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Biomedical subjects

T Funakoshi

Publications and source records attributed to T Funakoshi.

At least 127 records · Page 7Linked to original sources
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

[Long-term results of cerebral arteriovenous malformations--surgical and conservative treatment].

During the past 20 years, we have treated 187 cases with cerebral arteriovenous malformations (AVMs). These 134 patients were treated surgically and the remaining 53 patients were managed non-surgically. The purpose of this study is to clarify the surgical indications of AVMs, based on a comparison of the long-term follow-up results between the surgical and nonsurgical groups. Consequently, good results were obtained in the surgical group: the operative mortality was 7.5% and the morbidity was 12.7%. The long-term follow-up results were as follows: Of the 124 followed cases in the surgical group, there were 16 cases with improvement of neurological deficits (13%) and 3 cases with neurological aggravation (2%). Of the 47 followed cases in the nonsurgical group, there were 5 cases with improvement of neurological deficits (11%) and 6 cases with neurological aggravation (13%). As for the incidence of AVM hemorrhage, there were 8 cases with hemorrhage in the nonsurgical group including 4 cases (3 rebleeding cases) which were fatal (11%), in contrast to one case (subtotal resection) in the surgical group. On follow-up angiography, the size of AVMs were unchanged in the majority of cases in the nonsurgical group, with the exception of 2 cases in which there were slight regressions. In the surgical group, on the other hand, enlargement in 2 cases and spontaneous regression in 3 of residual AVM occurred following incomplete resection. Particularly in 2 cases involving unresectable AVMs, a newly formed aneurysm was discovered in the follow-up angiography, emphasizing the fact that serious follow-up angiography is required in cases of untreated AVMs.

Adolescent↗
PubMed1989

[Insulin-like growth factor (IGF) receptor in human fetal erythrocytes and fetal rat liver].

In order to clarify the potential role of IGF-I in fetal growth, the dynamics of IGF receptor were investigated in comparison with insulin receptor in human and rat fetuses. In humans, the serum levels of IGF-I measured by IGF-I radioimmunoassay after acid-ethanol extraction were significantly lower in fetuses than in adult controls. Conversely, serum insulin levels in fetuses were not indistinguishable from those in adults. On the other hand, specific binding of 125I-IGF-I to human fetal erythrocytes was 2.3%, which was significantly higher than that of adult women (1.6%). Insulin binding to the erythrocytes was also higher in human fetuses than in adult controls (cord: 3.8%, adult: 3.0%). By Scatchard analysis, the changes in the specific binding of IGF-I and insulin were mainly due to the changes in the binding capacity rather than those in the binding affinity. Additionally, IGF receptor on human fetal erythrocytes was recognized as type I IGF receptor, because the binding of 125I-labelled IGF-I and 125I-labelled IGF-II could be displaced by the addition of cold IGF-I, IGF-II and insulin. In rats, serum levels of IGF-I were also much lower in fetuses than in adult controls. Specific binding of 125I-IGF-I to liver microsomal membranes was 34.3% (per 400 micrograms protein) in fetal rats (D20), which was significantly higher than that of adult rats (3.2%). Scatchard analysis indicated that these changes in 125I-IGF-I binding was chiefly due to the changes in binding capacity. On the other hand, serum insulin levels increased with progress of pregnancy, and specific binding of insulin to microsomal membranes of fetal liver increased on D21 of gestation, mainly due to the increase in binding affinity rather than binding capacity. The bindings of 125I-labelled IGF-I and 125I-labelled IGF-II to fetal liver microsomal membranes were clearly displaced by cold IGF-I and IGF-II but not by excess of cold insulin, indicating that the receptor was type 2 IGF receptor. These results suggest that IGF-I possesses much more receptor in fetal tissues than in adult tissues despite its lower concentration in fetal sera. It is speculated that IGF-I may play an important role in fetal growth and development.

Adult↗
PubMed1989

Antibodies to an NH2-terminal myristoyl glycine moiety can detect NH2-terminal myristoylated proteins in the retrovirus-infected cells.

