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Biomedical subjects

K Enomoto

Publications and source records attributed to K Enomoto.

At least 217 records · Page 12Linked to original sources

Real-time imaging of intracellular calcium change with simultaneous single channel recording in mammary epithelial cells.

A method of continuous image subtraction of fura-2 fluorescence made it possible to observe real-time (video rate) changes in intracellular calcium (Cai). This simple method is very useful for simultaneous measurements in electrophysiology with a system containing cells of different states. A method for synchronous recording of Cai change and single channel activity is also described. In cultured mammary epithelial cells, these methods revealed a propagating Cai signal induced by mechanical stimulation and spontaneous Cai oscillation with synchronous activation of calcium-activated potassium channels.

Animals↗

Phenotype of preneoplastic and neoplastic liver lesions during spontaneous liver carcinogenesis of LEC rats.

The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and alpha-fetoprotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable positive marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induced liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying mechanisms of human liver cancer development.

Adenosine Triphosphatases↗

Clinical study of pirarubicin for breast cancer in Japan. Clinical Study Group of THP for Breast Cancer in Japan.

The efficacy and toxicity of (2''R)-4'-O-tetrahydropyranyl adriamycin (THP) were assessed in the treatment of patients with advanced breast cancer by the Japan THP Study Group. Mean plasma levels of THP after single-dose administration revealed triexponential decay characterized by an initial half-life of 0.89 h. A higher concentration of THP was obtained in the metastatic lymph nodes than in the breast cancer tissue at 4 h after administration (4.01 vs. 1.17 micrograms/g). Whereas 1 complete (CR) and 12 partial response (PR) were observed in 56 evaluable patients after administration of THP alone (23.2%), 1 CR and 12 PR were observed in 37 evaluable patients who had combination therapy including THP (35.1%). Multivariate analysis of prognostic factor revealed that the site of metastases had the most valuable prognostic significance; second was irradiation in the previous treatment, and third was the disease-free interval. Life-table analysis adjusted with the Cox proportional hazard model revealed a similar survival curve of patients receiving THP-cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) to that of those receiving CAF only in spite of the low incidence of toxicity in the THP therapy.

Adult↗

Cytochemical examination of the compartments involved in the transcellular transport of horseradish peroxidase in rat hepatocytes.

Horseradish peroxidase (HRP, 10 mg/100 g body weight) was intravenously injected into rats in order to investigate the nature of the compartments involved in the transcellular transport of the protein through hepatocytes into bile. Double cytochemistry for HRP and the marker enzymes for cytoplasmic organelles was used. HRP was shown to be taken up by hepatocytes via vesicles at the sinusoidal surface, some of which were positive for 5'-nucleotidase activity. HRP was then found in the smooth-surfaced vesicles and tubules which were negative in 5'-nucleotidase, glucose 6-phosphatase, thiamine pyrophosphatase and acid phosphatase activity, suggesting that the tubular structures are neither the endoplasmic reticulum, the Golgi apparatus nor lysosomes. Biochemical studies revealed that the lead procedures used for the double cytochemistry did not inhibit the peroxidatic activity of HRP, and conversely that HRP did not interfere with the marker enzyme activity. Such cytochemical observations seemed to be supported by the observation that administration of monensin (3.5 mg/100 g) and chloroquine (5 mg/100 g), which markedly altered the structure of the Golgi apparatus and lysosomes, respectively, slightly altered the biliary excretion of HRP but not to a significant extent.

5'-Nucleotidase↗

[Breast preserving surgery].

Psychological damage caused by radical mastectomy should be taken into consideration from the point of view of quality of life, in addition to sequelae such as disturbance in movement of the shoulder, lymph edema of the arm. Surgery preserving breast is recommended for resolution of the problem. The histopathological study of eighty seven early breast cancer which is defined by 1.0 cm or less in diameter on palpation revealed that sixty seven patients (77 percent) really had a tumor measuring 1.0 cm or less in the surgical specimen and fifty two patients (60 percent) had an invasion into surrounding tissue limited within 2.0 cm from a border of tumor and three patients (3.5 percent) had an invasion to nipple. The data suggested a possibility of surgery preserving breast for patient with early breast cancer satisfied with following condition: tumor is less than 1.0 cm in diameter; it is situated at least 3.0 cm distant from nipple: no involvement palpable in the axilla: no multiple lesion is found on x.p. mammography and ultrasonography: area with minute punctate calcifications is limited in circle measuring 2.0 cm in diameter. Ten patients underwent subcutaneous mastectomy and four patients had quadrantectomy and axillary dissection. A patient had local recurrence, at median follow-up time twenty three months range from three months to 36 months.

Breast Neoplasms↗

[Phase I study of FK 435].

We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide.

Adult↗

Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s.

