Biomedical subjects
Publications and source records attributed to N Kawamura.
Novel antibiotics, pyralomicins 1a approximately 1d, 2a approximately 2c were isolated from the culture broth of Microtetraspora spiralis MI178-34F18. The structures of pyralomicins were determined by various NMR spectral analyses including 1H-15N HMBC and 13C¿1H¿ NOE difference experiments.
The biosynthesis of pyralomicin 1a (1) was studied by feeding of 13C and 15N labeled compounds to the culture of Microtetraspora spiralis MI178-34F18. The result indicated that the benzopyranopyrrole unit of 1 was derived from two units of acetate, one unit of propionate and one unit of proline, and that the cyclitol unit of 1 was derived from glucose metabolites. And 4'-O-CH3 was derived from the S-CH3 group of methionine.
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A case of bronchial carcinoid was reported. A 39-year-old male was suffered from recurrent pneumonia. Bronchofiberscopy revealed a polipoid tumor nearly obstructing left superior bronchial trunk. CT scan showed a round tumor about 1 cm in diameter. Resection of the tumor was carried out by sleeve upper lobe loectomy. Histological diagnosis was typical carcinoid, and there was no lymph node matastasis. Postoperative course was uneventful. Granulation and stenosis were not observed at the part of anastomosis.
Certain diseases have been associated with micronutrient deficiencies in China, and nutritional assessments have become important means of preventing such diseases. In the present study, fat-soluble vitamins including vitamins A, D, E, K, and beta-carotene in the cord blood and colostrum of Chinese subjects in Guilin, China, were assayed and compared with those of Japanese subjects in Osaka, Japan. These vitamins were analyzed by high-performance liquid chromatography. Vitamin A and E levels in the cord blood and colostrum of the Chinese group showed almost the same values as those of the Japanese group. There was also no significant difference in vitamin D level in cord blood between the two groups, while significantly lower levels of beta-carotene and cryptoxanthin, and a higher level of PIVKA-II (protein induced in vitamin K absence) in cord blood were observed in the Chinese group. These findings pointed to a restricted intake of green-yellow vegetables in the Chinese group and an increased risk of hemorrhagic disease in newborn of that group is suggested.
We investigated whether lipoteichoic acid (LTA) induces the expression of E-selectin and neutrophil adhesion to human umbilical vein endothelial cells (HUVECs). LTA (0.01-30 micrograms/ml) induced the expression of E-selectin in a concentration-dependent manner with maximal response at 10 micrograms/ml. The expression level of E-selectin increased from 2 h after stimulation by LTA with the maximal level at 4-8 h. Neutrophil adhesion to LTA-treated HUVECs correlated with the levels of E-selectin expression. In addition, the adhesion was clearly inhibited by anti-human E-selectin monoclonal antibody CY-1787 as well as a sialyl Lewis X (SLeX) oligosaccharide. LTA-induced expression of E-selectin was inhibited by protein kinase C inhibitors, H-7 and staurosporine. These results indicate that LTA induced the expression of E-selectin and neutrophils adhered to HUVECs via E-selectin.
We investigated the presence of the carbohydrate ligand for E-selectin on the cell surface of rat polymorphonuclear leukocytes (PMN). Rat PMN, isolated from peripheral blood, adhered to recombinant rat E-selectin-coated microplates. The adhesion was inhibited either by an anti-rat E-selectin monoclonal antibody (MAb), a sialyl Lewis X (SLex) oligosaccharide or neuraminidase digestion. FACS analysis revealed the expression of SLex as well as other adhesion molecules such as L-selectin, CD11a, CD11b and CD18 on the cell surface of rat PMN. The binding of an anti-SLex MAb KM93 to rat PMN was inhibited competitively by a SLex but not by a Lewis X (Lex). The reactivities of two anti-SLex MAbs, KM93 and CSLEX-1, or an anti-Lex MAb BC90/45 to rat PMN differed from those to human PMN. These results suggest that rat PMN contain the SLex-moiety, which binds to rat E-selectin and is different from that of human PMN.
