Biomedical subjects

T Funakoshi

Publications and source records attributed to T Funakoshi.

At least 109 records · Page 6Linked to original sources

PubMed1992

Anticoagulant action of vanadate.

Sodium orthovanadate (vanadate) prolonged the clotting time of normal human plasma in a dose-dependent manner. The prolongation of clotting time by vanadate linearly decreased with an increase in the concentration of amiloride. Vanadate also was completely additive to prolongation by heparin. When factor Xa or thrombin was incubated with vanadate, the amidolytic activity of each decreased in a dose-dependent manner with vanadate. Amiloride protected the decrease of amidolytic activity of both factor Xa and thrombin by vanadate. The amidolytic activity of trypsin also was inhibited by vanadate, but that of alpha-chymotrypsin was not inhibited, suggesting that vanadate preferentially inhibits the amidolytic activity of trypsin and trypsin-like enzymes. These results show that vanadate prolongs the clotting time of plasma through mechanisms involving in part the inhibition of the activity of both factor Xa and thrombin.

Amino Acid Sequence↗

PubMed1992

Brain tumors manifesting as intracranial hemorrhage.

The clinical course and computed tomographic (CT) findings of 23 patients with brain tumors manifesting as tumoral hemorrhage were reviewed. The most common symptoms were headache and clouding of consciousness. A CT finding of a lesion located next to a solid or irregular clot indicated intratumoral hemorrhage. Precontrast CT demonstrating an indent on the hematoma surface was a valuable indicator of tumoral hemorrhage. A CT finding of accumulated levels of blood/fluid or a hyperdense mass containing small hematoma indicated intratumoral hemorrhage, and obscure hyperdensity indicated intratumoral hemorrhagic infarction. Such findings were often difficult to distinguish from spontaneous intracerebral hemorrhage due to other factors. The incidence of rebleeding from residual tumors was high, carrying a very poor prognosis, so radical removal of brain tumors with hemorrhage is very important.

Adolescent↗

PubMed1992

Anticoagulant action of rare earth metals.

Some of the lanthanides, the rare earth metals, lanthanum (La), cerium (Ce), neodymium (Nd), samarium (Sm), terbium (Tb), dysprosium (Dy), erbium (Er) and ytterbium (Yb) prolonged the clotting time of normal human plasma in a dose-dependent manner when clotting was induced either by thromboplastin or by kaolin in the presence of cephalin and Ca2+. They also prolonged the activated factor X induced clotting time of platelet-rich plasma. The amidolytic activities of activated factor X and thrombin progressively decreased with increasing amount of rare earth metals. These results suggested that the rare earth metals appear to show their anticoagulant effect with mechanisms in part the inhibition of the enzymatic activities of both activated factor X and thrombin.

Anticoagulants↗

PubMed1992

Effect of repeated administration of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats.

The effects of the repeated administration of D-penicillamine, 2,3-dimercaptosuccinic acid, 2,3-dimercaptopropane sulphonate, and N-(2-mercapto-2-methylpropanoyl)-L-cysteine 24 h after gold sodium thiomalate (AuTM) injection on the distribution, excretion, and renal toxicity of gold in rats were investigated. Three i.p. injections of these chelating agents (1.2 mmol/kg) at 1, 3, and 5 days after AuTM injection (0.026 mmol/kg) removed gold from kidney and liver through urinary and fecal excretion, and protected against the renal damage induced by AuTM. These findings indicate that these compounds are useful antidotes for gold toxicity.

Animals↗

PubMed1991

Acetazolamide reactivity on cerebral blood flow in patients with subarachnoid haemorrhage.

