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Biomedical subjects

M Kobari

Publications and source records attributed to M Kobari.

At least 127 records · Page 7Linked to original sources

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

Animals↗

[Experimental study of the intra-operative radiation therapy in pancreatic cancer].

The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[(4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidazole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50% tumor control dose (TCD50) against the pancreatic cancer were 3.5 Gy and 73.7 +/- 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35% of the tumor. ii) The dose of intraoperative irradiation (10-40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD50 of the pancreatic cancer to 53.8 +/- 1.57Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio: 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival.

Adenocarcinoma↗

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↗

CSF beta-endorphin and leu-enkephalin levels in the acute and chronic stages of cerebral infarction.

To investigate the role of endogenous opioid peptides in the pathophysiology of cerebral ischaemia, the CSF levels of immunoreactive beta-endorphin and leu-enkephalin in 16 patients with cerebral infarction were measured. Both the CSF beta-endorphin and leu-enkephalin levels in the acute stage of cerebral infarction were significantly higher than the values in the chronic stage. The CSF concentrations of the two peptides revealed a positive correlation in the acute but not the chronic stage. The increased endogenous opioid peptides in the CSF in the acute stage may modify the evolution of cerebral infarction.

Acute Disease↗

Comparison between pial and intraparenchymal vascular responses to sympathetic stimulation under hypercapnic conditions. With special reference to the mechanism for escape phenomenon.

We have shown that secondary vasodilation ('escape' phenomenon) during sympathetic nerve stimulation occurs in the intraparenchymal vessels but not remarkable in the pial vessels. To test a possible role of CO2 accumulation in the brain tissue in this phenomenon, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were investigated during hypercapnia in 9 cats by using a video camera photoelectric system. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min during hypercapnia (PaCO2 = 50 +/- 2 mm Hg). The intraparenchymal vessels as well as pial vessels remained constricted throughout the stimulation. Secondary dilation of the intraparenchymal vessels as seen at the later stage of sympathetic stimulation during normocapnia was not observed under the hypercapnic conditions. We assume that the arterial CO2 tension was so high that the constriction of inflow vessels could not result in accumulation of CO2 in the brain parenchyma. The accumulation of chemical metabolites as represented by CO2 is therefore considered to be the most probable mechanism underlying the escape phenomenon of the intraparenchymal vessels.

Animals↗

Bilateral thalamic infarction associated with selective downward gaze paralysis.

A 34-year-old man presented with transient downward gaze paralysis and impairment of convergence together with prominent psychic disturbances. Cranial CT and MRI clearly demonstrated a symmetric infarction extending from the bilateral thalamus to the rostral medial midbrain. The existence of downward gaze paralysis following ischemic stroke is contributory to the diagnosis of not only the location of but also the responsible artery for the infarction.

Adult↗

Clinicopathological study on hematogenous metastasis of pancreatic cancer.

Out of 272 pancreatic cancer patients, 94 with hematogenous metastasis were clinicopathologically analyzed. The incidence of hematogenous metastases on laparotomy was 31.3 per cent in the liver, 1.8 per cent in the lung, 1.1 per cent in the adrenal gland and 0.4 per cent in the navel, respectively. The incidence of liver metastasis, in 22.9 per cent of the patients with carcinoma of the head of the pancreas and in 47.3 per cent of those of the body and tail of the pancreas, was higher than that of carcinomas of the other digestive organs. In autopsy findings, early metastases to the liver, lung, cerebellum and ovarium were evident. A higher rate of liver metastasis with lymph node involvement in the early stage of the disease was peculiar to cases of pancreatic cancer.

Adrenal Gland Neoplasms↗

Comparison between pial and intraparenchymal vascular responses to cervical sympathetic stimulation in cats. Part 1. Under normal resting conditions.

To investigate the role of sympathetic regulation in both resistance and capacitance vessels in cerebral circulation, the response of pial and intraparenchymal vessels to sympathetic nerve stimulation were simultaneously examined in 14 cats by means of a newly developed video camera photoelectric system. The system consisted of a video camera system for measurement of pial vascular diameters and a photoelectric apparatus for estimating regional cerebral blood volume in the intraparenchymal vessels. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min. Initially, both the pial and intraparenchymal vessels constricted. The large pial arteries (173 +/- 25 micron, mean +/- SEM) remained constricted throughout the stimulation, whereas the intraparenchymal vessels began to dilate after the initial constriction and exceeded the control level at 175 +/- 25 s despite continued stimulation. In conclusion, such sympathetic nerve stimulation is considered to exert a constrictive effect on the intraparenchymal as well as the pial vessels at the early stage. The compensatory dilation of the intraparenchymal vessels was delayed 3 min after initiation of the stimulation.

Animals↗

Human pancreatic cancer associated antigen detected by monoclonal antibody.

Monoclonal antibody F30 was produced by the fusion of murine myeloma cell line P3-X63-Ag8-653 with spleen cells from a BALB/C mouse immunized with established human pancreatic cancer cell line (PK-1) and the reaction specificity was analyzed. The antigen recognized by monoclonal antibody F30 was different from HLA-associated antigen, beta 2-microglobulin, fetal bovine serum components, ferritin, AFP, or CEA. Monoclonal antibody F30 reacted with all of six pancreatic cancer cell lines established in our laboratory. Cross-reactivity was detected with a colon cancer cell line or an esophagus cancer cell line among various tumor cell lines tested. No reaction was detected with red blood cells, lymphocytes, or lymphoid and myeloid cell lines. By immunoperoxidase staining of frozen sections, the F30-defined antigen was detected not only on pancreatic cancer cell membrane but also on other adenocarcinomas. In addition, the monoclonal antibody F30 had a more wide-spread distribution on normal epithelial cells in the gastrointestinal organs, respiratory system, and urinary system. F30-defined antigen was composed of two protein components with molecular weight of 190 and 160 K. It was indicated that the antigen was an integral protein in the cell membrane since the antigen was not detected in the spent culture medium of antigen-positive cells.

