The functional maturation of fetal biological rhythm.
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Biomedical subjects
Publications and source records attributed to T Tamada.
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Ultracytochemical localization of NAD(P)H oxidase activity was demonstrated in the human term placenta by the cerium method. The activity of this enzyme was also compared to those of other oxygen-intermediates-metabolizing enzymes, such as xanthine oxidase, catalase, peroxidase and superoxide dismutase. NAD(P)H oxidase activity was exclusively confined to the apical microvillous membrane of the syncytiotrophoblast. Other enzymes studied showed no activity. We discuss the possibility that NAD(P)H oxidase might play a role in transferring substances between mother and fetus and that this enzyme might modulate placental H2O2 production.
In order to elucidate and characterize the transport pathway of the substances in the amniotic fluid, the permeability of the term human amnion was studied ultracytochemically, with lanthanum or horse radish peroxidase (HRP) as a tracer. Pieces of the term human amnion were exposed to the solutions containing lanthanum or HRP, and processed for electronmicroscopy. Precipitates indicating lanthanum or HRP were observed in the lateral intercellular spaces of the amniotic epithelial cells through the entire depth of the spaces. Generally, pinocytosis of HPR was not observed. In rare cases, however, diffuse uptake of HRP was noticed in the cells of the electron-lucent cytoplasm. These facts indicated that the human amniotic epithelium is quite permeable and that this particular intercellular pathway is important in the mechanism of the transfer of substances between the mother and the fetus.
The relationship between esophageal varices and the azygos vein, which is generally considered to drain the major part of the variceal blood flow, was evaluated by percutaneous transhepatic cineportography in 35 patients with portal hypertension. We classified the patients into three groups. Those patients in whom most of the variceal blood drained into the azygos vein were designated the azygos-type group (n = 18). Those in whom most of the blood flowed into the brachiocephalic venous system were defined as the cervical-type group (n = 5), and those in whom the varices were drained by both the azygos vein and the brachiocephalic venous system were called the combined-type group (n = 12). Highly developed esophageal varices were recognized endoscopically in all patients in the combined-type and cervical-type groups, whereas some of the patients in the azygos-type group had less well-developed varices. In the azygos-type group, a tendency for the varices to be more severe as their drainage into the azygos vein became more cephalad was noted. Evaluation of the drainage of esophageal varices was considered useful not only for obtaining full comprehension of the significance of the azygos vein but also for assessing the suitability for sclerotherapy. Percutaneous transhepatic cineportography was useful for this purpose because it enables visualization of even the most minute amounts of blood flow.
To evaluate the clinical significance of blood flow in the azygos vein and the oxygen partial pressure in azygos venous blood in portal hypertension, we examined 25 patients with liver cirrhosis, 4 with chronic hepatitis, 4 with idiopathic portal hypertension (IPH) and 16 controls by the continuous thermodilution method and azygos venous blood sampling. The azygos venous flow was significantly higher in the patients with chronic liver diseases than in the controls. There was a significant correlation between azygos venous flow and hepatic venous pressure gradient. In the patients with liver cirrhosis, about one half of the azygos venous flow was assumed to represent upward collateral flow, as the azygos venous flow was 3.4% of cardiac output in the controls, 6.3% in the liver cirrhosis patients, and 5.1% in the IPH patients. Oxygen partial pressure in azygos venous blood was higher in patients with portal hypertension, especially in the IPH patients, which indicates that part of splenic flow drains into the azygos vein.
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To investigate the immunological effect of Sizofilan (SPG) combined with radiotherapy, we evaluated the immunological parameters in 22 patients with uterine cervical cancers. Twelve cases were treated with SPG combined with radiotherapy (SPG group), and the other ten cases, with radiotherapy only (control group). As a result, 1) During radiotherapy, the numbers of lymphocyte and CD2 positive cell decreased in SPG and control groups. After radiotherapy, however, its numbers in SPG group became significantly higher than in control group (p less than 0.05). The number of CD3 positive cell also presented a tendency to increase after radiotherapy in SPG group. As for CD20 positive cell, its numbers were kept unchanged after radiotherapy in both two groups, and no significant difference was observed between them. 2) NK cell activity decreased during radiotherapy in both two groups. After radiotherapy, its activity in SPG group recovered to its pre-value and became significantly higher than that in control group (p less than 0.05). 3) SPG did not any prominent effect on CD4/CD8 ratio. 4) The adverse effect of SPG to liver or kidney function were not observed in our patients. The SCC level in SPG group decreased rapidly by radiotherapy as well as that in control group, and no significant difference was observed in SCC levels between them. So it was suggested that SPG did not suppress the cytocidal effect of radiation to cancer cells. Based on these findings, it was concluded that SPG prompted the recovery of not only lymphocyte, especially T cell, but also NK cell activity. These immunological findings presented a usefulness of clinical application of SPG to radiotherapy in patients with uterine cervical cancers.