Novel antibodies were raised against a synthetic NH2-terminal myristoyl glycine moiety which is characteristic of N-myristoyl-proteins. Antisera raised against N-myristoyl-Gly-hemocyanin reacted with N-myristoyl-Gly-[125I]albumin. The immunoreaction was competed for by albumin conjugated with N-myristoyl-glycine, while underivatized albumin had no effect. Of the [3H]myristate-labeled proteins detected, pp60v-src, which is a transforming protein of Rous sarcoma virus, and p19gag and p17gag, which are core proteins in the human T-cell leukemia virus and the human immunodeficiency virus, were identified as N-myristoylated proteins by the radioimmunoprecipitation analyses with the antibody.

Amino Acid Sequence↗
PubMed1989

[A case of leprechaunism with disorders of insulin-like growth factor-I(IGF-I)/somatomedin C(SMC) binding protein and its receptor].

Leprechaunism is a rare genetic disorder characterized by physical abnormalities, intrauterine and postnatal growth retardation, poorly developed subcutaneous fat and muscle at birth, and early death. This patient, who was a 1.5 year-old female with typical clinical features of leprechaunism, had relatively high levels of plasma GH and IGF-I/SMC but no glucose intolerance or insulin resistance. Studies were undertaken to elucidate (1) the differences among some kinds of methods for IGF-I/SMC measurement, (2) the distribution patterns of IGF-I/SMC between two kinds of its binding protein (SMBP) in plasma, and (3) the dynamics of IGF-I/SMC receptor in her erythrocytes and liver microsomal membranes. The results were as follows: (1) The level of IGF-I/SMC measured by Nichols radioimmunoassay kit was 1.33U/ml, which was higher than that of infants the same age. Conversely, it was lower than that of the control which was measured by radioimmunoassay using recombinant IGF-I/SMC after acid-ethanol or Seppak C18 extraction. (2) By Sephadex G150 gel-chromatography, immunoreactive IGF-I/SMC was eluted predominantly in 150K region, and two apparent peaks of unsaturated somatomedin binding protein (USBP) were determined in a neonatal infant (appropriate to date), a normal adult and an infant of the same age as this patient. On the other hand, immunoreactive IGF-I/SMC was located only in the fractions corresponding to 40K region, and only one peak of USBP could be estimated in the region of 40K dalton. (3) The IGF-I/SMC receptor in the patient's erythrocytes possessed significantly lower binding affinity but higher binding capacity in comparison with that of the normal neonate and adult. In addition, the receptor in liver microsomal membranes obtained from this patient at autopsy also indicated lower affinity but higher capacity than that of fetuses at more than 19 weeks of gestation. This was coincident to that of fetuses less than 19 weeks of gestation. These results suggested that this patient resembled the intrauterine fetus before midgestation not only in the co-relationship among GH, IGF-I/SMC and its binding proteins, but also in the characteristics of its receptor. The severe growth retardation existing in this patient may be, at least partly, due to the abnormality and/or immaturity of IGF-I/SMC function. It is speculated that leprechaunism could be classified in relation to fetal growth mechanism by aspects of biological functions of IGF-I/SMC during development.

Abnormalities, Multiple↗
PubMed1989

Analysis of reruptured cerebral aneurysms and the prophylactic effects of barbiturate therapy on the early stage.

During the past seven years, we have studied 661 cases of ruptured intracranial aneurysms. Rebleeding occurred in 65 cases (10%) and, within this group, 43 cases (70%) rebled within the first 6 hours after initial subarachnoid haemorrhage (SAH). Analysis of these 43 cases led to the following conclusions: 22 patients incurred rebleeding from causes such as transfer (6 cases), neuroradiological examinations (13 cases), and tracheal intubation during anaesthesia etc. (3 cases), while no special causative factors were discovered in the other 21 cases. Rebleeding occurred in 19 patients even while on absolute bed rest and in 11 patients who had induced systemic arterial hypotension (under 140 mmHg) through treatment. Six cases experienced rebleeding while undergoing angiography within 6 hours after the first subarachnoid haemorrhage. Eight of 17 reruptured anterior cerebral complex (Acom) aneurysm cases and 8 of 11 reruptured middle cerebral artery (MCA) aneurysm cases had an intracerebral haematoma on initial CT-scan following the first attack, demonstrating that the risk of rebleeding was very high in cases of intracerebral haematoma. The mortality rate for these rebleeding cases was high i.e. 65%. Therefore, because the time factor could precipitate rebleeding, early transfer and operation was considered optimal for minimizing rebleeding soon after an aneurysm rupture, even though angiography within 6 hours of the first SAH was a serious risk. Barbiturate therapy, performed as early as possible for serious cases, was considered to be effective in preventing rebleeding.

