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Biomedical subjects

T Nemoto

Publications and source records attributed to T Nemoto.

At least 181 records · Page 10Linked to original sources

[Altered expression of protooncogenes during clinical course in an AML case transformed from MDS].

The changes of expression of oncogenes in the mononuclear cells of MDS case was studied during his clinical course, in series. His bone marrow was considered to maintain its function partly in initial stage, since both peripheral blood and bone marrow responded to clinical episodes. However, his hematopoietic function was gradually impaired with the disease evolution to AML. We examined the expression of four oncogenes in the mononuclear cells of his three clinical stages, early RAEB-t, RAEB-t and AML, to study the cause of transformation from MDS to AML. Early RAEB-t cells expressed all oncogenes studied other than c-myb, while only c-myc was weakly observed in RAEB-t. AML cells expressed c-myc, c-jun and c-myb, except for c-fms. The expression of c-fms and c-jun of early RAEB-t was considered to reflect the monocytosis induced by infections, and the expressions of c-myb and c-myc of AML cells were regarded as one of malignant signs of tumor transformation. These findings suggest that the evolutional transformation of MDS to AML was affected by the altered expression of oncogenes.

Anemia, Refractory, with Excess of Blasts↗

[Improvement of mediastinal shift after left pneumonectomy by injection of sulfur hexafluoride].

We encountered a 53-year-old patient with a carcinoid in the left main bronchus. His left lung volume was decreased and the mediastinum was markedly shifted to left. After sulfur hexafluoride (SF6) was injected into the postpneumonectomy pleural space, the mediastinum gradually moved to the center. As reported by many authors, SF6 is generally used after pneumonectomy to prevent mediastinal shift and overinflation of the remaining lung. However, in our patient, SF6 injection reversed mediastinal shift and improved the overinflated lung.

Bronchial Neoplasms↗

Seroepidemiology and clinical aspects of human T-cell lymphotropic virus type I/II infection in a cohort of intravenous drug users in New York City.

To define further the magnitude, epidemiology, and clinical features of human T-cell lymphotropic/leukemia virus type I/II (HTLV-I/II) infection in 454 intravenous drug users in New York City, we evaluated previously frozen aliquots of sera for HTLV-I/II antibodies using enzyme-linked immunoassay, Western blot, and radioimmunoprecipitation techniques. We found HTLV-I/II infection in 18.9% of the subjects. Age (p = 0.001), race (p = 0.001), having a same gender sexual relationship (p = 0.01), and HIV-1 infection (p = 0.041) were clear correlates of HTLV-I/II infection. HTLV-I/II seropositive subjects, in contrast to seronegative subjects, had lower leukocyte counts (p = 0.05) and higher globulin (p = 0.005) and gamma globulin (p = 0.009) levels even when HIV-1 serostatus was controlled. The considerable prevalence of HTLV-I/II infection and the morbidity of HTLV-I/II-associated disorders strongly suggest a continued need to define the dimensions of HTLV-I/II infection.

Adult↗

The steroid-binding properties of recombinant glucocorticoid receptor: a putative role for heat shock protein hsp90.

The steroid-binding domain of the human glucocorticoid receptor was expressed in Escherichia coli either as a fusion protein with protein A or under control of the T7 RNA polymerase promoter. The recombinant proteins were found to bind steroids with the normal specificity for a glucocorticoid receptor but with reduced affinity (Kd for triamcinolone acetonide approximately 70 nM). Glycerol gradient analysis of the E. coli lystate containing the recombinant protein indicated no interaction between the glucocorticoid receptor fragment and heat shock proteins. However, synthesis of the corresponding fragments of glucocorticoid receptor in vitro using rabbit reticulocyte lystate resulted in the formation of proteins that bound triamcinolone acetonide with high affinity (Kd 2nM). Glycerol gradient analysis of these proteins, with and without molybdate, indicated that the in vitro synthesised receptor fragments formed complexes with hsp90 as previously shown for the full-length rat glucocorticoid receptor. Radiosequence analysis of the recombinant steroid-binding domain expressed in E. coli and affinity labelled with dexamethasone mesylate identified binding of the steroid to Cys-638 predominantly. However, all cysteine residues within the steroid-binding domain were affinity labelled to a certain degree indicating that the recombinant protein has a structure similar to the native receptor but more open and accessible.