Efficacy of intraoperative electron beam radiotherapy (IOER) on N-nitrosobis (2-hydroxypropyl) amine (BHP) induced pancreatic carcinomas transplanted into the pancreas of the Syrian golden hamsters were studied and the following results were obtained. 1. Selective electron beam application to the carcinoma transplanted into the pancreas of hamsters was accomplished using an electron beam collimator. 2. Intra-pancreatic transplantability of BHP-induced serially transplantable subcutaneous pancreatic carcinomas was 100%. 3. Intra-pancreatic transplanted pancreatic carcinomas disappeared in 2 out of 19 hamsters (11%) by 10 Gy irradiation and 7 out of 15 (47%) by 20 Gy irradiation given 2 weeks after intra-pancreatic transplantation. 4. In contrast to the linear growth of tumor size in the non-irradiated group, the tumor size showed an electron dose-dependent reduction in the irradiated group. 5. Histologically, marked necrosis was noted in the irradiated group, and the intensity of necrosis differed between the 10 Gy and 20 Gy groups. 6. Direct invasion of tumor to the stomach, small intestine, large intestine, liver and abdominal wall was noted. Its incidence tended to decrease as the electron dose increased (5/19 or 26% for the control group, 4/19 or 21% for the 10 Gy group, and 1/17 or 6% for the 20 Gy group), although the difference was not statistically significant. 7. The incidences of liver and lymph node metastasis were not different between the non-irradiated and the irradiated groups. These results suggest that selective IOER on BHP-induced pancreatic carcinomas has an effectiveness to kill cancer cells in hamsters.
We investigated the usefulness of CA602, a newly developed serum tumor marker, for ovarian cancer. When the cut-off value was set at 60 U/ml, the overall positive rate of this marker in ovarian cancer was 92%, a slightly high rate relative to CA125 measured at the same time (88%). Considering tumor histology, CA602 revealed a high positive rate of 100% in serous adenocarcinoma, whereas the positive rate was 67% in mucinous adenocarcinoma. However, the positive rate was relatively high in benign diseases such as endometrial cysts (64%) and benign ovarian tumors (29%). It is concluded that CA602 is a tumor marker with low specificity and high sensitivity in general. The definite correlation between CA602 and CA125 in ovarian tumors (R = 0.96) suggests that these markers have certain similarities. Thus, CA602 may be a useful serum tumor marker for ovarian cancer as a substitute for CA125.
Intra-tumoral concentrations of pheophorbide-a, a new photosensitizer, were measured by high-performance liquid chromatography after administration of pheophorbide-a to nude mice (BALB/c-nu) that had been implanted with human hepatocellular carcinoma. The results were as follows: 1) 0.009 +/- 0.007 microgram/g tissue in 1 mg/kg body p.o. administration group, 2) 0.22 +/- 0.06 microgram/g tissue in 250 mg/kg body p.o. administration group, 3) 0.85 +/- 0.14 microgram/g tissue in 5 mg/kg body intra-peritoneal administration group, 4) 3.42 +/- 2.84 microgram/g tissue in not-injected side, and 116 +/- 24 microgram/g tissue in injected side of 200 micrograms intra-tumoral administration group. Tumors in each group were irradiated using an Nd:YAG laser (Q-switch; mean power 0.5 W, duration 10 min.). Areas of tumor necrosis were larger than in the control group only in the intra-tumoral administration group. These results suggest that no photodynamic reaction occurs if the intra-tumoral pheophorbide-a concentration is less than 0.85 microgram/g tissue.