Cerebral vasodilatory capacity was evaluated by acetazolamide-activated N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) in 42 patients with subarachnoid haemorrhage (SAH). A low perfusion area was present in the corresponding region of haematoma seen on the CT and continued to be noted throughout the time courses. Deteriorated acetazolamide reactivity affected by surgical intervention was seen in 100% of the patients who underwent aneurysm repair in the 1st postoperative week, 92% in the second week, 73% in the third week, and 47% in the fourth week. Three patients with acute diffuse brain swelling seen on CT showed intracranial non-filling of 123I-IMP on SPECTs performed on Day 6, and all three died by Day 10. Some low perfusion areas, due to probable vasospasm, were present in 77% of Hunt and Hess grades I and II patients and in 100% of grades III, IV, and V patients throughout their time courses. Overall, low perfusion areas, due to probable vasospasm, were seen in 10 patients (31%) of 32 who underwent SPECT between Day 4 and 8,23 (77%) of 30 between Day 9 and 14, 21 (72%) of 29 between Day 15 and 21, and 11 (48%) of 23 between Day 22 and 28. The results suggest acetazolamide-activated 123I-IMP study is of value in evaluating changes in vasodilatory capacity in SAH patients in the acute and subacute stages.

Acetazolamide↗

PubMed1991

Comparative effects of N,N-disubstituted dithiocarbamates on excretion and distribution of cadmium in mice.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At 30 min after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium, and HBGD and CBGD significantly increased the urinary excretion of the metal. At 24 h after cadmium injection, BGD, HBGD, and MeOBGD significantly increased the biliary excretion of cadmium and HBGD was the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, HBGD and MeOBGD effectively depressed cadmium content in the liver and only HBGD among these chelating agents significantly reduced the cadmium content in the kidney. In another experiment, mice were injected i.p. with 109CdCl2 and three days later, they were injected with chelating agents every other day for 2 weeks. HBGD was the most effective on the fecal and urinary excretions of cadmium. The hepatic cadmium content was decreased after HBGD or MeOBGD injection. The injection of HBGD caused a much greater decrease in renal cadmium content than did BGD, CBGD, or MeOBGD. The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body, mainly through fecal excretion, without redistribution of cadmium to other tissues such as the brain, testes, and heart, more effectively than that of BGD, CBGD, or MeOBGD.

Animals↗

PubMed1991

Protective effects of dextran sulfate and polyvinyl sulfate against acute toxicity of paraquat in mice.

The protective effects of sodium dextran sulfate (SDS) and potassium polyvinyl sulfate (PPS) against the acute toxicity of paraquat (PQ) in mice were studied. The survival rates of mice treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after PQ ingestion (200 mg/kg) were 100% or 100%, respectively. When treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) 15 or 30 min after PQ ingestion (200 mg/kg), the survival rates were 83% or 67% for SDS-treated groups and 67% or 33% for PPS-treated groups, respectively. Treatment with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after oral administration of PQ (200 mg/kg) increased the fecal excretion of PQ, decreased the urinary excretion of PQ and decreased the contents of PQ in the lung, liver and kidney. Such effects of SDS and PPS were reduced in the treatment with these drugs at 15 min after PQ. The in situ small intestinal absorption of PQ was significantly reduced in the presence of SDS or PPS. The binding of PQ to SDS or PPS was determined by an ultrafiltration method. These results indicate that SDS and PPS inhibit the gastrointestinal absorption of PQ on the basis of the increased intestinal transit of PQ and the binding of PQ to the drugs resulting in the protective effectiveness of SDS and PPS on the acute toxicity of PQ.

Animals↗

PubMed1991

Correlation between magnetic resonance imaging and histopathology of intracranial glioma.