Affinity Labels↗

The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor.

High-salt treatment of cytosolic glucocorticoid receptor (GR) preparations reduces the steroid-binding ability of the receptor and induces the conversion of the receptor from a nontransformed (non-DNA-binding) 9S form to a transformed (DNA-binding) 4S entity. Therefore, we decided to investigate the possible relationship between these two phenomena. Steroid-free GR was converted from a 9S to a 4S form by exposure to 0.4 M NaCl. The binding of [3H]triamcinolone acetonide [( 3H]TA) to the 9S form was almost saturated at a concentration of 20 nM, whereas [3H]TA was hardly bound to the 4S form at this concentration. The 4S form was efficiently labeled at 200 nM. Scatchard analysis of the GR exposed to 0.4 M NaCl in the presence of 10 mM molybdate showed the presence of two types of binding sites with apparent dissociation constants of 0.52 +/- 0.07 and 64.1 +/- 16.2 nM, respectively. In the absence of molybdate, the ratio of the lower affinity site was increased, but the total number of binding sites was not modified. The GR with the low [3H]TA-binding affinity bound to DNA-cellulose even in its unliganded state, whereas the form with the high affinity did not. Immunoblot analysis using anti-GR monoclonal antibody revealed no difference in molecular size (Mr 94000) between the high- and low-affinity entities. These results indicate that the transformed GR has a reduced [3H]TA-binding affinity as compared to the nontransformed GR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Activation of the dioxin and glucocorticoid receptors to a DNA binding state under cell-free conditions.

The activation in vitro of dioxin and glucocorticoid receptors from a non-DNA binding to a DNA binding state was characterized. Ligand-free dioxin and glucocorticoid receptors were partially co-purified from rat liver cytosol, and both receptors sedimented at 9 S following labeling with the respective ligand. The 9 S forms of the dioxin and glucocorticoid receptors have previously been shown to represent heteromeric complexes containing the Mr approximately equal to 90,000 heat shock protein. The 9 S ligand-free or ligand-bound glucocorticoid receptor was converted to the monomeric 4-5 S form upon exposure to 0.4 M NaCl even in the presence of the stabilizing agent molybdate. Under identical conditions, the 9 S ligand-free and ligand-bound dioxin receptor forms remained essentially intact. However, in the absence of molybdate, the dioxin receptor could be converted to a 4-5 S form upon exposure to high concentrations of salt. These results indicate that the glucocorticoid receptor readily dissociates from the 9 S to the 4-5 S form even in the absence of hormone, whereas both the ligand-free and ligand-occupied 9 S dioxin receptor forms represent more stable species. Gel mobility shift experiments revealed that the 4-5 S glucocorticoid receptor interacted with a glucocorticoid response element both in the absence and presence of ligand. On the other hand, occupation of the dioxin receptor by ligand greatly enhanced the ability of the receptor to be activated to a form that binds to its target enhancer element. Once dissociated, the monomeric form of the dioxin receptor was also able to interact with its DNA target sequences even in the absence of ligand. Thus, ligand binding efficiently facilitates subunit dissociation of the dioxin receptor but is not a prerequisite for DNA binding per se. Given the apparent stability of its non-DNA binding 9 S form, the dioxin receptor system might be a useful model for the investigation of the mechanism of activation of soluble receptor proteins.

Animals↗

Adrenalectomy for adrenal metastasis from lung carcinoma.

In the past 3 years, five patients with lung carcinoma were found to have enlarged adrenal glands without any evidence of distant metastasis. The patients were treated with adrenalectomy. The cases are presented in order to discuss optimal methods of diagnosis and treatment for this condition.