The effect on photodynamic therapy (PDT) of using pheophorbide-a as a photosensitizer and Nd: YAG laser (Q-switch) was evaluated. Two hundred micrograms (0.1 ml) of pheophorbide-a was injected into tumors that had been subcutaneously implanted into the backs of nude mice (BALB/c-nu). Interstitial Nd: YAG laser irradiation (Q-switch; mean power 0.5 W, duration 10 min.) was performed 72 hours after pheophorbide-a injection. Forty-eight hours after laser irradiation, the areas of tumor necrosis were measured; these were larger in the group with the injection of pheophorbide-a than in those without. The areas of tumor necrosis after Nd: YAG laser irradiation at a higher mean power (Q-switch; mean power 2 W, control temperature 43-43.5 degrees C, duration 10 min.) were also measured. Again, the areas were larger in the group injected with pheophorbide-a. These results show that the injection of pheophorbide-a and interstitial irradiation using Nd: YAG laser induce a photodynamic reaction, and that this combination is useful in the treatment of deep-seated tumors.
Thirty-five complete arterial occlusions of pelvis and extremity in 29 patients were treated with intraarterial urokinase infusion therapy. In 28 limbs, the occlusions were due to arteriosclerotic change and in 7 lesions, the occlusions were due to Burger's disease. The patients with arteriosclerotic change ranged in age from 52 to 84 years with a mean age of 68 years, and the patients with Burger's disease ranged in age from 35 to 47 years with a mean age of 43 years. There were 24 men and 5 women. The estimated duration of the occlusion was from 5 days to 5 years with a mean duration of 11 months. The length of the occluded segments ranged from 1 to 45 cm with a mean length of 13.9 cm. The occlusion was located in the iliac artery in 13 patients, the femoral artery in 11 patients, both the iliac and the femoral artery in 2 patients, the popliteal artery in 5 patients, the femoro-popliteal artery in 1 patient, the brachial artery in 2 patients and the radial artery in 1 patient. The infusion catheter was gently advanced into the proximal portion of the clot over a flexible guide wire, and urokinase was infused at a rate of 5000-10000 IU/min, as a short term high dose infusion (SHI), until antegrade blood flow was reestablished. The catheter was then withdrawn to a point proximal to all of the remaining clot, and the infusion rate was reduced to 10000-20000 IU/h as a continuous low dose infusion (CLI). After thrombolytic recanalization, a percutaneous transluminal angioplasty (PTA) was performed in those cases which demonstrated a residual narrowing of the lumen. The initial success rate was 86%. Reocclusions were observed in 5 lesions (17%) and a second recanalization was successful in 2 of 3 patients. The 1-year cumulative patency rate following recanalization was 88.4% and the 2-year patency rate was 78.6%. No significant complications directly related to the procedure were observed. SHI combined with CLI and PTA appears to be an effective and safe therapy for chronic long segmental arterial occlusion.
We took advantage of routine hemodynamic examinations to determine the relationship between splenic and intestinal circulation by infusing prostaglandin E1 into the superior mesenteric artery and observing the portal hemodynamic changes in patients with chronic liver disease. Relative blood flow rate in various vessels of the portal system were measured percutaneously using an ultrasonic duplex system, while portal venous pressure was measured directly using a transducer. The superior mesenteric venous blood flow increased significantly as did the portal venous blood flow and pressure, though the degree of change of portal venous blood flow was less than was expected from the change of portal venous blood flow in the superior mesenteric venous blood flow. Splenic venous blood flow decreased significantly. This decrease is perhaps due to a mechanism that acts to compensate for the increase induced in the superior mesenteric venous blood flow to maintain portal flow at approximately the same level. The measured changes suggest a relationship between splenic and intestinal blood flows that is regulated according to the hepatic circulatory condition. The regulatory mechanism should be considered when designing the treatment of portal hypertension.
