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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 397 records · Page 22Linked to original sources

Characterization and changes of glycosphingolipids in the aorta of the Watanabe hereditable hyperlipidemic rabbit.

Characterization and elucidation of the changes of glycosphingolipids in the aorta along with the progression of atherosclerosis were performed in the Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia, as compared with in the normal rabbit. Neutral glycosphingolipids in aortae of both normal and WHHL rabbits were composed of glucosylceramide, galactosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, and galactosylneolactotetraosylceramide. The total amount of neutral glycosphingolipids in the aorta of the WHHL rabbit (557 nmol/g tissue) was increased about 5-fold compared to the normal level (107 nmol/g tissue). Prominent increases were observed in glucosylceramide (13-fold the normal level) and lactosylceramide (12-fold the normal level). The amount of total gangliosides in the aorta of the WHHL rabbit (207 micrograms NeuAc/g tissue) was markedly increased, being about 12-fold the normal level (17 micrograms NeuAc/g tissue). GM3 ganglioside was increased about 11-fold compared to normal. GD3 ganglioside, which was almost undetectable in normal aorta, also showed a marked increase in that of the WHHL rabbit (51.7 micrograms NeuAc/g tissue). Sulfatide, which was absent in the aorta of the normal rabbit, was markedly accumulated in that of the WHHL rabbit (280 nmol/g tissue). The fatty acid composition of neutral glycosphingolipids of WHHL rabbit was found to include a higher amount of C23:0, which is the major fatty acid of glycolipids in serum lipoproteins. Gangliosides in the aorta of the WHHL rabbit contained more C16:0 than in the normal rabbit. Sphingosine of sulfatide in the aorta of the WHHL rabbit was composed of sphingenine (86%), sphinganine (9%), 4-D-hydroxysphinganine (4%), and 4-D-hydroxyeicosasphinganine (less than 1%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The existence of galactosylceramide I3-sulfate in serums of various mammals and its anticoagulant activity.

Human, porcine, goat, sheep, bovine, horse, canine, rat, mouse, guinea pig, and chicken serums were investigated for the existence of sulfatide. Among the ten mammal serums, seven were found to be sulfatide positive, and the amounts of sulfatide were determined to be: 16.29 nmol/ml serum (porcine), 9.39 (bovine), 12.71 (goat), 7.75 (horse), 1.21 (sheep), 0.64 (human), and 0.16 (dog). The existence of sulfatide in the serums of human, goat, sheep, cow, horse, and dog is here reported for the first time. It is suggested that sulfatide is widely distributed in the serums of various mammals except for rodents and that it takes part in the anticoagulant systems. The fatty acids of those sulfatides comprised mainly non-hydroxy fatty acids and a significant amount (18-53% of the total fatty acid) of hydroxy fatty acids with chain lengths of C16, C22, C23, and C24. The long chain bases comprised sphingenine, sphinganine, and 4-D-hydroxysphinganine. Experiments to elucidate the mechanism of the anticoagulant activity of sulfatide revealed that it was specific to sulfatide and that the galactose-bound sulfate group is essential for this activity. The activity of clusters of sulfatide molecules was much more pronounced than that of single molecules.

Animals↗

Nucleolar organizer regions in vascular and neoplastic cells of human gliomas.

The number of nucleolar organizer regions in vascular cells and neoplastic cells of human gliomas was counted by a combined staining technique: one-step silver colloid method for nucleolar organizer region-associated argyrophilic protein (AgNOR) and periodic acid-Schiff staining for basement membrane of vascular components. The number of AgNORs (mean +/- SD) in the vascular and neoplastic cells of various tumors tested was as follows: benign astrocytoma (Grade 2, n = 4), 1.52 +/- 0.07 and 1.80 +/- 0.13, respectively; anaplastic astrocytoma (Grade 3, n = 7), 1.98 +/- 0.23 and 2.87 +/- 0.50; and glioblastoma multiforme (Grade 4, n = 11), 2.05 +/- 0.29 and 3.13 +/- 1.13. AgNOR scores in vascular cells of benign astrocytomas, anaplastic astrocytomas, and glioblastomas were significantly higher than those of vascular cells in normal brain tissue without neoplastic alteration (1.26 +/- 0.05; n = 3; P less than 0.01, P less than 0.001, and P less than 0.001, respectively). Moreover, the AgNOR scores of vascular cells in high-grade gliomas (Grades 3 and 4) were significantly higher than those in low-grade gliomas (Grade 2) (P less than 0.01). These results indicate that the proliferative activity of both vascular and neoplastic cells in gliomas increased as histological malignancy advanced, and that the quantification of AgNORs was useful in evaluating proliferative activity in vascular cells as well as in assessing the malignancy of neoplastic tissues.

Anaplasia↗

Chromosome changes in desmoid tumors developed in patients with familial adenomatous polyposis.

