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Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 19 recordsLinked to original sources

Immunohistochemical study of bone GLA protein in primary bone tumors.

METHODS: The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex. RESULTS: As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed. CONCLUSION: These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.

Bone Neoplasms

Demonstration of a possible link between high grade malignancy in dimethylbenz[a]anthracene-induced rat mammary carcinoma and increased urokinase plasminogen activator content.

Recent reports have suggested that tissue-type plasminogen activator activity is regulated by estrogen in 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma type I cells but is not necessarily regulated by estrogen in type II mammary carcinoma cells. We have compared the biological features of these two types of mammary carcinoma cells and have found that, although there is no difference in estrogen receptor content between these two cell types, the plasminogen activator activity markedly differs. Tissue-type plasminogen activator activity is significantly higher in type I carcinoma than in type II carcinoma, urokinase-type activity is significantly higher in type II carcinoma than in type I carcinoma. When these two types were compared in terms of rate of tumor growth, type II carcinomas clearly showed more rapid growth than type I carcinomas. Survival studies showed significantly shorter survival of type II tumor-bearing rats compared with type I tumor-bearing rats. Furthermore, type II carcinomas contained a greater proportion of aneuploid cells than type I carcinomas. These results suggest that type II carcinoma cells, in which estrogen is unable to regulate tissue-type plasminogen activator activity, are considered to be of a higher grade of malignancy than type I carcinoma cells.

9,10-Dimethyl-1,2-benzanthracene

Interleukin-8 is constitutively and commonly produced by various human carcinoma cell lines.

We examined the production of interleukin-8 and interleukin-6 by 30 human carcinoma cell lines. Serum levels of interleukin-8 were measured in 14 patients with hepatocellular carcinoma by enzyme-linked immunosorbent assay and Northern blotting. Furthermore, serum interleukin-8 was also investigated in a nude mouse bearing a tumor of the HuH7 hepatoma cell line producing interleukin-8. Of the 30 cell lines, 29 (96.7%) constitutively produced interleukin-8, and 19 of the 29 (65.5%) were high producers (> 1 ng/ml culture supernatant). Among the high producers, 4 cell lines released both interleukin-8 and interleukin-6. Interleukin-6 was constitutively produced by 17 of the 30 (56.7%) cell lines, 4 of which (23.5%) were high producers (> 1 ng/ml). By Northern blot analysis, mRNAs of interleukin-8 and interleukin-6 were detected in producing cell lines. Of 14 patients with hepatocellular carcinoma 4 (28.5%) showed increased levels of serum interleukin-8. Furthermore, inoculation of the HuH7 hepatoma cell line which produced the highest amount of interleukin-8 into a nude mouse resulted in tumor production accompanied by an elevated level of human interleukin-8 (646 pg/ml) in the peripheral blood. Thus, interleukin-8 is constitutively and commonly produced by various carcinoma cell lines. The production of interleukin-8 by carcinoma cells may be related to the elevation of serum interleukin-8 in patients with hepatocellular carcinoma. Finally, these cell lines may be valuable for studying the relationship between interleukin-8 and cancer.

Animals

Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer.

This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus.

Bone Neoplasms

Lymphocytic active myocarditis characterized by numerous clusters of lymphocytes: a chronic variant of myocarditis?

We report three patients with a particular form of myocarditis characterized by numerous clusters of lymphocytes. Their common clinical manifestation was progressive and fatal heart failure with a 3- to 6-year duration. Atrioventricular and intraventricular conduction disturbances were observed in two patients. At necropsy, the hearts weighed 480, 530, and 430 gm, respectively, and showed marked dilatation of the bilateral ventricles and atria, with frequent mural thrombi. Histologic examination revealed numerous lymphocytic clusters and scattered foci of acute myocardial cell damage on a background of extensive fibrosis. We propose the term "chronic active myocarditis" to denote clinicopathologic characteristics of the present cases.

Atrial Fibrillation

Regression of coronary atherosclerosis by combined LDL-apheresis and lipid-lowering drug therapy in patients with familial hypercholesterolemia: a multicenter study. The LARS Investigators.

The purpose of the LDL-Apheresis Regression Study (LARS) group, which included 13 institutions in Japan, was to investigate the effects on coronary atherosclerosis of LDL-apheresis combined with cholesterol-lowering drugs. Changes in coronary artery stenosis were assessed angiographically in 37 patients with familial hypercholesterolemia (7 homozygotes and 25 heterozygotes) and hypercholesterolemia which had not been defined as familial hypercholesterolemia (5 patients) by visual judgement and computer analysis. Definite regression was observed in 14 cases, including 4 homozygotes and 10 heterozygotes and others. Regression occurred as often in patients with severe coronary artery disease (2 or more vessel disease) as in those having less severe disease. Our results encourage initiation of aggressive cholesterol-lowering therapy to produce regression of coronary atherosclerosis in FH patients at high risk for cardiovascular events.

Adult

Glial cyst of the pineal gland with characteristic computed tomography, magnetic resonance imaging, and pathological findings: report of two cases.

