PubMed HealthSearch

Biomedical subjects

F Konishi

Publications and source records attributed to F Konishi.

At least 19 recordsLinked to original sources

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

Diacylglycerol formation from phosphatidylcholine in angiotensin II-stimulated vascular smooth muscle cells.

In cultured vascular smooth muscle cells (VSMC), angiotensin II (Ang II) induces a biphasic diacylglycerol (DAG) formation peaking at 15 sec and 5 min. Although it has been well established that the first peak is produced by the hydrolysis of inositol 4,5-bisphosphate (PIP2), the origin of the second DAG peak has never been examined in detail. In the present paper, we provide evidence that the second peak of DAG formation in Ang II-stimulated VSMC originates mainly from PC.

Angiotensin II

[Neo-adjuvant chemotherapy with tegafur suppository for rectal cancer--evaluation of the antitumor effects, tissue levels of 5-FU and inhibition of thymidylate synthase. Tochigi Colorectal Cancer Study Group].

We evaluated antitumor effect histologically and assayed the tissue levels of 5-fluorouracil (5-FU) and thymidylate synthase (TS) activity using surgical specimens obtained from the patients with rectal cancer, who were given tegafur suppositories prior to surgery. The antitumor effect was evaluated histologically according to classification of the general rules for the gastric cancer study (Japanese Research Society for Gastric Cancer). In 39 patients, 16 tumor specimens revealed no effect (grade-0), 22 tumors grade-1 effect, and one was not evaluable because of the severe inflammatory changes. In 23 of these patients, resected specimens were available for the assay. 5-FU levels in cancer tissues were significantly higher than those in normal tissues, and TS inhibition rates (TSIR) were almost identical, averaging around 20%, in both cancer and normal tissues. Comparing the 5-FU levels and TS activity according to the histological effects (i.e.: 'grade-0' vs 'grade-1'), the 5-FU levels in the tumors achieved grade-1 were significantly higher than in the tumors showed 'grade 0' (p less than 0.01), and TSIR in the former were relatively greater than in the latter (p = 0.053). It is suggested that both tissue levels of 5-FU and TSIR may be useful parameters to predict the anti-tumor effect against rectal cancer after administration of 5-FU and its derivatives.

Chemotherapy, Adjuvant

Phospholipase D in cultured rat vascular smooth muscle cells and its activation by phorbol ester.

We determined the phospholipase D (PLD) activity in rat vascular smooth muscle cells by the formation of phosphatidylethanol in cells prelabeled with [3H] myristic acid. The enzyme was markedly activated by a phorbol ester (TPA). Down regulation of protein kinase C (PKC) resulted in almost complete inhibition indicating PKC-dependent mechanism of its activation. Depletion of calcium by EGTA and TMB-8 caused 53% inhibition. Chelator-stable association of PKC to membrane by TPA was observed in the absence of extracellular Ca2+. The mitogenic peptide PDGF also caused a marked stimulation of PLD. These results indicate that PLD in vascular smooth muscle cells is stimulated by TPA through the activation of PKC both by calcium-dependent and independent mechanisms.

Animals

Rat angiotensin II receptor: cDNA sequence and regulation of the gene expression.

The nucleotide and amino acid sequences for rat type I angiotensin II receptor were deduced through molecular cloning and sequence analysis of its complementary DNAs. The rat angiotensin II receptor consists of 359 amino acid residues and has a sequence similar to G protein-coupled receptors. The expression of this receptor gene was detected in the adrenal, liver and kidney by Northern blotting. Sodium deprivation positively modulated the expression of the receptor gene in the adrenal. No detectable change was observed in the expression levels of this receptor gene between spontaneously hypertensive rats and Wistar-Kyoto rats in the tissues examined including the adrenal, brain, kidney and liver. Interestingly the expression of this receptor gene was developmentally regulated.

Amino Acid Sequence

Expression of various sialylated carbohydrate antigens in malignant and nonmalignant pancreatic tissues.

