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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 433 records · Page 24Linked to original sources

Phosphorylation-dependent subcellular translocation of a Ca2+/calmodulin-dependent protein kinase produces an autonomous enzyme in Aplysia neurons.

We have shown previously that the subcellular distribution of a major calmodulin-binding protein is altered under conditions causing increased synthesis of cAMP in Aplysia neurons (Saitoh, T., and J. H. Schwartz, 1983, Proc. Natl. Acad. Sci. USA, 80:6708-6712). We now provide evidence that this Mr 55,000 protein is a subunit of a Ca2+/calmodulin-dependent kinase: (a) both the Mr 55,000 calmodulin-binding protein and kinase activity are loosely attached to the membrane-cytoskeletal complex; (b) both kinase activity and the Mr 55,000 protein are translocated from the membrane-cytoskeleton complex to the cytoplasm under conditions that cause the change in the subcellular distribution of the Mr 55,000 calmodulin-binding protein; and (c) calmodulin-binding activity of the Mr 55,000 protein and the ability to carry out the Ca2+/calmodulin-dependent phosphorylation of synapsin I are purified in parallel. The subcellular localization of the Ca2+/calmodulin-dependent protein kinase appears to be under control of two second messengers: Ca2+ and cAMP. We find that the Mr 55,000 subunit is phosphorylated when the extracted membrane-cytoskeleton complex is incubated with Ca2+, calmodulin, and ATP, with the concomitant release of this phosphorylated peptide from the complex. Previously, we had found that, when translocation occurs in extracts in the presence of cAMP and ATP (but in the absence of Ca2+), there was no detectable phosphorylation of the Mr 55,000 subunit itself. The subcellular distribution of the subunit thus appears to be influenced by (a) cAMP-dependent phosphorylation, which, we infer, modifies some as yet unidentified structural component, causing the release of the enzyme; and (b) Ca2+/calmodulin-dependent phosphorylation of the Mr 55,000 subunit. These studies also suggest that phosphorylation has an important regulatory consequence: during the Ca2+/calmodulin-dependent translocation of the Mr 55,000 subunit, the kinase appears to be activated, becoming independent of added Ca2+/calmodulin.

Animals↗

Clinical use of the measurement of airway resistance during spontaneous respiration.

Airway resistance was measured during spontaneous respiration in healthy smokers and patients with chronic obstructive pulmonary disease, and the relationship between the airway resistance and respiratory frequency was examined. No significant difference was observed between the airway resistance in smokers and nonsmokers. In the chronic obstructive pulmonary disease group, patients with pulmonary emphysema had highest airway resistance. The determination of airway resistance during spontaneous respiration appears to be a very useful, noninvasive method of pulmonary function testing.

Adult↗

[Clinical evaluation of cefmenoxime in internal medicine, with special reference to infections associated with hematological disorders].

Clinical evaluation of cefmenoxime (CMX, Bestcall) was examined in the infection associated with hematological disorders, respiratory tract and other disorders. Clinical effectiveness for severe infection of hematological disorders was 47.4% in good and 84.2% in fair response, however, in the respiratory tract infections, 89.7% in good response was obtained. Opportunistic infection due to Gram-negative bacilli are often experienced in patients with hematological disorders. It was discussed that CMX would be a good therapeutic agent against infectious diseases associated with hematological disorders because it's antibacterial spectrum would be parallel to pathogens of such disorders.

Adolescent↗

[The mechanism of intracranial pressure-reducing effect of mannitol].

The effect of mannitol to decrease the raised ICP is well documented and mannitol is now widely used in clinical practice. However, its mechanism of lowering ICP still remains controversial, especially under the condition of vasogenic edema. The objective of this study is to reexamine and delineate the mechanism of ICP reducing effect of mannitol, using quantitative vasogenic edema model, specific gravimetric technique to measure the brain water content, and the method to estimate the CSF dynamics without disturbing the physiological condition of intracranial compartments in cats. Quantitative increase of water content of the white matter was produced by the infusion of 0.5 ml of normal saline though stereotaxically inserted 25-G needle into the left frontal white matter. In control group, cats were sacrificed and water content of the gray and white matter of each coronary sliced brain was measured by specific gravimetric technique. In the mannitol group, 20% of mannitol (2 g/kg) was administrated via femoral vein within 3 minutes. The maximum reduction of ICP was achieved at the average of 30 minutes. At this time, the cats were sacrificed and the water content of brain was measured in the same way as in the control group. PVI, Ro, If (Marmarou) were calculated before and after mannitol administration. In parameter group, BP, ICP, CVP, serum osmotic pressure and osmolarity were measured without terminating the experiment. The changes of water content of the gray and white matter before and after mannitol administration in the area of infusion edema were 80.7% to 80.8% and 76.8% to 77.1% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[2 cases of the independent coexistence of early cancer and leiomyosarcoma in the same stomach].

In the past 10 years, malignant diseases have been revealed in 157,836 autopsy cases (in Japan). Among them, gastric cancer was found in 17.5% and leiomyosarcoma in 0.45%. In addition, the frequency of leiomyosarcoma of the stomach was only 0.08%. In the literature, 20 cases of the coexistence of cancer and leiomyosarcoma in the same stomach (were) reported in Japan prior to (data). Eight of these were early cancer. Subsequently, three cases, including two of our own, were added. In our two patients, early cancer and leiomyosarcoma coexisted independently in the same stomach. It is suggested that the stomach with leiomyosarcoma may have a tendency to be cancerous.

Adenocarcinoma↗

[Cerebellar hemangioblastoma developing after nephrectomy for renal cell carcinoma].