Postmortem histopathology of eight gliomas was studied in correlation with magnetic resonance imaging (MRI) and computed tomography (CT) findings. MRI demonstrated the lesions more clearly and widely than CT. Also, T2-weighted images (T2WI) had a greater ability to depict the lesion than T1-weighted images (T1WI). The areas in which neoplastic cells had invaded corresponded to the high intensity areas on T2WI in four cases of glioblastoma multiforme. In the case of a grade II astrocytoma, neoplastic cells were scattered beyond the region corresponding to the high intensity area on T2WI. In the case of a grade III astrocytoma, neoplastic cells did not come up to the line corresponding to the margin of the high intensity area on T2WI. In the remaining two cases, although the high intensity areas on T2WI were depicted as being larger than the areas in which neoplastic cells were seen histopathologically, the high intensity regions corresponding to the outside zones of the tumour-infiltrated area were thought to be a radiation necrosis in one case and a 'periventricular high intensity' in the other. The high cellularity of the glioma was seen mainly as a low intensity area on T1WI and as an isointensity or a slightly high intensity area on T2WI. However, the signal intensities of glioma on MRI, reflecting T1 or T2 values of the tumour tissues, did not correlate with the malignancy of the tumour.

Adult↗

PubMed1991

Mobilization of renal and hepatic cadmium by dithiocarbamates in rats.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected intraperitoneally with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/one animal) and 30 min or 24 h later, they were injected with chelating agents (400 mumol/kg). At both 30 min and 24 h after treatment with cadmium, these chelating agents all significantly enhanced the biliary excretion of cadmium. At 24 h after cadmium injection, BGD and MeOBGD were the most effective on the biliary excretion of the metal. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after cadmium treatment. At 24 h after cadmium treatment, BGD and MeOBGD significantly depressed cadmium content in the liver. In another experiment, rats were injected intraperitoneally with 109CdCl2 and 3 d later, they were injected with BGD, HBGD, or MeOBGD every other day for 2 weeks. The fecal excretion of cadmium was significantly increased by these chelating agents and MeOBGD was the most effective. The hepatic and renal cadmium contents were significantly decreased after BGD, HBGD or MeOBGD injection. The injection of MeOBGD to rats pretreated with cadmium was more effective than that of BGD, HBGD, or CBGD in removing cadmium from the liver. HBGD injection was more effective in decreasing the cadmium content in the kidney. The treatment with these chelating agents did not cause the redistribution of cadmium to brain, testes, and heart.

Animals↗

PubMed1991

N-fatty acyl compounds inhibit myristoyl acylation of pp60v-src and reduce tumorigenicity of Rous sarcoma virus-infected cells.

Prevention of NH2-terminal myristoylation of pp60v-src was determined with N-fatty acyl glycinal derivatives. Of all the compounds tested, N-myristoyl and N-lauroyl glycinal diethylacetal, N-myristoyl glycyl glycinal diethylacetal, and N-myristoyl-4-aminobutyl aldehyde diethylacetal strongly inhibited myristoylation of pp60v-src; but N-myristoyl diglycyl, N-myristoyl triglycyl, N-decanoyl glycinal diethylacetal, and N-palmitoyl glycinal diethylacetal did not. N-Myristoyl glycinal diethylacetal (25 or 50 microM) suppressed both morphological transformation and colony formation of Rous sarcoma virus-infected chick embryo fibroblasts.

Acylation↗

PubMed1991

[Intracranial accumulation of 99mTc-phosphorous compound on bone scintigraphy].

Bone scintigrams of 99mTc-phosphorous compound in 4,579 cases were reviewed concerning the intracranial accumulation. Intracranial accumulations were demonstrated in 8 cases (0.17%). The lesions with intracranial accumulation were two cases of primary brain tumor (1 meningioma and 1 astrocytoma), five cases of metastatic brain tumor (1 rectal cancer, 1 gastric cancer, 1 uterine cervical cancer and 2 lung cancers) and one case of cerebral infarction. Calcification was detected in one of eight cases on CT scans. It is important to pay attention to the intracranial accumulation on routine bone scintigram because brain tumor or infarction may be detected.