Chromosome analyses were performed on benign desmoid tumors obtained from two female patients with familial adenomatous polyposis (FAP), one of whom was diagnosed as having Gardner syndrome (GS). The modal chromosome number was 46 in both specimens, and detailed Q-banding analysis in Case 1 (GS) revealed a clonal abnormality of an interstitial deletion of the long arm of chromosome 5, del(5)(q21q31). The deleted region included an assigned locus for an FAP major gene (5q21-q22). All of the metaphases analyzed in this case showed an extra segment of bright fluorescence on the short arm of chromosome 15, but this unusual chromosome (15p+) was observed in both peripheral lymphocyte and skin fibroblast cultures from the patient, indicating that the 15p+ was constitutional in nature. In Case 2, no clonal rearrangements were identified and most cells had a normal karyotype. However, two cells showed rearrangements involving a 17q with non-identical breakpoints, one of which was observed as a solitary chromosome change. Based on the present findings in Case 1 and those reported so far, the chromosomal defect on 5q might be one of the causal genetic events primarily associated with the development of both benign desmoid tumors and colorectal adenomas and carcinomas in FAP patients.

Adenomatous Polyposis Coli↗

Refractory variant angina relieved by denopamine--a case report.

A 48-year-old man with severe variant angina refractory to conventional treatment with calcium antagonists and nitrates, or prazosin, or trihexyphenidyl hydrochloride, became symptom free rapidly when treated with denopamine, a adrenergic beta-1 agonist. Denopamine may prove to be an additional therapeutic agent in the management of severe variant angina. Therefore the response to denopamine and the lack of response to prazosin in this patient suggests that not only the adrenergic alpha receptor but also the adrenergic beta-1 receptor plays an important role in the production of coronary spasm, at least in some patients.

Adrenergic beta-Agonists↗

The effect of furosemide on the endocochlear potential in ears with experimentally induced endolymphatic hydrops.

The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery.

Animals↗

Norepinephrine inhibits human natural killer cell activity in vitro.

The effect of norepinephrine on human NK cell activity was investigated using a flow cytometry assay. NK cell activity was found to be inhibited by direct addition of norepinephrine to lymphocyte/target cell mixtures in a dose-dependent fashion. This inhibitory effect of norepinephrine was blocked by propranolol but not by atenolol. The results suggest that norepinephrine has a negative influence on NK cell activity and that the effect of norepinephrine is mediated via beta 2-adrenoceptors.

Atenolol↗

[A comparative study of CHOP therapy and COP-BLAM therapy for non-Hodgkin's lymphoma in elderly patients].

Elderly patients (aged greater than or equal to 65 years) with non-Hodgkin's lymphoma were treated either with CHOP or COP-BLAM therapy, and the effectiveness and reverse effects of COP-BLAM therapy were compared with those of CHOP therapy. Thirty-three patients (aged greater than or equal to 65 years) with previously untreated non-Hodgkin's lymphoma were entered either on CHOP or COP-BLAM regimen between September, 1979 and February 1990. To CHOP therapy was performed in 15 patients (median age; 70 years). Eight of them had diffuse large cell type lymphoma (large), five had diffuse medium-sized cell type (medium) and two had diffuse mixed cell type (mixed). As to clinical stage, there were patients in stage II, 4 in stage III and 9 in stage IV in CHOP group. Of 18 patients (median age; 68 years), who were treated with COP-BLAM therapy, 8 had of large lymphoma and 10 medium lymphomas in histopathological classification. In terms of clinical stage, there were 5 patients in stage II, 4 in stage III and 9 in stage IV. CHOP therapy and COP-BLAM therapy were performed according to the method reported by McKelvey et al, and by Laurence et al., respectively, using the full doses of drugs without consideration the age. Complete remission (CR) was achieved in seven (46.7%) of 15 patients treated with CHOP therapy. In this group, five (38.5%) of 13 patients in advanced stages (stage III or IV) entered CR. Of 18 patients subjected to COP-BLAM therapy, 15 (83.3%) achieved CR. Among 13 patients in advanced stage treated with COP-BLAM therapy, CR was achieved in 11 (84.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Flow cytometric measurement of NK cell cytotoxicity.

A simple and fast method to measure the natural killer (NK) cell cytotoxicity has been established. In our novel assay, following the incubation of K562 target and effector cells, the cells were stained with FITC-conjugated anti-transferrin receptor (CD71) mAb. The K562 targets alone were labeled with anti-CD71 mAb, since CD71 is highly expressed on K562 cells but not on mononuclear cells. The fluorescence intensity of CD71 on K562 cells were analyzed using flow cytometry, and the cytotoxicity was evaluated. In our assay, designated as a "CD71 assay", no spontaneous release of anti-CD71 mAb was observed from labeled K562 cells and living K562 cells were able to be divided from dead K562 cells. The data obtained by this assay was well correlated with that by the standard 51Cr-release assay as well as the C-FDA assay. In addition, the CD71 assay is a safe and simple analytic procedure since no isotope is required.