Adult↗
PubMed1989

[Intraoperative radiation therapy for malignant glioma].

Intraoperative radiation therapy (IOR) is an ideal means of exterminating residual tumor after surgical resection. In this study, the clinical results of IOR using a Scanditronix Microtron MM-22 were evaluated in 14 patients with malignant glioma, five of whom had recurrent tumors. Between July, 1985 and October, 1986, 11 patients with glioblastoma multiforme (GB) were irradiated 18 times (mean, 1.6 times/case), and three with astrocytoma (Kernohan grade III) underwent IOR once each. The target-absorbed dose at 1 to 2 cm deeper than the tumor resection surface was 15 to 50 Gy. During irradiation, a cotton bolus was placed in the dead space after over 91% of the tumor had been resected. As a rule, external irradiation therapy was also given postoperatively at a dose of 30 to 52 Gy. One patient died of pneumonia and disseminated intravascular coagulation syndrome 1 month postoperatively. The 1- and 2-year survival rates of the remaining 13 patients were 84.6% and 61.5%, respectively; among the 10 with GB, they were 80% and 50%. Generally, the smaller the tumor size, the better the results. There were no adverse effects, despite the dose 15 to 50 Gy applied temporally to the tumor bed. IOR was especially effective against small, localized tumors, but was not always beneficial in cases of large tumors, particularly those with a contralateral focus. The improved survival rate in this series demonstrates that IOR is significantly effective in the "induction of remission" following surgical excision of malignant gliomas.

Adult↗
PubMed1989

[Artifacts in magnetic resonance imaging of the head].

The results of 505 magnetic resonance (MR) imaging examinations of the head disclosed several different types of artifact. Various artifacts observed with two-dimensional Fourier transformation are described and illustrated. All images were obtained with a 0.5 Tesla superconducting MR imager. About 70% of all images contained artifacts. Phase encoding artifacts due to motion or flow were most frequently observed. Center, "zipper," truncation, radiofrequency, and ferromagnetic artifacts and contrast error on inversion recovery (IR) images were noted less frequently. Phase encoding artifacts and contrast errors on IR images totally degraded the images, and "zipper" artifacts were regional. Center artifacts resembled small infarctions, and ferromagnetic artifacts sometimes mimicked hematomas. It is important to recognize these artifacts and to devise methods to avoid their influence on the region of interest.

Brain↗
PubMed1989

Clinical features and outcome in 68 cases of aneurysmal subarachnoid hemorrhage without aneurysm repair--a community hospital study.

The authors studied the clinical features and outcome at 6 months in 191 patients with subarachnoid hemorrhage (SAH) from ruptured aneurysms. Aneurysm repair (AR) was undertaken in 123 cases (64.4%). In the non-AR group (n = 68), 48.5% of the patients were 70 years of age or older, compared with 12.2% in the AR group. The duration from onset to admission was less than 3 hours in 48 non-AR cases (70.6%) and in 42 AR cases (34.1%). Among non-AR patients, 63.2% were Hunt and Hess grade IV or V, whereas the figure for AR patients was only 14.7%. By 6 months after SAH, 94.1% of non-AR patients had died, and the remainder were vegetative or severely disabled. In contrast, only 15.4% in the AR group died, and over 50% showed good recovery. The large majority of non-AR patients were treated conservatively because they were judged to be poor surgical risks and, among these patients, nearly one half were elderly. In the 10 elderly patients considered good surgical candidates, vasospasm was the most common reason (70%) for not performing AR.

