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Biomedical subjects

Y Akutsu

Publications and source records attributed to Y Akutsu.

At least 73 records · Page 4Linked to original sources
PubMed1989

Fine structural and immunohistochemical properties of dysplastic melanocytic nevi: comparison with malignant melanoma.

This study will review the clinical features of dysplastic melanocytic nevi (DMN) in Japanese cases, and then show the fine structure of melanosomes/melanogenesis in the dysplastic melanocytes and the immunohistochemical property of DMN as identified by monoclonal antibodies against human melanosome specific antigen (HMSA). The incidence of DMN is quite low in the Japanese. It is indicated that this fact may partly explain the low incidence of malignant melanoma in Japanese; in particular, low incidence in sun-exposed areas. The patients with DMN were largely males. They were different from ordinary Japanese in that they usually burn and tan poorly after sun exposure. In addition, the synthesis of melanosomes in the dysplastic melanocytes was found to be abnormal and characterized by a significant alteration in the fine structure of the melanosomal matrix and the pattern of melanization. These abnormal melanosomes reacted positively with MoAb HMSA-1 and HMSA-2, which identify the structural matrix protein of melanosomes unique to neoplastic melanocytes. Importantly, HMSA was present in both dysplastic melanocytes and melanoma cells, but not in epidermal melanocytes (nevus cells) of common melanocytic nevi.

Antigens, Neoplasm↗
PubMed1989

Effects of glycyrrhizin (SNMC: stronger Neo-Minophagen C) in hemophilia patients with HIV infection.

Glycyrrhizin (GL) not only has an inhibitory effect on HIV replication but also exhibits interferon-inducing and natural killer (NK)-enhancing effects and improves liver dysfunction. Thus, large doses of GL (200-800 mg/day) were intravenously administered for more than 8 weeks to 9 hemophilia A patients with HIV infection (asymptomatic carrier, AC). Lymphocyte count increased in all 9 cases. OKT4 OKT8 ratio was elevated in 6 out of the 9 cases and OKT4-positive lymphocytes increased in 8 out of the 9 cases; 66.7% and 88.9% improvement, respectively. Changes in NK cell activity and mitogenic responsiveness to PHA, Con A and PWM were not significant. Liver dysfunction, noted in 4 cases, clearly improved. Serum electrolytes, protein, lipids, and renal function were within normal levels and no serious side-effects were observed during treatment. On the other hand, in 3 cases of hemophilia without HIV infection, the number of OKT4 lymphocytes was not significantly altered during treatment. From these results, large dose administration of GL to HIV-positive hemophilia patients (AC) seems to be effective in preventing development of AC into AIDS by raising the number of decreased OKT4 lymphocytes and improving liver dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[Disseminated necrotizing leukoencephalopathy accompanied with multiple calcium deposits following antineoplastic and radiation therapy in a case of intracranial germ cell tumor: computerized tomographical study].

A form of disseminated necrotizing leukoencephalopathy and the shaping process of calcification was observed by CT scan in a 9-year-old boy with intracranial germ cell tumor who had received systemic combined chemotherapy, brain radiation, and intraventricular administration of methotrexate and bleomycin for the meningeal involvement of tumor cells. He was admitted to our hospital complaining of hemiparesis and gait instability. Hormonal examination revealed abnormality of high serum HCG and testosterone. An initial CT scan showed a ring enhancing lesion in the right side of the caudate head. He received a course of irradiation, which was 5,000 rads locally, and combined chemotherapy using cisplatin, vinblastine and bleomycin for ectopic germ cell tumor. Unfortunately, consecutive CT examinations revealed that the tumor recurred with hormonal abnormality and ventricular seeding of tumor cells. Therefore, the patient received two courses of irradiation, which were each 3,000 rads locally, and intraventricular administration of methotrexate and bleomycin via an Ommaya tube at about one year intervals. However, 23 months after the first irradiation, a serial CT scan revealed an abnormal diffuse low density area in the deep white matter of the frontal lobe, predominantly the paraventricular region. Furthermore, 31 months after the first irradiation, a serial CT scan revealed fine and granular calcification in the above mentioned lesion. The Hounsfield number of high density areas was 103.00 in the round calcification of the left parietotemporal lobes. Finally, 34 months after the first irradiation, a serial CT scan revealed large round calcifications in the left temporal lobe and right occipital lobe. The patient died three years and six months after the initial symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Gray platelet syndrome: relationship between morphological abnormality of the dense tubular system (DTS) and intracellular Ca++ mobilization in the platelet.

