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Biomedical subjects

T Amano

Publications and source records attributed to T Amano.

At least 271 records · Page 15Linked to original sources
PubMed1988

Photodynamic effect in an experimental bladder tumor treated with intratumor injection of hematoporphyrin derivative.

Photodynamic therapy (PDT) is an experimental treatment modality for malignant tumors. It is based on the principle that a photosensitizer, such as hematoporphyrin derivative (HPD), is retained in higher concentrations in tumors than in surrounding nonmalignant tissues and that photoactivation of the sensitizer can be used to evoke tumor destruction. However, retention of the systemic injection of HPD is not limited to malignant tissues. This lack of specific tumor localization thus reduces the therapeutic ratio of the treatment and causes skin photosensitivity and possible systemic toxicity. Injection of HPD directly into the tumor, on the other hand, has been shown to yield higher levels of the drug in the tumor and lower levels in normal tissues, in comparison with systemic administration. In this study, we examined the photodynamic effect on s.c. implanted mouse bladder tumors subjected to intratumor (i.t.) and i.p. HPD injections. Tumor cell killing, measured by cell survival, was observed in both the it. and i.p. groups and was dependent on fluence and HPD dosage. However, no significant enhancement of cell killing was observed in the i.t. injected tumors, despite the higher porphyrin levels in these tumors. Histological examination of the effect of PDT on the blood vessels indicated that while cell death accompanied severe hemorrhage in the i.p. injected tumors, in the i.t. tumors there was much less hemorrhage and intact blood vessels remained. This observation suggests that with i.t. administration, direct photodynamic action may play a significant role in the tumor cell killing, in contrast to systemic administration, in which destruction of the blood vessels is believed to be the main cause of tumor destruction.

Animals↗
PubMed1988

Physiological inducers of the acrosome reaction.

This article reviews recent studies on physiological inducers of the acrosome reaction in starfish. Upon encountering the jelly coat of eggs, starfish sperm undergo the acrosome reaction in response to a cooperation of three jelly components: a sulfated glycoprotein named acrosome reaction-inducing substance (ARIS), a group of steroidal saponins named Co-ARIS, and an oligopeptide presumably having an activity to increase the intracellular pH of sperm. ARIS induces the acrosome reaction in high Ca2+ or high pH sea water. In normal sea water, both ARIS and Co-ARIS are required for the induction. In addition to ARIS and Co-ARIS, a third jelly component, the oligopeptide, is necessary to mimic the full capacity of the jelly coat to induce the acrosome reaction. ARIS and Co-ARIS cooperatively increase the intracellular Ca2+ by stimulating Ca2+ channels, while the oligopeptide increases the intracellular pH by stimulating Na+/H+ exchange systems. When sperm meet the eggs, both changes are simultaneously achieved in them and thus they undergo the acrosome reaction.

Acrosome↗
PubMed1988

Intratumor injection as a more effective means of porphyrin administration for photodynamic therapy.

Photodynamic therapy (PDT) with hematoporphyrin derivative (HpD) as the photosensitizer is a promising new cancer treatment. The major drawback of this procedure is the resulting skin photosensitivity. Patients must remain in subdued light for four to six weeks to avoid cutaneous phototoxicity. In this study, we examine the possibility of reducing the skin photosensitization while maintaining the tumor phototoxic effect by administering the drug directly into the tumor. A subcutaneously implanted mouse bladder tumor (MBT-2) was used. HpD was administered either intraperitoneally (I.P.; 20 mg./kg. b.w.) or by intratumor injection (I.T.; 0.4 mg./cc tumor). The concentrations of HpD in tumor and various tissues (skin, muscle, liver, spleen, kidney, bladder and whole blood) were analyzed at various times after the injection, by 3H-HpD method and by a fluorometric method. Results indicated that at three to 96 hours after the administration, porphyrin levels in tumor were about three to 15 times higher by I.T. than by I.P. injection, while the concentrations in skin and other tissues were 1.3 to 10 times lower. Consequently, at 24 hours after injection ratios between tumor to skin porphyrin were 14 to 92 times higher for I.T. than I.P. injection. Higher porphyrin levels in tumor and lower in normal tissues would indicate lower skin photosensitivity, systemic cytotoxicity and possible greater tumor photosensitivity. This method of porphyrin administration may be useful for the PDT of certain single lesions that are accessible for direct injection.

