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Biomedical subjects

N Murakami

Publications and source records attributed to N Murakami.

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

Advanced gastric cancer effectively treated by neoadjuvant continuous low-dosage 5-fluorouracil and cisplatin (FP regimen): a case report.

We have experienced a case of advanced gastric cancer with para-aortic lymph node metastasis effectively treated by neoadjuvant continuous low dosage 5-fluorouracil and cisplatin (FP regimen). The patient was a 67-year-old man diagnosed as having advanced gastric cancer type 4 with para-aortic lymph node metastasis. This patient was treated by continuous infusion of 5-fluorouracil (5-FU) 500 mg/day, for 28 days, and infusion of cisplatin 10 mg/day over 1 hr on days 1-5, 8-12, 15-19, and 22-26. At 4 weeks later, a CT revealed that swelling in the para-aortic lymph node had disappeared, and the thickening in the stomach wall had diminished. This patient underwent a curative operation, and both the serum level of carcinoembryonal antigen (CEA) and carbohydrate antigen (CA 19-9) decreased to normal. These results suggested that the FP regimen was an effective neoadjuvant treatment for advanced gastric cancer with para-aortic lymph node metastasis.

Aged↗
PubMed2001

Long-term survival after gastric cancer with liver metastasis: a report of two cases.

We have experienced two cases of long-term survival after surgery for gastric cancer case with liver metastasis. One case was of a 66-year-old male patient diagnosed as having type 1 advanced gastric cancer located in the posterior wall of the lower body with liver metastasis. The stage of this case was P0H1N1T2M0 stage IV. This patient underwent distal gastrectomy with D2 lymph node resection, partial hepatectomy of the S3 region including the metastatic liver tumor and coagulation of metastatic liver tumors in the S6 and S7 regions. This patient was treated by intra-hepatic arterial infusion of 5-FU, CDDP and peroral administration of UFT after surgery. This patient has died at 3 years and 7 months after surgery. The other case was of a 55-year-old male patient diagnosed as having type 2 advanced gastric cancer located in the lesser curvature of the cardia with liver metastasis. The stage of this case was P0H1N1T3 M0 stage IV. This patient underwent total gastrectomy with D2 lymph node dissection, wedge resection of the S8 region including the metastatic liver tumor and coagulation of a metastatic liver tumor in the S4 region. This patient was treated by obstruction of the hepatic artery using coils, peroral administration of UFT, lentinan, MMC, and continuous low-dosage 5-FU and CDDP after surgery. This patient has died at 3 years and 6 months after surgery. These results suggest that for long-term survival in cases of gastric cancer with liver metastasis, hepatectomy or coagulation of the metastatic tumor with postoperative chemotherapy are indicated in cases that have no non-curative factors and only a few metastatic tumors.

Aged↗
PubMed2001

Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone.

BACKGROUND: Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. Collagen from animal sources has previously been the preferred carrier material in animal experiments. More recently, synthetic biodegradable polymers have been tested as a delivery vehicle for osteoinductive agents. In earlier studies performed in our laboratory, it was found that the polylactic acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery systems. METHODS: To obtain new PLA-PEG polymers that exhibit greater plasticity, the molecular sizes of PLA and PEG segments in the copolymer chains were increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650-PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral density (BMD) of the ectopic new bone were measured by means of single energy X-ray absorptiometry (SXA). RESULTS: All of the PLA6,500-PEG3,000 implants with 10 or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control implants that lacked rhBMP-2 did not show new bone formation. Radiographic and histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2 harvested 3 weeks after implantation had normal bone characteristics with hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2 were significantly higher than those obtained with the liquid PLA650-PEG200 polymers (p < 0.001 for each of the three values). CONCLUSIONS: These results indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works effectively as a BMP delivery system. These data suggest that the total molecular size and ratio of PLA size to PEG size is an essential factor in determining the efficacy of a BMP delivery system. After implantation, it is possible that the PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen, resulting in bone formation that exceeded the size of the original implants. This expansion characteristic is a potentially beneficial property, given the intended practical application of the polymer in the repair of bone defects. CLINICAL RELEVANCE: New synthetic biodegradable delivery systems will play an important role in the clinical applications of rhBMPs in which local formation of bone via an osteoinductive graft material is needed. Further pre-clinical and clinical work is necessary to establish the safety of these implants before they are adopted for widespread clinical use.

Animals↗
PubMed2001

[Significance of pyrimidine nucleoside phosphorylase (PyNPase) and dihydropyrimidine dehydrogenase (DPD) in advanced gastric cancers].