Adult↗
PubMed1989

Depression of prolylendopeptidase activity in the delayed hypersensitive guinea pig skin lesion induced by bovine gamma-globulin.

Prolylendopeptidase activity was increasingly depressed with time from 6 to 24 hr after the start of sensitization in the delayed hypersensitive guinea pig skin lesion induced by bovine gamma-globulin as an antigen. The remarkably depressed activity of the enzyme in the violently inflamed skin began to be restored slowly 48 hr after sensitization, and its activity was ultimately recovered to the original level by 504 hr after a single sensitization in vivo. Depression of the enzymatic activity is caused by a novel prolyendopeptidase inhibitor, whose amino acid composition is 7 Glu, 1 Ser, 2 Gly, 1 Ala, 2 Pro, and 1 Val, generated by inflammation.

Amino Acids↗
PubMed1989

[Estimation of passive smoking during pregnancy by cotinine measurement and its effect on fetal growth].

Maternal cigarette smoking has been associated with some complications of pregnancy, including low birth weight and increased morbidity. Recently, it has been reported that maternal passive smoking also affects the fetal environment and causes fetal growth disturbance. In this study, we aimed to investigate the effects of maternal passive smoking on pregnant women and their fetuses by measuring cotinine concentrations in maternal urine and umbilical cord blood. The results were as follows: 1) Among 259 pregnant women, 17 cases (6.6%) were active smokers. The women who were not aware of passive smoking at all, were only 39 cases (15.1%). More than 80% of the pregnant women smoked either passively or actively each day. 2) Cotinine concentrations in both maternal urine and umbilical cord blood increased with the increase in passive smoking. Those in maternal serum, however, did not correlate with the increase in passive smoking. 3) The relative birth weight (R.B.W.) of the newborn infants delivered by the mothers whose cotinine concentration was more than 9.0ng/ml (This value represented the mean +1.5SD of the cotinine concentration in the urine from the mother who did not passively or actively smoke) was significantly lower than that of the mothers whose cotinine concentration was less than 9.0ng/ml. It is concluded that the measurement of the cotinine concentration in maternal urine or umbilical cord blood is very useful in estimating the effects of passive smoking on pregnant women. And passive smoking as well as active smoking also has a harmful effect on the fetal growth mechanism.

Birth Weight↗
PubMed1988

Placental anticoagulant proteins: isolation and comparative characterization four members of the lipocortin family.

Previously we isolated and characterized a placental anticoagulant protein (PAP or PAP-I), which is a Ca2+-dependent phospholipid binding protein [Funakoshi et al. (1987) Biochemistry 26, 5572] and a member of the lipocortin family [Funakoshi et al. (1987) Biochemistry 26, 8087]. In this study, three additional anticoagulant proteins (PAP-II, PAP-III, and PAP-IV) were simultaneously isolated from human placental homogenates prepared in the presence of 5 mM ethylenediaminetetraacetic acid. The isoelectric points of PAP-I, PAP-II, PAP-III, and PAP-IV were 4.8, 6.1, 5.9, and 8.1, respectively, and their apparent molecular weights were 32,000, 33,000, 34,000, and 34,500, respectively. Amino acid sequences of cyanogen bromide fragments of these proteins showed that PAP-III was a previously unrecognized member of the lipocortin family, while PAP-II was probably the human homologue of porcine protein II and PAP-IV was a derivative of lipocortin II truncated near the amino terminus. Comparative studies showed that all four proteins inhibited blood clotting and phospholipase A2 activity with potencies consistent with their measured relative affinities for anionic phospholipid vesicles. However, PAP-IV bound to phospholipid vesicles approximately 160-fold more weakly than PAP-I, while PAP-II and PAP-III bound only 2-fold and 3-fold more weakly. These results increase to six the number of lipocortin-like proteins known to exist in human placenta. The observed differences in phospholipid binding may indicate functional differences among the members of the lipocortin family despite their considerable structural similarities.

Amino Acid Sequence↗
PubMed1988

Electrophoretic and spectroscopic analyses of equine alpha 2-macroglobulin with cleavage of the thiol ester bonds by methylamine.