The expression of six sialylated carbohydrate antigens (CA19-9, CA-50, SLEX, SLX, DU-PAN-2, ST-439) was examined in malignant and nonmalignant pancreatic tissues using an immunohistochemical method to elucidate the characteristics of these carbohydrate antigens as tumor markers. All carbohydrate antigens except for sialyl SSEA-1 (SLX, 52.4%) were expressed in more than 80% of the pancreatic cancer. CA19-9 and CA-50, belonging to type I blood group antigens, and DU-PAN-2 and ST-439 were localized predominantly in the cytoplasm of cancer cells, while sialyl Lex (SLEX) and SLX, belonging to type II blood group antigens, were stained mainly on the apical membranes of malignant glands. Although type I antigens were expressed in most nonmalignant pancreatic tissues, the type II antigens and ST-439 were absent in almost all of the normal tissues and faintly expressed in few chronic pancreatitis tissues, suggesting the high tumor specificity of these antigens. Each antigen was expressed on the apical surface of ducts in normal pancreas. However, in about 30% of chronic pancreatitis cases, type I antigens and DU-PAN-2 were observed in the cytoplasm of ductal cells. All patients showing stromal stain, possibly caused by loss of antigen polar expression and shedding into the surrounding stroma adjacent to malignant glands, revealed high levels of serum antigen. This finding suggests that the stromal appearance of antigens is a significant factor in the elevation of serum antigen levels.

Antibodies, Monoclonal

Enzyme histochemical, immuno histochemical and electron microscopic studies of two cases of leukemic malignant histiocytosis.

Two cases of leukemic malignant histiocytosis had similar morphologic and enzyme histochemical findings. Large blasts with low nuclear/cytoplasmic ratios, occasional azurophilic granules, and immature nuclei with nucleoli were seen in peripheral blood and bone marrow smears. Case 1 had occasional erythrophagocytosis, while in Case 2 it was rare. They were peroxidase negative, and very strongly positive by alpha-naphthyl butyrate esterase stain, the latter being inhibited by sodium fluoride. Acid phosphatase stains were also very strongly positive and were inhibited with tartaric acid. They were also stained granularly with PAS. Surface marker analysis revealed myeloid surface antigens, CD11+, CD13+ and HLA-DR+ in Case 1, and CD11+, CD13+, CD33+ and HLA-DR+ in Case 2. Immunoperoxidase stains of bone marrow biopsies revealed that lysozyme was positive in both cases. S-100 protein was strongly positive in Case 1, but weakly so in the skin tumor and negative in the bone marrow of Case 2. Electron microscopy showed both cases to be myeloperoxidase negative and rich in cytoplasmic organelles, such as lysosomes, mitochondria, and endoplasmic reticuli. Nuclei were irregularly shaped and nucleoli were present in virtually all the cells. These findings suggest that the malignant histiocytes in these two cases derive from bone marrow macrophages, and S-100 protein can also be detected in monocyte-macrophage derived histiocytes.

Adenocarcinoma

[Peripheral blood involvement accompanied with hypercalcemia in the malignant lymphoma of iliac bone].

We reported a rare case of non-Hodgkin's lymphoma of iliac bone which developed peripheral blood involvement associated with hypercalcemia. 42-year-old man was admitted to Fukui Medical School Hospital because of right iliac bone pain. An X-ray film of the pelvis disclosed the osteolytic change of right iliac bone. A CT scan of the pelvis showed soft tissue density tumors involved bilateral iliac bone. He had no superficial lymphadenopathy or organomegaly. Examination of peripheral blood and bone marrow did not show any abnormalities. Monoclonal immunoglobulin was not detected in serum. Examination of biopsied specimens from iliac bone tumor showed infiltration of round cells. Immunocytochemical analysis showed only MT-1 positive. He was treated with combination chemotherapy of vindesine, cyclophosphamide, prednisolone and pirarubicin followed by radiation therapy. But, there was no significant response. Following radiation therapy, he developed coma. Serum calcium was 9.8 mEq/l. The pathologic immature cells were found in peripheral blood. The bone marrow aspirates showed 63% pathologic cells. These cells expressed CD19, CD20, HLA-DR antigens. He was diagnosed as having leukemic non-Hodgkin's lymphoma, B-cell type, and was treated with combination chemotherapy. But he died of systemic fungal infection.

Adult

Solid, infiltrating variety of papillary cystic neoplasm of the pancreas.

Four tumors with histologic, histochemical, and ultrastructural characteristics of papillary cystic neoplasm of the pancreas but lacking the capsule commonly observed in papillary cystic neoplasm and infiltrating interiorly into the pancreatic parenchyma were seen in two men and two women who were 39 to 51 years old. These tumors contrasted with typical encapsulated papillary cystic neoplasms that show extrapancreatic growth and that are detected as a palpable abdominal mass in young women. These four tumors, although unpalpable, were all detected by nodular images of calcification in abdominal plain radiography. The tumors had a mean diameter of 3.1 cm (range, 1.7 to 4.5 cm), were confined within the pancreatic parenchyma, and showed central fibrosis accompanied by dystrophic changes such as calcification and ossification. A small necrotic cyst contiguous to the fibrous focus also was observed in the tumor in three patients. Tumor cells similar to those of a papillary cystic neoplasm had infiltrated among the pancreatic parenchyma in solid and pseudopapillary patterns, and pleomorphic atypism was observed in some parts of the tumor in three patients. These tumors were tentatively designated solid, infiltrating variety of papillary cystic neoplasms to differentiate them from ordinary encapsulated papillary cystic neoplasms. Although no signs of recurrence have been noticed after surgical treatment in these patients, the infiltrating growth pattern and the presence of pleomorphic atypism suggest higher malignancy than the ordinary papillary cystic neoplasm. The contrasting growth pattern and possible malignancy may warrant establishment of these tumors as a papillary cystic neoplasm subclass.