In the first familial case of gray platelet syndrome (GPS) reported in Japan in which the subjects showed platelet release abnormalities, we investigated the relationship between intracellular Ca++ mobilization in platelets and marked morphological abnormalities of the DTS. The subjects for the Aequorin assay were 12 controls and 11 GPS cases, whereas the subjects for the Fura-2 assay were 10 controls and 6 GPS cases. In order to discriminate between Ca++ influx from outside of the cells and Ca++ mobilization from DTS within the cells, the experiments were conducted under two conditions; one in the presence of 1 mM Ca++ in the external fluid, and the other with the addition of 2 mM EDTA as a Ca++ chelator. Stimulation by A-23187 in the presence of 1 mM Ca++ in the external fluid caused 2 peaks or shoulder formation; that is, normal cases showed 1 peak at all concentrations of A-23187 tested, whereas GPS showed 2 peaks or shoulder formation in 7 of the 11 cases and conspicuously good reproducibility in each case. These facts indicated that it took time for the stimulus to reach the inside of the DTS, which showed marked morphological abnormalities. During stimulation by 1.0 U/ml thrombin under the same conditions, the GPS exhibited 1 peak with a wide skirt pattern, compared with the control. In one case of GPS, which revealed one peak by thrombin and 2 peaks by A-23187 in the presence of 1 mM Ca++, 2 peaks were also noted by thrombin and the luminescence peak become lower, when Ca++ was chelated by EGTA, using the Aequorin method.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1989

[The present status in prophylaxis and treatment of HIV infected patients with hemophilia in Japan].

Thirty six hemophiliacs with HIV infection were treated with high-dose glycyrrhizin, Stronger Neo-Minophagen C (SNMC). The dose was 100-200 ml of SNMC in eighteen patients and 400-800 ml in the other 18. The patients were divided into an asymptomatic carrier (AC) group and AIDS related complex (ARC)/AIDS group. SNMC was administered intravenously daily for the first 3 weeks, every second day for the following 8 weeks to 36 HIV positive hemophilia patients in accordance with the protocol proposed by the Japanese National Research Committee. The CD 4/CD 8 ratio and CD 4 positive lymphocyte counts did not change during the treatment period. However, significant improvement was noted in some cases. A slight increase in mitogenic responsiveness to phytohemagglutinin, Concanavalin A and pokeweed mitogen was noted in most patients of both groups, especially in the AC group administered over 400 ml of SNMC. Furthermore, complete improvement was noted in liver dysfunction, which has been thought to be a major problem in hemophiliacs treated with blood products. Thus prophylactic administration of high-dose SNMC to HIV positive hemophiliacs having impaired immunological ability and liver dysfunction was considered to be effective to prevent the development from AC/ARC to AIDS.

AIDS-Related Complex↗
PubMed1988

Immunoelectron microscopic demonstration of human melanosome associated antigens (HMSA) on melanoma cells: comparison with tyrosinase distribution.

Previously, we have developed a mouse monoclonal antibody (MoAb) HMSA-1 (human melanosome-associated antigen-1) against the melanosome fraction of human malignant melanoma, and demonstrated the selective distribution of the HMSA-1 in neoplastic melanocytes on routine paraffin sections. This study examined, by using enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy, the subcellular distribution of the HMSA-1 in malignant melanocytes. Fractionation of cell organelles and ELISA assay indicated that the HMSA-1 is rich in fractions of large granule, melanosome and endoplasmic reticulum (ER) in melanoma cells. Immunoelectron microscopic study showed that the HMSA-1 is localized in the melanosomes of various developmental stages and vacuolar structures, which appeared to be the stage I melanosomes and which contained the matrix protein. Dopa cytochemistry revealed that the distribution of MoAb HMSA-1 reaction product is localized in the area different from that of tyrosinase, indicating that the synthetic processes of melanosomal matrix protein and tyrosinase are different. Furthermore, the reaction product with MoAb HMSA-1 was seen in the rough ER, indicating that the melanosomal matrix protein is synthesized by membrane-bound ribosomes and processed through the channel of ER.

