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Biomedical subjects

A Moriyama

Publications and source records attributed to A Moriyama.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pepsinogens and pepsins from house musk shrew, Suncus murinus: purification, characterization, determination of the amino-acid sequences of the activation segments, and analysis of proteolytic specificities.

Three pepsinogens, namely, pepsinogens A, C-1, and C-2, were purified from gastric mucosa of adult house musk shrew (Suncus murinus) by conventional chromatographic and gel filtration procedures. The molecular masses were 40, 39, and 41 kDa for pepsinogens A, C-1, and C-2, respectively. Pepsinogen C-2 contains an Asn-linked carbohydrate chain(s) of about 2 kDa. Each pepsinogen was converted to pepsin through an intermediate form under acidic conditions. By NH2-terminal sequence analysis of these protein species, the amino acid sequences of activation segments (proparts) of pepsinogens A and C-1 were determined to be LYKVPLVKKKSLRQNLIENGLLKDFLAKHNVNPASKYFPTE and KVTKVTLKKFKSIRENLREQGLLEDFLKTNHYDPAQKYHFGDF, respectively. The similarity of these two sequences is nearly 50%. Each pepsin cleaved preferentially peptide bonds between hydrophobic and aromatic amino acids, or bonds on either side of these amino acids. Although each activation segment had several sites susceptible to pepsin action, activation proceeded by limited cleavages of the segment, presumably due to the steric inflexibility of the segment in native pepsinogen. The activity of pepsin A was inhibited completely in the presence of a more than equimolar amount of pepstatin, while a hundred-molar excess amount of pepstatin was needed for the complete inhibition of the activity of pepsins C-1 and C-2.

Amino Acid Sequence↗
PubMed1997

Gliostatin/platelet-derived endothelial cell growth factor as a clinical marker of rheumatoid arthritis and its regulation in fibroblast-like synoviocytes.

The objective was to assess the congruity of gliostatin/platelet-derived endothelial cell growth factor (GLS PD-ECGF) with other clinical markers of rheumatoid arthritis (RA) and to define its molecular mechanism of action in the complicated cytokine network during RA pathogenesis. Immunoassay systems were used to quantify GLS or cytokine levels in laboratory and clinical samples. Expression levels of GLS were determined by reverse transcription-polymerase chain reaction methods. The GLS levels in synovial fluid were correlated with interleukin-1 (IL-1) and IL-8. The serial data of serum GLS levels reflected well changes in the disease activity during the clinical course of four representative patients with RA. In cultured fibroblast-like synoviocytes, tumour necrosis factor-alpha (TNF-alpha), IL-1, IL-6 and IL-8 induced GLS expression. In conclusion, our results suggest that the serum GLS level, mostly derived from cytokine-stimulated synoviocytes, was a useful clinical marker of RA.

Arthritis, Rheumatoid↗
PubMed1997

High plasma concentrations of nitrite/nitrate in patients with hepatocellular carcinoma.

OBJECTIVES: Nitric oxide (NO) is considered to play a central role in macrophage or Kupffer cell-induced tumor cytotoxicity. Hepatocytes also produce NO in response to several inflammatory stimuli. Thus, there is a possibility that NO production by hepatic tissue is accelerated in patients with hepatocellular carcinoma (HCC). We, therefore, measured plasma nitrite/nitrate levels as an index of in vivo NO production in patients with HCC. METHODS: Plasma nitrite/nitrate levels were measured using Griess reaction in 95 patients with chronic hepatitis (CH) and compensated liver cirrhosis (LC) with (n = 48) or without HCC (n = 47), as well as 45 healthy control subjects. Possible factors related to nitrite/nitrate levels were evaluated for each subject. RESULTS: Plasma nitrite/nitrate levels in patients with HCC based on CH (mean +/- SD, 71.7 +/- 23.1 microM) and LC (52.4 +/- 20.2 microM) were significantly higher than those without HCC (CH, 31.1 +/- 15.0 microM; LC, 34.6 +/- 16.1 microM) (p < 0.01). Plasma nitrite/nitrate levels in patients with HCC based on CH were significantly higher than those in patients with HCC based on LC (p < 0.05). Simple regression analysis showed that plasma nitrite/nitrate levels significantly correlated with both tumor surface area (r = 0.577, p = 0.001) and tumor volume (r = 0.532, p = 0.003). CONCLUSION: Patients with HCC have elevated plasma nitrite/nitrate levels correlating to tumor volume as well as tumor surface area.

