[Growth and alkaloid production of Datura tissue cultures].
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Biomedical subjects
Publications and source records attributed to M Tabata.
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A flow injection chemiluminometric assay for urea has been developed based on a minicolumn bioreactor packed with immobilized enzyme-bearing glass beads. The reactor contains immobilized urease, L-glutamate dehydrogenase and L-glutamate oxidase, aligned in this order (upstream to the downstream). When the sample is introduced into the bioreactor, urea is first hydrolysed by urease to produce ammonia, which is then converted into L-glutamate by L-glutamate dehydrogenase. L-Glutamate is finally oxidized by L-glutamate oxidase to produce hydrogen peroxide, which is quantified by measuring chemiluminescence emitted upon admixing with luminol and potassium ferricyanide. One assay cycle is completed within 1 minute. The method is sensitive (detection limit 0.5 nmol) and is linear in the range 0-30 mmol/l. It can be readily applied to the determination of urea in human serum, and requires no blank corrections for ammonia and/or L-glutamate present in serum samples.
To clarify the clinical significance of the status of surgical margins, especially the dissected margin in the transverse direction, a clinicopathologic study was performed on 60 patients with carcinoma of the bile duct who underwent radical resection. The patients in group A (n = 28) had no cancer invasion within 5 mm of the dissected margin in the transverse direction. They had a higher incidence of the well differentiated type of carcinoma and a lower incidence of lymph node metastasis and microscopic tumor extension than the patients in group B. Group B (n = 32) included patients with cancer involvement within 5 mm of the dissected margin in the transverse direction. Some group A patients were found to have advanced carcinoma of the lower bile duct, but they were the only ones whose lesions were at an early stage (e.g., lesion restricted to subserosal involvement or less) among those with carcinoma of the hepatic duct and the upper and middle bile ducts. Local recurrence was found to occur more frequently as the tumor approached the liver, and the incidence of local recurrence was significantly higher in patients in group B than in group A (75.0% versus 28.5%). These results indicate that patients with cancer invasion within 5 mm of the surgical margin develop early recurrence of tumor even after conventional radical resection and that further radical dissection of the hepatoduodenal ligament with hepatectomy or pancreatoduodenectomy may be required to improve survival for these cases.
We treated 65 patients with carcinoma of the hepatic duct confluence between 1976 and 1991, 57 (87.7%) of whom were treated surgically; of the 57, 55(96.5%) underwent resection. Radical resection was performed at a rate of 50.9%. Procedures for these 55 patients included resection of the extrahepatic bile duct plus hepatectomy (n = 33; 60.0%), and resection of the duct without hepatectomy (n = 22; 40.0%). In addition, the caudate lobe was resected in 28 of these patients, and the portal vein, hepatic artery, or both were resected in 6. The overall operative morbidity was 21.8%; morbidity occurred in 33.3% of patients with hepatectomy, a significantly higher percent than the 4.5% rate in those without hepatectomy (p < 0.05). Operative death occurred in only 1.9%. As the depth of cancer invasion in the bile duct wall advanced, the incidence of tumor spread (e.g., lymphatic permeation, venous invasion, perineural invasion, lymph node metastasis) increased significantly. The prevalence of extramural tumor extensions in a transverse direction was higher than that in the longitudinal direction along the bile duct wall; and the distance from the margin of the primary tumor to the site of tumor extensions along the bile duct wall was much longer on the hepatic side than on the duodenal side. Cancer invasion of the caudate lobe was observed in 36.4%, and invasion at the surgical margins was found more frequently in those without hepatectomy than those with hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Based on the histological findings of 1,686 resected cases of gallbladder carcinoma and operative results collected from 172 major hospitals in Japan, the present status of radical operation was assessed with respect to the relationship between the depth of carcinoma invasion and the operative results. The depth of carcinoma invasion was classified into 5 groups, i.e., limited to the mucosal layer (m) in 11.9%, advanced to the proper muscle layer (pm) in 9.8%, extending to the subserosal layer (ss) in 29.6%, serosal involvement (se) in 21.8%, and carcinoma invading the adjacent organs (si) in 26.9%. Tumor extension, such as lymph node metastasis, invasion of lymphatic and venous vessels, and perineural infiltration, were