Adrenal Gland Neoplasms↗

In vivo dynamics of pulmonary lymphoid cell subpopulations generated against pulmonary metastasis: evaluation by bronchoalveolar lavage fluid.

The dynamics of lymphoid cell subpopulations in bronchoalveolar lavage fluid (BALF) and the systemic lymphoid organs of mice after intravenous injection of B16 melanoma cells were examined with a fluorescence-activated cell sorter. The lymphoid cell subpopulations of BALF and mediastinal lymph nodes showed significant changes in numbers and proportions, while those of other lymphoid organs including inguinal lymph nodes, thymus and spleen, showed little change. In week 1, the cells with a Thy-1.2+, Lyt-1+, L3T4-, Lyt-2- phenotype and asialo-Gm1+ cells in BALF significantly increased and L3T4+ cells slightly increased in number. By week 3, the numbers of Lyt-2+ cells in BALF markedly increased in number (by about 90 times) compared with controls. The number of Thy-1.2+ cells in mediastinal lymph nodes also increased significantly by week 3. Mice that had been pretreated with an immunosuppressive dose of cyclophosphamide were also inoculated intravenously with B16 melanoma cells. In these mice, a significantly increased number of pleural tumors developed and the number of Thy-1.2+ cells in BALF was markedly reduced from week 1 to 3. The results indicate that L3T4 and Lyt-2 double negative T-cells and natural killer (NK) cells may be generated and/or mobilized to the lung in an early phase of experimental metastasis of B16 melanoma cells and that at a later stage, when multiple metastases develop, T-cells with a Lyt-2+ phenotype markedly increase, probably as an expression of a host reaction against proliferating metastatic tumor cells.

Animals↗

Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A.

A case-control study of breast cancer was conducted in Buffalo. Participants completed a food frequency questionnaire and donated a fasting blood sample before definitive workup for breast masses. Dietary and plasma concentrations of carotenoids and retinol for 83 women found to have breast cancer were compared with those of 113 women found to be free of breast cancer (control subjects). There were no case-control differences in dietary estimates of vitamin A intake or in plasma alpha-carotene and lycopene. However, subjects with breast cancer had lower concentrations of plasma beta-carotene than did control subjects (P = 0.02). There was no overall association between plasma retinol and breast cancer but a positive relationship was observed between retinol and breast cancer in the subgroup with low beta-carotene values. These results suggest that low plasma beta-carotene is associated with increased risk of breast cancer. Other studies will need to determine whether low carotene concentrations are a subtle effect of the disease or might be causally related to breast cancer.

Adult↗

Feasibility of intraoperative cytodiagnosis of lung cancer.

Of 354 thoracotomies, 114 cases involved intraoperative cytopathologic evaluation. The study included 86 men and 28 women, and 184 specimens were examined. Smears were taken from the lung lesion or lymph node and the chest wall or bronchial stump by imprint or needle aspiration. Intraoperative evaluations were compared with histologic findings. In 85 cases not diagnosed as malignant preoperatively, malignancy was confirmed in 97.6 percent of cases and histologic type in 71.8 percent. In the 28 cases diagnosed as malignant preoperatively, there was only one false-negative. The most important finding during thoracotomy is whether a lesion is malignant or not. The time required to obtain a pathologic diagnosis also is important. We are able to obtain the results of a cytologic diagnosis within 10 min. Cytologic diagnosis of malignancy during thoractomy may be a feasible and convenient method of diagnosis, especially where malignancy is suspected.

Adenocarcinoma↗

Treatment options and recurrence potential for cystosarcoma phyllodes.

The surgical treatment and outcome of 31 women with a pathologic diagnosis of cystosarcoma phyllodes at Roswell Park Memorial Institute were reviewed. Surgical excision was performed upon 20 patients with a mean tumor size of 4.5 centimeters (range of 1.0 to 9.0 centimeters). Mastectomy was performed initially upon 11 patients with a mean tumor size of 15 centimeters (range of 3 to 40 centimeters). Local recurrence was seen in five patients treated by excision and one patient treated by mastectomy. All patients retreated by repeat excisions were controlled; one patient retreated with mastectomy died with local recurrence and distant disease. Routine axillary dissections were not performed. Involvement of the axillary lymph nodes occurred in one patient and was associated with advanced systemic disease. Local recurrences did not imply associated systemic spread and were controlled in five of six patients by repeat excision or mastectomy. Although the benign behavior of this tumor is commonly emphasized, four of the patients we studied died of malignant spread of cystosarcoma phyllodes.

