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Biomedical subjects

T Funakoshi

Publications and source records attributed to T Funakoshi.

At least 37 records · Page 2Linked to original sources

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

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

[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

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

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

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

[Morphological detection of placental anticoagulant protein-I (PAP-I) in human placenta].

It has been reported that placental anticoagulant protein-I (PAP-I) inhibits the intrinsic and extrinsic pathways of blood coagulation and also the reconstituted prothrombinase activity. However, morphological study on the distribution of PAP-I in whole placenta or in placental cells has not been reported yet. We detected the PAP-I antigen, under light- and electron-microscope, by mean of immuno-cytological techniques. PAP-I was also present in microvilli of the placental syncytiotrophoblast cells and their cortical cytoplasm beneath the villi.

Annexin A5

[Cerebellar infarction: analysis of 33 cases].

During the past 9 years and 2 months we have encountered 33 cases with cerebellar infarction. These patients were classified into 3 types according to their clinical course. Type 1 (18 cases); The course was benign, and symptoms and signs improved without surgical treatment. Type 2 (11 cases); The course was progressive with deterioration of consciousness between 24-72 hours after the onset. Type 3 (4 cases); The course was rapid resulting in lapse into coma within a few hours. Also, its prognosis was fatal due to coexisting brain-stem infarction regardless of any treatment. Surgical intervention was required for Type 2 in which the lesion included the region of the vermis or occupied more than one-third of the cerebellar hemisphere, and had subsequently compressed the brain-stem and caused obstructive hydrocephalus. In 9 cases out of Type 2, ventricular drainage alone was performed and prompt improvement of consciousness level was detected except in one case. We consider that ventricular drainage is not so invasive a method, and it is beneficial. However, in 2 cases of Type 1 and 4 cases of Type 2, hemorrhagic infarction occurred. Thus, one should be aware of the possibility of hemorrhagic infarction, even though it may be asymptomatic infarction. If prompt improvement of consciousness is not detected after ventricular drainage, suboccipital craniectomy should be recommended.

Adult

[Cerebellar AVM--clinical analysis of 14 cases].

The authors report on their experience with 14 cases of cerebellar arteriovenous malformation (AVM), with emphasis on their clinical symptoms and treatment problems. The incidence of cerebellar AVM was 7.5% in all cases of intracranial AVM. Twelve of them presented with hemorrhages, one with a headache and one with a focal neurological deficit related to the "steal" phenomenon. Three out of 4 poor risk patients with intracerebellar hematoma recovered well after their operations. Thus, we can say that surgical treatment should be performed even if the patient's state seems hopeless. The nidus was located at the vermis in 7, at the cerebellar hemisphere in 5, and at the tonsil in 2 cases. The surgical approach to the superior surface of cerebellum or the tonsil near the brainstem became a problem. In our series, all surgically treated cases were approached through the suboccipital route with the patient in the prone position and the surgical results were favorable. On the other hand, one case which underwent conservative treatment died due to rebleeding. Thus, as the follow-up mortality with conservative treatment is higher and the results of surgery are better, surgical treatment should be attempted. Preoperative MR imaging is one of the useful methods used to determine whether an excision is possible without significant deficit, especially in cases in which the AVM is located near the brain stem. In our series, two patients had concomitant aneurysms related to feeding arteries. Another interesting case of a neonate who had a small tonsillar AVM is reported.

Adult

[Peripheral arterial aneurysm of the brain occurring after brain abscess extirpation and healing spontaneously-report of a case and review of the literature (author's transl)].

In 33 year-old man an aneurysm of a pheripheral branch of the right middle cerebral artery was disclosed by angiography 8 days after extirpation of a parietotemporal brain abscess. The aneurysm was absent in the preoperative angiogram. Since the site of the aneutysm coincided with the operative field, it is sure that the etiology of the aneurysm was related to operative trauma and/or arteritis. Although inflammatory or mycotic factor could not be excluded from its etiology, it seems reasonable that traumatic factor was major one. The aneurysm was found to have disappeared eventually in the angiogram made on 372th postoperative day. Traumatic aneurysms arising from peripheral branches of the intracranial arteries are very rare. The first case was reported by Krauland in 1949. We collected 32 such cases from the literature. Of the 33 cases including the present one, 5 are iatrogenic. In more than half of the 33 cases, aneurysms were formed within 14 days following head injury. Posttraumatic delayed hemorrhage was found in 15 cases, the hemorrhage occurring within one month following injury in 12 cases. Of 31 cases with known prognosis, 11 died, 6 of them dying of delayed hemorrhage. Aneurysm operation was performed in 21 cases and 15 of them survived. In the present case, aneurysm luckily healed spontaneously. There are two cases including the present one, of spontaneous healing in the 33 cases. We believe surgical treatment is one of choice whenever possible.

Adult