observed more frequently in patients with ss, se, and si than in those with m and pm. The cumulative 5-year survival rates were 82.6% and 72.5% in patients with m and pm, which were significantly higher than 37.0%, 14.7%, and 7.5% in those with ss, se, and si, respectively. The choice of operative procedures should depend on the depth of carcinoma invasion. Cholecystectomy alone is done only in patients with tumor limited to the mucosa, and more radical procedures such as extended cholecystectomy should be performed in those with carcinoma invasion beyond the mucosa. Pancreatoduodenectomy is indicated in those with lymph node metastasis posterior to the head of the pancreas and with invasion to the duodenum. When the tumor directly invades the liver, major hepatic resection is recommended.(ABSTRACT TRUNCATED AT 250 WORDS)
The pineal organ and its secretory product melatonin are regarded as synchronizers of daily rhythms to the external light/dark (LD) cycle. In fish, the pineal organ acts as a direct photoreceptor, transducing light information into neural and humoral (melatonin) signals. In the present study, we investigate a possible role for the pineal organ and melatonin in the regulation of feeding rhythms of rainbow trout, Oncorhynchus mykiss. We used individual rainbow trout placed in an insulated room at constant temperature (14 degrees C). Fish were self-fed ad lib by means of self-feeders coupled to a computer that continuously recorded demand-feeding activity. Before and after pinealectomy, the fish were exposed to a LD cycle of 16:8 h and then constant light (LL) to test the effect of pinealectomy on demand-feeding rhythms. Feeding records revealed that trout fed exclusively during daytime (96% of feeding confined to the light phase), and that removal of the pineal organ did not disrupt this daily feeding profile, with synchronization to the LD cycle persisting. Moreover, the appearance of circadian feeding rhythms was not affected by pinealectomy: most of the operated fish free-ran with an average tau longer than 24 h. Plasma melatonin rhythms persisted in the pinealectomized trout, but with small amplitude. These results suggest that the pineal may not be the site of the pacemaker that controls feeding rhythms in trout, although further research is required to study the involvement of other photoperiod-transducing systems and melatonin (of nonpineal origin) in the regulation and expression of circadian rhythms in this species.
Recently we have been performing S4a + S5 with total resection of the caudate lobe (S1) by using a dome-like dissection along the root of the middle hepatic vein at the pinnacle, which we refer to as the Taj Mahal liver parenchymal resection, for carcinoma of the biliary tract. This procedure offers the following advantages: (1) It allows total resection of the caudate lobe, including the paracaval portion (S9), and (2) because the cut surface of the liver is large, it allows intrahepatic jejunostomy to be performed more easily with a good field of view. The indications for this procedure include hilar bile duct carcinoma, gallbladder carcinoma, and choledochal cyst (type IVA). Because of the high rate of hilar liver parenchyma and caudate lobe invasion associated with hilar bile duct carcinoma, the liver must be resected. The Taj Mahal procedure is indicated in cases where extended liver resection is impossible. The dissection limits of this procedure are, on the left side, the B2+3 bifurcation at the right margin of the umbilical portion of the portal vein and, on the right side, the B8 of the anterior branch and the B6+7 bifurcation of the right posterior branch. This procedure could also be described as a reduced form of extended right hepatectomy and extended left hepatectomy. For gallbladder carcinoma, this procedure is indicated to ensure an adequate surgical margin and eradicate transvenous liver metastasis, particularly in cases of pT2 lesions. Hilar and caudate lobe invasion also occurs in liver bed-type gallbladder carcinoma, and bile duct resection and caudate lobe resection are required for the surgery to be curative. We performed this procedure in four cases of hilar bile duct carcinoma, five cases of gallbladder carcinoma, and one case each of choledochal cyst (type IVA) with carcinoma of the bile duct and gallbladder adenomyomatosis. Curative resection was possible in all except the patient with adenomyomatosis, and all of the patients are alive and recurrence free 10 to 37 months postoperatively. This procedure, in addition to preserving liver function, provides a wide field of view and facilitates reconstruction of multiple intrahepatic bile ducts. Thus it can be said to be a curative operation not only in patients considered high risk but also in those whose hilar bile duct carcinoma is limited to the bifurcation area (Bismuth type IIIa and IIIb) and in gallbladder carcinoma up to pT2 with slight extension on the hepatic side.