Antibodies, Monoclonal↗

Establishment of six human pancreatic cancer cell lines and their sensitivities to anti-tumor drugs.

Six human pancreatic cancer cell lines PK-1, -8, -9, -12, -14 and -16, were established. They originated from either primary pancreatic cancer biopsy or liver metastasis biopsy, or xenografts of these biopsy specimens in athymic nude mice. The primary tumors were all well differentiated adenocarcinomas of pancreatic duct origin. The six established PK cell lines were all CEA positive and had tumorigenicity in athymic nude mice. Morphology of the xenografted tumors was closely similar to that of the original tumor. PK cells grew slowly with the doubling time of 41.3 to 82 hr and showed aneuploid chromosome pattern. High levels of glucose-6-phosphate dehydrogenase (G6PDH) and lactic dehydrogenase (LDH) were found in each cell extract. Trypsin was not detected in cell extracts except PK-8 and PK-9. In chemosensitivity test, all of PK cell lines were sensitive to aclacinomycin A (ACM), and PK-1 and PK-8 were sensitive to 5-Fluorouracil (5-Fu) at concentrations of 0.02 microgram/ml, ACM and 1 microgram/ml, 5-Fu, when the drugs were used for over 48 hr. At higher concentrations, they showed time independent sensitivity to mitomycin C (MMC). PK-9 was resistant to 5-Fu and MMC.

Adenocarcinoma↗

[Met-enkephalin-Arg-Gly-Leu-like immunoreactivity-containing nerve fibers and cell bodies in the abdominal sympathetic ganglia of the rat--an immunohistochemical study].

The occurrence and localization of Met-enkephalin-Arg-Gly-Leu (Met-Enk-Arg-Gly-Leu)-like immunoreactivity in the lumbar paravertebral ganglion and the superior mesenteric ganglion in the rat were investigated by immunocytochemistry. Colchicine was employed as an axonal flow blocker to accumulate Met-Enk-Arg-Gly-Leu in the nerve cell bodies. The Met-Enk-Arg-Gly-Leu serum (R 0171) was produced by immunizing a mixed breed female rabbit with synthetic Met-Enk-Arg-Gly-Leu conjugated to ascaris protein by the glutaraldehyde method. Sections, 7 micron in thickness, of Bouin-fixed and paraffin-embedded tissues were immunostained by the peroxidase-antiperoxidase (PAP) method. Results obtained were summarized as follows: Colchicine-untreated rats possessed no strongly-immunoreactive nerve cell bodies for Met-Enk-Arg-Gly-Leu in the lumbar paravertebral ganglion, though a few of them were weakly immunopositive. Met-Enk-Arg-Gly-Leu-like immunoreactivity showing nerve fibers were occasionally seen in nerve fiber bundles of the lumbar paravertebral ganglion. In the superior mesenteric ganglion, a dense network of positively immunostained nerve fibers with a beaded appearance were seen around nerve cell bodies which were immunonegative for Met-Enk-Arg-Gly-Leu. In colchicine-treated rats, 55 percent of nerve cell bodies of the lumbar paravertebral ganglion showed various degrees of positive immunoreactivities for Met-Enk-Arg-Gly-Leu. Many strongly immunostained nerve terminals were seen in the lumbar paravertebral ganglion of colchicine-treated rats. In the superior mesenteric ganglion, the immunoreactivity for Met-Enk-Arg-Gly-Leu in the beaded nerve fibers around nerve cell bodies was intensified by the colchicine treatment, whereas the nerve cell bodies themselves remained immunonegative for Met-Enk-Arg-Gly-Leu.

Animals↗

Effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels in cats.

To elucidate the fundamental actions of endogenous opioids and naloxone on the cerebral circulation, the effects of (D-Met2,Pro5)-enkephalinamide and naloxone on pial vessels were investigated in cats. Pial arteries (165.7 +/- 24.9 microns) were found to dilate after the intravenous administration of 1 mg/kg of (D-Met2,Pro5)-enkephalinamide, and a definite dilatation of 7.1-7.6% persisted for 15 min. Pial veins (100.6 +/- 20.2 microns) also dilated but to a lesser degree. The MABP (118.7 +/- 10.5 mm Hg) decreased by 20 mm Hg immediately after the injection, but gradually returned to the initial value 15 min later. The observed cerebral vasodilatation may be attributable to sympathetic inhibition mediated either by the presynaptic opiate receptors of the cerebral vessels or by the opiate receptors in the brainstem. After the intravenous administration of 1 mg/kg of naloxone, pial arteries (122.0 +/- 17.2 microns) showed a slight but significant dilatation of 2.3-5.3%. There were no significant changes in pial veins (87.0 +/- 12.4 microns). MABP (130.4 +/- 12.3 mm Hg) was slightly increased after the injection. Although the mechanism involved was unclear, the cerebral vasodilatation occurring after the administration of naloxone may contribute to its ameliorating effect on the neurological symptoms following cerebral ischemia.

Animals↗