Cerebellar hemangioblastomas are known to be occasionally associated with abdominal tumors such as renal cyst and renal cell carcinoma. But most of the abdominal tumors reported are clinically silent and usually diagnosed after the hemangioblastomas have been found in the central nervous system. We report a rare case in which a renal cell carcinoma preceeded in its onset of symptoms 4 years to a cerebellar hemangioblastoma. A 56-year-old female underwent left nephrectomy because of a left renal cell carcinoma at the age of 49. About 4 years after the nephrectomy, she developed signs and symptoms of intracranial hypertension and was operated on for a cerebellar tumor which was histologically diagnosed as hemangioblastoma. Her family history was non-contributory. Four years later, recurrence of the cerebellar tumor was found on the CT scan and abdominal studies were negative except for a suspected parapelvic cyst in the right kidney on abdominal ultrasonography. Subtotal removal of the cerebellar hemangioblastoma was performed followed by irradiation.

Carcinoma, Renal Cell↗

Serotonin alters the subcellular distribution of a Ca2+/calmodulin-binding protein in neurons of Aplysia.

We purified and radioiodinated calmodulin from Aplysia nervous tissue. Using blot analysis, we detected 14 calmodulin-binding proteins in extracts of the abdominal ganglion after gel electrophoresis in NaDodSO4. All 14 components are present in extracts from each of the major central Aplysia ganglia, but their relative proportions differed characteristically from one ganglion to another. When neural components are extracted with nonionic detergents in 2 M glycerol, we obtain a cytoplasmic and a membrane-cytoskeleton fraction. Of the 14 calmodulin-binding proteins, 2 are cytoplasmic, 10 are loosely associated, and 2 remain bound to the membrane-cytoskeleton complex. Treatment of isolated ganglia with serotonin, which has been shown to increase the content of cAMP within neurons, or with dibutyryl cAMP causes the partial dissociation of one of the loosely associated proteins, which has an apparent Mr of 55,000. In extracts prepared in the presence of glycerol and cAMP, this component also is dissociated from the membrane-cytoskeleton complex, but only if ATP is also present. These results suggest that a cAMP-dependent protein phosphorylation controls the subcellular distribution of the Mr 55,000 calmodulin-binding protein, whose state of phosphorylation itself, however, does not appear to be increased by cAMP.

Animals↗

[Clinical effects of chlormadinone acetate (Prostal) on patients with prostatic hypertrophy--with reference to estimation of size and weight of prostate by means of transrectal ultrasonotomography].

Twenty patients with benign prostatic hypertrophy were treated with an anti-androgenic agent, chlormadinone acetate ( Prostal ), 50 mg daily for 3 months. As a control, 20 patients with prostatic hypertrophy were treated with Eviprostat which was a non-hormonal remedy consisting of plant extracts 6 tablets daily for the same duration. Subjective symptoms of 14 patients (70%) in the Eviprostat group and 18 cases (90%) in the Prostal group were improved significantly. Although there were no significant changes in size or weight of the prostate after 3 months in the patients in the Eviprostat group as measured by transrectal ultrasonotomography, remarkable reduction in size and weight of the prostate was observed after 3 months in 11 patients (55%) in the Prostal group. Four cases complained of impotency during Prostal treatment, but no other side effects to the hepatic and/or renal functions were observed.

Aged↗

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗

Effect of hyperdynamic therapy on cerebral ischaemia caused by vasospasm associated with subarachnoid haemorrhage.

Ten patients who developed neurological deficits associated with angiographically proven cerebral vasospasm caused by ruptured aneurysm were treated with hyperdynamic therapy induced by administration of a large amount of human serum albumin. No vaso-active drugs were administered. Cardiopulmonary function and intracranial pressure were monitored during the treatment. Marked improvement of neurological function was observed in all cases. Nine patients recovered completely without any neurological residual following treatment. The degree of the improvement observed during treatment closely correlated with the decrease in total peripheral resistance. Infusion of albumin did not cause elevation of intracranial pressure. It was concluded that the hyperdynamic therapy induced by administration of albumin has a dramatic effect on the ischaemic cerebral insult caused by vasospasm. It is postulated that the main effect of this treatment is produced by cerebrovascular dilatation.

Brain Ischemia↗

[Antineoplastic effect of UFT therapy (uracil-FT-207 combination therapy) on experimental pancreatic cancer transplanted in the pancreas and subcutaneous region].

The pancreatic duct cell adenocarcinoma induced by di-isopropanol nitrosamine could be easily and repeatedly transplanted into the subcutaneous or pancreatic tissues of the homologous animals. We established a tumor bearing animal design in which tumor tissues were transplanted simultaneously into subcutaneous and pancreatic tissues. At the first week after the transplantation, the animals were divided into three groups: In FT group FT-207 was given at a dose of 15 mg/kg/day, in UFT group FT-207 and uracil were given at a dose of 3 mg/kg/day and; 6.7 mg/kg/day (molar ratio; 1:4), respectively and in control group a solvent of FT-207 was given. In all groups the drugs were administrated orally for ten days. The size of tumors transplanted in subcutaneous and pancreatic tissues increased more slowly in FT and UFT groups, as compared with that of control group. The inhibitory effect on tumor growth observed in UFT group was more striking than that in FT group. No major side effects were observed in all groups. At the fourth weeks after subcutaneous and intrapancreatic transplantation, the animals were divided into two groups: In FT group FT-207 was given at a dose of 30 mg/kg and in UFT group FT-207 and uracil were given at a dose of 30 mg/kg and 67.2 mg/kg, respectively. In both groups the drugs were given orally, and at one hour after the administration all the animals were killed to determine 5-FU concentration in various tissues. The 5-FU concentrations of subcutaneous and intrapancreatic transplanted tumor tissues were significantly higher in UFT group than those in FT group. UFT therapy, therefore, seems to be hopeful for the treatment of human pancreatic cancer.

Animals↗