinin (BK) is a major kinin with well-documented pharmacological properties including vascular leakage and induction of a variety of cytokines. However, the intracellular signalling mechanisms by which BK induced proinflammatory cytokine production have not been fully elucidated. This study investigated the role of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in the BK-induced interleukin (IL)-6 and IL-8 production by human lung fibroblasts. Lung fibroblasts were stimulated with BK in the presence or in the absence of PD98059, a specific MAPK/ERK kinase-1 inhibitor, or SB203580, a specific p38 MAPK inhibitor, and IL-6 or IL-8 production and their gene expression was examined. BK-induced ERK 1/2 or p38 MAPK phosphorylation was also analysed by Western blot analysis. BK at nanomolar concentrations stimulated lung fibroblasts to produce IL-6 and IL-8 along with increased ERK 1/2 and p38 MAPK phosphorylation. BK-induced IL-6 and IL-8 synthesis was inhibited by a B2-type BK receptor antagonist. Furthermore, PD98059 or SB203580 significantly suppressed BK-induced IL-6 and IL-8 production and their gene expression. These results indicate that bradykinin-induced interleukin-6 and interleukin-8 production are at least partly mediated through the extracellular signal-related protein kinase 1/2 and p38 mitogen-activated protein kinase pathway-dependent activation in human lung fibroblasts, and suggest that bradykinin appears to be involved in the inflammatory reaction leading to acute lung injury through stimulating interleukin-6 and interleukin-8 production by lung fibroblasts.

Blotting, Northern↗
PubMed2000

Effect of low-friction ion-treated femoral heads on polyethylene wear rates.

Polyethylene wear is a major contributor to osteolysis and subsequent aseptic loosening of prosthetic components in total hip arthroplasty. Use of ion implantation as a surface modification to the metallic bearing component of orthopaedic implants may be an effective means of reducing wear debris at the bearing interface. In July 1991, low friction ion treated femoral heads were introduced. This study evaluates the effect of the low friction ion treated femoral head on polyethylene wear. Fifty-five total hip arthroplasties (53 patients) with low friction ion treated femoral heads followed up a minimum of 3 years were matched with 55 total hip arthroplasties (47 patients) without low friction ion treated femoral heads for the same postoperative period. Socket wear was evaluated radiographically. Case matching and strict inclusion criteria were used to control for known factors influencing polyethylene wear. These criteria included: (1) cases matched for gender and age within 2 years; (2) diagnosis limited to osteoarthritis or avascular necrosis of the femoral head only; (3) femoral head diameter limited to 26 or 28 mm only; (4) hydroxyapatite coated femoral stem of the same design and a metal backed socket of the one of two designs with the same polyethylene insert; and (5) minimum followup of 3 years. The linear wear rate of polyethylene was 0.161 +/- 0.095 mm per year in the group without the low friction ion treated heads and 0.116 +/- 0.101 mm per year in the low friction ion treated group. The volumetric wear rates were 74.5 +/- 44.3 mm3 per year for the group without the low friction ion treated heads and 57.8 +/- 51.1 mm3 per year for the low friction ion treated group. Assuming the sensitivity of these measurements can detect these small differences in wear accurately, these results suggest low friction ion treated prosthetic heads are useful in reducing polyethylene wear at 3-year minimum followup.

Adult↗
PubMed2000

Low-dose atropine attenuates muscle sympathetic nerve activity in healthy humans.

Central muscarinic receptors play an important role in the regulation of cardiac vagal nerve activity. We studied the inhibition of central muscarinic receptors and sympathetic nerve function in humans, since very little information is currently available on this subject. We examined the effects of graded doses of atropine (five doses, range 0.001 to 0.016 mg/kg) on heart rate, arterial pressure, heart rate variability, and muscle sympathetic nerve activity in 13 healthy young volunteers. Atropine caused biphasic effects on heart rate and the high-frequency (HF) power of R-R interval variability. At lower doses (< or =0.002 mg/kg for heart rate, 0.001 mg/kg for HF power), atropine decreased heart rate and increased HF power. In contrast, at higher doses, atropine increased heart rate and decreased HF power. Low-dose atropine significantly attenuated muscle sympathetic nerve activity, burst rate (bursts/min) by -30.5 +/- 6.0% and burst incidence (bursts/100 heart beats) by -23.8 +/- 6.9% at 0.002 mg/kg. Systolic and diastolic arterial pressure did not change with atropine infusion. Low-dose atropine (< or =0.002 mg/kg) did not significantly affect either low frequency (LF) power or LF/HF. These results suggest that central muscarinic receptors may modulate not only cardiac vagal nerve activity but also sympathetic nerve activity in the skeletal muscle vasculature.

Adult↗
PubMed2000

Accumulation of identical T cell clones in the right and left lobes of the thyroid gland in patients with Graves' disease: analysis of T cell clonotype in vivo.