Analysis of Variance↗
PubMed1997

[Ten years experience of home parenteral nutrition or hydration in advanced cancer patients].

From April 1987 to May 1997, ninety-six advanced cancer patients including ninety-one among 159 home care patients and five outpatients were administered parenteral nutrition or hydration. Eventually, 67 patients died at home. We concluded through our experience that advanced cancer patients who were unable to eat or drink might live at home with the support of parenteral nutrition or hydration. But four conditions are needed for satisfactory home care of these patients. First, patients understanding their disease condition therefore together with their family hope for home care. Second, the home care support team is organized in an institution. Third, the home care support team is on call for emergencies. Fourth, the home care support team can not only manage home parenteral nutrition but also provide palliative care, including pain control.

Adult↗
PubMed1996

Tissue distribution of human gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression.

Human tissue contents of gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression in tumor cells were currently examined by a sandwich enzyme immunoassay (EIA) system and a reverse transcription-polymerase chain reaction (RT-PCR) method. Gliostatin/PD-ECGF was found to distribute in rather ubiquitous than specific human tissues and organs, with a relatively high levels in the tissues of digestive system (esophagus and rectum), brain, spleen, bladder and lung, but not in gall bladder, aorta, muscle, fat and kidney. Most of examined human tumor cell lines showed 4- or 5-fold higher contents (21.5 +/- 3.9 ng/mg protein) than normal tissue contents (4.4 +/- 1.1 ng/mg protein) on the average. While gliostatin/PD-ECGF is known to lack a signal sequence, some tumor cells (A431 and MKN74) appeared to release it into the conditioned medium. Expression of gliostatin/PD-ECGF in epidermoid carcinoma cell (A431) and stomach cancer cell (MKN45) was induced by dibutyryl cyclic AMP and phorbol ester, and uniquely in MKN45 by hydrocortisone. In particular, this hydrocortisone specifically caused an increase of the apparent secretion of MKN74 without its cytotoxic effects, suggesting a possible secretion of gliostatin/PD-ECGF in the restricted but not universal cell line. Biological significance on the chemical induction of gliostatin/PD-ECGF in tumor cells and on its extracellular secretion are discussed.

Cell Line↗
PubMed1996

Potential sites for processing of the human invariant chain by cathepsins D and E.

Seven peptides of 15-30 amino acid residues were synthesized that covered almost the entire sequence of the lumenal domain of the human invariant chain (Ii), and their hydrolysis by cathepsins D and E was investigated. Two sites were identified that were very susceptible to such cleavage. One site, the Leu174-Phe175 bond, was cleaved by both cathepsins, and the other site, the Met99-Gln100 bond, was specifically cleaved by cathepsin E. These two sites could be the sites at which native Ii is cleaved by aspartic proteinases. The cleavage of the Met99-Gln100 bond by cathepsin E might be important in the inactivation of Ii and its functional derivatives.

Amino Acid Sequence↗
PubMed1996

Hyperthermia induces apoptosis in malignant fibrous histiocytoma cells in vitro.

The effect of mild hyperthermia on a cultured rat malignant fibrous histiocytoma (MFH) cell line, MFH-2NR, was investigated. MFH cells in log-phase (growing phase) were heated at 41 degrees-44 degrees C for 1 hr. Hyperthermic treatment at 41 degrees C did not substantially affect cell proliferation and treatment at 44 degrees C caused necrosis. After hypothermic treatment at 42 degrees or 43 degrees C, proliferation of MFH cells was arrested and morphological changes characteristic of apoptosis, cell shrinkage accompanying apoptotic bodies and chromatin condensation, became apparent. Hyperthermia-induced apoptosis was further confirmed by terminal deoxynucleotidyl transferase staining and a ladder pattern on agarose gel electrophoresis. Flow cytometric analysis indicated that the population in the G1 phase of the cell cycle significantly decreased with a concomitant increase in apoptotic cells, indicating that apoptosis might occur mainly in the G1 phase population.

Animals↗
PubMed1996

Development of Sjögren's syndrome during treatment with recombinant human interferon-alpha-2b for chronic hepatitis C.

