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Biomedical subjects

I Nagata

Publications and source records attributed to I Nagata.

At least 19 recordsLinked to original sources

[The effect of nicardipine on angiogenesis in vitro].

We studied the effect of nicardipine, a calcium channel blocker, on the morphological change of endothelial cells in vitro. Cultured endothelial cells derived from bovine carotid artery make tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9)-10(-5) M of nicardipine in a dose dependent manner. Migration of endothelial cells was also suppressed by the same dose of nicardipine. However, proliferation of endothelial cells was not enhanced. These findings suggest that nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells.

Animals

Adjuvant effects of antineoplastic prostaglandins to cisplatin in nude mice bearing human ovarian cancer cells.

Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of delta 7-PGA1 was most marked, followed by that of delta 12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and delta 12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with delta 12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or delta 7-PGA1, compared to the results in groups treated with PGD2 alone, delta 7-PGA1 alone or cisplatin alone. Combination of PGJ2 or delta 12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or delta 7-PGA1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.

Animals

Modulation of human lymphocyte response to phytohemagglutinin by antineoplastic prostaglandins.

The effects of antineoplstic prostaglandins (PGs) (PGE1, PGE2, PGA1, PGA2, delta 7-PGA1, PGD2, PGJ2 and delta 12-PGJ2) on human peripheral blood lymphocyte (PBL) responses to phytohemagglutinin (PHA) were studied in vitro. All PGs used in this study alone had no mitogenic effect on the PBL. The PBL response to PHA was significantly stimulated at low concentrations (10(-7) and 10(-8) M) of the PGE series while the high concentration (10(-5) M) markedly inhibited the PHA response. PGA1 and PGA2, metabolites of the PGE series, and also delta 7-PGA1 stimulated the PHA response in a dose-dependent manner between 10(-6) and 10(-8) M, and showed a significant stimulatory effect at 10(-6) M while significantly inhibiting the PHA response at 10(-5) M. Similarly, 10(-6) and 10(-7) M (but not 10(-8) M) of PGD2 stimulated significantly the PHA response. PGJ2 and delta 12-PGJ2, which are metabolites of PGD2, also stimulated the PHA response in a dose-dependent manner between 10(-6) and 10(-8) M, and had a significant stimulatory effect at 10(-6) and 10(-7) M. The degree of the stimulatory effect was most marked with the PGD2 series among the antineoplastic PGs examined in this study. On the other hand, PGs (PGF1 alpha and PGF2 alpha) having no antineoplastic effect did not show such effects on the PHA response. These results suggest that antineoplastic PGs may have immunoregulatory effects through negative and positive feedback.

Antineoplastic Agents

Mother-to-infant transmission of hepatitis C virus.

Prospective studies of an infant of a mother infected with hepatitis C virus indicated that an HCV infection developed in the infant in early life. Perinatal transmission appeared to be the most likely explanation.

Female

Insulin sensitivity during very-low-calorie diets assessed by minimal modeling.

The time course of plasma glucose, insulin, and C-peptide after intravenous glucose (300 mg/kg body wt) injection was analyzed with minimal model approach in nine normal females and seven obese females. Glucose tolerance, estimated by glucose assimilation coefficient (KG), was positively correlated with glucose effectiveness (SG), but not correlated with peripheral insulin sensitivity (SI) in obese females as well as normal females. These factors were estimated before and after weight loss with 1.8-MJ (420-kcal) very-low-calorie diets (VLCDs) or with 2.5-3.3-MJ (600-800-kcal) low-calorie diets in two obese subjects. KG and glucose effectiveness decreased after acute weight loss with VLCD, although insulin sensitivity increased. Weight loss with low calorie diets resulted in improvement of KG and glucose effectiveness. These results suggest that a significant amount of glucose is taken up through insulin-independent mechanisms during the intravenous glucose tolerance test (ivGTT) in these subjects. This insulin-independent glucose uptake may be an important determinant of the fate of glucose in obese females as well as normal females.

Blood Glucose

The introduction of microvascular surgery to hepatic artery reconstruction in living-donor liver transplantation--its surgical advantages compared with conventional procedures.