We measured pyrimidine nucleoside phosphorylase (PyNPase), a known angiogenetic factor, and dihydropyrimidine dehydrogenase (DPD) in advanced gastric cancers. PyNPase was expressed in cytoplasm of the cancer cells and surrounding interstitial cells. The levels of PyNPase and DPD were significantly higher in cancer tissue. With respect to tumor factors, the level of PyNPase was significantly higher in cases positive for venous invasion. We divided patients into two groups, with high and low activities of IAP and MMP-9. The level of PyNPase was significantly higher in the high IAP activity group. A correlation was suggested between the level of PyNPase and the activity of IAP. 5'-Deoxy-5-fluorouridine (5'-DFUR) is transformed into 5-FU by PyNPase and manifests antitumor effects. DPD is a rate-limiting enzyme in the process of degradation of 5-FU. In the present study, the level of PyNPase/DPD was significantly higher in cancer tissue. PyNPase/DPD suggests not only the malignant potential of the tumor but also the efficiency of chemotherapy using 5-FU, especially 5'-DFUR.

Aged↗
PubMed2001

[Bone marrow aspiration: practical aspects].

Bone marrow aspiration is the most valuable diagnostic examination for the evaluation of hematopoiesis of the bone marrow. Appropriate smear-sampling and reliable stainings in hematological sections are essential for the precise diagnosis of bone marrow cells, and give important insight into pathological and clinical hematology.

Bone Marrow Examination↗
PubMed2001

Human herpesvirus 8 DNA in HIV-negative Japanese patients with multicentric Castleman's disease and related diseases.

Multicentric Castleman's disease (MCD) is a lymphoproliferative disorder characterized by systemic lymphadenopathy and hypergammaglobulinemia. Recently, a French group reported that human herpesvirus 8 (HHV8) DNA was detected in tissue samples of MCD patients. The detection rate was especially high in human immunodeficiency virus (HIV)-positive MCD patients. Thus, HHV8 infection seems to be closely related to HIV infection. In Japan, the HIV infection rate in the general population is very low. To examine whether HHV8 is actually related to MCD in Japan, we performed nested polymerase chain reaction for the HHV8 genome using DNA samples from 7 patients with MCD and 23 patients with related diseases such as POEMS syndrome, amyloidosis, myeloma and lymphoma. They were all HIV-negative Japanese. Three of 7 MCD patients were positive for HHV8. There were no clear differences in clinical characteristics between HHV8-positive patients and negative ones. All other patients were negative for HHV8. Thus, we have shown that some MCD patients in Japan are also infected with HHV8.

Adult↗
PubMed2001

[Delayed paraparesis after osteoporotic vertebral fracture--with special reference between mechanism of symptoms, fracture level, age and operative methods].

We examined the operated 53 cases with delayed paraparesis after osteoporotic vertebral fracture. The causes of the symptoms were complicated and the analysis indicated that the anterior approach should be the first choice, however the posterior approach could be indicated for the following cases ; the main causes are posterior elements, multiple involvement, at middle and lower lumbar level, with severe osteoporosis, with systemic complication, over 80 years old. For high aged and osteoporotic patients, careful analysis of factors causing symptoms and less invasive operation as possible are needed.

English Abstract↗
PubMed2000

New multidrug resistance modulators from Atractylodis Lanceae Rhizoma.

Three new oligoacylated sucroses designated atractysucroses-I, -II, and -III were obtained from Atractylodis Lanceae Rhizoma as multidrug resistance (MDR) modulating substances against human carcinoma cell lines and their chemical structures were characterized as a mixture of acyl groups. Atractysucrose-I modulates MDR in KB-C2 cells as strongly as verapamil. This is the first example of an MDR-modulator classified as a carbohydrate.

Asteraceae↗
PubMed2000

Both corticotropin releasing factor and neuropeptide Y are involved in the effect of orexin (hypocretin) on the food intake in rats.

Orexin (hypocretin) is a peptide that has been found to stimulate food intake in rats. However, we have recently demonstrated that orexin stimulates the release of corticotropin releasing hormone (CRF) which has been known to decrease the food intake. Therefore, we examined the mechanism of effect of orexin on food intake. Although the other appetite stimulating peptides; neuropeptide Y (NPY), agouti-related peptide (AGRP) and one of the growth hormone releasing secretagogue (GHRP-6) stimulated dose-dependently the food intake during 2 h in the early light period, orexin did not increase significantly the food intake. No significant increase was also observed during 2 h in the early dark period. However, pretreatment with alpha-helical CRF, an antagonist of CRF, or anti-CRF antiserum resulted in significant increase of food intake by orexin. Orexin-stimulated feeding under these conditions was blocked by NPY Y1 receptor antagonist (1229U91). In an 8 h-fasting rat, anti-orexin serum decreased slightly the food intake. These results suggest that effect of orexin on the food intake may be complex because of orexin-CRF and orexin-NPY linkage.

Agouti-Related Protein↗
PubMed2000

Central effects of neuromedin U in the regulation of energy homeostasis.