Antigens, CD↗

Possible role of the hormonal form of vitamin D3 in the granuloma-associated angiotensin-converting enzyme activity.

We studied effects of the hormonal form of vitamin D3 on the angiotensin-converting enzyme (ACE) activity of hepatic granulomas in mice infected with Schistosoma mansoni. During 7 to 11 weeks after infection, mice were given orally 0.1 or 1.0 microgram/kg of 1 alpha (OH)D3 or only medium solution every other day. Granulomatous livers were removed at 7, 9 and 11 weeks after infection, and ACE activity was measured in the granulomas isolated from each liver tissue using a fluorometric method. Oral administration of 0.1 or 1.0 microgram/kg/2 days of 1 alpha (OH)D3 for 4 weeks significantly enhanced ACE activity in the granuloma tissue. Since the DNA content relative to a unit weight of protein in the granulomas did not change with the 1 alpha (OH)D3 treatment, it is suggested that the elevated tissue ACE activity is due to an actual increase of the enzyme activity in each granuloma cell. The present observation may have relevance to sarcoid granulomas characterized by an increased tissue ACE activity, since macrophages from patients with sarcoidosis synthesize a biologically active hormonal form of vitamin D3. Namely hormonal form of vitamin D3 locally produced by macrophages is involved not only in systemic Ca++ metabolism but also in the stimulation of macrophages themselves to produce ACE in the granulomas.

Animals↗

[Salvage chemotherapy with IMV-triple P for relapsed or refractory malignant lymphoma].

Twelve patients with relapsed or refractory malignant lymphoma were treated with IMV-triple P regimen consisting of ifosfamide (IFM), mitoxantrone (MIT), vindesine (VDS), pepleomycin (PEP), procarbazine (PCZ) and prednisolone (PDN). Three of 12 patients achieved complete remission (CR), and 5 patients achieved partial remission (PR). Hence, the overall response rate was 66.7% (8/12). Of 9 relapsed patients who had attained CR after the former chemotherapy, 3 had CR and 4 had PR. The overall response rate was 77.8% (7/9). Side effects were relatively mild, including leukopenia (less than 1,000/microliters) (33.3%) and thrombocytopenia (less than 5 X 10(4)/microliters) (8.3%). There was no severe cardiac toxicity such as heart insufficiency and severe arrythmia. These results suggest that IMV-triple P regimen is effective in the treatment of relapsed or refractory malignant lymphoma.

Adult↗

[The COP-BLAM III therapy of non-Hodgkin's lymphoma].

COP-BLAM III therapy was given to 18 patients with non-Hodgkin's lymphoma, and the therapeutic effects as well as adverse effects of the treatment were examined. Of the 18 patients 16 had a complete remission (CR) and 2 showed an partial remission (PR) with a total response rate of 100%. In terms of the stage of disease, CR was achieved in all patients in stage III and in 11 of 13 patients in stage IV. Patients with neutrophil counts less than 1,000/microliters were given rhG-CSF (1.5 micrograms/kg/day, sc), which significantly shortened the duration of neutropenia and decreased the number of days with episodes of fever when compared with those not given rhG-CSF, consequently facilitating the treatment without prolonging the dosing intervals. No serious infection was observed. Adverse effects included neutropenia of less than 1,000/microliters in 6 of the 18 patients (33.3%), thrombocytopenia less than 5 x 10(4)/microliters in 3 (16.7%), nausea and vomiting in 8 (44.4%), peripheral neuropathy in 4 (22.2%) and stomatitis in 4 (22.2%). There were no fatalities caused by the treatment. The above findings indicate that COP-BLAM III therapy is capable inducing high frequency of complete remissions in non-Hodgkin's lymphoma and that its combination with G-CSF can improve the results of the therapy and relieve adverse reactions.

Adolescent↗

[Hodgkin's disease associated with LDH-M subunit deficiency].

The patient was a 60-year-old man who had complained of left cervical swelling from the end of June, 1984. He was diagnosed as having Hodgkin's disease (mixed-cell type) by lymph node biopsy, and was admitted to our hospital for thorough examination and treatment on July 23rd. Diagnosis of stage IA Hodgkin's disease involving only the left cervical lymph node was made. On admission, laboratory data revealed that the LDH activity in his serum and erythrocytes consisted of only type 1 (LDH-H4), hence LDH-M subunit deficiency (homogeneous type) was diagnosed. However, the muscle rigidity, myoglobinuria, and skin lesions that are usually seen in this abnormality were not observed. After two course of C-MOPP therapy, beginning on August 1st. complete remission was obtained. He was subsequently given a total of 6 courses of C-MOPP therapy and 40 Gy of irradiation on an outpatient basis. He eventually died of heart failure on November 3rd, 1986. Only five families with LDH-M subunit deficiency have been reported to date in Japan. This is the first report in Japan of the condition being complicated by Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of Farber's disease--histochemical, electron microscopic and biochemical studies].