Adolescent↗

[The trend of surgery for breast cancer in USA].

Breast cancer continues to increase in incidence among the American women, and an increasingly larger proportion of patients are found to have earlier cancers. For the past decade, the modified mastectomy prevailed as the standard surgical procedure. As the smaller cancers are diagnosed more frequently, they are also treated with breast-conserving surgery. The proportion of patients treated by breast conservation has been reported to be 20 to 50 percent of all operable breast cancer patients. Selection for lumpectomy or breast conservation is based upon tumor size, tumor location in the breast and type of tumor; but more frequently, patient's desire for breast conservation is the deciding factor. Interestingly, in the patients without axillary nodal metastasis, adjuvant systemic treatment has demonstrated its effective role. In this decision making for adjuvant therapy in women without nodaL metastasis, some of the prognostic factors such as tumor size, pathologic grades, nuclear grades, DNA flow cytometry, receptor status are weighted. Here again, each patient has the deciding voice after discussion of available treatment options.

Breast Neoplasms↗

Behavioral risk factors of human immunodeficiency virus infection among intravenous drug users and implications for preventive interventions.

Risk behaviors for HIV infection in relation to drug and sexual activities among 262 intravenous drug users (IVDUs) from methadone clinics in New York City were investigated using a structured questionnaire in 1986. The overall seroprevalence rate was 60.1 per cent. Intravenous heroin and cocaine users were found to be significantly more likely to be HIV positive than those who used heroin and cocaine intranasally. Among female IVDUs, excluding prostitutes (defined by self-report of sex for money or drugs), the HIV positive participants reported higher numbers of sex partners than those participants who were HIV negative. The female IVDUs who reported prostitution during the last 12 months were less likely to be HIV positive than those who did not. All males who reported passive anal and oral sex without using condoms during the last 12 months were found to be HIV positive. All female prostitutes who reported use of condoms during the last 12 months were found to be HIV negative. Interventions in methadone maintenance programs should focus on the IVDUs who are still using heroin, cocaine, and marijuana; sexually active females; and those IVDUs not using condoms (particularly among prostitutes).

Acquired Immunodeficiency Syndrome↗

Therapeutic oophorectomy in metastatic breast cancer.

One hundred five patients undergoing therapeutic oophorectomy for metastatic breast cancer (n = 105) from 1975 to 1985 were reviewed. There were 54 responders (51%) to oophorectomy, with a median duration of response of 16 months (range, 3 to 129 months). Thirty of 42 (71%) estrogen receptor (ER)-positive patients responded to oophorectomy versus five of 24 (21%) ER-negative patients (P less than 0.001). Of the 39 patients with unknown ER status, 19 (49%) responded to oophorectomy. Osseous, soft tissue, and pulmonary metastases responded at similar rates. Of the 16 patients who had received adjuvant chemotherapy, there were five responders (31%) to oophorectomy. Second-line endocrine therapy was effective in 29 of 53 (55%) patients. Fifteen of 28 (54%) ER-positive patients responded to second-line endocrine therapy while two of six (33%) ER-negative patients responded. Twenty-three of 37 (62%) oophorectomy responders responded to second-line endocrine therapy versus six of 16 (38) nonresponders. Oophorectomy appears to be a valuable palliative treatment for metastatic breast cancer. ER-positive patients have the best chance of responding to this therapy. However, ER-negative patients have a reduced but definite chance of responding with a good duration of response. Response to further endocrine treatments is predicted by response to oophorectomy and to a lesser degree by ER status.

Adrenalectomy↗