Neuromedin U (NMU) is a brain-gut peptide whose peripheral activities are well-understood but whose central actions have yet to be clarified. The recent identification of two NMU receptors in rat brain has provided a springboard for further investigation into its role in the central nervous system. Intracerebroventricular administration of NMU to free-feeding rats decreased food intake and body weight. Conversely, NMU increased gross locomotor activity, body temperature, and heat production. NMU, a potent endogenous anorectic peptide, serves as a catabolic signaling molecule in the brain. Further investigation of the biochemical and physiological functions of NMU will help our better understanding of the mechanisms of energy homeostasis.

Animals↗
PubMed2000

Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3).

GPR66 is an orphan G-protein-coupled receptor (GPCR) whose structure is similar to the ghrelin and motilin receptors. We have tried to purify a natural ligand for GPR66 in rat tissues and identified a 23-amino-acid peptide as the endogenous ligand. Sequence analysis revealed the peptide as neuromedin U (NMU), a smooth-muscle-contracting peptide that was first purified from porcine spinal cord by our group. NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization. When NMU was injected intracerebroventricularly (ICV) into rats, it potently suppressed food intake. In contrast, ICV injection of NMU-antibody increased food intake. These results suggest that NMU is a potent endogenous anorexic peptide.

Amino Acid Sequence↗
PubMed2000

Two distinct mechanisms for regulation of nonmuscle myosin assembly via the heavy chain: phosphorylation for MIIB and mts 1 binding for MIIA.

In search of the regulation mechanisms for isoform specific myosin assembly, we have used the COOH-terminal fragments of nonmuscle myosin isoforms MIIA and MIIB (MIIA(F46) and MIIB(alpha)(F47)) as a model system. Phosphorylation by protein kinase C (PK C) or casein kinase II (CK II) within or near the nonhelical tail-end domain inhibits assembly of MIIB(alpha)(F47) [Murakami, N., et al. (1998) Biochemistry 37, 1989]. In the study presented here, we mutated the kinase sites to analyze the inhibition mechanisms of MIIB assembly by phosphorylation. Replacement of the CK II or PK C sites with Asp (MIIB(alpha)(F47)-CK-5D or -PK-4D) strongly inhibited the filament assembly, with or without Mg(2+), by significantly increasing the critical concentrations for assembly. Without Mg(2+), MIIB(alpha)(F47)-CK-5D or -PK-4D inhibited the assembly of wild-type (wt) MIIB(alpha)(F47) by either mixing as homofragments or forming heterofragments. With 2.5 mM Mg(2+), MIIB(alpha)(F47)-wt promoted assembly of MIIB(alpha)(F47)-CK-5D and -PK-4D in homofragment mixtures, but not by forming heterofragments. MIIA(F46) coassembled with MIIB(alpha)(F47)-wt and -CK-5D and altered their assembly patterns. In contrast, assembly of MIIB(alpha)(F47)-PK-4D was unchanged by MIIA(F46). A metastasis-associated protein, mts 1, bound in a Ca(2+)-dependent manner to MIIA(F46), but not appreciably to MIIB(alpha)(F47). At 0.15 M NaCl, mts 1-Ca(2+) not only inhibited MIIA(F46) assembly but also disassembled the MIIA(F46) filaments. Mts 1, however, did not affect the assembly of MIIB(alpha)(F47) in MIIA(F46) and MIIB(alpha)(F47) mixtures, indicating that mts 1 is an inhibitor specific to MIIA assembly. Our results suggest strongly that assembly of MIIA and MIIB is regulated by distinct mechanisms via tail-end domains: phosphorylation of MIIB and mts 1 binding to MIIA. These mechanisms may also function to form MIIA or MIIB homofilaments by selectively inhibiting MIIB or MIIA assembly.

Actin Cytoskeleton↗
PubMed2000

Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats.

Ghrelin, a novel growth-hormone-releasing acylated peptide, was recently isolated from rat stomach by the search of an endogenous ligand to an "orphan" G-protein-coupled-receptor. Ghrelin neuron is present in the arcuate nucleus of rat hypothalamus, but its central effect on growth hormone (GH) release has yet to be clarified. We determined the plasma GH concentration and GH mRNA level in the pituitary in response to central administration of ghrelin. A single intracerebroventricular (ICV) administration of ghrelin to rats increased the plasma GH concentration dose-dependently. A continuous ICV administration of ghrelin via osmotic pump for 12 days increased the plasma GH concentration on day 6, but did not keep the high GH concentration on day 12. The GH mRNA levels in both groups of single and continuous administration of ghrelin were not significantly different from those of controls. A single administration of growth-hormone secretagogue also did not stimulate GH synthesis. Central ghrelin stimulated GH release but did not augment GH synthesis. In addition to gastric ghrelin, hypothalamic ghrelin functions to regulate GH release.

Animals↗
PubMed2000

Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease).

"Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.

Antigens, CD↗