Two cases of glial cyst of the pineal gland are documented. Preoperative computed tomography and magnetic resonance imaging revealed cystic lesions of the pineal region with contrast enhancement of the walls, suggesting neoplastic lesions rather than true cysts. However, the histopathological examination of the resected specimens revealed the presence of glial tissue and normal structure of pineal gland and capsule, characteristics that were consistent with those of glial cysts of the pineal gland. Headache and visual disturbance were resolved after total removal of the cysts.

Adolescent

Hormone control of total plasminogen activator activity is specific to malignant DMBA-induced rat mammary tumours.

Hormonal regulation of plasminogen activator expression in 7,12-dimethylbenz[a]anthracene (DMBA)--induced rat mammary carcinomas was studied both in vivo and in vitro and was compared to that in DMBA-mammary dysplasia induced in neonatally androgenised rats. The plasminogen activator activity in DMBA-mammary carcinomas, but not in DMBA-mammary dysplasia, was regulated by oestrogen. This suggests that expression of this enzyme is hormonally regulated in carcinoma cells. Furthermore, in two of six DMBA-mammary carcinoma groups classified in terms of hormonal treatment, plasminogen activator activity was not under the control of oestrogen. Thus, the present results suggest that at the time of carcinogenesis, the hormonal milieu determines the hormone sensitivities of the malignant cells.

9,10-Dimethyl-1,2-benzanthracene

Specific stimulation by estradiol of tissue-type plasminogen activator production in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor cells.

The hormonal regulation of two plasminogen activators, tissue-type plasminogen activator (t-PA) and urokinase (u-PA), was studied both in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma and in DMBA-induced rat mammary dysplasia. t-PA activity in DMBA-mammary carcinoma was decreased markedly by oophorectomy and recovered upon estradiol administration to reach the maximum level at 12 hr. In contrast to its effect on DMBA-mammary carcinoma, estradiol had no effect on t-PA activity in DMBA-mammary dysplasia. Furthermore, DMBA-mammary carcinoma cells in primary culture displayed similar estrogen-dependency in production of t-PA, while t-PA production in DMBA-mammary dysplasia cells was not under the control of estradiol in vitro. Moreover, estrogen-stimulated production of u-PA activity was not observed in DMBA-mammary carcinoma cells or DMBA-mammary dysplasia cells both in vivo and in vitro. Taken together, these results suggest that estrogen stimulates the production of t-PA but not u-PA and that this estrogen dependency of t-PA is limited to malignant DMBA-mammary tumor cells.

9,10-Dimethyl-1,2-benzanthracene

Cardiac effects of local angiotensin-converting enzyme inhibition in hypertensive patients.

1. The direct cardiac effects of angiotensin-converting enzyme (ACE) inhibitor in 22 hypertensive patients were investigated. Radionuclide ventriculography and echocardiography were performed to measure left ventricular function before and 60 min after administration of a subdepressor dose of captopril. 2. Since the response to ACE inhibitor is not uniform, patients were classified into 12 patients without significant blood pressure change following captopril (group I) and 10 patients with reduction of blood pressure (group II). 3. Clinical and baseline haemodynamic characteristics were similar for the two groups. 4. Ejection fraction (EF) increased without changes of heart rate and end-diastolic dimension after ACE inhibitor in group I as well as group II. The change of EF was not different for the two groups. No correlation was found between changes in EF and blood pressure in group I patients. 5. This study indicates that ACE inhibitor might directly influence left ventricular function independent of systemic haemodynamic changes.

Adult

Temporal lobe CO2 vasoreactivity in patients with complex partial seizures.

The topography of CO2 vasoreactivity during hyperventilation in 8 patients with complex partial seizure (CPS) was visualized using the regional cerebral blood flow (rCBF) as measured by H(2)15O-PET (positron emission tomography) and compared with that of 10 normal volunteers. In the normal volunteers, the vascular response to CO2 (VrCO2 = delta CBF%/delta PaCO2) in the temporal lobe was 2.46 +/- 0.56 (%/mmHg). In the patients with CPS, VrCO2 in the temporal lobe of the affected side was 2.08 +/- 0.40 (%/mmHg), while VrCO2 on the contralateral side was 2.30 +/- 0.46 (%/mmHg). There was a significant difference in VrCO2 between the affected side of the temporal lobes and the temporal lobes of the normal volunteers. Furthermore, there was a tendency for VrCO2 to be lower in the affected than in the contralateral side of the temporal lobe in patients with CPS. As CO2 is the main regulator of CBF, this impaired vasoreactivity may reflect the brain dysfunction in the seizure focus and adjacent areas.

Adolescent

Reduced left ventricular diastolic asynchrony after captopril in single vessel coronary artery disease.

Impaired left ventricular diastolic function is often found preceding systolic functional abnormality in coronary artery disease. To assess whether captopril improves diastolic function, radionuclide ventriculography was performed before and 1 h after captopril administration in 10 stable effort angina patients with severe isolated stenosis of the left anterior descending coronary artery and in 8 controls. Resting global peak filling rate (PFR) was significantly (p < 0.05) reduced in association with significantly (p < 0.01) increased left ventricular diastolic asynchronous index (delta t) in patients with angina pectoris. Neither global PFR nor regional cardiac function was affected by captopril, although delta t was significantly (p < 0.05) reduced from 70 +/- 18 (SD) to 51 +/- 25 ms in patients with angina pectoris. A significant (p < 0.01) correlation was observed between percentage changes in peak ejection rate and in PFR in all subjects. Thus, captopril improves left ventricular asynchrony in patients with stable angina, although global diastolic function affected by systolic function remains unchanged.

