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Biomedical subjects

T Nemoto

Publications and source records attributed to T Nemoto.

At least 199 records · Page 11Linked to original sources

Differential response to chemotherapy in metastatic breast cancer in relation to estrogen receptor level. Results of a prospective randomized study.

The predictive value of estrogen receptor (ER) level for response to chemotherapy was studied in 182 patients with metastatic breast cancer in a prospective study. Patients were stratified according to ER status and dominant site of disease and randomized to one of three regimens: cyclophosphamide, 5-Fluorouracil, and prednisone (CFP) versus CFP, methotrexate, and vincristine (CFPMV) versus doxorubicin and cyclophosphamide (AC). There was no significant differences in all response categories (P = 0.21), was taken as a predictor for response to chemotherapy, there was no significant difference in overall response (P = 0.61) between ER+ (62/108, 57%) and ER- patients (31/49, 63%). However, there was a significant trend toward a higher degree of response in ER- patients (more complete response [CR] nine of 49, 18%, and fewer failures six of 49, 12%) than in ER+ (less CR seven of 108, 7%, and more failures 37/108, 34%) (P = 0.006). Patients with higher measured levels of ER showed worse response (Kendall's tau C, P = 0.026). This trend for ER- patients to have better response than ER+ patients was generally consistent, regardless of the predominant site of metastases or chemotherapy regimen (P = 0.04 for CFP; P = 0.08 for CFPMV; and P = 0.20 for AC). The advantage of a better response for ER- patients was nullified by an earlier relapse which was reflected in longer duration of remission, time to treatment failure, and survival in favor of ER+ patients (12.3 months versus 7.3 months remission duration, 18.7 months versus 13.6 months survival in partial responders). These data suggest that ER- patients respond to a higher extent to chemotherapy but relapse sooner than ER+ patients, suggesting a more rapid growth for ER- tumors. In patients with ER- tumors and poorer prognosis on conventional chemotherapy, new trials of intensive consolidation after response should be considered.

Antineoplastic Combined Chemotherapy Protocols↗

Aminoglutethimide in patients with metastatic breast cancer.

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.

Adult↗

Serum level of cryptic tumor antigens in breast cancer patients as determined by two monoclonal antibodies (M85/F36) and its comparison with CA 15-3.

An enzyme immunoassay system that measures cryptic epitopes on breast cancer mucinlike antigens (BCM-EIA) was evaluated in a double-blind manner in sera from 58 normal blood donors, 36 sex- and age-matched controls, 36 patients with benign breast diseases, and 47 patients with breast cancer. Two murine monoclonal antibodies, M85 (IgM) as the solid-phase and F36/22 (IgG3) as the probe, were used in the configuration of the assay kit. The assay additionally utilized neuraminidase to remove terminal sialic acid from carbohydrate side-chains to expose cryptic epitopes that were masked in serum specimens. BCM-EIA monoclonal assay from the normal healthy blood donors resulted in 17.34 +/- 7.04 units/ml (mean +/- 1 S.D.) with an upper normal cutoff of 31.4 units/ml. The distributions of serum BCM in the sex- and age-matched controls (17.77 +/- 11.17) and benign breast diseases (14.34 +/- 11.46) were similar to that of normal blood donors. A mean value of 66.04 units/ml and 27.74 units/ml was obtained from breast cancer patients with active disease and without evidence of disease, respectively, a level much greater than those of normals, controls, and benign breast diseases. Simultaneous analysis of CA 15-3, a putative breast tumor marker, in the normal donors and breast cancer patients revealed correlation regression of (CA 15-3) = 0.876 (BCM) + 1.972, r = 0.856; and (CA 15-3) = 0.66 (BCM) + 16.094, r = 0.730, respectively. These data showed that there is a statistically significant correlation of CA 15-3 and BCM in normal blood donors' specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Cyclic and sequential therapy with tamoxifen and medroxyprogesterone acetate in metastatic breast cancer.

A clinical trial of sequential tamoxifen and medroxyprogesterone acetate (MPA) was carried out in 36 women with metastatic breast cancer in order to evaluate the therapeutic efficacy of this regimen and to determine if tamoxifen would increase progesterone receptor (PR) levels and thereby increase response to MPA. Fourteen patients (39%) responded to this treatment, with the duration of remission ranging from 2 to 24 + months (the mean and median were 11 months). In 22 patients, PR levels were measured both before and after 7 days of tamoxifen administration. In PR-positive patients, PR changes induced by tamoxifen did not appear to increase the response rate. In PR-negative patients, PR became positive in 3 patients following tamoxifen treatment, with 2 of 3 responding to treatment, whereas in 11 others whose PR levels remained negative, only one response was observed. Our results suggest that potentiation by tamoxifen was not observed, since in our previous study, MPA alone was equally effective. Thus, tamoxifen and MPA should be given independently for palliation of metastatic breast cancer, and MPA should be administered following therapy with tamoxifen.