Animals↗
PubMed1988

Hepatoma formation in ddY mice with chronic schistosomiasis japonica.

Three hundred and ninety-five four-week-old SPF female ddY mice were each exposed to 5 or 6 cercariae of Schistosoma japonicum (Japanese strain) on their shaved abdomens and were maintained in a conditioned clean environment and fed on sterilized food and water. Fecal examinations at 8 to 10 weeks postinfection (PI) revealed 169 mice to be infected. More than half of them died within 30 weeks PI and 70 mice that survived to the 50th week PI were sacrificed. At autopsy, we could find no schistosome eggs in the liver or intestinal wall of 9 mice, and they were excluded. Out of 61 mice which showed S. japonicum eggs in their livers, 48 had single or multiple hepatoma, while no tumor was observed in the livers of the 60 control mice. The tumors were yellowish-white in color with distinct boundaries and the centers of the tumors were depressed in some cases. The size of the tumors varied from 1 to 20 mm in diameter. Most of the tumors retained the normal trabecular pattern, but in some cases the trabeculae were thickened, having wide vascular spaces. The tumor cells were PAS-negative and showed varieties of pleomorphism. The sizes of cells and nuclei varied greatly. These findings suggested some causal relationship between S. japonicum infection and the hepatoma formation in the host's liver. In the chronic course of schistosomiasis japonica in the endemic areas, S. japonicum infection probably plays a role in hepatoma formation of patients.

Animals↗
PubMed1988

Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats.

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.

Animals↗
PubMed1988

[3H]GBR-12935 binding sites in human striatal membranes: binding characteristics and changes in parkinsonians and schizophrenics.

The binding of the diphenyl-substituted piperazine derivative, [3H]GBR-12935, a selective dopamine uptake inhibitor, to the post-mortem human putamen was studied. Inhibition curves by dopamine uptake inhibitors suggested the existence of two populations of [3H]GBR-12935 binding sites: one is potently inhibited by mazindol and/or nomifensine, and the second binding site is benztropine- and/or GBR 12909-sensitive. In the human putamen, [3H]GBR-12935 labeled both these two distinct binding sites. The [3H]GBR-12935 binding displaced by mazindol was enriched in the mouse and rat striatum, but not in the cultured mouse neuroblastoma cell N1E-115. The mazindol-sensitive [3H]GBR-12935 binding site increased in the presence of sodium and markedly decreased in the putamen from parkinsonians (45% of controls). On the other hand, the [3H]GBR-12935 binding displaced by benztropine showed no sodium-dependent increase and was not decreased in the putamen from parkinsonians. In the putamen from schizophrenics, the [3H]GBR-12935 binding did not significantly change in the density, while that displaced by mazindol tended to increase. It is concluded that in the human putamen, [3H]GBR-12935 binds to two distinct sites. One site is partially sodium-dependent and appears to be associated with a high-affinity dopamine uptake system on dopaminergic nerve terminals. The second binding site shows no sodium-dependency and may be associated with a nondopaminergic and/or extraneuronal DA uptake system.

Aged↗
PubMed1988

[Carcinoma of Papilla Vater with celiac axis stenosis--application of percutaneous transluminal angioplasty].

In a case of carcinoma of Papilla of Vater with angiographically proved celiac axis stenosis, PTA (Percutaneous transluminal angioplasty) was performed to restore sufficient blood flow, followed by standard pancreaticoduodenectomy. This would be the first case to have PTA applied to the cancer-bearing celiac axis stenosis. The patient was 58 year old female, presented with acute abdominal pain and vomiting. DIC revealing protruding defect in the choledochus and hypotonic duodenography showed elevated tumor at Papilla of Vater. Aortography revealed 75% circumferential stenosis at the celiac artery and superior mesenteric angiography visualized all the branches of the celiac axis via dilated pancreaticoduodenal arcades. PTA with Grüntzig Dilaca (4.3Fr), 5 atm for 60 seconds serially every two min for 4 times was performed with the immediate relief of the stenosis down to 25%. Intraoperatively 70-80ml/sec flow confirmed, pancreaticoduodenectomy was done without sacrificing curability. PTA would be superior strategy to restore sufficient blood flow in cases with GI anastomoses, compared with other bypass or reimplantation surgery.

Ampulla of Vater↗
PubMed1988

[Effects of OK-432 on UFT activation].