Reaction of equine alpha 2-macroglobulin (alpha 2M) with methylamine caused generation of 3.7 mol of thiol groups per mole of the protein, and the second-order rate constant of the generation was calculated to be 3.5 M-1 s-1. The inhibitory profile of caseinolytic activity of trypsin indicated that one molecule of equine alpha 2M inhibited two molecules of trypsin, similar to human alpha 2M. The methylamine-treated equine alpha 2M, with complete cleavage of the thiol ester bonds, still inhibited the activity of trypsin, though human alpha 2M lost its inhibitory activity by treatment with methylamine. These results indicate that the mode of inhibition of trypsin by equine alpha 2M is substantially unperturbed by cleavage of the thiol ester bonds and that the intact thiol ester bonds per se are not essential for the ability of equine alpha 2M to bind the enzyme. Ultraviolet absorption difference, intrinsic fluorescence, and circular dichroism spectra of the methylamine-treated equine alpha 2M showed that this treatment caused only a small change in conformation of the protein. Reaction of the methylamine-treated protein with trypsin induced appreciable changes in the spectra, indicating a large change in conformation of the protein. These findings were consistent with the results obtained by electrophoresis: The band of methylamine-treated equine alpha 2M showed indistinguishable mobility from that of the unmodified protein, indicating that no appreciable change in conformation occurred, and distinctly different mobility from that of the unmodified or methylamine-treated equine alpha 2M when each had reacted with trypsin.

Animals↗
PubMed1987

Primary structure of human placental anticoagulant protein.

The primary structure of human placental anticoagulant protein was determined by a combination of amino acid and nucleotide sequencing techniques. The carboxymethylated protein was digested with cyanogen bromide, and the resulting peptides were separated by gel filtration and high-performance liquid chromatography. A total of 239 out of 319 amino acid residues were identified from 7 cyanogen bromide fragments. A full-length cDNA clone encoding placental anticoagulant protein was isolated from a human placenta cDNA library. This clone was 1.6 kilobases long and contained a translation initiation site coding for methionine, 957 nucleotides encoding for the mature protein, a stop codon, a poly(A) recognition site, and a poly(A) tail. Analysis of the tryptic-blocked peptide that originated from the NH2-terminus of the protein showed that the terminal methionine was removed and the adjacent alanine residue was acetylated by posttranslational events. Placental anticoagulant protein is composed of 319 amino acids with acetylalanine as the NH2-terminus and has a high degree of sequence identity with lipocortins I and II. It contains four internal repeats, each including a sequence corresponding to a putative Ca2+-dependent phospholipid binding site. Placental anticoagulant protein is a member of the lipocortin/calpactin family.

Amino Acid Sequence↗
PubMed1987

Inhibition of human factor VIIa-tissue factor activity by placental anticoagulant protein.

Previous studies indicated that human placental anticoagulant protein, a member of the lipocortin family, prolonged the clotting time of normal plasma when clotting was induced by brain thromboplastin or by kaolin in the presence of cephalin and calcium. Using a two-stage amidolytic assay to assess factor X activation and a tritiated peptide release assay to assess factor IX activation, we have examined the ability of purified preparations of placental anticoagulant protein (Mr = 36.5 kDa) to inhibit the activation of either factor X or factor IX by a complex of human factor VIIa-tissue factor. Placental anticoagulant protein markedly inhibits factor X and factor IX activation by factor VIIa-tissue factor in a non-competitive manner with Ki values of 40 nM and 70 nM, respectively. Placental anticoagulant protein had no effect on factor Xa amidolytic activity, and its inhibitory activity was not diminished by prior incubation with antibody raised against partially purified plasma extrinsic pathway inhibitor. Binding of placental anticoagulant protein to phospholipid vesicles, crude tissue factor and purified, relipidated human brain tissue factor apoprotein was observed only in the presence of calcium ions. These results indicate that placental anticoagulant protein is a potent factor VIIa-tissue factor inhibitor and suggests that its mechanism of action involves binding to the phospholipid portion of the tissue factor lipoprotein.

Annexins↗