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Biomedical subjects

M Kobari

Publications and source records attributed to M Kobari.

At least 19 recordsLinked to original sources

The mucus-hypersecreting tumor of the pancreas. Development and extension visualized by three-dimensional computerized mapping.

BACKGROUND: Mucus-hypersecreting tumor of the pancreas appears as dilated ducts and cystic spaces filled with mucus. To determine where such tumors arise and how they extend, computer-aided three-dimensional reconstruction was done of the ductal system. This also was used to visualize the spatial relationships among epithelial hyperplasia, dysplasia, and carcinoma in situ (CIS). METHODS: Surgically removed pancreases were studied from 12 patients with mucus-hypersecreting tumors. The specimens were fixed in buffered formaldehyde solution 10%, embedded in paraffin and semiserially sectioned at 3 microns at an interval of 60 microns. The ductal contours were differentiated among ducts lined by ordinary epithelia, hyperplastic epithelia, dysplastic cells, or CIS and were inputted into a computer system that integrated a three-dimensional image of ducts in the display. RESULTS AND CONCLUSIONS: (1) The tumors arose in the main pancreatic duct or its subbranches, and the cysts corresponded to segments expanded by the superficial growth of tumor cells; (2) areas of CIS arose in zones of preceding dysplasia, suggesting a dysplasia-carcinoma sequence; and (3) dysplastic or cancerous cells often extended intraductally over the dilated segments of ducts.

Aged

Local cerebral blood flow and its response to intravenous levodopa in progressive supranuclear palsy. Comparison with Parkinson's disease.

The local cerebral blood flow (LCBF) at steady state and after the intravenous administration of levodopa (1 mg/kg) was measured by the xenon-enhanced computed tomographic method in six patients with progressive supranuclear palsy (PSP) and in nine patients with idiopathic Parkinson's disease. The baseline LCBF values in most brain regions in patients with PSP were lower than those in patients with Parkinson's disease, and hyperfrontality of the LCBF was lost. In patients with Parkinson's disease, the injection of levodopa markedly increased LCBF, especially in the striatum, thalamus, and internal capsule (approximately 40%). In patients with PSP, however, levodopa did not increase the LCBF in all brain regions examined. The LCBF increases after the administration of levodopa in patients with Parkinson's disease may be secondary to metabolic activation of the dopaminergic system. The different LCBF responses to levodopa between patients with PSP and those with Parkinson's disease may reflect differences in pathologic features, such as in the degree of preservation of nigrostriatal dopaminergic neurons and the distribution and density of dopamine receptors, and are also related to the clinical effectiveness of levodopa therapy.

Aged

Cerebral microcirculatory changes during and following transient ventricular tachycardia in cats.

Although reduced cerebral perfusion is believed to be the cause of syncope due to cardiac arrhythmias, investigations on the cerebral microcirculation during cardiac arrhythmias have been rare. We therefore studied the effects of transient ventricular tachycardia on the local cerebral blood volume and blood flow. Experimental ventricular tachycardia was induced in cats by electrically stimulating the ventricle of the heart at a rate of 300/min for 1 min. Using our photoelectric method, the local cerebral blood volume, mean transit time of blood, and cerebral blood flow in the parieto-temporal region were measured during and for 3 h after ventricular tachycardia. Transient ventricular tachycardia of as short as 1 min caused cerebral ischemia with a blood flow reduction of approximately 30%. This was considered to be due to reduced blood pressure plus transient autonomic dysfunction, or dysautoregulation, during the ventricular tachycardia. Mild and transient reactive hyperemia occurred immediately after termination of the dysrhythmia, but continuous reductions of cerebral blood flow were observed thereafter for 3 h. This delayed hypoperfusion is attributable to either vasoconstriction of the large resistance vessels or changes in the hemorheological properties of the blood caused by cerebral ischemia. Ventricular tachycardia of the type reported has significant and long-lasting effects on the cerebral microcirculation.

Animals

Animal species differences in erythrocyte aggregability.

Species differences in erythrocyte aggregability were investigated employing our whole blood erythrocyte aggregometer. Blood was sampled from seven species, including humans and anesthetized (30 mg/kg pentobarbital) animals. The erythrocyte aggregation rates were the following (in s-1): cats, 0.213 +/- 0.027 (means +/- SD); dogs, 0.164 +/- 0.027; men, 0.112 +/- 0.025; rats, 0.111 +/- 0.005; domestic rabbits, 0.049 +/- 0.021; and mongolian gerbils, 0.034 +/- 0.015. Domestic fowls did not exhibit erythrocyte aggregograms like those seen in the other species. Statistical analysis revealed significant differences among the erythrocyte aggregation rates of the different species (multiple-comparisons with an overall significance level of 0.05) except between men and rats and between rabbits and gerbils. No single factor which is known to accelerate the erythrocyte aggregation rate (hematocrit, fibrinogen, etc.) was correlated with the erythrocyte aggregation rate except the globulin concentration in the blood. The failure to detect erythrocyte aggregation in domestic fowls was probably attributable to their erythrocyte shape. These results suggest that each species has its own proper tendency for erythrocyte aggregation. This factor must be taken into consideration when the blood circulation is discussed among different animal species.