A 63-year-old woman with type C chronic active hepatitis developed Sjögren's syndrome after being treated with recombinant interferon-alpha-2b. After 3 months' interferon-alpha administration, serum levels of gamma-globulin (4.5 g/dl) and titers of antinuclear and anti-SS-A antibodies were greatly increased, anti-SS-B antibody appeared, and the erythrocyte sedimentation rate was elevated. Although no xerostomia was exhibited, the patient experienced conjunctival dryness. Schirmer's test showed reduced lacrimal gland function and a gum test showed reduced salivary gland function. Sialography revealed scattered pools of retained contrast media with a diameter of around 1-2 mm. Based on these findings, a diagnosis of Sjögren's syndrome was made. This present case may provide important information regarding the pathogenesis of Sjögren's syndrome.

Biopsy, Needle↗
PubMed1996

[Trial of home anti-cancer chemotherapy with infusion of 5-FU and low-dose cisplatin].

We tried home anti-cancer chemotherapy for patients with advanced or recurrent cancer of the digestive system, using two disposable balloon pumps connected to an implantable drug delivery system via central venous line. There were 33 patients under 75 years old, including 20 cases of gastric cancer, 9 cases of colorectal cancer, 2 cases of cholangiocarcinoma and 2 cases of esophageal cancer enrolled in this study. The protocol was combined chemotherapy with continuous intravenous infusion of 5-FU (300 mg/body/day) and low-dose intravenous injection of cisplatin (5 mg/body/day) in 10-day courses for two weeks, and it was repeated 3 times for 6 weeks. Because of side effects such as nausea, vomiting and bone marrow suppression, treatment was discontinued in 12 cases with peritoneal cancer infiltration. In two of 10 with estimable disease, the reduction of the metastatic lymph node was observed, but no effect was shown in the colorectal metastatic liver tumor. Thanks to the portability of the pump with this method, the patient need not undergo hospitalization. Moreover, there is no renal dysfunction or other major side effects, quality of life is not compromised and a return to family and social life is possible. Thus, if the patient cannot take the oral nutrition, it is easy to start home hyper-alimentation.

Aged↗
PubMed1996

[How to palliate the symptoms of terminally ill patients at home].

We reported the kind of symptoms and how they could be palliated in terminally ill patients at home based on our experience of about 9 years. Cancer pain, which was the most frequent symptom, appeared in 67 among 126 patients receiving home care, and it could be effectively controlled with morphine; no patient returned to the hospital because of aggravation of pain. Very few patients stayed in the hospital and never returned home due to uncontrollable pain. Home parenteral infusion was done for 63 patients who were unable to eat or drink because of peritonitis carcinomatosa or cancer cachexia. High fever in the tumor mass was controlled by glucocorticoid hormone, and ascites was drained continuously when the patients suffered from abdominal distension. From analysis of the cases in which home care was interrupted or those in which patients were unable to transfer to home care, symptoms that were difficult to palliate at home were nausea caused by bowel obstruction, acute symptoms (bleeding, disturbance of consciousness, and so on), and dyspnea. But if the patients and family are eager for home care and an adequate medical support system is in place, home care may be possible despite these symptoms.

Hospice Care↗
PubMed1995

Effects of dibutyryl guanosine 3',5'-cyclic monophosphate and sodium nitroprusside in pepsinogen secretion from guinea pig chief cells with respect to intracellular Ca2+.

Both Ca2+ and adenosine 3',5'-cyclic monophosphate act as intracellular second messengers in pepsinogen secretion from chief cells. However, the role of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) in this process has not been defined. Although dibutyryl cGMP (dbcGMP), a membrane-permeable derivative of cGMP, has been shown to inhibit pepsinogen secretion only stimulated by cholecystokinin (CCK), the intracellular mechanism of this effect remains unclear. We evaluated the role of intracellular cGMP in pepsinogen secretion from monolayer cultured guinea pig chief cells using dbcGMP and sodium nitroprusside, both of which increase intracellular cGMP. Dibutyryl cGMP and sodium nitroprusside have now been shown to inhibit pepsinogen secretion induced by not only CCK octapeptide but also carbamylcholine chloride and ionomycin in a dose-dependent manner. Furthermore, dbcGMP reduced the increase in intracellular free Ca2+ concentration induced by carbamylcholine chloride, CCK octapeptide, and ionomycin. These results suggest that intracellular cGMP may inhibit pepsinogen secretion by reducing the intracellular free Ca2+ concentration.