Activin A, a member of the transforming growth factor beta supergene family, modulates DNA synthesis in cultured rat vascular smooth muscle cells (VSMC) (Kopma et al. (1993) Exp. Cell. Res. 206, 152-156). In the present study, we studied the production of activin A and follistatin in VSMC. When VSMCs cultured in a 24-well plate were cultured with 10% fetal calf serum (FCS) for 24 h, 0.94 +/- 0.20 pmol/well (mean +/- SE, n = 6) of bioactive activin was released into the culture media. Reverse-transcription polymerase chain-reaction revealed the expression of mRNA for the beta A subunit of inhibin but not for either the beta B or alpha subunit. Bioactivity of activin was increased in quiescent cells treated with FCS or platelet-derived growth factor (PDGF) but not with angiotensin II (Ang II) or insulin-like growth factor-I (IGF-I). Ang II or IGF-I did not stimulate DNA synthesis by itself but, when these two agents were combined, they increased nuclear labeling by 16.4% and release of bioactive activin by 170% of basal. The dose-response relationship and time course study indicated that PDGF-mediated release of activin correlated with initiation of DNA synthesis. Steady state expression of mRNA for the beta A subunit was markedly elevated 12 h after the addition of PDGF and was reduced thereafter. To assess the significance of autocrine activin, the effect of PDGF was determined in the presence and absence of excess of exogenous follistatin. The PDGF-mediated DNA synthesis was enhanced by the addition of excess follistatin.(ABSTRACT TRUNCATED AT 250 WORDS)
We report a patient who presented with colicky abdominal pain, hematemesis, and melena following a blunt abdominal injury sustained in an automobile accident. Serologic tests suggested liver dysfunction and computed tomography (CT) revealed dilatation of the intrahepatic bile duct. Duodenoscopy demonstrated hemobilia originating from the duodenal papilla of Vater. Angiography revealed a pseudoaneurysm of the hepatic artery and angiographic embolization sucessfully stopped the hemorrhaging. However, even following the angiographic embolization, the patient remained symptomatic and repeat CT demonstrated thickening of the gallbladder wall and a lesion resembling a blood clot. We strongly suspected cholecystitis and performed a laparoscopic cholecystectomy. Grossly, the resected specimen revealed wall thickening with a congested mucosa and three blood clots; histologically, these changes were consistent with a diagnosis of chronic cholecystitis. The clinical message of this paper is that patients should be observed for this usual complication of hemobilia after liver injury.
The susceptibility of mice at different developmental stages to a relatively low titer of cell culture-passaged murine cytomegalovirus (MCMV) infection was compared in terms of the urinary excretion of MCMV examined by plaque assay and in terms of the distribution of viral infection, determined by immunohistochemistry, using antibodies specific to the early nuclear antigen of MCMV. Viral infection on day 8.5 of gestation (E8.5) into the conceptus and intraperitoneal infection on day 15.5 of gestation (E15.5), postnatal day 2 (P2), postnatal day 11 (P11), and 30 days after birth (P30), respectively, were performed. Embryonal and perinatal mice were more susceptible to MCMV in terms of urinary excretion of the virus and the presence of viral antigen-positive cells in the brain, lungs, and kidneys. In the embryonal and perinatal infection, the viral antigen-positive cells in the neurons of the cerebral cortex and hippocampus were retained late after birth, even though the positive cells in the lungs and kidneys had disappeared. In the mice infected on E8.5, small clusters of viral antigen-positive cells were detected only in the cortex and hippocampus late after birth, without the urinary excretion of virus. These results suggest that when mice are infected with MCMV at the embryonal and perinatal stages, elimination of the infected neurons is delayed compared with that of the other cells in the lungs and kidneys. These findings provide a model for the analysis of pathogenesis of the subclinical congenital CMV infection that manifested clinically late after birth in humans as brain disorders.
