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Biomedical subjects

M Sakamoto

Publications and source records attributed to M Sakamoto.

At least 559 records · Page 31Linked to original sources

Chronic intracerebroventricular infusions of endothelin elevate arterial pressure in rats.

We investigated the effects of intracerebroventricular infusions of endothelin on cardiovascular and endocrinological responses using conscious, unrestrained rats. Chronic intracerebroventricular infusions of endothelin, 10 pmol/h for 7 days, elevated arterial pressure significantly on days 5, 6 and 7 of the infusion, compared with intracerebroventricular infusions of the vehicle. Heart rate decreased from day 1 of the infusion of endothelin until the end of the experiment. The urinary excretion of norepinephrine increased on day 3 and epinephrine increased on days 3, 4 and 5 of endothelin infusion. The urinary excretion of arginine vasopressin increased on day 5, 6 and 7 of the infusion. These findings suggest that chronic intracerebroventricular infusions of endothelin elicit elevations in arterial pressure and that the initiation of blood pressure rises can be related to sympathetic activation although the actual role for the pressor responses has been played by the released arginine vasopressin.

Animals↗

Characterization of high-molecular-mass forms of basic fibroblast growth factor produced by hepatocellular carcinoma cells: possible involvement of basic fibroblast growth factor in hepatocarcinogenesis.

Growth factor(s) with a strong mitogenic effect on BALB/c3T3 cells was purified from an extract of C-Li21 cells, a human hepatocellular carcinoma line, by a combination of heparin-affinity chromatography and reversed-phase high-performance liquid chromatography (HPLC). Two major peaks of mitogenic activity were obtained by reversed-phase HPLC. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the two peaks revealed that one was composed of three proteins with relative molecular masses of 27, 24 and 23 kilodaltons (kD), whereas the other was a single 19-kD protein. Immunoblot analysis showed that all four of these molecules were immunoreactive species of human basic fibroblast growth factor (bFGF). N-Terminal sequence analysis of these molecules revealed that most of them were N-terminally blocked. However, small proportions of the 23- and 19-kD molecules were not blocked, and their respective N-terminal sequences were found to correspond to Gly-40-Gly-27 and Pro29-Phe40 of human bFGF deduced from the cDNA sequence of a human hepatoma cell line, SK-HEP-1. Expression of bFGF in hepatocellular carcinomas was then investigated by RNA blot analysis. All of the examined hepatocellular carcinoma cells expressed bFGF, and the degree of expression was higher in surgically resected hepatocellular carcinomas than in the corresponding adjacent non-cancerous liver tissue. Transcripts of bFGF were not detected in normal liver. These results suggest that C-Li21 cells produce four molecular forms of bFGF, and that bFGF may be involved in hepatocarcinogenesis. Moreover, it appears that bFGF is a potent mitogen toward primary-cultured hepatocytes, and that high-molecular-mass forms of bFGF produced by C-Li21 cells have stronger mitogenic effects on hepatocytes and are more stable under acidic conditions than the low-molecular-mass form, composed of 146 amino acids.

3T3 Cells↗

[Bacteriological examination of infections in the field of oral surgery].

Etiology of bacterial infections in the field of oral surgery was studied. A total of 270 samples collected from patients with encapsulated abscess in their oral cavities was examined and bacteria were isolated from the 244 samples (90.4%). The following results were found; 1) Organisms more than one from one sample were frequently isolated from cases with parodontitis, pericoronitis and gnathitis. Isolation of anaerobic bacteria was common (54.2%). 2) Streptococcus milleri and Streptococcus sanguis and Capnocytophaga species were the most common isolates among aerobic gram-positive and gram-negative bacteria, respectively. 3) Peptostreptococcus micros and Eubacterium lentum were most frequent isolates among gram-negative anaerobic bacteria. Among gram-negative bacteria, Oral Group Bacteroides, especially Bacteroides gingivalis, Bacteroides intermedius, Bacteroides buccae and Bacteroides oralis were most prominent. 4) Isolation frequency of bacteria (both species and strains) was high from samples obtained from patients before antibiotic chemotherapy. 5) Most strains were sensitive to Midecamycin acetate and Josamycin. Minimum inhibitory concentration of 80% isolates (MIC80) against these antibiotics was 0.39 microgram/ml.