Antibodies, Monoclonal↗
PubMed1988

[Histopathological study of a recurrent malignant glioma after an intratumor local injection of adriamycin].

This paper presents interesting morphological findings, which have never been previously reported, on tumor tissues after a local injection of an anticancer agent into three patients with malignant glioma. Following a craniotomy, 0.5 mg of Adriamycin (ADM) was injected through an Ommaya reservoir into the tumor bed. Light microscopy of the recurrent tumor and surrounding necrotic tissue revealed massive coagulation necrosis of the tumor tissues and fibrinoid necrosis of vascular channels, centering at the tip of the Ommaya tube. In the surrounding area of the massive coagulation necrosis, considerable reactive collagenous tissue, infiltrating lymphocytes and foreign body giant cell were found as well as so-called "organized" necrotic tissue. Electron microscopic findings of the same specimens revealed deposits of lipofuscin, lipid droplets, lysosome, abundant myelin figures and fibrous strands. It can therefore be assumed that this or similar anticancer agents, when may be directly incorporated into the residual tumor cells, are apparently reduced by coagulation necrosis and reactive collagenous tissue.

Adult↗
PubMed1988

Nature and biosynthesis of structural matrix protein in melanosomes: melanosomal structural protein as differentiation antigen for neoplastic melanocytes.

Two major classes of protein, i.e., structural matrix and enzymic, exist in the melanosome. In normal melanocytes, synthesis of these two components is under a strict genetic control with regulatory steps associated with transcription and translation coded with appropriate pigment genes. In abnormal neoplastic melanocytes, they become markedly aberrant. The aberrant melanogenesis can be typically manifested by an abnormality in fine structure of the melanosome. The fine structural heterogeneity of the melanosome can often be diagnostic to certain forms of malignant melanoma and dysplastic melanocytic nevus. This study brings about the importance of the structural matrix protein for the expression of fine structural heterogeneity in the melanosome by developing the 2 monoclonal antibodies, MoAb HMSA-1 and HMSA-2. The 2 MoAbs recognized the cytoplasmic antigen on paraffin embedded sections, which under immunoelectron microscopy and cell fractionation studies, were found to be localization the melanosome and smooth ER, but not Golgi complex and coated vesicles as seen in the tyrosinase studies. It is indicated (a) that the sites of the synthesis for the melanosomal protein and tyrosinase are different, (b) that the melanosomal structural protein is accumulated in the dilated vacuole of smooth ER from which the stage I melanosome is synthesized, (c) that the synthesis of melanosomal protein becomes markedly aberrant and directly reflects the abnormal fine structure of the melanosome and (d) the heterogeneity in synthesis of melanosomal protein as expressed by MoAb HMSA-1 and HMSA-2 is a useful adjunct for immunohistopathological differentiation of malignant melanoma cells from benign nevoid cells and normal melanocytes.

Antigens, Differentiation↗
PubMed1987

Dysplastic melanocytic nevus. Electron-microscopic observation as a diagnostic tool.

Dysplastic melanocytic nevi (DMN) are distinctive cutaneous nevomelanocytic lesions that possess unique clinical and histopathological features. In our previous study, we showed that the fine structure of melanosomes in epidermal melanocytes of DMN are abnormal and reveal deranged melanogenesis. This study is an extension of our previous study and clarifies the fine structure of melanosomes in both epidermal melanocytes and keratinocytes with observations in an additional 10 cases of DMN with and without a marked mesenchymal response. We found that a poor mesenchymal response does not exclude fine structural abnormality of melanosomes in DMN; that abnormal melanosomes are manifested by a spherical shape with either fine granules or incompletely developed lamellae and/or both; that melanization occurs unevenly on the spherical granular and/or incompletely on the lamellar matrices; and that these abnormal melanosomes are transferred to keratinocytes before being completely melanized, and they reveal marked degradation. We suggest that the fine structural characterization of abnormal melanosomes is a new adjunct for histopathological diagnosis of DMN.

Dysplastic Nevus Syndrome↗