A pharmacological comparison between the enantiomers, shikonin (R) and alkannin (S), was made with regard to their inhibitory effects on the increased capillary permeability and thermal edema in rats, using phenylbutazone as a positive control in both models. The results of experiments have shown that there is no significant difference in the anti-inflammatory activity between the two compounds.
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The fruit juice of Ecballium elaterium, used as a folk medicine in Turkey for the treatment of sinusitis, was investigated for its anti-inflammatory activity in mice. Fractions obtained from the juice were tested in mice for their effects on increased vascular permeability, as induced by HOAc ip. The active principle was isolated from the CHCl3 extract as well as the H2O-insoluble part of the fruit juice and identified as cucurbitacin B. This is the first report that cucurbitacin B has a significant anti-inflammatory activity.
A follow-up study was conducted from 1967 to 1987 for patients diagnosed as having itai-itai disease, subjects who were suspected of having the disease, and controls. Ninety-five subjects per category were selected after matching for age, sex, and residential area. The cumulative survival rate of the patients who had a definite diagnosis of itai-itai disease was significantly lower than that of the control group in every period after the first 3 y. The cumulative survival rate of the subjects who were suspected of having itai-itai disease and who had severe renal dysfunction due to cadmium pollution was significantly lower than that of the control group. These results demonstrate (1) the enduring negative influence of itai-itai disease on prognosis and (2) that the cadmium pollution-induced renal disorder adversely affects the health of the inhabitants of a cadmium-polluted area.
A 9-y follow-up study of 3,178 persons who lived in a cadmium-polluted area was conducted to assess the influence of environmental cadmium exposure on long-term outcome. The standardized mortality ratios of the urinary beta 2-microglobulin-positive subjects (> 1,000 micrograms/g creatinine) of both sexes were higher than those of the general Japanese population, whereas the cumulative survival curves were lower than those of the urinary beta 2-microglobulin-negative group. A significant association was also found between urinary beta 2-microglobulin and mortality, using a Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary beta 2-microglobulin excreted. These results suggest that the prognosis for cadmium-exposed subjects with proximal tubular dysfunction is unfavorable. The mortality rate tended to become higher as the severity of renal dysfunction progressed.
The aim of the present study was to analyse bile samples from cases with gallstones by high performance liquid chromatography according to the type of stones present, with special reference to the glucoside and xyloside conjugates of bilirubin, and to investigate their deconjugation. The composition of bilirubin conjugates in bile was similar between cholesterol and black pigment stones except that the total bilirubin concentration was about 5 times higher in black pigment stone cases with haemolysis. Unconjugated bilirubin was higher in brown pigment stone cases than in cholesterol stone cases, although total bilirubin concentration was lower in the former. In addition, in brown pigment stone cases, bile contained statistically less bilirubin diglucuronide and more bilirubin diglucoside and monoglucoside than in bile with cholesterol stones (P less than 0.05). Glucoside and xyloside conjugates are also major components, regardless of the types of gallstones present, accounting for as much as 18 to 25%. Incubation experiment revealed that bilirubin diglucuronide was more readily deconjugated than bilirubin diglucoside or bilirubin monoglucoside monoxyloside. Therefore, glucuronide conjugates were likely to be the main source of unconjugated bilirubin in the formation of pigment gallstones.