Animals

Intraoperative radiation therapy combined with hyperthermia against pancreatic carcinoma.

Fourteen patients with pancreatic carcinoma were treated by intraoperative radiation therapy (IORT) combined with hyperthermia (hyperthermia group). Their treatment results were compared with those of fifty five patients treated by IORT without hyperthermia (control group). Most of patients underwent some kind of chemotherapy for the carcinoma and some of them received post-operative irradiation. Although there was no significant difference in pain relief between hyperthermia group and control group, the local tumor control rate of the former group was a little better. The survival rate of all patients was 14.5% at one year, 2.9% at two years, 2.9% at three years and 0% at four years after surgery. The survival rate of the hyperthermia group was 21.4% at one year and 7.1% at two years and that of the control group was 12.7% at one year and 1.8% at two years. The survival of the hyperthermia group was a little better than that of control group, but the difference was not significant. Only 36% of patients of hyperthermia group were successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would be possibly improved.

Adenocarcinoma

Initial pathophysiological changes in chronic pancreatitis induced by pancreatic ductular obstruction model.

An experimental chronic pancreatitis model was made in five dogs with chronic pancreatic fistula by injection of microspheres into the peripheral pancreatic duct. Sequential changes of pancreatic exocrine and endocrine functions with morphology were studied. Significant decreases in volume bicarbonate output and amylase output were detected in each sample collected separately on secretin and secretin cerulean stimulation. While the viscosity of pancreatic juice was significantly increased with a concomitant increase in hexosamine concentration, chronic pancreatitis was demonstrated morphologically. These results suggest that concentrated pancreatic juice caused by a decrease in volume and an increase in viscosity of pancreatic juice with a concomitant increase in hexosamine concentration brings about the progression of chronic pancreatitis in this experimental model.

Amylases

Changes of duodenal pH and pancreatic exocrine function after upper G-I intraluminal ethanol administration.

Using 3 outbred dogs with pancreatic, gastric and jejunal fistulas, we examined changes in pancreatic exocrine secretion, duodenal pH and plasma CCK concentration after intragastric or intrajejunal administration of ethanol. Intragastric administration of 20% or 40% ethanol significantly lowered the pH in the duodenal cavity, and pancreatic fluid secretion and bicarbonate excretion were stimulated. Intrajejunal administration of ethanol elicited stronger responses. Plasma CCK concentration was not changed or was only slightly lowered by ethanol administration in the digestive tract. It is assumed that stimulation of pancreatic exocrine secretion was mediated by the secretion of gastric acid.

Animals

[The growth rates of liver metastases in pancreatic cancer--comparison on growth rates between clinical cases and established human pancreatic cancer cell lines].

By measuring the doubling time both of clinical liver metastases and cultured human pancreatic cancer cell lines, we studied the possibility of occult liver metastases at the time of pancreatectomy in patients with pancreatic cancer. Doubling times of 3 pancreatic cancers were obtained from the measurements of size of liver metastases after pancreatectomy and those were compared with those of cultured human pancreatic cancer cell lines established from two of these cases. Doubling time of liver metastases were about fifteen times as long as those of cultured cell lines. On the assumption that growth rates of liver metastases were constant, the size of liver metastases at the time of pancreatectomy was calculated in three cases. The calculated sizes of these liver metastases were 140 microns, 2.4 mm, and 8.3 mm respectively. These results indicate that occult liver metastases have already existed in patients with pancreatic cancer even though they were clinically undetectable at the time of operation. And some adjuvant therapies against occult liver metastases are necessary for achievement of the better prognosis.

Aged

Undifferentiated sarcoma of the liver in a 21-year-old woman: case report.

A successful surgical case of malignant undifferentiated (embryonal) sarcoma of the liver (USL), a rare tumor normally found in children, is reported. The patient was a 21-year-old woman, complaining of epigastric pain and abdominal fullness. Chemical analyses of the blood and urine and complete blood counts revealed no significant changes, and serum alpha-fetoprotein levels were within normal limits. A physical examination demonstrated a film, slightly tender lesion at the liver's edge palpable 10 cm below the xiphoid process. CT scan and ultrasonography showed an oval mass, confined to the left lobe of the liver, which proved to be hypovascular on angiography. At laparotomy, a large, 18 x 15 x 13 cm tumor, found in the left hepatic lobe was resected. The lesion was dark red in color, encapsulated, smooth surfaced and of an elastic firm consistency. No metastasis was apparent. Histological examination resulted in a diagnosis of undifferentiated sarcoma of the liver. Three courses of adjuvant chemotherapy, including adriamycin, cis-diaminodichloroplatinum, vincristine and dacarbazine were administered following the surgery with no serious adverse effects. The patient remains well with no evidence of recurrence 12 months after her operation.