Aged↗

PubMed1991

Comparison of the effectiveness of dithiocarbamates on the excretion and distribution of cadmium in mice.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-methoxybenzyl-D-glucamine dithiocarbamate (MeOBGD) were evaluated for their efficacy in the distribution and excretion of cadmium in mice exposed to cadmium. Mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 74 kBq of 109Cd/mouse) and 30 min or 24 h later, they were injected i.p. with chelating agents (5% of an LD50). The results of this study indicated that the injection of HBGD to mice pretreated with cadmium can remove cadmium from the body without redistribution of cadmium to the brain, testes, and heart more effectively than that of BGD or MeOBGD.

Animals↗

PubMed1991

Novel anticoagulant peptides from the functional site of human placental anticoagulant protein.

Histidine-containing peptides SHLRKV and DHTLIR, corresponding to placental anticoagulant protein-I (PAP-I) residues 204-209 and 266-271, respectively, are included in the functional site of PAP-I and exhibit anticoagulant activity, but the peptides in which alanine is substituted for histidine do not. However, the peptide KHALKG, corresponding to the region from Lys-97 to Gly-102, did not exhibit an anticoagulant activity, showing that it is not included in the functional site. These findings thus suggest that His-205 and His-267 are involved in the Ca(2+)- or the phospholipid-binding site of PAP-I but that His-98 is not.

Amino Acid Sequence↗

PubMed1991

[An experimental study on the etiology of chondromalacia patellae].

Chondromalacia patellae is one of the common causes of patellofemoral disorders in young subjects. It frequently occurs in patients with lateral subluxation of the patella. However, the etiology of this disease is still obscure. The purpose of this study was to elucidate the histological changes of articular cartilage and bone in chondromalacia patellae. Lateral subluxations of the patellae were produced experimentally in forty New Zealand white rabbits. The mean tilting angle of the patellae was 14.2 degrees just after surgery, 10.7 degrees after 6 weeks, and 7.1 degrees after 12 weeks respectively. Contact pressure was lower on the medial facets than on the lateral facets and both facets of the controls. Macroscopic changes on the patellar cartilage did not appear until 12 weeks postoperatively. On the other hand, histological changes such as vascular invasion of the calcified layer, irregularity of tidemark and a decrease in the number of chondrocytes in the deep layer of the cartilage were observed on the medial facet about 4 weeks postoperatively. The degeneration of chondrocytes and matrix gradually progressed from the deep layer to the superficial layer. Twelve weeks after, a depressed area was shown in the medial facet macroscopically. Repairing process was substantiated such as the proliferation of synovial tissue, the cluster formation of chondrocytes and the recurrence of the tidemark about 30 weeks postoperatively. From the results mentioned above, it is suggested that cartilaginous and bony degeneration were caused by a decrease in contact pressure on the articular cartilage. The histological features of the chondromalacia patellae would be eventually developed by degenerative changes and restorative reaction.

Animals↗

PubMed1990

Human cellular src gene product: identification of the myristoylated pp60c-src and blockage of its myristoyl acylation with N-fatty acyl compounds resulted in the suppression of colony formation.

A p60K protein in human colon adenocarcinoma tumor cell lines was identified as a myristoylated pp60c-src by fluorography and radioimmunoprecipitation analysis. Prevention of the myristoylation of pp60c-src was determined with N-fatty acyl glycinal compounds. Of the compounds tested, N-myristoyl glycinal diethylacetal, N-lauroyl glycinal diethylacetal, N-myristoyl glycyl glycinal diethylacetal, and N-myristoyl-4-aminobutyl-aldehyde diethylacetal strongly blocked the myristoylation, but N-decanoyl glycinal diethylacetal and N-palmitoyl glycinal diethylacetal did not. The myristoyl blocking compounds depressed colony formation, cell proliferation, and specific localization to the plasma membrane of pp60c-src. The results taken together suggest that myristoylation of the c-src oncogene product may be very important for tumorigenicity of c-src gene expressed cells.

Acetaldehyde↗

PubMed1990

Myristoylated src-oncogene products are potently detected by the monoclonal antibody to the NH2-terminal myristoyl-Gly-Ser-Ser-Lys src-peptide.

