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Biomedical subjects

H Higashi

Publications and source records attributed to H Higashi.

At least 145 records · Page 8Linked to original sources

[Measurement of serum PSA by DELFIA PSA kit and its application for mass screening. The Gunma Urological Oncology Study Group].

The significance of prostate specific antigen (PSA) measured by DELFIA PSA kit in the 1,177 serum samples examined by mass screening for prostate cancer was evaluated. All subjects were examined by questionnaire, digital rectal examination (DRE) and prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening for the presence of prostate cancer. All serum specimens used for this study were kept in our serum bank. The cut-off value was investigated between non-cancer subjects (diagnosed as normal, voiding disturbance or BPH) and prostate cancer patients. When the cut-off value was 2.89 ng/ml, the sensitivity, specificity and accuracy as prostate marker was 80.6%, 90.0% and 89.4%, respectively. Therefore, the cut-off value was determined as 3.0 ng/ml. The significance of PSA was retrospectively evaluated compared to PAP in the subjects examined by our mass screening. Twenty eight of the 39 palpable prostate cancers which could not be detected from the PAP level were detected from the PSA level, namely the sensitivity of the detection using the PSA level is more excellent than that using PAP. However, the false negative rate obtained using PSA was high (30.3%) in the patients with stage B disease. The relationship among serum PSA concentration, prostate size estimated by DRE and age was investigated. PSA was increased with age and prostate size. This estimation should be confirmed by using an ultrasonography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasonography.

Adult↗

[A case of low grade glioma with Takayasu disease (aortitis syndrome)].

We experienced a rare case of Takayasu disease with low grade glioma. A 36 year-old female had an episode of right hemiconvulsion. On admission, she complained a slight memory disturbance, urination difficulty and motor weakness of right extremities. CT scan demonstrated a low density lesion in the left frontal lobe. MRI showed an inhomogeneous low intense mass on T 1 WI and a homogeneous high intense mass on T2 WI in the same site. No abnormal contrast enhancement was observed in both CT and MRI. Bilateral carotid angiograms demonstrated a filling defect of the left anterior cerebral artery. An aortogram revealed moderate stenosis of the left carotid artery and the brachiocephalic artery, and complete obstruction of the left subclavian artery. CT-guided stereotactic biopsy was performed using BRW stereotactic system and histological diagnosis was astrocytoma grade II. She was followed by interstitial irradiation of 50 Gy at tumor periphery for 10 days. Her neurological symptoms gradually improved, and she is doing well without neurological deficits at the time of this report. The CT scan obtained 13 months after the brachytherapy revealed a decrease in the extent of low density. Brachytherapy seems to be useful for patients with low grade glioma in the eloquent area of the brain.

Adult↗

[Two cases of metastatic brain tumor treated by interstitial brachytherapy].

The prognosis of patients with metastatic brain tumor is very poor. Median survival of these patients has ranged from 1 month with no therapy, to 2 months with steroid, and from 3 to 6 months with brain radiation therapy of the whole brain. A more recent study comparing radiation therapy alone with surgery plus radiation, has shown good results in the combined surgery and radiation therapy group. But surgical excision is usually limited to patients with a surgically accessible solitary metastasis. And therapeutic options are limited once the tumor recurs locally after whole brain irradiation. Interstitial irradiation allows the delivery of a high dose of localized irradiation in the area of tumor recurrence with minimal risk of radiation damage to the surrounding brain tissue. But brachytherapy for brain metastasis has been performed in few cases. We reported two patients with unresectable metastatic brain tumors who were successfully treated with iridium-192 interstitial brachytherapy, and we discuss the strategy of the treatment. Case 1: A 78 year-old-man underwent a total gastrectomy for gastric cancer. Five months after surgery, he developed right hemiparesis. CT scan revealed a left occipital tumor with massive brain edema and a tiny nodule of tumor in the left thalamic region. The primary site was well-controlled and no systemic disease was seen during subsequent whole body examination. The occipital lesion was surgically excised and he received a postoperative radiation therapy of 50 Gy to the whole brain. The thalamic tumor had not responded to the irradiation and the size of tumor rapidly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Butyrolactone I, a selective inhibitor of cdk2 and cdc2 kinase.