Adult↗

Ligand-dependent interaction of the dioxin receptor with target DNA.

Wild type and nuclear transfer deficient mouse hepatoma cell lines were used to study the specific DNA binding of a dioxin inducible factor. This factor interacts with XRE only after dioxin treatment and is absent in receptor mutant containing cells even after treatment. Thus, evidence is provided to substantiate the claim that the dioxin receptor is involved in the specific DNA interaction with dioxin response enhancer elements. It is also shown that the molybdate stabilised dioxin-receptor interacts with hsp90 suggesting that, in similarity to the glucocorticoid receptor, the dioxin receptor is kept in a non-transformed state in the absence of ligand.

Animals↗

An instrument for the long-term continuous measurement of oxygen uptake.

We developed an instrument for the continuous measurement of oxygen uptake. The instrument consists of a hood which covers the whole head of the subject, a flowmeter, an oxygen meter and a microcomputer. A servocontrolled blower draws room air through the hood, adjusting its volume flow so that the oxygen concentration in the hood is kept constant. The flow rate of the blower is measured with a heated-air transfer-type flowmeter, and oxygen concentration is measured by a solid electrolyte oxygen meter. Oxygen uptake can be calculated from the flow rate and oxygen concentration using the microcomputer, and each of these values is stored on a floppy disk. By this technique the instrument is able to measure oxygen uptake continuously for a prolonged period of time. We then compared the oxygen uptake measurements obtained with this instrument and those obtained with the Douglas bag method. The relationship between the volumes obtained by the two methods showed a high correlation (r = 0.98). The instrument was shown to be capable of measuring the slight change occurring in oxygen uptake between a subject at rest and performing isometric exercise.

Diagnosis, Computer-Assisted↗

[Study on the clinical usefulness of RAST using insect and mite allergen discs].

In order to examine the usefulness of mite and insect RAST, RAST was carried out on 79 asthmatic patients using mite, cockroach, mosquito and larval chironomid midge (Chironomus thummi thummi, CTT) allergen discs supplied from Pharmacia AB, and discs of two species of adult chironomid midge (Tokunagayusurika akamusi, TA and Chironomus yoshimatsui, CY in Japan) which were prepared in our laboratories. The results were as follows. 1) The positive rate of RAST in 65 randomly selected asthmatic patients was 62% in the case of mite, 25% for TA, 20% for CY, 14% for cockroach, 11% for CTT, 8% for silk and 6% for mosquito. The positive rates of silk and mosquito RAST were low. However, these RAST seemed to be clinically useful when patients were positive to these RAST. 2) The rate of coincidence between skin test and RAST was 86.5% in the case of mite and 30% in the case of silk. The rate of coincidence between prick test using adult CY and RAST using larval CTT was 46.5%. 3) The positive rate of larval CTT RAST was about half that of adult TA or adult CY. However, larval CTT RAST seemed clinically useful when patients were positive to the RAST, because all the patients who were positive to larval CTT RAST were also positive to both adult TA and CY RAST. 4) A significant correlation was found among the three kind of chironomid midge RAST and also between cockroach RAST and any of the three kinds of chironomid midge RASTs.

Allergens↗

[Electron microscopic studies of fine structure on the oral spirochetes].

Of the strains isolated from periodontitis patients in this laboratory, seven pure cultures with different characteristics were subjected to a scanning electron microscope and transmission electron microscope (negative staining, thin section and freeze-etching method were employed) for the cell morphology investigations. The following results were obtained; 1) Cells were thin, long and twisted to make thme spirals. Some differences were observed in cell length and width, even though in a same isolated strain. 2) It was obvious that the basic cell structure of oral spirochetes consisted of the following seven parts; i.e., outer envelope, axial fibrils, main body, cytoplasm, nucleous structure, ribosomes and fine fibrils. 3) The specific structures, which should be called tubulous and/or ring-like structures, were shown in certain strains. They obviously located at the cell surface of oral spirochetes. 4) Outer envelope, which locates at the most outside layer of the cell, composed with two membranous structures holding one fine granular structures in it, and fold completely the main body and axial fibrils. 5) It was noted that the one end of axial fibrils locating at the space between outer envelope and main body fused with main body resulting in formation of a specific disk-like structure. 6) The surface of the main body was double-layered membranous structures. 7) Nucleous structure, ribosomes, and fine fibrils which were slender than axial fibrils were in the cytoplasm.