Adult

Papillary-cystic neoplasm of the pancreas. A clinicopathologic study concerning the tumor aging and malignancy of nine cases.

Nine female patients with papillary-cystic neoplasms (PCN) of the pancreas were studied clinicopathologically. The ages of seven of these patients ranged from 8 to 24 years. The remaining two patients, who were 47 and 60 years of age, were considered to have had the onset in their youth. There were few subjective symptoms, and the lesion was most often detected as a palpation of a mass by the patients themselves. Although the prognosis was generally favorable, the two older patients died of metastases. This suggested low-grade malignancy of PCN. The tumors were large (6.9 cm in mean diameter) and encapsulated, and their cross-sections showed an intermingling of solid tumoral areas and cystic necrotic areas. The histologic features of the solid tumoral portion were relatively uniform, with the tumor cells showing solid and pseudopapillary or pseudoglandular proliferation but few mitoses or atypism. Histochemical, immunohistochemical, and electron microscopic examinations showed polymorphic differentiation, which means that part of the tumor cells differentiated into duct epithelium, acinus, and endocrine cells (primary constituents of the pancreas). These findings suggest that the origin of PCN is totipotential primordial cells found in the development of the embryonic pancreas.

Adolescent

Endorectal ultrasonography with a 7.5 MHz linear array scanner for the assessment of invasion of rectal carcinoma.

An endorectal 7.5 MHz linear array scanner was used for the assessment of invasion in rectal tumours. As a preliminary study normal rectal wall of the resected specimen was scanned with the 7.5 MHz linear array scanner. The rectal wall was depicted in seven layers. The anatomical identification of these seven layers was made. Forty nine patients with rectal tumours were examined by endorectal ultrasonography with the 7.5 MHz linear array scanner. The sensitivities for T1, T2 and T3 tumours using the UICC TNM classification were 81%, 100% and 90% respectively, and the specificities were 100%, 85% and 100% respectively. Definite discrimination of lesions confined to the mucosa from those invading submucosa was difficult, even using this kind of high frequency ultrasonography. When the sonographic assessment was mucosal, or mucosal or submucosal involvement, local excision was performed. When the assessment was invasion in the muscularis propria or invasion penetrating the muscularis propria, bowel resection was performed. Except in one case, the histology of the resected specimens of the 49 cases confirmed the adequacy of the operation methods selected. Although there was some difficulty in making the distinction between mucosal and submucosal lesions, endorectal ultrasonography with the 7.5 MHz linear array scanner was considered to provide useful information in deciding on the type of operation offered to the patient.

Carcinoma

Enhanced resistance against Escherichia coli infection by subcutaneous administration of the hot-water extract of Chlorella vulgaris in cyclophosphamide-treated mice.

The effects of Chlorella vulgaris extract (CVE-A) on the recovery of leukocyte number and the augmentation of resistance to bacterial infection were examined in CDF1 mice made neutropenic by cyclophosphamide (CY). They were treated intraperitoneally with CY (150 mg/kg) on day 0, and were given CVE-A (50 mg/kg) subcutaneously (s.c.) every other day from day 1 to day 13 after CY treatment. CVE-A accelerated the recovery of polymorphonuclear leukocytes (PMN) in the peripheral blood in CY-treated mice. The number of granulocyte/monocyte-progenitor cells (CFU-GM) in the spleen increased rapidly and highly after the administration of CVE-A in CY-treated mice, in contrast to the absence of change due to CVE-A in the number of bone marrow cells in CY-treated mice. Administration of CVE-A in CY-treated mice enhanced the accumulation of PMN in the inflammatory site and the activity of the accumulated leukocyte cells in luminol-dependent chemiluminescence. The mice became highly susceptible to an intraperitoneal infection with E. coli on day 4 after CY treatment, whereas the mice given CVE-A showed an enhanced resistance against E. coli infection, irrespective of the timing of challenge. The bacterial number in CY-treated mice increased explosively after inoculation, resulting in death within 24 h. A progressive elimination of bacteria was observed from 6 h in the peritoneal cavity, spleen and liver of CY-treated mice given CVE-A s.c. These results indicate that CVE-A can be used as a potent stimulant of nonspecific resistance to infection in neutropenic mice.