Bacteria↗

Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts.

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.

Adenosine Triphosphate↗

Syntheses and biological properties of new 8-fluorocarbapenem derivatives.

8-Fluorocarbapenem derivatives having various C-3 side chains were synthesized to study for the structure-activity relationship of carbapenems by in vitro biological evaluation. The introduction of fluorine at C-8 of racemic PS-5 led to slight improvements of the antimicrobial activity and the stability to renal dehydropeptidase-I. When D-cysteine was additionally introduced to the C-3 position of (+/-)-8-fluorocarbapenem, the diastereomeric separation of the 8-fluorocarbapenems became feasible. As expected from penicillins and cephalosporins, (+)-8-fluoro-3-D-cysteinylcarbapenem (+)-7a was antimicrobially active, whereas (-)-7b was inactive. It is worth noting, however, that (+)-7a was significantly more sensitive to renal dehydropeptidase-I than (-)-7b. Irrespective of the presence of fluorine at C-8, basic S-side chains at C-3, such as the pyridyl and pyrrolidyl groups, significantly improved in antimicrobial activity and dehydropeptidase-I stability. The combination of 8-fluorination with C-3 basic side chains in 7c--g resulted in a marked improvement of antimicrobial activity and dehydropeptidase-I stability.

Anti-Bacterial Agents↗

Low molecular weight heparin enhances prostacyclin production by cultured human endothelial cells.

Confluent cultures of vascular endothelial cells derived from the human umbilical vein were incubated in a serum-free medium in the presence of low molecular weight heparin (LMWH) with molecular weights of 4000-6000 dalton (Da), or of unfractionated heparin (UFH) with average molecular weight 12,000 Da, and prostacyclin production was determined by radioimmunoassay for 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. LMWH at 1 U/ml as anti-factor Xa activity significantly increased prostacyclin production after 6h or longer; however, UFH at 1 USP U/ml did not induce such a significant change. The LMWH-induced increase in prostacyclin production occurred at 0.1 U/ml and above after 6 h of treatment. Since prostacyclin is both a potent inhibitor of platelet aggregation and a vasodilator, it was suggested that the increased endothelial cell prostacyclin production induced by LMWH may be a component of the anticoagulant activity of the drug.

Cells, Cultured↗

Kinetic analysis of dehydropeptidase-I and comparative in vitro and in vivo stabilities of PS-5 derivatives modified at the C-3 side chain.

With partially purified kidney dehydropeptidase-I (DHP-I) preparations, the hydrolysis kinetics of glycyldehydrophenylalanine (Gly-dPh) by DHP-I were found to be completely non-Michaelian, whereas those of PS-5 and imipenem were composed of at least two-phase reactions which were also observed using Bacillus cereus type II beta-lactamase. Thus the DHP-I stabilities of 34 PS-5 carbapenem derivatives which were synthesized by chemical modification at the C-3 side chain of PS-5 were examined in vitro using fresh mouse, dog and human DHP-I preparations, and are tentatively expressed in reference to the DHP-I stabilities of PS-5. The in vitro DHP-I stability of PS-5 was significantly improved by introduction of basic side chains and cysteines at C-3. More particularly, the D-cysteinyl side chain was more stable relative to DHP-I than the L-cysteinyl. In vivo, however, the degree of improvement of the DHP-I-stability by chemical modification at C-3 was not sufficient enough to establish therapeutically effective levels of serum concentrations and urinary recoveries of the carbapenem derivatives after parenteral administration.

Animals↗

Nicorandil (2-nicotinamidoethyl nitrate) inhibits both vaso-dilating and -constricting effects of endothelin in a vascularly isolated hind-limb preparation in rats.

