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Biomedical subjects

F Konishi

Publications and source records attributed to F Konishi.

At least 91 records · Page 5Linked to original sources
PubMed1995

Histological classification of the neoplastic changes arising in ulcerative colitis: a new proposal in Japan.

Patients with total ulcerative colitis with a longstanding course of the disease have a high risk of developing colorectal carcinoma. Colonoscopic surveillance to detect precancerous tissue and/or cancer in these patients has been carried out in countries with a high incidence of ulcerative colitis. Riddell's classification has been widely used for the interpretation of biopsy specimens obtained from the colonoscopic surveillance. In Japan, however, there are problems in accepting Riddell's classification, mainly because the intramucosal carcinomas diagnosed by Japanese histopathologists are included in the category of high-grade dysplasia in Riddell's classification. Based on the results of a meticulous slide review carried out by seven histopathologists in this study, a new classification is proposed: UC-I, inflammatory change; UC-II, indefinite; UC-IIa, probably inflammatory; UC-IIb, probably neoplastic; UC-III, neoplastic but not carcinomatous; and UC-IV, carcinoma. Intramucosal carcinomas is included in the category UC-IV. We consider that the diagnosis of intramucosal carcinoma is to be made when there is a high grade of cytological and structural atypia consistent with carcinoma. Interobserver and intraobserver variability with this classification was acceptable. We believe this new classification will be widely use in cancer surveillance in ulcerative colitis in Japan.

Biopsy↗
PubMed1994

Participation of diacylglycerol kinase in mitogenic signal transduction induced by platelet-derived growth factor in vascular smooth muscle cells.

In rat vascular smooth muscle cells, platelet-derived growth factor (PDGF), stimulated phosphatidic acid synthesis by activating both of the two alternative pathways, diacyglycerol kinase (DGK) and phospholipase D (PLD). Genistein, a tyrosine kinase inhibitor, inhibited PLD activation but not DGK activation, the latter was inhibited selectively by R 59022. PDGF-induced DNA synthesis was partially inhibited by genistein or R 59022, but these inhibitors had no effect on phorbol ester-induced DNA synthesis. Further, the specific effects of these inhibitors on PDGF-induced DNA synthesis were additive.

Alkaloids↗
PubMed1994

Alpha-fetoprotein-producing gastric carcinoma with enteroblastic differentiation.

BACKGROUND: Alpha-fetoprotein (AFP) is a useful tumor marker for hepatoma and yolk sac tumor. Recently, elevations of serum AFP were reported in patients with other malignancies, especially gastric cancers. Two distinct tumor morphologies, hepatoid and clear cell, have been correlated with AFP production. METHODS: Two patients with AFP-producing gastric carcinoma were evaluated with immunohistochemical, ultrastructural, and biochemical studies. RESULTS: In Patient 1, the primary and metastatic carcinomas consisted homogeneously of tubulopapillary carcinoma with clear cytoplasm. In Patient 2, the cancer was composed of three different areas: tubulopapillary carcinoma with clear cytoplasm, tumor cartilage, and so-called hepatoid carcinoma. The morphologic characteristics of tubulopapillary carcinoma with clear cytoplasm were similar to those of the developing gut epithelium at the stage of 2-4 months' gestation. The elution patterns of the serum AFP on lectin-affinity sepharose column study also suggested a correlation with fetal gut differentiation. CONCLUSIONS: AFP-producing clear cell gastric carcinomas are differentiated into fetal intestine. One patient also had hepatocytic and cartilaginous differentiation, indicative of a blastomatous characteristic of the tumor. These tumors arose in association with intestinal metaplasia.

Carcinoma↗
PubMed1994

Enhanced phospholipase D activity in vascular smooth muscle cells derived from spontaneously hypertensive rats.

When cultured in the presence of fetal calf serum, aortic vascular smooth muscle cells (VSMC) derived from spontaneously hypertensive rats (SHR) grow faster than those from normotensive control Wistar-Kyoto (WKY) rats. In order to investigate the mechanism underlying this growth abnormality, we measured phospholipase D (PLD) activity in VSMC taken from both SHR and WKY rats. Upon stimulation with serum, platelet-derived growth factor (PDGF) and porbol 12-myristate 13-acetate (TPA), phosphatidylethanol (PEt) was produced in the presence of ethanol. The responses of the VSMC from SHR (SHR-cells) to all stimuli were significantly greater than those of the VSMC from WKY rats (WKY-cells), which suggests an enhanced PLD activity in the SHR-cells. Since PLD is regarded as an enzyme involved in signal transduction leading to cell proliferation, this PLD hyper-reactivity in the SHR-cells may account at least partially for the growth abnormality in the SHR-cells.