An experiment to gauge the effect of OK-432 on UFT activation under a combined administration of UFT and OK-432 at a therapeutic dose has been pursued clinically by determining the blood and intratumoral 5-FU concentrations after administration of UFT. UFT was administered orally to a group of AH-130-bearing rats at a dose of 12 mg/kg or 8 mg/kg. In another group that was given combined treatment with OK-432, the OK-432 was administered subcutaneously at a dose of 0.1 KE/kg together with UFT. The intratumoral 5-FU concentration at 4 hours after UFT 12 mg/kg administration showed higher values in th single UFT treated group than in the combined treated group, but at 8 hours no significant difference was found between these two groups as the concentrations were 0.133 +/- 0.027 microgram/g and 0.128 +/- 0.021 microgram/g, respectively. Further, no significant differences were noticed in the blood and intratumoral 5-FU concentrations between both groups after administration of UFT at a dose of 8 mg/kg. Clinically, the blood FT-207 and 5-FU concentrations after UFT administration showed no significant difference between the single UFT treated group and the combined OK-432 treated group, nor was there a significant difference in the intratumoral concentration. In summary, it is considered that OK-432 has little effect on UFT activation when UFT and OK-432 are administered in combination.

Administration, Oral↗
PubMed1988

[Lymphatic flow of the remnant stomach].

Aiming at establishing an appropriate lymph node dissection for carcinoma of the remnant stomach and of the lower esophageal carcinoma in the status post-gastrectomy, lymphatic flow was investigated clinically as well as experimentally. Nineteen cases of carcinoma of the remnant stomach and 8 cases of esophageal carcinoma after partial gastrectomy were studied. Lymph node metastasis of the remnant stomach carcinoma were more frequently seen at perigastrium, splenic hilum, and along splenic artery. Those further extended to para-aortic and diaphragmatic nodes. Three cases of lower esophageal carcinoma after gastrectomy had massive nodal involvement at perigastrium, as well as intra-thoracic lymph nodes. Experimentally 5-Fu emulsion was injected submucosally under endoscope in 25 dogs and subserosally in 6 rabbits. 5-Fu contents in lymph nodes were measured 30 minutes after injection. The most prominent difference in lymphatic flow from the remnant stomach was increase in ascending flow into intrathoracic lymph nodes through para-aorta. This increment was seen irrespective of Billroth I or II anastomosis. On the contrary, descending lymphatic flow from the lower esophagus into the intra-abdominal lymph nodes was not disturbed by gastrectomy. Cardiac lymph node dissection in rabbits accelerated ascending flow. Those results would indicate the necessity of complete block of ascending flow in cases of the remnant stomach carcinoma and of intra-abdominal lymph node dissection in those of the lower esophageal carcinoma after gastrectomy.

Aged↗
PubMed1988

[Chemosensitivity studies of urological malignancies].

Chemosensitivity tests to anticancer agents using human tumor clonogenic assay (HTCA), novel dye exclusion method (NDE assay), sub-renal capsule assay (SRCA), and chick embryo method (CE method) were utilized to measure the sensitivity of urological malignancies. Surgical tumor specimens from 67 patients with urological malignancies were subjected to HTCA developed by Hamburger and Salmon. An appreciable growth of colonies was obtained in 20 out of 33 renal cancers, 20 out of 30 urothelial cancers and 1 out of 4 testicular tumors examined and colonial growth adequate for chemosensitivity was obtained in 30 of the 67 patients. More than 70% decrease in the plating efficiency after anticancer drug exposure according to Von Hoff's definition, or more than 1.0 value of the "in vivo -in vitro therapeutic index" in terms of the ratio of IC90 to the peak plasma concentration of the drug tested was defined as susceptible. According to Von Hoff's definition, susceptibility to vinblastine (VBL) and cis-dichlorodiammine platinum (CDDP), was seen in 4 out of 11 patients with renal cancer, in 4 out of 15 patients with urothelial cancer and 1 out of 4 patients with renal cancer, respectively. With adriamycin (ADM) it was seen in 3 out of the 15 patients with urothelial cancer, 2 out of 10 patients with renal cancer and 1 patient with testicular tumor. According to TI, susceptibility to VBL was seen in 3 out of 7 patients with renal cancer, and with CDDP it was seen in 2 out of 12 patients with urothelial cancer, and 1 out of 2 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effects of the new calcium antagonist 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate on cerebral circulation in cats.