Production of activin was studied in four cell lines of epithelial cells: FRTL-5, JCT-12, GH4C1, and FHs74Int cells. Bioactivity of activin was detected in conditioned media of FRTL-5, JCT-12, and FHs74Int cells. Among these three cell lines, FHs74Int cells, which were derived from human embryonic intestine, released a relatively f1p4e amount of bioactive activin. In these cells, serum and epidermal growth factor (EGF), which were capable of stimulating DNA synthesis, augmented release of bioactive activin in middle to late G1 phase. In addition, basic FGF (bFGF), which had no effect on DNA synthesis in these cells, also increased release of activin. In bFGF-treated FHs74Int cells, bioactive activin was released within 4 hr of the addition of bFGF. The reverse-transcription polymerase chain reaction reveals that mRNA for only the beta A subunit of activin is expressed in these cells. Immunoblotting of lysate from serum-treated cells using anti-human activin A antibody indicated the existence of a 12.5-kDa protein under a reducing condition. FHs74Int cells did not express binding site for [125I]activin A and exogenous activin A did not affect DNA synthesis in these cells. These results indicate that FHs74Int cells derived from human embryonic intestine synthesize and release activin A. Activin A released from intestinal epithelial cells might be a modulatory factor in cells in intestinal mucosa.
This study explored the efficacy of hepatic arterial therapy, comparing both injection and infusion of 5-fluorouracil (5-FU) in prolonging the survival of 92 patients with recurrent unresectable hepatic metastasis from colorectal cancer. With respect to pretreatment carcinoembryonic antigen doubling time (CEA-DT), 56 patients were treated with intra-arterial injection, and 36 with intra-arterial infusion. In 21 patients with a CEA-DT of less than 40 days, the cumulative survival of patients treated with arterial injection was significantly longer than that of patients treated with arterial infusion. In 45 patients with a CEA-DT of 40-80 days, the survival curves of patients did not differ from each other. Of the remaining 26 patients with a CEA-DT of more than 80 days, those treated using arterial infusion had an excellent prognosis, in contrast to those treated using arterial injection, with statistical significance. CEA-DT may be useful when choosing a chemotherapy regimen, and may help to accurately establish the prognosis of patients with unresectable hepatic metastasis from colorectal cancer.
Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer, renal cancer or neuroblastoma to investigate the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after the initiation of culture. In contrast, the proliferation of TIL cultured with IL-2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly disappeared from the culture. To determine the generation of autologous tumor-reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2-activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of lymphokine-activated killer activity against a variety of tumor cells. However, TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented cytotoxicity against autologous tumor cells compared with that induced by IL-2 alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody, indicating that these CTL recognize autologous tumor antigen through T cell receptor. These results imply that IL-12 is a novel cytokine which facilitates the generation of autologous tumor-reactive CD8+ CTL from TIL.
Since all-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), and its effectiveness appears to be related to the plasma or serum level, a pharmacokinetic study of ATRA was undertaken in nine patients with various leukemias. After oral administration at a dose of 30 mg/m2, the time required to reach the peak plasma level of ATRA (20-1198 ng/ml) was between 120 and 240 min and the apparent plasma elimination half life was 21-51 min. In addition, 13-cis retinoic acid was detected in the plasma of seven patients, indicating the occurrence of ATRA isomerization in vivo. ATRA therapy did not induce complete remission in all patients, even when high plasma levels were achieved. Among the six APL patients given ATRA therapy, one who failed to respond had a very low plasma ATRA level. These findings suggest that it may be useful to monitor plasma levels during oral ATRA therapy in order to achieve an appropriate treatment regimen.
OBJECTIVE: To investigate the susceptibility of primary renal cell carcinoma (RCC) and metastatic RCC to lymphokine-activated killer (LAK) cells using three RCC cell lines derived from the primary and metastatic tumours in a male patient with advanced RCC. MATERIALS AND METHODS: Three RCC cell lines (named HANKS) were derived from a 44-year-old man with advanced RCC. HANKS-Pr, HANKS-Lu and HANKS-LN were established from the primary lesion and the metastatic lung and lymph node lesions, respectively. The susceptibility of HANKS cell lines to 18 different LAK cells obtained from either patients with urological cancer or from healthy volunteers was studied. The three groups of LAK cells were divided as follows: (A) LAK cells from RCC patients (n = 6); (B) LAK cells from patients with transitional cell carcinoma (TCC)/prostatic carcinoma (CaP) (n = 4) and (C) healthy volunteers (n = 8). A 51Cr-releasing cytotoxic assay was used to determine susceptibility. RESULTS: The mean percentage lysis of the HANKS cell lines to the 18 allogenic LAK cells were 28.1% in HANKS-Pr, 20.2% in HANKS-Lu and 10.4% in HANKS-LN. The susceptibility of HANKS-LN to LAK cells was significantly lower than that of HANKS-Pr and HANKS-Lu in all three groups (P < 0.05). In contrast, the susceptibility of HANKS-Pr was significantly higher than HANKS-Lu in group A only (P < 0.01). CONCLUSION: This is the first report to describe the different susceptibilities of primary RCC and metastatic RCC derived from the same patient. HANKS-LN itself might be the least susceptible to LAK cells because it was not related to the source of LAK cells. Furthermore, RCC may affect the cytotoxicity of LAK cells to HANKS-Pr. These data indicate there are at least two different types of mechanisms leading to the different susceptibilities of HANKS cells to LAK cells.