Animals↗
PubMed1994

[Tissue blood flow of the sigmoid colon for safe anastomosis following ligation of the inferior mesenteric artery].

We examined the tissue blood flow (TBF) of the sigmoid colon to determine which level of inferior mesenteric artery. In 13 patients, TBF of the sigmoid colon was measured in the control state and the clamped state, in which the inferior mesenteric artery (IMA), left colic artery and the rectal were wall clamped. In the clamped state, means of TBF at 10 cm and 15 cm distal to the descend-sigmoid junction were 1.87 +/- 0.77 and 1.10 +/- 0.40, respectively. Mean of TBF at 15 cm was significantly lower than that at 10 cm. In conclusion, TBF which is enough for safe anastomosis reaches as far as 10 cm distal from the descend-sigmoid junction after ligation of IMA. Anastomosis at this level in anterior resection of the rectum is safe in concerning with TBF.

Adult↗
PubMed1994

[Clinical efficacy of arbekacin in deep MRSA infection. Including follow-up study after the termination of chemotherapy].

We analyzed the efficacy of arbekacin (ABK) using monotherapy or combined therapy on deep MRSA infection to find the most adequate usage of the drug. We also followed-up the isolation incidence of MRSA after the end of chemotherapy. The results are summarized as follows: 1. Clinical efficacy of ABK on 29 pneumonia and 3 septicemia due to MRSA was 42.9% in ABK monotherapy (9 patients), 62.5% in combined therapy with ABK and minocycline (9 patients), 100% with ABK and imipenem/cilastatin (IPM/CS) (7 patients), and 100% with ABK and other drugs (7 patients). 2. As for microbiological efficacy, combined therapy with ABK and IPM/CS or other drug was superior to other methods. Among patients from whom two or more species of bacteria were isolated, causative bacteria persisted in many cases, and some replacements occurred. 3. Kidney functions deteriorated in two patients that underwent monotherapy or combined therapy with ABK and IPM/CS, but they recovered when therapy was completed the completion. 4. In the three month follow-up study after ABK therapy, we found four cases of renewed infections after disappearance of MRSA. When just decreases in the number of MRSA resulted upon the chemotherapy, the relapse occurred in all cases. 5. Above results indicate that ABK is effective in MRSA infection, and combined therapy with beta-lactams is superior to other methods in serious MRSA infections. We also suggest that chemotherapy should be continued until the complete disappearance of MRSA is achieved.

Adult↗
PubMed1993

Coexistence of somatic and germ-line mutations of APC gene in desmoid tumors from patients with familial adenomatous polyposis.

Desmoid tumors, which are locally invasive with recurrence but without metastasis, are frequently observed in patients with familial adenomatous polyposis after abdominal surgery or during pregnancy. This study analyzed mutation of the adenomatous polyposis coli gene in 8 desmoid tumors from 7 familial adenomatous polyposis patients using polymerase chain reaction-single-strand conformation polymorphism and the direct sequencing method. Seven somatic mutations, 1 somatic allele loss, and 6 germ-line mutations were detected. The majority of adenomatous polyposis coli gene mutations were deletions of 1 to 19 base pairs in exon 15, and all mutations led to the formation of stop codons. A somatic mutation with repetition of 82 base pairs from codon 1399 to 1426 was also observed in a desmoid, which was most likely caused by an error during replication or repair replication. No mutation was detected in exons 1 to 2 of H-ras, K-ras, and N-ras genes and in exons 5 to 8 of p53 gene, in these tumors. The simultaneous existence of somatic and germ-line alterations of adenomatous polyposis coli gene observed in all 8 tumors strongly suggests that inactivation of both alleles of adenomatous polyposis coli gene is involved in the development of desmoid tumors.

Adenomatous Polyposis Coli↗
PubMed1993

Differing signal transductions elicited by three isoforms of platelet-derived growth factor in vascular smooth muscle cells.