Adult

Growth-inhibitory effect of combination chemotherapy for human pancreatic cancer cell lines.

Sensitivities to anti-tumor drugs, mitomycin C (MMC), aclarubicin hydrochloride (ACR), doxorubicin hydrochloride (ADR), cisplatin, and 5-fluorouracil (5FU), were examined using PK-1, -8, -9, -12, -14, and -16 cell lines derived from human pancreatic cancer. These cell lines showed different sensitivities to each of the above anti-tumor drugs. The concentrations required for 50% growth-inhibition (IC50) after 2 hours of exposure were 0.096 to 0.35 micrograms/ml for MMC, 0.0074 to 0.0076 micrograms/ml for ACR, 0.033 to 0.23 micrograms/ml for ADR, 0.35 to 1.9 micrograms/ml for cisplatin, and 21 to 42 micrograms/ml for 5FU, IC50 of each anti-tumor drug decreased significantly after 48 hours of exposure. The combination of any two out of MMC, ACR, and 5FU showed synergistic inhibition of the growth of PK-1 and PK-8 cell lines. These results show that MMC, ACR, ADR, cisplatin, and 5FU have sufficient anti-tumor effect against six human pancreatic cancer cell lines even at clinically achievable concentrations and exposure times, and chemotherapy for pancreatic cancers requires naturally effective drug delivery into cancer tissues.

Aclarubicin

Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal aging.

To elucidate the role of leuko-araiosis observed on computed tomographic imaging among normal populations, 37 neurologically and cognitively normal volunteers ages 18 to 88 years were studied. Local cerebral blood flow was measured using stable xenon-enhanced computed tomography. Severity of leuko-araiosis and cerebral atrophy were graded on computed tomographic images. Leuko-araiosis was observed in 21.6% of normal volunteers, in 52.2% of patients with multi-infarct dementia (n = 23), and in 61.5% of patients with dementia of the Alzheimer type (n = 13). When multiple regression analysis was applied among normal volunteers, the degree of cerebral atrophy, advancing age, and local cerebral blood flow reductions of subcortical white matter correlated and contributed in that order of precedence to the presence and severity of leuko-araiosis. Combination of the unusual vascular anatomy of periventricular white matter together with cerebral hypoperfusion appears to be related to the occurrence of leuko-araiosis observed among neurologically and cognitively normal subjects. Further investigations should determine whether leuko-araiosis among this population is a risk factor for later cognitive impairments.

Adolescent

The mechanical filtration coefficient (Lp) of the cell membrane of cultured glioma cells (C6).

The mechanical filtration coefficient (Lp) of the membrane of cultured glioma cells was determined from the rate of swelling of the cells. The swelling was induced by exposing the cells to distilled water. Assuming that cells swell in a symmetrical manner, Lp was 2.2 x 10(-8) cm/s.mmHg, or 1.7 x 10(-4) microns/s.cmH2O when calculated from changes of the cell diameter.

Cell Membrane

Cortical and subcortical hyperperfusion during migraine and cluster headache measured by Xe CT-CBF.

High-resolution, color-coded images of local cerebral blood flow (LCBF) were made utilizing stable xenon-enhanced computed tomography among patients with common migraine (n = 18), classic migraine (n = 12) and cluster headache (n = 5). During spontaneously occurring headache in common and classic migraine patients, LCBF values for cerebral cortex and subcortical gray and white matter were diffusely increased by 20-40% with the exception of the occipital lobes. LCBF increases involved both hemispheres whether the head pain was unilateral or bilateral. No significant differences were noted in the degree or pattern of LCBF increases during headaches of common and classic migraineurs. Similar cerebral hyperperfusion of greater magnitude was observed during cluster headaches but was more prominent on the side of the head pain. Present observations do not support the hypothesis of spreading cortical depression as a cause of classic migraine. From a hemodynamic viewpoint, LCBF increases during headaches of common or classic migraine or cluster appear similar. Evidence is adduced that sympathetic hypofunction with denervation hypersensitivity of cerebral vessels plays a role in the cerebral hyperperfusion of migraine headaches. More pronounced unilateral autonomic derangements appear to account for the symptoms and cerebral hyperperfusion associated with cluster headaches.

Adult

Immuno-electron microscopic study of keratin distribution in the cochlea using monoclonal antibody.

Keratin distribution in the cochlea has been studied immuno-electron microscopically by both pre-embedding and postembedding methods. Keratin immunoreactivity in the guinea pig cochlea was clearly demonstrated in Hensen's cells, the reticular lamina surrounding both outer and inner hair cells, outer and inner pillar cells, Claudius' cells, inner and external sulcus cells, interdental cells of the spiral limbus, Reissner's membrane, border cells, inner phalangeal cells, Deiters' cells, and spiral prominence cells. Keratin expression at the ultrastructural level showed a nonfilamentous keratin system in the cytoplasm of cochlear supporting cells.

Animals