Effects of CD-349 (2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate) on cerebral circulation were studied in 10 cats. The cats were fixed in a stereotactic head-holder, and two burr holes were made at 3-mm intervals over the left parietal cortex. Through one cranial window, the pial artery and vein diameters were measured continuously by a newly developed videocamera system in conjunction with a width analyzer, and the other one was used for measurement of cerebral blood volume (CBV). The pial artery (141 +/- 14 micron) was dilated by 16.6 +/- 4.9% (p less than 0.01) 1 min and 24.8 +/- 5.1% (p less than 0.01) 5 min after the CD-349 injection. The pial vein (101 +/- 20 micron) was also dilated with the percent increase of the diameter being 11.4 +/- 4.0% (p less than 0.01) 1 min and 11.3 +/- 4.9% (p less than 0.05) 5 min after the CD-349 administration. The CBV was also increased. The mean arterial blood pressure was decreased by 39.8 +/- 7.3 mmHg (p less than 0.01) 1 min and 34.4 +/- 5.5 mmHg (p less than 0.01) 5 min after drug injection. Thereafter, the blood pressure gradually returned to the pre-drug level. Form these results it is suggested that CD-349 exerts direct vasodilatory action via inhibition of calcium influx across vascular cell membranes into cerebral vessels.

Animals↗
PubMed1987

Expression of beta-nerve growth factor mRNA in rat glioma cells and astrocytes from rat brain.

A 50-base synthetic oligodeoxynucleotide complementary to a portion of mouse nerve growth factor (NGF) mRNA was used as a probe for analysis of the expression of NGF gene. Northern blot analysis showed the presence of a major 1.3 kb transcript, which was identical in size to mouse NGF mRNA, in both C6Bu1 cells and rat astrocytes cultured from newborn rat brain. Further, the rearrangement of DNA sequence in and around the NGF gene locus of C6Bu1 cells was not detected by Southern blot analysis. These results indicate the expression of NGF mRNA in both C6Bu1 cells and astrocytes from rat brain, suggesting that astrocytes may produce NGF protein in the rat brain, especially in developing rat brain.

Animals↗
PubMed1987

Optical monitoring of excitatory synaptic activity between cultured hippocampal neurons by a multi-site Ca2+ fluorometry.

The fluorescence intensities from cultured hippocampal neurons loaded with a Ca2+-indicator (fura-2), showed spontaneous, periodical oscillations, which were synchronized among the cells. Tetrodotoxin or 2-aminophosphonovalerate, a glutamate-receptor antagonist, blocked the oscillation. The rising phase of the fluorescence was accompanied by a burst of inward currents, as monitored by a patch electrode. It is thus suggested that the fluorescence elevation represents an increase in intracellular Ca2+ concentration accompanied by excitation of neurons which formed synaptic connections between each other. This method for detection of neuronal activity including synaptic excitation escapes from the limitations of the conventional technique employing microelectrodes.

2-Amino-5-phosphonovalerate↗
PubMed1987

Chemosensitivity study of urological malignancies using a novel dye-exclusion method.

The chemosensitivity of several urological malignancies was determined using a novel dye-exclusion method. The tests proved to be successful in 22 out of 33 urothelial transitional-cell carcinomas, 21 out of 29 renal-cell carcinomas, and in 8 out of 13 testicular tumors, but in 0 out of 4 Wilms' tumors. At 10% of the peak plasma concentration of anticancer drugs achievable after single bolus injection, the sensitivity rates of urothelial transitional-cell carcinomas for cis-platinum, adriamycin, and carboquone were 27.3%, 13.3%, and 5.6%, respectively. At the peak plasma level, urothelial transitional-cell carcinomas were 'susceptible' to cis-platinum, carboquone, and adriamycin, the sensitivity rates being 60%, 50%, and 30%, respectively. The number of these carcinomas susceptible at the peak plasma level was significantly larger than that at 10% of the peak plasma level (P less than 0.01). However, renal-cell carcinomas exhibited a low sensitivity rate of 38% even when exposed to the peak plasma level. A similar trend was observed when tumor chemosensitivity was determined using a modified human tumor clonogenic assay. These results suggest that urothelial transitional-cell carcinomas may show good responses when anticancer drugs are given at high concentrations using methods such as intra-arterial infusion and intravesical instillation.

Antineoplastic Agents↗