We screened cdc2 kinase inhibitors from cultured mediums of micro organisms using purified mouse cyclin B-cdc2 kinase and a specific substrate peptide for cdc2 kinase. A selective inhibitor of cdc2 kinase was isolated from the cultured medium of Aspergillus species F-25799, and identified as butyrolactone I. Butyrolactone I inhibited cdc2 and cdk2 kinases but it had little effect on mitogen-activated protein kinase, protein kinase C, cyclic-AMP dependent kinase, casein kinase II, casein kinase I or epidermal growth factor-receptor tyrosine kinase. Its inhibitory effect was found to be due to competition with ATP. Butyrolactone I selectively inhibited the H1 histone phosphorylation in nuclear extracts. It also inhibited the phosphorylation of the product of retinoblastoma susceptibility gene in nuclear extracts and intact cells. Thus butyrolactone I should be very useful for elucidating the function of cdc2 and cdk2 kinases in cell cycle regulation.

4-Butyrolactone↗

[A case of glial microtumor treated with brachytherapy using MRI guided stereotactic system].

A 34 year old male suffered from convulsion on his right side with loss of consciousness. Neither plain nor enhanced CT could clearly demonstrate a lesion. However, a Gd-DTPA enhanced T1 weighted image (T1WI) demonstrated an enhancing lesion (2 cm in diameter) in the left frontal lobe including the motor cortex. This lesion was not identified on plain T1WI. A T2 weighted image (T2WI) showed a high intensity lesion without mass effect slightly larger than the enhanced area on T1WI. This lesion was suspected to be a glial microtumor, but, because it was difficult to differentiate it from a cerebral infarction, it was confirmed to be a neoplasm by means of an MRI guided stereotactic biopsy. The histological diagnosis of the frozen section was a grade 2 astrocytoma. Subsequently brachytherapy with 192Ir seeds was performed, and about 80Gy of interstitial irradiation was given to the edge of the enhanced area on MRI. The minimum dose in the high intensity area on T2WI was about 50Gy. The patient was discharged with no neurological deficits. The Gd-DTPA enhanced lesion decreased in size six months after the treatment. MRI guided stereotactic system makes it possible to target a high intensity lesion on T2WI in brachytherapy. Brachytherapy using this system is considered to be useful in the treatment of glial microtumor in an area in which it is difficult to identify it on CT.

Adult↗

Extracorporeal hepatic resection for previously unresectable neoplasms.

BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past.

Extracorporeal Circulation↗

Full activation without calmodulin of calmodulin-dependent cyclic nucleotide phosphodiesterase by acidic glycosphingolipids: GM3, sialosylneolactotetraosylceramide and sulfatide.

Among calmodulin-non-binding glycosphingolipids, GM3, sialosylneolactotetraosylceramide (LM1), and sulfatide potently activated calmodulin-dependent cyclic nucleotide phosphodiesterase with or without Ca2+ showing ED50 1-5 microM. In contrast to calmodulin-binding gangliosides, these glycosphingolipids activated the enzyme up to the maximum level achieved by Ca2+/calmodulin and did not inhibit the activity at higher concentrations. Competition studies with GD1b that bind both to calmodulin and the enzyme suggest that the calmodulin-non-binding glycosphingolipids activate the enzyme through interaction with the same site of the enzyme as GD1b interacts.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Mechanism for ganglioside-mediated modulation of a calmodulin-dependent enzyme. Modulation of calmodulin-dependent cyclic nucleotide phosphodiesterase activity through binding of gangliosides to calmodulin and the enzyme.