Microvascular surgery for the reconstruction of the graft artery has been used since the 8th case in our series of 14 liver transplantations using living-related donors, and the clinical results have been compared between the first seven cases (the Loupe group) and the last seven cases (the Micro group). Seven arteries in 7 grafts were reconstructed with the use of loupe magnification in the Loupe group, while 8 arteries in 7 grafts were anastomosed with microscopic techniques in the Micro group. Statistically, there was no difference between the two groups in general background, including age, body weight and primary disease of the recipient, and in medical and surgical factors possibly relating to postoperative thrombosis of the hepatic artery. In two cases in the Loupe group, one or two additional reconstructions were necessary to obtain sufficient blood flow, while 8 arteries were anastomosed in the Micro group without any arterial complication in the postoperative period. There was no difference in time required for completing the arterial reconstruction (45.1 +/- 18.1 min in the Loupe versus 44.4 +/- 6.9 min in the Micro [mean +/- SEM]). Postoperative ultrasonic Doppler duplex study demonstrated a temporary decrease in the arterial flow in 2 cases of the Loupe group, and partial thrombosis of the artery was suspected. Additionally there were two episodes of hepatic artery thrombosis in 1 case of the Loupe group, in which emergent revision for thrombectomy and reanastomosis was performed at the first episode. This illustrated the higher incidence of arterial complications in the Loupe group compared with the Micro group (4 episodes/7 arteries in the Loupe versus 0/8 arteries in the Micro, P less than 0.05). In the present series there were no graft failures or arterial complications in the three deaths in the series. The clinical improvements achieved by microvascular surgery in living-donor liver transplantation suggest an alternative technical strategy for dealing with problematic arterial reconstruction in adult liver transplantation.

Child

Leiomyosarcoma of the uterus: ultrasonography and serum lactate dehydrogenase level.

Between January 1, 1979, and September 30, 1990, a total of 1,886 patients in the National Defense Medical College Hospital, a self-referred population, had a hysterectomy because of signs and symptoms presumably resulting from uterine myomas. After hysterectomy with presumed benign disease, a histologic diagnosis of leiomyosarcoma was made in 7 patients (0.37%). Preoperative diagnosis of leiomyosarcoma was not made in any of the 7 patients. However, serum lactate dehydrogenase levels were abnormally elevated in 3 of them, and degenerative changes were found within the tumor by ultrasonography in 5 of them. Furthermore, increased lactate dehydrogenase levels and degenerative changes within the tumor were found in 3 of the patients whose tumors had 10 or more mitoses per 10 high-power fields. The prognosis for the leiomyosarcomas with increased mitotic rates is very poor. Therefore, a degenerative change within the uterine mass and an increased lactate dehydrogenase level, when present, should suggest the diagnosis of leiomyosarcoma.

Adult

Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro. METHODS: Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine. RESULTS: Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced. CONCLUSIONS: Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy.

Animals

Rapid morphological changes in bovine brain microvascular endothelial cells on extracellular matrices.

The morphological changes in endothelial cells derived from bovine brain microvasculature, carotid artery, and aorta during growth on extracellular matrices were compared. All cells formed tubular structures on a basement membrane. Ultrastructural studies showed that the tubular structures had lumens surrounded by many endothelial cells. On type I collagen gel, brain microvascular endothelial cells still formed tubular structures, but the other two cell types formed confluent monolayers. However, when a second layer of collagen gel was laid over these cells, tubular structures developed within 2-3 days. Brain microvascular endothelial cells form tubular structures more readily than endothelial cells derived from large vessels on both basement membrane and type I collagen gel.

Animals

Pathogenic factors responsible for glucose intolerance in patients with NIDDM.

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergman's minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 +/- 112 pM.min) than in control subjects (4643 +/- 885 pM.min, P < 0.01). SI was not statistically different in normal control subjects (1.27 +/- 0.18 x 10(-4) min-1.pM-1) versus diabetic patients (1.62 +/- 0.33 x 10(-4) min-1.pM-1). However, SG was significantly lower in diabetic subjects (1.11 +/- 0.17 x 10(-2) min-1) than in control subjects (2.35 +/- 0.26 x 10(-2) min-1, P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index.

Adult

Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Saphenous vein graft to the distal vertebral artery between C-1 and C-2 using a lateral-anterior approach. Technical note.

The authors present a modified surgical procedure for extracranial vertebral artery reconstruction. The use of the proposed technique results in access to the V3 segment of the vertebral artery between the C-1 and C-2 vertebrae through the retrojugular space without requiring bone rongeuring. A saphenous vein bypass graft was placed between the common carotid artery and the V3 segment of the vertebral artery in three patients with bilateral occlusive lesions of the proximal vertebral arteries.

Cervical Vertebrae

[Cytokinetic effects of cisplatin on cisplatin-resistant ovarian cancer cell lines].

Cytokinetic effects of cisplatin on human ovarian cancer cell lines with natural cisplatin-resistance was examined by means of flow cytometry. These ovarian cancer cell lines derived from patients with clear cell carcinoma and serous cystadenocarcinoma were established and designated "KK" and "MH", respectively. Both KK and MH cells have shown resistance to cisplatin and IC50 of them were 0.95 microM and 3.28 microM, respectively. Cisplatin inhibited cell cycle progression at G2 +M phase up to IC50 of each cell from the analysis of cell cycle. Similar results had been obtained in the case of "KF" cell which was sensitive to cisplatin. Further studies of these cells should be performed to elucidate the mechanism of cisplatin resistance.

Adenocarcinoma

[Rapid morphogenesis of brain microvascular endothelial cells in culture system].

Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were cultured on type I collagen and Matrigel. BBECs make tubular structures and BCECs and BAECs grow and make confluent monolayer on type I collagen gel. But BCECs and BAECs make tubular structures when second layer was overlaid. BBECs, BCECs and BAECs make tubular structures on Matrigel. These morphological changes were not affected by basic fibroblast growth factor. These results suggest that BBECs have more potent angiogenic ability than BCECs and BAECs.

Animals

[Individualization of operative procedures for uterine prolapse based on categorization using X-ray urethrocystohysterography and postoperative outcomes evaluated with a scoring system].

A urethrocystohysterography (UCHG) and a prolapse scoring system (PSS) have been used to assess the types of uterine prolapse and postoperative outcomes since 1979. UCHG was useful in identifying the type of uterine prolapse and in selecting operative procedure. UCHG was done by injecting contrast medium into the bladder and uterine cavity and inserting a metallic bead chain into the urethra. A lateral pelvic X-ray was then taken at rest and during straining. The length of the uterus (UL), distance from the pelvic outlet (PO) to the bladder base (BB), distance from PO to the uterine fundus (UF), and distance from the ischial spine (IS) to UF were measured on the UCHG. We found that there were three types of uterine prolapse on the UCHG findings, type 1: cervical elongation without descent of uterine fundus and cystocele, type 2: uterine prolapse with moderate descent of uterine fundus and cystocele, and type 3: giant vaginal eversion including completely prolapsed uterus, marked cystocele, enterocele and rectocele. The operative time of vaginal hysterectomy with anterior and posterior colporthaphy (VH with AP repair) correlated well with UL and PO-UF distance on UCHG, and blood loss. Operating time was significantly shorter and amount of blood loss was significantly smaller in cases of Machester operation (cervical amputation, fixation of cardinal ligament stumps to the anterior wall of the remaining cervix and AP repair) than in those of VH with AP repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Effects of opioid peptides on the tumoricidal activity of spleen cells from nude mice with or without tumors.

The present study was designed to explore the effects of opioid peptides on the immune systems of intact nude mice and nude mice bearing human ovarian cancer cells (KF). When spleen cells from intact nude mice were incubated with medium alone, a significant ability of spleen cells to lyse the KF cells was not observed. However, incubation of the spleen cells with 1 microM beta-endorphin or 1 microM alpha-endorphin induced a significant lytic activity on the KF cells. The control-level lytic activity was increased significantly to about 4.5-fold by 1 microM beta-endorphin and about 3.7-fold by 10 microM met-enkephalin. These results suggest that opioid peptides play a crucial role in cellular immunity. Thus, we examined plasma levels of beta-endorphin in patients with ovarian or uterine carcinoma. The plasma beta-endorphin levels in patients with ovarian or uterine carcinoma were significantly higher (more than twofold) than those of age-matched healthy women.

Adult

1,25-Dihydroxyvitamin D3 inhibits thromboxane release from activated macrophages.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) in concentrations from 0.1 to 10 nM suppressed immunoreactive thromboxane B2 (iTXB2) release from Propionibacterium acnes (P. acnes)-elicited liver adherent cells stimulated with lipopolysaccharide (LPS, 1 microgram/ml). These suppressive effects of 1,25-(OH)2D3 were also observed in oyster glycogen-elicited peritoneal macrophages. On the contrary, it did not inhibit iTXB2 release from both resident Kupffer cells and peritoneal macrophages stimulated with the same concentration of LPS. Furthermore, 1,24(R)-dihydroxyvitamin D3 (1,24(R)-(OH)2D3), a vitamin D3 analogue, also inhibited iTXB2 release from liver adherent cells, but, another synthesized vitamin D3 analogue, 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) tended to decrease iTXB2 release only at higher concentrations. These results suggest that active vitamin D3 analogues inhibit iTXB2 release from activated macrophages.

Animals

[In vitro and in vivo effects of ginsenoside Rh2 on the proliferation of serous cystadenocarcinoma of the human ovary].

Inhibition of human ovarian cancer cell proliferation in vitro and in vivo by Ginsenoside Rh2(Rh2) isolated from Red Ginseng was examined by using a cell line (HRA) derived from ascites of a patient with serous cystadenocarcinoma of the ovary. The HRA cell proliferation in vitro was inhibited in a dose-dependent manner with between 10 and 100 microM of Rh2. The uptake of radiolabeled precursors (3H-thymidine, 3H-uridine, and 3H-varine) by HRA cells was also inhibited in a dose-dependent manner with between 30 and 100 microM of Rh2. The growth of HRA cells transplanted into nude mice was not significantly inhibited by Rh2 alone. On the other hand, when cisplatin was administered together with 10 microM, 30 microM, or 50 microM Rh2, the growth of HRA cells was inhibited 31 and 35 days after tumor inoculation. Survival was also prolonged when cisplatin was administered with 10 microM and 30 microM Rh2. These results suggest that there is a synergistic effect between cisplatin and Rh2.

Animals