Humans↗

[Pulmonary nodule confirmed by rib consolidation on thoracic computed tomography].

Coin lesions in the thoracic cavity, skin, muscle and connective tissue are clearly observed by computed tomography (CT). However, it is very difficult to detect abnormal shadows in the ribs by thoracic CT at the mediastinal level. We describe 3 cases of pulmonary nodules that were not detected by CT at the mediastinal or lung field level, however, but could be detected at the bone level. When pulmonary nodules cannot be detected by thoracic CT at the mediastinal or lung field level, it is recommended to change the window to the bone level.

Adult↗

Human immunodeficiency virus infection in a cohort of intravenous drug users in New York City. Demographic, behavioral, and clinical features.

In 1985, 454 intravenous drug users were recruited from among patients scheduled for physical examination in methadone treatment clinics in New York City. A questionnaire was administered, and serum was collected for human immunodeficiency virus (HIV) serology. The HIV seroinfection rate was 60.6%, with antibody and antigen detected in 58.4% and 4.3%, respectively, of the population. Nineteen percent of 307 subjects were in Group III or Group IV of the Centers for Disease Control (CDC) classification system for HIV-associated infections. Only behavioral factors (p = 0.001) and clinical indicators (p = 0.003) were found to distinguish the HIV-infected from the non-infected subjects. Frequent use of intravenous drugs (p = 0.016), duration of drug use (p = 0.050), and duration of drug treatment enrollment (p = 0.038) were significantly associated with HIV seroinfection status and CDC stage of HIV disease. These findings strongly support aggressive efforts to reduce parenteral drug use and enroll intravenous drug users into effective drug treatment programs.

Acquired Immunodeficiency Syndrome↗

Breast cancer survival among Orientals and whites living in the United States.

Data from the 1982 breast cancer survey of the American College of Surgeons were used to study the survival differences between Oriental and white women. Oriental women were significantly younger than white women. Oriental women were reported with a slightly higher percent of localized breast tumors (59.2% vs. 53.8%) and a slightly higher percent with negative nodes (60.3% vs. 56.2%) compared with whites. Oriental women in the United States have a higher 5-year survival rate compared to whites. Multivariate analyses taking into account differences in age, stage of disease, and histology did not alter the finding of a significant difference in survival experiences.

Breast Neoplasms↗

Characterization of the nontransformed and transformed androgen receptor and heat shock protein 90 with high-performance hydrophobic-interaction chromatography.

The hydrophobicity of the nontransformed and transformed androgen receptor from rat submandibular gland and heat shock protein 90 (hsp90) from rat submandibular gland and liver was characterized by using high-performance hydrophobic-interaction chromatography on TSK gel Ether-5PW. In the absence of molybdate, cytosol [3H]R1881-androgen receptor complexes were mainly eluted in the 1.3 M region (Peak 1) with a small peak in the 0.8 M region (Peak 2) of a descending salt gradient (2 to 0 M) of ammonium sulfate. In the presence of molybdate, Peak 2 was predominant. When labeled-cytosol was applied after being heated at 25 degrees C for 30 min, a third peak (Peak 3) at around 0.64 M ammonium sulfate was newly observed. Peaks 2 and 3 were observed, while Peak 1 completely disappeared with the labeled-cytosol precipitated at 40% saturated ammonium sulfate. The Stokes radius of Peak 1 was 7 nm, and of Peak 2 was 8 nm. Both peaks were retained poorly by DNA-cellulose but bound rather well to DEAE-cellulose. These results suggest that these two peaks represent the nontransformed receptor, indicating that there are isoforms of the nontransformed androgen receptor which are distinguished by their hydrophobic properties and Stokes radii. Peak 3 had a Stokes radius of 5 nm and preferentially bound to DNA-cellulose, suggesting that this peak corresponds to the transformed receptor. These results indicated that the transformation of the androgen receptor accompanies the enrichment of the hydrophobicity of the receptor molecule. Hsp90 purified from rat livers and hsp90 in the cytosol both from livers and submandibular glands were eluted from Ether-5PW at 0.8 M ammonium sulfate, at almost the same position as Peak 2. This finding suggests that the enrichment of hydrophobicity on transformation is due to dissociation of hsp90 from the nontransformed androgen receptor.

Animals↗