Gangliosides were recently shown to bind to calmodulin (Higashi, H., Omori, A., and Yamagata, T. (1992) J. Biol. Chem. 267, 9831-9838). This prompted us to investigate the effects of gangliosides on the calmodulin-dependent enzyme, cyclic nucleotide phosphodiesterase. Several species of gangliosides competitively inhibited calmodulin-stimulated phosphodiesterase activity, with GD1b, GT1b, and GD1a being noted to do so particularly (group 1). GM1, GQ1b, and GM2 (group 2) were less inhibitory, and GM3, GM3(NeuGc), GalCer, sulfatide, GgOse4Cer, and oligosaccharide portions of inhibitory gangliosides showed no inhibition in accordance with the binding specificity of calmodulin to gangliosides. Trypsin-activated phosphodiesterase was inhibited by gangliosides with similar specificity, indicating interactions of gangliosides with the enzyme. Inhibition, however, was less than that of calmodulin-dependent activity by these compounds and, in both cases, was eliminated by excess calmodulin. In the absence of calmodulin, group 1 gangliosides at lower concentrations activated the intact enzyme but inhibited it over a certain range of increase in concentration. Ganglioside-dependent modulation of calmodulin-dependent phosphodiesterase activity is thus shown to be due to interactions of gangliosides with both calmodulin and the enzyme, and consequently, ganglioside-calmodulin binding is likely the mechanism for regulation of the enzyme.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Calmodulin, a ganglioside-binding protein. Binding of gangliosides to calmodulin in the presence of calcium.

Ca(2+)-dependent ganglioside-binding protein was isolated from a soluble cytosol fraction of mouse brains using a ganglioside affinity column prepared with a mixture of bovine brain gangliosides. It was identified as calmodulin based on the following features identical with those of calmodulin: molecular weight, pI, chromatographic profile and amino acid sequences of lysyl-endopeptidase digests, and ability to activate cyclic nucleotide phosphodiesterase. Bovine brain calmodulin derivatized with 5-dimethylaminonaphthalene-1-sulfonyl (dansyl-calmodulin), tetramethylrhodamine isothiocyanate, or biotin was also shown to bind to the ganglioside affinity column Ca2+ dependently and elute with gangliosides GD1a, GD1b, GT1b, GQ1b, GM1, and GM2, melittin, and trifluoperazine but not with GgOse4Cer and oligosaccharides of GM1, GD1a, and GT1b. Modification of the Lys94 residue of calmodulin by biotinylation drastically reduced the capacity for ganglioside binding. Ganglioside GD1b caused a blue shift and increase in intensity of the fluorescence emission spectrum of dansyl-calmodulin in the presence of Ca2+. The increment in fluorescence was proportional to the amount of GD1b added and was maximal at the molar ratio of GD1b to calmodulin, approximately 7.8. Gangliosides are thus shown to specifically bind to calmodulin, and this binding may be a general mechanism for regulating calmodulin-dependent enzymes with consequent cellular response, such as cell differentiation.

Amino Acid Sequence↗

Tyrosine phosphorylation and its possible role in superoxide production by human neutrophils stimulated with FMLP and IgG.

Superoxide production by human neutrophils stimulated with FMLP and soluble aggregated human IgG were inhibited in a dose dependent manner by two kinds of tyrosine kinase inhibitors, erbstatin and genistein. Superoxide production stimulated with surface bound IgG, however, was scarcely inhibited by either inhibitor. Protein tyrosine phosphorylation studies with immunoblotting revealed specific tyrosine phosphorylation of a 40 Kd protein by soluble aggregated and surface bound IgG, and that of a 39 Kd protein, as well as the 40 Kd protein, by FMLP. These were all inhibited by the tyrosine kinase inhibitors. These data suggest that superoxide production induced by FMLP and soluble aggregated IgG are, at least in part, tyrosine kinase dependent, but the tyrosine kinases and/or substrates of tyrosine kinases involved may be different. In addition, tyrosine kinase independent pathways are also suggested to be involved in superoxide production by stimulation with surface bound IgG.

Humans↗

Endoscopic injection sclerotherapy for 1,000 patients with esophageal varices: a nine-year prospective study.

We report here the results of endoscopic injection sclerotherapy performed in 1,000 consecutively treated Japanese patients with esophageal varices. This prospective study covered the period from 1982 to 1990. Variceal bleeding was controlled in 215 (97.7%) of 220 patients. Esophageal varices were completely eradicated in 778 patients (77.8%); the mean number of sessions was 4.2. In only 3 of the 778 patients did esophageal varices of the same size recur. Small, dilated, venous vessels that required additional sclerotherapy in follow-up endoscopy at 3-mo intervals appeared in 171 (22.2%) of 778 patients. The cumulative nonbleeding rate at 5 yr was 94.5% in patients in whom the varices had been eradicated. Deaths caused by upper gastrointestinal bleeding accounted for 2.6% of cases, whereas the rates of liver failure and hepatoma were 4.6% and 47.3%, respectively. The 5-yr cumulative survival rate was 54.1% in patients without concomitant hepatoma; it was 12.0% in patients with hepatomas. Multivariate analysis showed that hepatoma, Child classification, indication (acute, elective or prophylactic) and eradication were independent factors that significantly influenced survival time. This study clearly shows that close follow-up with endoscopy and complete eradication lead to significant reduction in bleeding from esophageal varices and reduction of mortality related to this bleeding.