A case of Farber's disease (disseminated lipogranulomatosis) is reported. A Japanese boy presented with progressive joint deformity, a hoarse voice, mental retardation and skin granulomatous lesions. He died of bronchopneumonia at the age of 2 years. Biopsied specimen from the perianal granulomatous lesion showed many macrophage contained lipids, and acidic oligo-, or polysaccharides, or, glycoconjugates. Electron microscopic study revealed, in addition to curvilinear tubular bodies (Farber's bodies), numerous granular structures accumulated in the cytoplasm of the macrophage. Biochemical analysis demonstrated a storage of free ceramide in the patient's liver, and confirmed the patient's diagnosis. This is the 5th case reported in Japan.

Amidohydrolases↗

[A case of vasospastic angina: development of transient collateral circulation lessen the degree of myocardial ischemia during coronary artery spasm].

A 57-year-old man was admitted to our hospital because he had had attacks of chest pain at rest for more than a year, in spite of daily oral diltiazem (90 mg/day) and isosorbide dinitrate (15 m/day). The diagnosis of variant angina was made for him based on ST elevation in chest leads of the electrocardiogram during his first attack. However, one year later, the electrocardiograms during attacks showed only ST depression or T wave inversion in chest leads. The coronary arteriogram during spontaneous chest pain revealed that the left anterior descending artery was totally occluded at its middle portion, and that its peripheral portion was perfused by collateral circulation from the right coronary artery. The coronary arteriograms after administration of nitroglycerin were apparently normal, and no signs of collateral circulation were observed. These findings indicated that the transient collateral circulation could develop after repetitive coronary artery spasms even in the absence of significant coronary stenosis, and that it could lessen the degree of myocardial ischemia during coronary artery spasm.

Angina Pectoris, Variant↗

[Non-Hodgkin's lymphoma localized at the right ocular medial rectal muscle].

This paper reports a rare case of extranodal non-Hodgkin's lymphoma localized at the ocular muscle, which achieved a long-term remission by combination chemotherapy and irradiation. A 41-year-old man visited the ophthalmology department of Toho University Hospital in December, 1982 because of right conjunctival injection and right exophthalmos which were first manifested in June. The patient was diagnosed as having non-Hodgkin's lymphoma (diffuse medium-sized cell type) by biopsy of the right medial rectal muscle, and was referred to our department on January 17, 1983. A series of examinations revealed that the disease had no invasion into any lymph nodes and other organs. After treatment with two courses of C-MOPP regimen and two courses of ACOP regimen, the patient achieved complete remission and was discharged on July 30. Subsequently he completed two courses of CHOP regimen followed by irradiation (46 Gy). Seven years and three months after the initiation of chemotherapy, the patient has been in a complete remission, requiring no treatment.

Adult↗

Immunohistochemical demonstration of the placental form of glutathione S-transferase, a detoxifying enzyme in human gliomas.

Expression of the human placental form of glutathion S-transferase (GST-pi) in human gliomas was investigated by immunohistochemical methods, and the result was compared with that of normal human glial cells. The gliomas in this study were composed of five benign astrocytomas (Grade 2), ten anaplastic astrocytomas (Grade 3), and 16 glioblastomas (Grade 4). Normal human glial cells showed only a weak immunostaining response for GST-pi in the cytoplasm or some nuclear membranes. All of benign astrocytomas had diffusely weak GST-pi immunostaining, resembling that of normal glial cells. With increasing grade, gliomas showed a strongly positive reaction for GST-pi. The positive reactions were remarkable especially in the gemistocytes and giant cells in the high-grade gliomas. These results suggest that cells of gliomas have some detoxifying function and the expression of this detoxifying enzyme, GST-pi, is related to the degree of malignancy of the gliomas.

Astrocytoma↗

Effects of various lysosphingolipids on cell growth, morphology and lipid composition in three neuroblastoma cell lines.

The cell numbers of three mouse neuroblastoma cell lines were decreased upon incubation with lysosphingolipids in the following order of effectiveness: lysosulfatide (lysoCS) greater than psychosine (Ps) greater than sphingosylphosphocholine (SPC). The different cell lines showed characteristic sensitivities to various concentrations of lysolipids less than 150 microM. Interestingly, only SPC induced neurite outgrowth and changed the lipid composition, modifying the amounts of cholesterol, sphingomyelin (SM) and ganglioside GM3 in all cell lines. The effect of SPC on these cell lines was comparable to the effect of N-acetyl SPC (NAcSPC) rather than that of SM.

Animals↗