Effects of nucleotides and cations on 2-[125I]iodomelatonin binding sites in the goldfish brain were examined. Nucleotides (10(-6)-10(-3) M) dose-dependently inhibited the specific binding with the following order of potency: guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) > GTP = GDP > GMP = ATP > cyclic GMP. Cyclic AMP was ineffective. The treatment of membranes with GTP gamma S induced rapid dissociation of 2-[125I]iodomelatonin from membranes when added at the steady state, increased the Kd and decreased the Bmax values as revealed by saturation analysis, and increased the IC50 value of melatonin to inhibit the specific binding. The treatment decreased the specific binding to membrane preparations obtained from six brain regions as well. Inorganic salts (5-200 mM) dose-dependently inhibited the specific binding with the following order of potency: CaCl2 > MgCl2 > LiCl > NaCl > choline chloride > KCl, except for 5 mM MgCl2, which enhanced the specific binding. Saturation experiments demonstrated that 75 mM CaCl2, 100 mM MgCl2 and 200 mM NaCl increased the Kd and decreased the Bmax while 5 mM MgCl2 increased the Bmax value. These results imply that G protein and physiological concentrations of cations are involved in the regulation of melatonin binding sites in the goldfish brain.
Photic and circadian regulations of melatonin rhythms in the pineal organ and the retina of several teleosts were studied to investigate the regulatory mechanisms of melatonin rhythms in fishes. In the eyecup preparations of the goldfish, Carassius auratus, both time of day and lighting conditions affected melatonin production, with high melatonin production observed only in the dark-treated group incubated during the 'subjective' night. Thus, in the goldfish retina, local photoreceptors and an ocular circadian clock seem to regulate melatonin production, as in the zebrafish retina and in the pineal organ of a number of teleosts, including the goldfish. However, this circadian regulation of melatonin rhythms is not universal among fishes. Although the superfused pineal organ of the masu salmon Oncorhynchus masou secreted melatonin in a rhythmic fashion under light-dark (LD) cycles, the rhythm disappeared under constant darkness (DD), as in the rainbow trout, with a large amount of melatonin released both during the subjective day and the subjective night. These results suggest that all salmonids lack circadian regulation of melatonin rhythms. Furthermore, when ocular melatonin rhythms were compared in two cyprinids, the ugui Tribolodon hakonensis and the oikawa Zacco platypus occupying different ecological niches, ocular melatonin contents exhibited daily variations, with higher values during the dark phase of LD cycles in both species. The rhythmic changes persisted in the ugui under DD, with higher levels at subjective midnight than at subjective midday; however, ocular melatonin levels in the oikawa were consistently high under DD. Thus, the circadian regulation of melatonin rhythms in fishes is influenced not only by phylogeny, but also by the ecological niches of the animals. These results suggest that the physiological functions of melatonin in the circadian and photoperiodic systems differ among fishes.
BACKGROUND: We investigated the feasibility and efficacy of high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide (HD-ICE) facilitated by autologous peripheral blood progenitor cell transplantation (ABPCT) for the treatment of small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eleven patients aged 44 to 63 years old (5 with extensive disease [ED] and 6 with limited disease [LD]) were entered into this study. Induction chemotherapy consisted of 3 to 4 cycles of cisplatin and irinotecan for ED-SCLC, and cisplatin and etoposide for LD-SCLC. Patients with LD-SCLC received concurrent chest radiotherapy along with the first cycle of induction chemotherapy. After induction therapy, peripheral blood progenitor cells (PBPC) were collected following G-CSF administration during a recovery phase from high-dose etoposide (1,500 mg/m2). Eight patients (4 with ED and 4 with LD) with adequate organ function were treated with HD-ICE (15 g/m2 ifosfamide, 1,200 mg/m2 carboplatin and 1,500 mg/m2 etoposide) followed by ABPCT. RESULTS: Hematologic recovery was rapid and non-hematological toxicities were acceptable without treatment-related mortality. In ED-SCLC, all of the 4 patients achieved complete response (CR) or near CR but developed a relapse of the disease. In LD-SCLC, 2 of 4 patients with LD-SCLC are alive in continuous CR for 18 and 21 months after the beginning of induction therapy. CONCLUSIONS: Despite a limited number of patients and short follow-up time, these preliminary results indicate that marrow-ablative therapy (HD-ICE) supported by ABPCT is feasible in the treatment of elderly patients with LD- and ED-SCLC.