Endoscopy↗

Pretransplant assessment of human liver grafts by plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors.

In spite of the improved outcome of orthotopic liver transplantation (OLTx), primary graft nonfunction remains one of the life-threatening problems following OLTx. The purpose of this study was to evaluate plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors as a predictor of liver allograft viability prior to OLTx. Thirty-nine donors were studied during a 5-month period between April and August 1988. Allograft hepatectomy was performed using a rapid technique or its minor modification with hilar dissections, and the allografts were stored cold (4 degrees C) in University of Wisconsin (UW) solution. Early post-transplant allograft function was classified as good, fair, or poor, according to the highest SGOT, SGPT, and prothrombin time within 5 days following OLTx. Procurement records were reviewed to identify donor data, which included conventional liver function tests, duration of hospital stay, history of cardiac arrest, and graft ischemic time. Blood samples from the donors were drawn immediately prior to aortic crossclamp, and from these plasma LCAT activity was determined. Plasma LCAT activity of all donors was significantly lower than that of healthy controls (12.4 +/- 8.0 vs 39.2 +/- 13.3 micrograms/ml per hour, P less than 0.01). LCAT activity (16.4 +/- 8.3 micrograms/ml per hour) in donors of grafts with good function was significantly higher than that in those with fair (8.6 +/- 4.5 micrograms/ml per hour, P less than 0.01) or poor (7.3 +/- 2.4 micrograms/ml per hour, P less than 0.01) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Preliminary results of interstitial 192Ir brachytherapy for malignant gliomas.

Twenty-six patients with recurrent or unremovable malignant gliomas were treated by interstitial brachytherapy with iridium-192 seeds. Stereotactic implantation of the afterloading catheters using the Brown-Roberts-Wells computed tomography (CT)-guided stereotactic system was performed in 24 patients and surgical implantation in two patients with pontine glioma. The response to therapy was measured by serial CT, magnetic resonance imaging, and clinical examination. Tumor regression was seen in 17 patients 1-3 months after implantation. Tumor progression was seen in only three patients. After interstitial brachytherapy, the most commonly observed CT finding was central low density. Median survival time was 18 months after implantation. Autopsies in five patients revealed the delayed effects of radiation injury such as typical vascular changes, microcalcification, and coagulative necrosis in the implant area and tumor recurrence at the periphery. The results suggest that brachytherapy is not curative but prolonged the median survival time by 6 months.

Adult↗

[A case of encephalitis with MRI abnormalities localized in the bilateral amygdala and hippocampus].

We report a patient with encephalitis who showed anterograde and retrograde amnesia with MRI abnormalities localized in the bilateral amygdala (AM) and hippocampus (HIPP). A 25-year-old man suddenly experienced a generalized tonic-clonic seizure (GTCS). He was admitted because of increasing lethargy with two further GTCSs during the following 6 days. The patient had high fever, and neurological examination revealed somnolence, disorientation, amnesia, and nuchal stiffness. MRI revealed bilateral symmetrical abnormalities localized in the AM and HIPP, which showed low intensity on T1-weighted images and high intensity on T2-weighted images. Cerebrospinal fluid examination showed a mildly elevated cell count. We suspected herpes simplex virus type I encephalitis and began treatment with acyclovir. After the patient regained a clear consciousness, his antero- and retrograde amnesia continued for several months. The MRI abnormality became less distinct with the improvement of amnesia. We consider that the MRI abnormality was indicative of inflammation and edema, and that the lesion in the AM and HIPP had induced the amnesia.

Acyclovir↗

[A cross-sectional study of lipid peroxide levels (plasma TBA levels) in a mass health examination].