We studied complexes composed of C1q and beta 2-microglobulin (C1q.beta 2M) or serum amyloid P-component (C1q.SAP) in the sera of 38 patients receiving hemodialysis (HD) and 20 healthy control subjects using an enzyme-linked immunoassay. We also compared complex levels in HD patients with and without symptoms of HD-associated amyloidosis (HA). Serum C1q-beta 2M levels were significantly higher in HD patients without HA than in healthy control subjects and significantly higher in HD patients with HA than in HD patients without HA. Serum C1q.SAP levels were significantly lower in patients with HA than in those without HA. These results suggest that C1q.beta 2M may contribute to HA.
The effects of potassium channel openers NIP-121 ((+)-7,8-dihydro-6,6-dimethyl-7-hydroxy-8-(2-oxo-piperidine-1-yl)-6H- pyrano[2,3-ss]benz-2,1,3-oxadiazole) and levcromakalim were examined in vitro and in vivo. In isolated canine vascular beds, NIP-121 (3 x 10(-9) to 10(-7) M) and levcromakalim (3 x 10(-8) to 10(-6) M) produced a concentration-dependent reduction in the vasoconstrictor responses to U46619. The effects were antagonized by glibenclamide, an ATP-sensitive potassium channel blocker. The maximal relaxation was more than 70% of the maximal vasodilation induced by papaverine (10(-4) M), except in the basilar artery. These compounds had very potent effects on the coronary and cranial mesenteric arteries and saphenous vein. In the coronary perfused rat heart, both compounds (10(-7) M) also increased coronary perfusion flow. The effects were also inhibited by glibenclamide (10(-6) M). In anesthetized dogs, NIP-121 (1 to 10 micrograms/kg (3.2 to 32 nmol/kg), i.v.) and levcromakalim (3 to 30 micrograms/kg (10.5 to 105 nmol/kg), i.v.) dose-dependently increased coronary and renal blood flow. NIP-121 and levcromakalim at higher doses produced the greatest increase in coronary blood flow among the blood vessels examined, in spite of the hypotensive effect. In conclusion, NIP-121 and levcromakalim were similarly selective vasodilators on the canine isolated coronary and cranial mesenteric arteries and saphenous vein, and they selectively increased coronary blood flow in vivo. With respect to increasing the coronary blood flow, NIP-121 had a fourfold greater potency than levcromakalim. This effect might be related to the glibenclamide-sensitive potassium channels.
A 79-year-old bedridden female in whom bilateral small renal calculi were pointed nine months previously, presented with a high fever and non-specific abdominal symptoms. A diagnosis of bilateral renal and ureteral stones causing hydronephroureters with severe infection was made. She was referred to the urology department and treated with extracorporeal shock wave lithotripsy (ESWL). Persistent urinary tract infection caused by urease-producing bacteria, often seen in the bedridden elderly contributes to form infection-induced renal calculi. Such calculi are sometimes found in bilateral kidneys, can grow rapidly, and can often form with few, if any, symptoms. ESWL has been established as noninvasive treatment of choice for the great majority of upper urinary tract stones. All types of stones, including renal staghorn calculi, can be treated by ESWL with endourological support. Recurrence of stones after treatment is expected in approximately 40% of cases. In order to prevent recurrence, the stone should be removed totally and the patients must be observed carefully to keep the urinary tract totally free of infection.