Animals

Oral administration of Chlorella vulgaris augments concomitant antitumor immunity.

Chlorella vulgaris, an unicellular green algae, or its acetone-extract (Ac-Ex) were administered orally to Meth A tumor bearing BALB/c or (BALB/c x DBA/2)F1 (CDF1) mice. When CDF1 mice were fed daily with 10% dried powder of Chlorella vulgaris (CVP) containing diet before and after Meth A tumor inoculation, the growth of rechallenged Meth A tumor was significantly suppressed in an antigen-specific manner. Augmentation of antitumor resistance was exhibited also by Winn assay using lymph node cells of tumor-bearing mice orally administered with CVP or Ac-Ex. Antigen-specific concomitant immunity in these mice were mediated by cytostatic T cells but not by cytotoxic T cells. Natural killer cells seemed not to contribute in antitumor resistance in this system.

Adjuvants, Immunologic

[Histological localization of TAG72 in gastric cancers and a clinico-pathological study of the CA72-4 serum values].

A histochemical localization of TAG72, obtained through a reaction to MoAb CC49 and B72.3 in gastric cancer tissues, demonstrated a negative reaction in normal epithelium and a positive reaction in the cellular membranes of patients with enteric metaplasia and/or a well-differentiated adenocarcinoma, as well as a positive reaction in the cytoplasm in the majority of patients with a gastric adenocarcinoma. A CA72-4 (TAG72) serum assay was conducted on those with a gastric cancer and/or another malignant disease and then compared with other tumor markers. The overall positive rate of CA72-4 in patients with a malignant disease was 33.1% (59/178 cases). A significant elevation was found in cases of a colonic, gastric, and ovarian cancer, 55.0%, 53.3%, 54.5%, respectively.

Adenocarcinoma

[A case of Borrmann type 4 colon cancer with a metastasis into hepatoma].

A rare case of a colon cancer with a hepatomatous metastasis is reported. A 79 year old female was admitted hospital in April, 1988 with liver cirrhosis. On death in November, 1988, an autopsy revealed a primary, linitis plastica type diffuse adenocarcinoma of the total colon with an extensive metastases into lungs, kidneys, liver, small intestine, bladder, spleen, the bone marrow, and the lymph nodes. In the cirrhotic liver two hepatomatous nodules were found. As a focus of one of these nodules, there was a metastatic linitis plastica lesion of the colon.

Adenocarcinoma, Scirrhous

[Primary plasmacytoma of the thyroid--report of an autopsy case and review of the literature in Japan].

Primary extramedullary plasmacytoma (PEMP) of the thyroid is rare. Only nine patients with PEMP of the thyroid have been reported in Japan to date. We describe an additional autopsy case with PEMP of the thyroid and review of the literature in Japan. A 67-year-old women complaining of swelling of the anterior neck exhibited thin scalp hair, edematous face and a giant, hard, nodular goiter. Laboratory examination showed elevated levels of ESR, collagenous reaction, gammaglobulin, and a M-bow of the IgG-k type in immunoelectrophoresis. No Bence-Jones protein was found in the urine. Thyroid function test revealed a subclinically hypothyroid state, showing a T3 of 1.32 ng/ml, a T4 of 10.0 micrograms/dl, a TSH of 23.4 microU/ml and positive thyroid antibodies. The scintigram and the CT scan of the thyroid showed deviation of the trachea by the thyroid tumor and calcification within homogeneous thyroid gland. She underwent total thyroidectomy because of suspected malignancy. The histological examination of the removed thyroid weighing 117gr revealed a proliferation of plasma cells and lymphocytes and small amounts of atrophied thyroid follicles. The immunohistological examination of the removed thyroid showed the monoclonality to IgG-k chain. Plasma cells were stainable with methylgreenpyronine. Twenty-six months after thyroidectomy, she died due to progressive emaciation, anemia, hypoalbuminemia and ascites. Postmortem examination revealed widespread metastasized plasma cell tumors in the liver, intestine, spleen and mesentery with ischemic changes in heart and kidney. Based on our autopsy case and the nine cases reported in Japan, clinical and histological characteristics of PEMP of the thyroid were discussed.

Aged