Animals↗
PubMed1995

Mediation of pepsinogen secretion from guinea pig chief cells by Ca2+/calmodulin-dependent protein kinase II.

In the presence of Ca2+ bound to calmodulin, Ca2+/calmodulin-dependent protein kinase II (CaMK II) exhibits an intramolecular autophosphorylation and modulates many cell functions. In this study, the role of CaMK II in pepsinogen secretion was investigated in cultured guinea pig chief cells by using a specific CaMK II inhibitor, 1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipera zin e (KN-62), and an antibody for the Thr-286-autophosphorylated alpha subunit of CaMK II which specifically recognized the autophosphorylated form of CaMK II. KN-62 inhibited the pepsinogen secretion stimulated by carbamylcholine chloride, cholecystokinin octapeptide, and ionomycin in a dose-dependent manner without affecting intracellular Ca2+ concentrations, but had no effect on the secretion by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and forskolin. Heavy staining with the antibody for autophosphorylated CaMK II was observed in the cytoplasm of chief cells treated with carbamylcholine chloride or ionomycin, but only light staining was seen in cells treated with TPA or forskolin. Thus, CaMK II and its autophosphorylation may be a critical step in the intracellular pathway in which Ca2+ causes pepsinogen secretion from guinea pig chief cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Pericardiac metastasis from advanced gastric cancer.

A 64-year-old man complaining of anterior chest pain, weight loss, and neck tumors was found to have advanced gastric cancer with pleuritis carcinomatosa and multiple lymph node and bone metastases. The patient was treated with combination chemotherapy consisting of mitomycin C (MMC), tegafur (UFT), and lentinan, and then with MMC and 5-fluorouracil (5FU) instillation into the pleural spaces after pleural drainage. With these treatments, the primary tumors and cancerous ulcers of the stomach improved markedly, and the lymph node enlargement and pleural effusion disappeared completely. Afterwards pericardiac metastasis complicated by cardiac tamponade occurred, but repeated pericardiocentesis and administration of MMC into the pericardiac cavity effectively eliminated the effusion. These treatments appeared potentially useful for advanced gastric cancer with generalized metastases including pericardiac involvement. However, the patient died of cardiac tamponade with massive pericardiac bleeding, probably due to the repeated pericardiocentesis and/or the administration of anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Four important subjects of successful care at home for patients of terminally ill].

From April 1987 to May 1995, we have had care at home for 103 patients of terminally ill, and at this through our experience, we pointed out four important subjects for successful care at home. The first is prompt consultation at anytime when the patient or its family need. It is especially important when the patient's end time is near and previously we must fully instruct to patient's family how to consult and how to care. The second is effective palliative care. In these palliative care pain control with morphine is most important and we must master how to use morphine. The third is truth telling and informed consent. At treatment we have to communicate true information to patient. Home care must be started under patient's will. The fourth is organization of medical care, health care and welfare care. We have to make up network system of these office at first, and finally we have to make up community for supporting patients and these family.

Attitude to Death↗
PubMed1994

Aberrant production of gliostatin/platelet-derived endothelial cell growth factor in rheumatoid synovium.

OBJECTIVE: To purify a protein inhibitor from rheumatoid arthritis (RA) synovial fluids which suppresses the apparent incorporation of 3H-thymidine into fibroblasts and synovial cells, and to define its biochemical features that have clinical relevance to the pathogenesis of RA. METHODS: Several standard chromatographic techniques were employed for the purification of the protein. Immunochemical methods with monoclonal antibody were used to quantify and visualize the protein in sera, synovial fluids, and tissues from RA patients. RESULTS: The chemical properties of purified inhibitor from RA synovial fluids confirmed its identity as gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF), a potent angiogenic factor. The gliostatin/PD-ECGF level in synovial fluid and serum was higher in RA patients than in osteoarthritis controls. CONCLUSION: These findings strongly suggest that gliostatin/PD-ECGF might play an important role in the aberrant neovascularization of rheumatoid synovium.

3T3 Cells↗