Differences in plasma thiobarbituric acid (TBA) levels were studied by sex and age in 1,178 adults (471 males and 707 females) participating in a mass health examination conducted in a town of Kumamoto Prefecture in 1989. The relationships between plasma TBA levels and obesity, the consumption of cigarettes, alcohol, and fish, and various indices for health status derived from the data of physiological examinations were analyzed in age-groups 40-59 and 60-79 for both sexes. The prevalence of abnormal physiological findings by plasma TBA levels were further investigated. The results were as follows; 1. The highest plasma TBA levels for males were observed in the group aged 40-49, with levels gradually decreasing with age thereafter. The plasma TBA levels for females increased with age and the highest levels were obtained at age 60-69. The plasma TBA levels for males were significantly higher than for females at aged 40-49. 2. Plasma TBA levels for both sexes increased with obesity and the amount of fish consumed. 3. Plasma TBA levels in all examined groups had significant and strong positive correlations with serum total cholesterol levels and atherogenic indices, and had significant positive correlations with serum calcium and gamma-GTP levels. 4. A stepwise multiple regression analysis showed that plasma TBA levels for males were associated with serum total cholesterol, gamma-GTP, fish consumption and serum HDL-cholesterol in that order. The levels for female were associated with serum total cholesterol, body mass index, serum HDL-cholesterol and serum calcium in that order. The relationship with serum HDL-cholesterol was a negative correlation. 5. Prevalence of abnormal values of serum total cholesterol, atherogenic index and body mass index were significantly higher in the high-plasma TBA level group than in the group with median-plasma TBA level. These results suggest that plasma TBA levels may be useful as an index of undesirable lipid metabolism. Further studies should be performed to establish the significance of the relation of plasma TBA levels to fish consumption.

Adult↗

[A case report of primary pulmonary hypertension: congestive heart failure induced by pregnancy and delivery].

A thirty-year-old woman had complaints of general fatigue and gain in body weight, which had developed since the third trimester of pregnancy. On admission, she had lip cyanosis, general edema, and tachycardia. A chest rentogenogram showed cardiomegaly and dilatation of the pulmonary arteries. On cardiac catheterization, pulmonary artery pressure and pulmonary vascular resistance were elevated moderately. A pulmonary perfusion scintigram revealed a defect in the left lower lung field with no evidence of thrombus in a pulmonary artery angiogram. In this case, an underlying disease which caused pulmonary hypertension might have been the underfined cause. For this reason, primary pulmonary hypertension was the diagnosis. In the present case there is a danger that congestive heart failure may be induced by pregnancy and delivery and, furthermore, there is a possibility that during the clinical course of the illness pulmonary infarction might occur.

Adult↗

Quantitative determination of N-glycolylneuraminic acid expression in human cancerous tissues and avian lymphoma cell lines as a tumor-associated sialic acid by gas chromatography-mass spectrometry.

N-Glycolylneuraminic acid (NeuGc) is distributed in most animals except humans and chickens. However, human and chicken cancerous tissues often synthesize this heterophilic sialic acid as a tumor-associated Hanganutziu-Deicher antigen [M. Naiki and H. Higashi, Adv. Exp. Med. Biol., 152: 445-456, 1982; H. Higashi et al., Cancer Res., 45: 3796-3802, 1985]. In this paper, NeuGc in human cancerous tissues and chicken Marek's disease lymphoma cell lines was determined quantitatively with gas chromatography-mass spectrometry analysis using mass fragmentography. The detectable limit of NeuGc was 40 pg (0.12 pmol) in each injection using 5 ng of trideuteriomethyl ester trideuteriomethyl glycoside of the sialic acid as an internal standard sample when a pair of ions at m/e 386 and 389 was chosen for ion monitoring. NeuGc was detected in ganglioside-rich fractions of various human cancerous tissues from 5 of 8 patients examined but was not detected in glycosphingolipids of normal human tissues. The contents of NeuGc in these cancerous tissues ranged from 0.02 to 0.5% of the total sialic acid content. NeuGc was also detected in freeze-dried samples of 5 different cell lines from chicken Marek's disease lymphomas but was not detected in a cell line from chicken lymphoid leukosis lymphoma and normal chicken skeletal muscle tissue. The contents of NeuGc in the positive cell lines ranged from 0.03 to 0.11% of the total sialic acid content. These results indicate that NeuGc can be synthesized in both humans and chickens in some cancers.

Animals↗