Aged

Interphotoreceptor matrix in the colored-light-adapted rat.

The interphotoreceptor matrix (IPM) was examined histochemically using colloidal iron, wheat germ agglutinin and Ricinus communis agglutinin-1 for rats adapted to blue, green or red light before tissue preparation. In blue- and green-light-adapted animals, IPM was intensely stained in the apical zone of photoreceptor outer segments and in the outer and inner segment junction, conforming to the light pattern of IPM distribution in previous studies. In red-light-adapted animals, the IPM was prominent and uniform in the interstitial zone of photoreceptor outer segments, consistent with the dark pattern. The results indicate that rod photoreceptors are predominantly responsible for light-evoked changes in IPM.

Animals

Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.

Mucopolysaccharidosis type IVA (MPS IVA) results from a genetic deficiency of N-acetylgalactosamine-6-sulfate (Gal-NAc6S) sulfatase. We have identified two different exonic mutations causing GalNAc6S sulfatase deficiency in two unrelated Japanese families, in one patient with classical Morquio disease, and in two brothers with a mild form of MPS IVA. The nucleotide sequence of the full-length cDNA derived from a patient with classical Morquio disease revealed a two-base deletion at nucleotide position 1343-1344 (1344-1345 or 1345-1346) that altered the reading frame (designated 1342delCA). This mutation, inherited from the proband's consanguineous parents, was revealed by TaqI restriction analysis of a cDNA fragment amplified by the polymerase chain reaction. In the proband with the mild form of the disease, a C to G transversion at nucleotide 667 predicted the substitution of Lys for Asn204 (N204K). Since a new AluI site was created by the N204K mutation, restriction analysis indicated that the affected brothers were homozygous for this mutation, as confirmed by the finding that both their parents had this lesion. Transient expression in GalNAc6S sulfatase deficient fibroblasts of these two mutant alleles showed completely deficient or markedly decreased enzyme activities, thereby indicating that these two mutations were responsible for the enzyme deficiency.

Acetylgalactosamine

Calcium requirement for protoplast transfection mediated by polyethylene glycol of Lactobacillus casei by PL-1 Phage DNA.

The effects of some divalent cations on protoplast transfection mediated by polyethylene glycol of Lactobacillus casei ATCC 27092 by PL-1 phage DNA in 50 mM Tris-maleate buffer (pH 6.0) were investigated. The efficiency of transfection increased about 30 times in the presence of 10 mM Ca2+. Sr2+ increased the transfection rate as well, but Ba2+, Mn2+, and Mg2+ did not. Co2+ and Zn2+ inhibited transfection. The simultaneous use of Ca2+ and Mg2+ increased the transfection efficiency. Impairment of transfection caused by lack of Ca2+ could not be reversed by the addition of Ca2+ later. A decrease in the Ca2+ concentration to an ineffective level before transfection ended immediately inhibited transfection. Protoplasts were transfected with a phage adsorption mutant resistant to PL-1, also, and these metal ions had the same effect. Multiplication of phages in the transfected protoplasts was independent of the presence or absence of calcium ions. Calcium ions seemed to be involved in the entry of PL-1 DNA into the host protoplasts.

Bacteriophages

Recurrent hemoptysis due to aortobronchopulmonary fistula of false aortic aneurysm associated with repair of rupture of the sinus of Valsalva.

A 54-year-old man presented with recurrent hemoptysis of one year duration. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated a saccular aneurysm of the ascending aorta. The aneurysm was intraoperatively found to have formed on the superior surface of the site of aortotomy suture placed during previous repair of rupture of the sinus of Valsalva and to have a fistulous communication to the lung. CT and MRI were very useful in the diagnosis of the aneurysm as the cause of hemoptysis.

Aortic Aneurysm

A familial case of hereditary angioneurotic edema in Japan.

A 53-year-old man was admitted with impairment of breathing following laryngeal edema. Serum levels of CH50 (22 U/ml), C4 (3 mg/dl), C1-INH protein (10.6 mg/dl) and C1-INH activity (LT 25%) were low. Complement study of the patient's family members revealed that he was one of 5 patients in 3 generations with hereditary angioneurotic edema (HANE). Administration of the androgen derivatives Danazol (600 mg/day) and Oxymetholone (30 mg/day) effectively increased serum levels of C1-INH activity and C4. Though eruption and hepatic dysfunction attributable to administration of the drugs appeared, these side effects improved after withdrawal of the drugs. Subsequently, the treatment with Danazol at a low dose (100 mg/day) was resumed, and the patient has had no episodes of edema for the past 3 years. Regarding the familial cases of HANE, fewer than 20 have been reported in Japan.

Angioedema