The efficacy of sialyl SSEA-1 antigen (SLX), a tumor-associated carbohydrate antigen, as a test for gynecological cancer was investigated. The test was found to be positive in 64.5% of all patients with ovarian cancers; this rate is lower than that obtained with CA 125. On the other hand, relatively few false-positive results were observed. Tests were false-positive in 25.0% of patients with endometrial cysts; 25.0% of women in the first trimester of pregnancy and 0.0% of menstruating woman had false-positive results. These percentages were lower than those for CA 125. It is concluded that SLX is a tumor marker with inferior sensitivity and high specificity, compared with CA 125. Since positive tests with SLX in patients with ovarian cancer mostly overlapped the positive tests for CA 125, the usefulness of a combination assay was considered to be low. The SLX test was positive in 18.6 and 25.0% of patients with cervical cancer and endometrial cancer, respectively, and it was concluded that SLX is useless as a serum tumor marker for uterine cancer.
The thymidylate synthase (TS) content of tumor tissue was assayed and the levels of 5-fluorouracil (5-Fu) in serum and tumor tissue were determined in 21 patients with cervical cancer who were treated with UFT, a fluorinated pyrimidine. Subrenal capsule assay, a predictive tumor sensitivity test, was conducted concurrently on cervical tumor samples. TS inhibition and serum and tissue 5-Fu levels widely varied between both samples. Investigation of the relationship between the tumor growth inhibition rate determined by subrenal capsule assay and the above parameters (TS inhibition, serum and tissue 5-Fu levels) showed that TS inhibition and tumor growth inhibition were well correlated (r = 0.73). This suggests that a TS inhibition assay in tumor tissue can be a useful predictive test for tumor sensitivity of fluorinated pyrimidines.
A biliary endoprosthesis constructed of self-expanding metallic "Z" stents was placed in 23 patients with obstructive jaundice. The biliary obstruction was due to a malignant neoplasm in 21 patients and a postoperative biliary stricture in two patients. The lesions affected the intrahepatic biliary ducts in 13 patients. Twelve patients had undergone radiation therapy before stent placement. The endoprostheses consisted of 196 expandable metallic biliary stents placed singly (n = 10) or in tandem (n = 186). As many as 18 stents were used to relieve an obstruction in one patient. A transhepatic approach was employed in all patients except one in whom stents were placed through a T-tube tract. Within 1 week after placement, all stents expanded to at least 90% of their original diameter. Three misplaced, two deformed, and two dislodged stents caused no obvious clinical problems. At follow-up, which ranged from 2 to 59 weeks, five patients experienced recurrent jaundice. Two patients with recurrent jaundice due to obstruction of the bile duct containing the stent were treated with external catheter drainage. The expandable biliary endoprosthesis is suggested as an effective treatment for benign and malignant biliary obstruction.
We investigated, by case-control study, the relevance of psychosocial factors on the prevalence of acute ischemic heart disease (IHD) in middle aged Japanese men. We questioned 109 acute IHD patients and 80 individuals in an age-adjusted sampled control group. Multiple logistic regression analysis showed the following statistically significant factors: hypertension (odds ratio 4.01, p less than 0.001), Type A behavior pattern (2.25, p less than 0.05) and high job demand (2.23, p less than 0.02). No direct influence of family function or social support to the prevalence of acute IHD was apparent. These results suggest that, among men in Japan, Type A behavior pattern and high job demand represent psychosocial risk factors of IHD. Due to the case-control protocol, causal relationships cannot be decided. The limitation of the study design is discussed within that context.
We examined the 1H-NMR spectra of the lipid region of human plasma according to the method of Fossel et al. as the specific blood test for cancer. The study group included 20 patients with hepatocellular carcinoma (HCC), 10 patients with liver cirrhosis (LC) and 10 normal controls (NC). We measured the linewidths of methyl and methylene resonances of lipoprotein lipids at a proton resonance frequency of 400 MHz using a JNM GX400 FT NMR spectrometer. The mean linewidth values and the standard deviation of methyl were as follows: 41.3 +/- 7.2 Hz (NC), 34.8 +/- 6.9 Hz (LC), 29.6 +/- 5.7 Hz (HCC). There was thus a significant difference between NC and HCC. On the other hand, there was no significant difference between the three groups in the case of methylene. Although the spectrum in the HCC and LC groups had a blunt head but narrow body, that of the NC group had a pointed head but wide body, and the linewidth values thus showed wide dispersion. This difference in spectral patterns between the two groups was characteristic. Linewidth values, however, did not correlate well with the laboratory data.