Effects of nicorandil (2-nicotinamidoethyl nitrate), a nitrate derivative with a K+ channel-opening action, on endothelin-1 (ET)-induced effects on peripheral blood vessels were studied using a hind-limb perfusion preparation in rats. ET injected into this circuit increased the perfusion pressure for more than 30 min following a transient, initial vasodepression of the perfusion system. The magnitude of both responses was dose-dependent. Pretreatments with nicorandil infused into this preparation significantly attenuated both the initial vasodilation and the sustained vasoconstriction caused by ET. The initial vasodepression caused by ET could be mediated by the release of endothelium-derived relaxing factor (EDRF). The sustained phase would be due to increased intracellular calcium elicited by ET. Nicorandil inhibited both the initial and the sustained phase of the ET-responses, probably by inhibition of intracellular phosphoinositide metabolism in both endothelium and vascular smooth muscle cells.

Analysis of Variance↗

[Relationship between reactivation and tumor markers in prostatic cancer].

Twenty-seven cases of reactivated prostatic cancer between 1979 and 1990 were investigated. Reactivation took place in the form of local aggravation in 3 cases, occurrence or aggravation of metastasis to bones in 8 cases, and in both forms in 16 cases. The elevation of tumor markers preceded the clinical findings in 11 cases (41%). In 75% of the cases with occurrence or aggravation of metastasis, the elevation of tumor markers preceded the clinical findings. This showed that tumor markers were useful in most cases for early detection of reactivation. However, in 3 cases with local aggravation, the clinical findings preceded the elevation of tumor marks. Therefore, it is also important to check the clinical findings at the follow-up. At the time of reactivation, positive rates of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PA) were 78%, 83% and 80%, respectively. Thus gamma-Sm and PA appeared to be more reliable than PAP for monitoring of prostatic cancer.

Acid Phosphatase↗

Accelerated tumor growth and changes in images concomitant with vascularization in a patient with hepatocellular carcinoma.

We examined serial changes of tumor images in a patient with hepatocellular carcinoma. The hepatocellular carcinoma was initially detected as a homogeneous low-echo area with unclear margins, which was not enhanced by contrast media on computed tomograms, and did not reveal any vascular abnormalities on hepatic angiography. About 11 months later, the tumor growth accelerated, with a parallel increase in serum alpha-fetoprotein levels, and the ultrasonographic features of the tumor changed from a homogeneous low-echo area to a mixed low- and high-echo area with a peripheral low-echo zone. Hepatic angiography revealed a hypervascular tumor at this time. The present case indicates that tumor growth and imaging patterns of hepatocellular carcinoma are closely related to vascularization of the tumor.

Carcinoma, Hepatocellular↗

Distribution of substance P and vasoactive intestinal peptide in the human liver: light and electron immunoperoxidase methods of observation.

The localization of substance P (SP) and vasoactive intestinal peptide (VIP) in 12 normal human liver tissues was examined by light and electron immunohistochemistry using immunoperoxidase methods. SP and VIP immunoreactive nerve fibers were observed around portal veins, bile ducts, and hepatic arteries in portal areas, along sinusoids and hepatocytes in hepatic lobules, and around central veins. More SP and VIP immunoreactive nerve fibers were present in the portal areas than in other regions. Moreover, SP and VIP containing nerve endings were localized close to myofibroblasts, Ito cells, fibroblasts and endothelial cells of blood vessels, and sinusoids. The results suggested that part of the innervation of the human liver may be related to the contraction and relaxation of the cells close to nerve endings, and to the regulation of hemodynamic processes by the neurotransmitters such as SP and VIP at the hepatic lobular level.

Adult↗

Spontaneous massive hemorrhage within a malignant tumor of the liver: diagnostic features in sonography and CT.