To elucidate the involvement of intrathyroidal T cells in the thyroid antigen-specific immune response in Graves' disease (GD), we investigated whether identical T cell clonotypes accumulate clonally in the right and left lobes of thyroid glands of GD patients. mRNAs extracted from thyroid glands of five females patients with GD were reverse-transcribed to cDNA and then the genes coding the T cell receptor B chain variable (V-NDN-J) region were amplified using polymerase chain reaction. Single strand conformation polymorphism analysis and subsequently nucleotide sequencing were also performed to determine the clonotype of accumulating T cells. T cells infiltrating the thyroid glands showed oligoclonal expansion. The expanded T cell clonotypes were not detected in peripheral blood of the same patients. Importantly, the majority of expanding T cell clonotypes in the two lobes of the thyroid glands were identical. Our findings suggest that the clonal expansion of identical T cell clonotypes in the two lobes is driven by factors common to both lobes, such as thyroid-specific antigens, in patients with Graves' disease.

Adult↗
PubMed2000

[Prediction of progression in patients with mild cognitive impairment using IMP-SPECT].

To examine the difference in functional brain imaging between mild cognitive impairment (MCI) and normal aging, we measured rCBF on functional brain imaging using 123I-IMP single photon emission computed tomography (IMP-SPECT) in 19 MCI patients who progressed to develop AD on follow-up and 23 probable Alzheimer's disease (AD) patients as well as 15 age-matched normal subjects. Baseline MMSE score was 25.3 (SD 1.2) in the MCI group and 17.5 (SD 3.3) in the AD group. The regions of interest (ROI) in the posterior cingulate gyrus, frontal, temporal and parietal cortices were drawn on the image of IMP-SPECT with reference to an individual MRI image. The rCBF ratio was calculated using ROI value in the cerebellum as a reference. Voxel-based analysis was also preformed using statistical parametric mapping (SPM). The rCBF ratio in the posterior cingulate gyrus was significantly reduced in the MCI group (mean 0.956, SD 0.080) and the AD group (mean 0.833, SD 0.118) compared to that in the normal group (mean 1.083, SD 0.084). In the frontal, temporal and parietal cortices, the rCBF ratio was significantly reduced only in the AD group compared to the normal group. At a fixed specificity of 80%, the diagnostic sensitivity in the discrimination between MCI patients and normal subjects was 80.5% when using rCBF ratio in posterior cingulate gyrus. In the SPM analysis, significant reduction of the rCBF in MCI group was observed only in the posterior cingulate gyrus, compared with normal subject group. Our results suggest that MCI patients presenting with a posterior cingulate hypoperfusion are at higher risk for transition from MCI to clinically recognizable AD.

Aged↗
PubMed2000

Pregnancy rates after laparoscopic treatment. Differences related to tubal status and presence of endometriosis.

OBJECTIVE: To examine how preexisting tubal adhesions and endometriosis affect pregnancy outcome after laparoscopic treatment in infertile women with no apparent causes of infertility other than tubal factors. STUDY DESIGN: Pregnancy outcomes in 186 infertile women for a follow-up period of 18 months after laparoscopy were analyzed. Laparoscopic manipulations consisted of adhesiolysis of tubes and removal of endometriotic lesions. RESULTS: The patients were classified into three groups, those with no tubal adhesions (group A, n = 83), unilateral tubal adhesions (group B, n = 46) and bilateral tubal adhesions with at least one tube patent (group C, n = 57). The cumulative pregnancy rate in group C (13.2%) was lower than in groups A (41.8%) and B (45.7%) 18 months after laparoscopy. The average time to conception in group A (6.7 +/- 0.8 months) tended to be shorter than that in group B (10.6 +/- 1.2 months). In group A, pregnancy rates were essentially the same between minimal/mild endometriosis and moderate/severe endometriosis. Regarding group B, women with minimal/mild endometriosis exhibited significantly higher pregnancy rates than those with moderate/severe endometriosis, while pregnancy rates in women without endometriosis fell in between. CONCLUSION: Pregnancy rates after laparoscopic treatment are different in relation to tubal status and the presence of endometriosis.

Adult↗
PubMed2000

[Rheumatoid arthritis-associated bronchiolitis successfully treated with erythromycin].

A 52-year-old man with a 4-year history of rheumatoid arthritis, and who had an episode of suspected BOOP in early 1994, was admitted to our hospital because of cough and fever. A chest X-ray film on admission showed small patchy infiltrates, and a computed tomographic (CT) scan showed centrilobular nodules and patchy infiltrates with thickened broncho-vascular bundles in both lungs. Transbronchial and thoracoscopic lung biopsies disclosed the coexistence of interstitial pneumonia with BOOP pattern, follicular bronchiolitis, and diffuse panbronchiolitis-like purulent and obliterative bronchiolitis. Due to findings of chronic sinusitis, the patient was treated with erythromycin for 8 weeks, and the abnormal CT shadows regressed. This was an interesting case of various pulmonary lesions associated with rheumatoid arthritis, and successfully treated with erythromycin.

Anti-Bacterial Agents↗