Monoclonal antibodies were raised against a synthetic NH2-terminal myristoyl tetrapeptide (N-myristoyl-Gly-Ser-Ser-Lys) which is characteristic of an NH2-terminal portion of pp60src, the transforming protein of src-oncogene. The antibody reacted with the albumin conjugated with both the N-myristoyl and N-lauroyl-tetrapeptides, but concentrations at which 50% of the immunoreaction was inhibited were 5 pmol for the N-myristoyl and 830 pmol for N-lauroyl tetrapeptidyl albumin. On the other hand, N-palmitoyl tetrapeptidyl and underivatized albumin, and Gly-Ser-Ser-Lys-Ser-Lys-Pro-Lys octapeptide had no effects. These results suggest a high affinity of the antibody for an N-myristoyl-Gly-Ser-Ser-Lys moiety. src-Oncogene products in Rous sarcoma virus-transformed cells and human colon carcinoma tumor cells were selectively identified as myristoylated pp60src by immunoprecipitation analyses with the antibody.

Adenocarcinoma↗

PubMed1990

[Studies on insulin-like growth factors (IGF-I, -II) and there binding proteins in normal human pregnancy].

In order to elucidate the roles of Insulin-like Growth Factors (IGF-I, -II) in human pregnancy, the levels of IGF-I and IGF-II, the distribution of binding proteins for IGF-I or IGF-II and profiles of unsaturated somatomedin binding proteins (USBP) were estimated in maternal and cord plasma. IGF-I levels in maternal plasma gradually elevated in late gestation, reaching 304.4 +/- 130.1ng/ml at term, and were significantly higher than those in nonpregnant women (188 +/- 58). IGF-II levels, which were 414.9 +/- 75.4ng/ml in women in the third trimester of gestation, did not produce any remarkable changes in the levels in nonpregnant women (395.9 +/- 72.6). On the other hand, IGF-I in cord plasma also increased according to gestational age, reaching 37.3 +/- 14.6ng/ml at term, but it was significantly lower than that in maternal weight (r = 0.50, p less than 0.005) and relative birth weight (r = 0.41, p less than 0.005). IGF-II in cord plasma showed no significant changes during gestation, however, IGF-II levels in AFD (appropriate for date) newborns delivered at term (203.8 +/- 59.4) were significantly lower than those in maternal plasma. And they had no positive correlations with birth weight and relative birth weight. On Sephadex G150 gel-chromatography of cord plasma from AFD newborns at term, more than 70% of immunoreactive IGF-I in plasma was eluted at 150K region, and 150K USBP could be detected as observed in adult plasma. On the other hand, most of the immunoreactive IGF-II was eluted at 40K region, and 150K USBP was not detected in AFD newborns at term. In adult plasma, most of the immunoreactive IGF-II was eluted at 150K region, but 150K USBP could not be detected. From these results, it is supposed that IGF-I plays an essential role in fetal growth rather than IGF-II.

Adult↗

PubMed1990

The functional site of placental anticoagulant protein: essential histidine residue of placental anticoagulant protein.

Placental anticoagulant protein (PAP) rapidly lost its anticoagulant effect due to photooxidation in the presence of methylene blue at pH 7.9 and 8 degrees C. Photooxidized PAP failed to bind the phospholipid vesicle. It seemed unlikely that the protein underwent a change in molecular size during the photooxidation on the basis of its behavior in electrophoresis and gel filtration. Photooxidized PAP had significantly decreased histidine contents, whereas the contents of other amino acids remained essentially unchanged. The peptide, SHLRKV, was included in the functional site of PAP and still showed an anticoagulant activity. On the other hand, the peptide which substituted histidine by alanine, SALRKV, no longer showed the activity. It was shown that the histidine residue is involved in Ca2+ or the phospholipid binding site of the protein.

Amino Acid Sequence↗