The differing signal transductions elicited by three isoforms of platelet-derived growth factor (PDGF) were studied in cultured rat vascular smooth muscle cells (VSMC), which show different mitogenic responses to the three PDGF isoforms. PDGF-BB elicited a variety of cellular signals, including the phosphorylation on tyrosine of phospholipase C-gamma 1 (PLC-gamma 1) and the PDGF receptor, formation of inositol 1,4,5-trisphosphate and diacylglycerol, degradation of phosphoinositides (phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate) and elevation of intracellular calcium ([Ca2+]i). However, PDGF-AB failed to show some of these signals, although it stimulated [3H]thymidine incorporation to almost the same extent as PDGF-BB. Importantly, phosphorylation on tyrosine of the PLC-gamma 1 was far less (< 6.25%) in the case of PDGF-AB than that of PDGF-BB when assessed by immunoblotting. On the other hand, calcium ion entry from the extracellular medium was comparable in PDGF-AB- and PDGF-BB- stimulated VSMC. PDGF-AA, which did not stimulate [3H]thymidine incorporation, failed to show any of these effects with the exception of diacylglycerol formation. These observations suggest that the three PDGF isoforms stimulate different signal transduction pathways and that calcium ion entry, but not tyrosine phosphorylation of PLC-gamma 1, is essential for PDGF-induced mitogenesis in VSMC.

Animals↗
PubMed1993

Isolation and characterization of an endogenous Na+,K(+)-ATPase-specific inhibitor from pig urine.

A Na+,K(+)-ATPase inhibitor was purified from 88.6 l pig urine with a yield of approximately 10 micrograms. It inhibits the ouabain-sensitive uptake of 86Rb into human erythrocytes and the specific binding of ouabain to Na+,K(+)-ATPase. It also exhibits cross-reactivity to anti-ouabain serum. The purification procedure consisted of adsorption chromatography on an Amberlite XAD-2 column, preparative scale C18 low-pressure liquid chromatography (LPLC), and five steps of HPLC with five different types of reverse-phase columns. The dose dependence of the purified substance for the inhibition of ouabain-sensitive Na+,K(+)-ATPase activity and 86Rb uptake into human erythrocytes, and for the ouabain-displacing activity, paralleled those of ouabain, spanning two orders of magnitude in concentration range. However, the curve obtained from the cross-immunoreactivity with anti-ouabain serum did not parallel that of ouabain. The inhibitory potencies of the purified substance against the Na(+)-pump and ouabain-binding were diminished with increasing K+ concentration, exhibiting characteristics typical of cardiac glycosides. This substance had no effect on Ca(2+)-ATPase activity in human erythrocyte plasma membrane and skeletal-muscle sarcoplasmic reticulum, nor on Mg(2+)-ATPase activity. Acid treatment with 6 M HCl at 115 degrees C for less than 1 min destroyed approximately 82% of the inhibitory activity of the purified substance against Na(+)-pump activity. Alkaline treatment with 0.2 M NaOH at 23 degrees C for 2 h and heat treatment at 150 degrees C for 30 min partially destroyed the inhibitory activity. Boiling for 10 min and digestion by various enzymes did not affect the activity. Molecular mass was estimated to be 620 Da by gel-filtration column chromatography. Preliminary MS analysis suggested that the purified substance has a molecular mass of 625 Da. An 1H-NMR study revealed that this substance does not contain a tertiary methyl group. The results suggest that the purified Na+,K(+)-ATPase inhibitor is not a peptide and is distinct from any of the known cardiotonic steroids or various substances previously reported to exhibit Na+,K(+)-ATPase inhibitory activity. Thus, the purified substance may be a novel endogenous regulator of Na+,K(+)-ATPase.

Animals↗
PubMed1993

Multifocal intraductal papillary adenocarcinoma of the pancreas: report of a case.

This paper describes a case of a mucin-producing tumor of the pancreas, histologically diagnosed as multifocal intraductal papillary adenocarcinoma. The patient had a markedly dilated main pancreatic duct, detected by ultrasound (US) and computed tomography (CT), and endoscopy showed a papillary tumor projecting from the patulous orifice of the enlarged papilla of Vater. Several biopsies taken from the tumor indicated a diagnosis of papillary adenocarcinoma. Total pancreatectomy was thus performed, revealing a multifocal papillary tumor growing along the main duct in the head, body, and tail of the pancreas. Microscopically, these multiple tumors were found to be mucin-producing papillary adenocarcinoma of the main and subsidiary pancreatic ducts with nodular and microfocal periductal invasion. The surgical treatment of multifocal tumors, may therefore necessitate total pancreatectomy to achieve curative resection, in some cases.