Computed tomography (CT) and sonography performed on four patients with histopathologically proven massive intratumoral hemorrhages in the liver were compared with pathological findings. Unenhanced CT showed a round low-density mass, and enhanced CT produced slight enhancements in the peripheral portions of the masses in two patients which corresponded to histopathologically viable cancerous portions. In contrast, sonography showed multilocular cystic masses with variously shaped septa, assuming a honeycomb appearance. Histopathologically, the septa were made up of blood clots with or without granulation tissue, scar and viable tumor, and the cystic spaces were filled with exudate and erythrocytes. Combined study by CT and sonography could be useful in differentiating massive hemorrhagic malignancies from cystic and necrotic masses and/or simple hemorrhagic lesions. The danger of malignant tumors with massive hemorrhage possibly being diagnosed as benign lesions, such as hematomas and abscesses, is also stressed.

Adolescent↗

[Establishment and characterization of endometrial undifferentiated carcinoma cell line (TMCC-2.U)].

We established new cell line designed TMCC-2.U, which suggested transformation to undifferentiated carcinoma, derived from endometrial clear cell carcinoma cell line (TMCC-2). The monolayer culture cell showed a pavement arrangement and spindle like shape. A rough-endoplasmic reticulum, mitochondria etc. are well developed. But cytoplasmic endocrine granulosa were so poorly, it suggests functional developments are poor. The TMCC-2.U cells were transplanted to nude mice which showed no typical pattern suggested undifferentiated carcinoma. Their chromosome number varied and the mode is 78. Marker chromosome were found frequency. Growth pattern and production of tumor marker are clearly differentiate from TMCC-2. As mensioned above, TMCC-2.U cell line will be very valuable in basic research on mechanism of transformation and effects of patient's serum on hystogenesity.

Adenocarcinoma↗

[Establishment and characterization of endometrial clear cell carcinoma cell line (TMCC-2)].

A new cell line, designated TMCC-2, has been established from operation material from a woman with endometrial clear cell carcinoma. TMCC-2 was successively subcultured 40 times in about 1 year. The monolayer culture cell showed a pavement-like arrangement of polygonal and short spindle-shaped cells, and had a tendency to pile-up without contact inhibition. Since PAS positive and Alcian-Blue negative substance could be seen in the cytoplasm, the cells were found to produce glycogen. The population doubling time, the saturation density and plating efficiency of the 25th passage cells were 24 hours, 1.8 x 10(5) and 23%, respectively. The nuclear DNA histogram obtained by flow cytometry showed two peaks at 2.1C and 4.1C. Therefore, the DNA index was 1.05. A tumor maker assay of the culture medium revealed significantly high values for TPA, CA125, CA19-9, and SLX compared with the control medium. The TMCC-2 cells produced the tumors in nude mice after subcutaneous transplantation. In addition, the histological findings were similar to those in the original tumor. As mentioned above, the TMCC-2 cell line derived from endometrial clear cell carcinoma will be very valuable in basic research on clear cell carcinoma of the endometrium.

Adenocarcinoma↗

[IgD-lambda multiple myeloma associated with bone marrow fibrosis].

A few cases of multiple myeloma associated with myelofibrosis has been reported. In Japan, such cases have been less reported. We report a case of IgD-myeloma with remarkable marrow fibrosis. A 44-year-old female was admitted to our hospital because of back pain. On admission her peripheral blood revealed anemia and leukopenia. Serum immunoelectrophoresis revealed M-protein of IgD and serum IgD level remarkably increased to 5420 mg/dl. Bone marrow aspiration resulted in dry tap every three times and its biopsy at iliac bone showed remarkable infiltration of myeloma cell and remarkable increase of reticulin fiber with marked decrease of normal hematopoietic cells. Her liver and spleen were not palpable and tear drop cells of erythrocytes were not shown in peripheral blood. We could not find view of myelofibrosis with chronic myeloproliferative disorders. Multiple myeloma associated with myelofibrosis is a interesting syndrome as clinical signs and course. So further investigation must be needed.

Adult↗