Adenocarcinoma, Mucinous↗
PubMed1993

A novel endogenous sodium-pump inhibitor in pig urine: purification and comparison with the inhibitor purified from bovine adrenal glands.

To clarify the chemical nature and pathophysiological significance of an endogenous, specific Na-pump inhibitor, extracts of various tissues have been examined. The activities were extracted by an Amberlite XAD-2 adsorbent and fractionated by high-performance liquid chromatography (HPLC) on an ODS column. Among many tissues and fractions tested, the extract of pig urine has been found to contain a large amount of 86Rb uptake inhibitory activities. The strongest inhibitory activity for 86Rb influx into erythrocytes also exhibited a cross-reactivity with anti-ouabain antibodies. This activity has been purified to homogeneity using five steps of reverse-phase HPLC. Although most of the dose-response curves for this purified Na-pump inhibitor, designated as uroxin, in the various assay systems paralleled those of ouabain and the inhibitor purified from bovine adrenal glands (designated as adrexin C), the cross-reactivity curve with anti-ouabain antibodies did not. The retention time of uroxin on an ODS HPLC column was also different from that of digoxin, ouabain, or adrexin C. 1H nuclear magnetic resonance spectroscopic study suggests that uroxin is a novel Na-pump inhibitor that is structurally different from any of the known cardiotonic steroids or the substances previously reported to exhibit Na-pump inhibitory activity. Thus, uroxin may be a new type of endogenous regulator for the Na pump.

Adrenal Glands↗
PubMed1993

[Clinical usefulness of tumor markers in breast cancer].

Currently, many tumor markers are routinely measured in patient serum, but none appears to adequately detect cancer-specific substances for breast cancer. Four tumor markers (CEA, CA15-3, BCA225, c-erbB-2) were compared for sensitivity and specificity to breast cancer in 393 patients with breast disease (fibrocystic disease; 40, benign tumor; 21, primary cancer; 22, recurrent or advanced cancer; 22, non-recurrent; 288), and the following results were obtained: In cases of primary breast cancer excluding stage IV cases, the positive rates of CEA, CA15-3 and BCA225 were 4.5%, 13.6% and 13.6%, respectively. These rates were not higher than the positive rates found in fibrocystic disease or benign tumor. In cases of recurrent or advanced breast cancer, the positive rates of CEA, CA15-3, BCA225 and c-erbB-2 were 31.8%, 50.0%, 40.9% and 27.3%, respectively. In the recurrent cases, the combination assay using CA15-3, BCA225 and c-erbB-2, showed more useful diagnostic value (72.7%) than other combination assays with three tumor markers. High levels of CA15-3 in eight cases, BCA225 in five and CEA in one were found during the follow up of 15 patients with initial recurrence. Serum c-erbB-2 exceeded the normal range in 6 of 7 cases with advanced breast cancer. Serum c-erbB-2 should be considered a marker of progressive breast cancer. These results suggested that CA15-3, BCA225, c-erbB-2 and combination assays are useful tumor markers for not only detecting the recurrence of breast cancer, but also diagnosing the progression of primary breast cancer.

Antigens, Neoplasm↗
PubMed1992

Phospholipase D mimics platelet-derived growth factor as a competence factor in vascular smooth muscle cells.

Recent studies have suggested the importance of phosphatidylcholine (PC) metabolism in growth factor-stimulated cells. In these cells, PC is hydrolyzed not only by PC-specific phospholipase C but also by phospholipase D (PLD). In the present investigation, we show that the simple addition of PC-hydrolyzing PLD from Streptomyces chromofuscus to the culture medium of vascular smooth muscle cells elicits choline release into the medium accompanied by the formation of phosphatidic acid. In the presence of ethanol, this treatment elicits a formation of phosphatidylethanol (PEt) at the expense of phosphatidic acid. Furthermore, we show here that exogenous addition of S. chromofuscus PLD induces a marked DNA synthesis in quiescent vascular smooth muscle cells. This DNA synthesis induced by S. chromofuscus PLD is, like platelet-derived growth factor (PDGF)-elicited DNA synthesis, largely dependent on the presence of insulin. In addition, S. chromofuscus PLD-induced PEt formation and DNA synthesis were not affected by protein kinase C down-regulation, whereas PDGF-induced PEt formation and DNA synthesis were significantly inhibited. These observations strongly suggest that protein kinase-dependent activation of PLD is involved in mitogenic signal in PDGF-stimulated cells and that exogenously added PLD acts as a competence factor in the same way as PDGF.

Animals↗