The metabolism of lidocaine by human hepatic microsomes and purified human cytochrome P-450s, P-450NF (P450IIIA4), P-450MP (a P450IIC form) and P-450PA (P450IA2) was examined and their metabolism was compared with that by rat hepatic cytochrome P-450s. Human hepatic microsomes produced monoethylglycinexylidide (MEGX) and 3-hydroxylidocaine (3-OH-LID) from lidocaine. In a reconstituted system with dilauroylphosphatidylcholine, P-450NF efficiently produced MEGX. P-450PA was not efficient in lidocaine N-deethylation (formation of MEGX) but produced 3-OH-LID. P-450NF and P-450MP did not produce 3-OH-LID. Lidocaine N-deethylation activity of P-450NF was enhanced in a modified reconstituted system with a phospholipid mixture and sodium cholate. P-450NF appears to be an ortholog to rat P450 PB-1 (P450IIIA2). Anti-P450 PB-1 antibody cross-reacted with P-450NF and efficiently inhibited lidocaine N-deethylation in human hepatic microsomes. The correlation of lidocaine N-deethylation activity with the concentration of P-450NF determined immunochemically with anti-P450 PB-1 antibody was good (r = 0.81). In addition, correlation between P-450NF content estimated with anti-P450 PB-1 and anti-P-450NF preparations was good (r = 0.96). These results suggest that rat P450 PB-1 and human P-450NF have closely related properties and P-450NF is the major enzyme involved in lidocaine N-deethylation in human hepatic microsomes.

Adult↗

Single calcium-activated potassium channel in cultured mammary epithelial cells.

The properties of Ca2+-activated K+ channels in mouse mammary epithelial cells in primary culture were studied by the patch-clamp technique. In cell-attached patches, spontaneous channel openings were sometimes observed; the slope conductance of the currents was about 12 pS at negative membrane potentials with a physiological solution (152 mM Na+, 5.4 mM K+) in the pipette. External application of A23187, a calcium ionophore, activated this channel. In excised inside-out patches, the channel was activated by increasing the internal Ca2+ concentration (10(-7) to 10(-6) M). No voltage dependence of the channel was activated was observed. Internal Na+ blocked the outward K+ current in a voltage dependent manner and this block led to the non-linear I-V relationship at positive membrane potentials. The channel was blocked by internal Ba2+ (0.1 mM) and tetraethylammonium (TEA+, 20-50 mM). Ba2+ reduced the open probability but not the single channel conductance, whereas TEA+ reduced the single channel conductance. The single channel conductance of this channel, measured from the inward current with a high-K+ solution (150 mM K+) in the pipette, was large (about 40 pS), and showed inward rectification. These results suggest that this channel is different from the usual small conductance Ca2+-activated K+ channels observed in many other cells.

Animals↗

The effects of estrogen on human breast carcinomas serially transplanted into nude mice.

The effect and mechanisms of 17 beta-estradiol (E2) on breast cancer cells were studied in vivo and in vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E2 at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E2 in 3 out of the 4 ER positive tumors, the Td of the E2 treated groups being 17.6 days for MCF-7 (control: -17.8 days), 12.8 days for R-27 (control: -12.5 days approximately 14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E2 in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E2. Discrepancies between the effects of E2 on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conducting in vitro growth studies. In vitro clonogenic cell assay reproduced the antitumor activity of E2, indicating that E2 directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.

Animals↗

A randomized controlled study of (2"R)-4'-O-tetrahydropyranyladriamycin and adriamycin in combination with cyclophosphamide and 5-fluorouracil in the treatment of advanced and recurrent breast cancer. Clinical Study Group of THP for Breast Cancer in Japan.

The chemotherapeutic treatment of advanced and recurrent breast cancer was examined in a randomized controlled comparison test. Group A received (2"R)-4'-O-tetrahydropyranyladriamycin (THP) in combination with 5-fluorouracil (5-FU) and cyclophosphamide (CPA), while Group B was administered adriamycin (ADR) together with 5-FU and CPA. These combined chemotherapies were administered in a dosage regimen that was repeated in a 28-d cycle. On d 1 and d 8, THP and ADR were given at a dose of 30 mg/m2 IV and 5-FU was administered at a dose of 500 mg/m2 IV. CPA was administered at a dose of 100 mg/body, PO on consecutive days from d 3 to d 16. Among 37 complete cases in Group A, a complete response (CR) was noted in one patient and a partial response (PR) in 12, to give a rate of 35.1%. CR was noted in one patient and PR was observed in 7 out of 27 complete cases in Group B, giving a response rate of 29.6%. The mean PR duration was 19 wk (range, 4+--63) in Group A, and 14 wk (range, 4+--51+) in Group B. The 50% survival duration was 20.6 mo and 14.3 mo in Groups A and B, respectively, while mean survival duration was 17.9 mo and 16.6 mo in Groups A and B, respectively. No significant between-group differences were found for any of these measures. There were fewer side effects in Group A than in Group B, with Group A showing significantly less alopecia (P less than 0.01) and a lower incidence of anorexia (P greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metastatic squamous cell carcinoma of the paranasal sinuses from a primary squamous cell carcinoma of the urinary bladder.

Metastatic tumours of the paranasal sinuses from primary lesions of the urogenital tract are rare, with about 50 cases so far being reported in the literature. The most frequent primary lesions is a renal carcinoma. We have experienced a case of paranasal sinus malignancy. There were no symptoms of urinary tract carcinoma preceding those in the paranasal sinuses. This case was later revealed at autopsy to be a metastasis from a diverticulum of the urinary bladder.

Aged↗

[Performance evaluation of X-ray computed tomography "TCT-700 S". 2].

UNLABELLED: The performance of the rotate/rotate CT scanner TCT-700 S (Toshiba) was evaluated on the basis of the item entitled "User's initial acceptance tests (phase II)" set forth in "Standard of performance evaluation for x-ray computed tomography (second recommendation)" proposed by Takenaka et al. (1982). This second report in the series describes measurements of exposure and the relation between exposure and such other performance aspects as noise and contrast resolution. The exposure-performance recommendation proposes measurements of average exposure in the scanning field and a radial exposure profile. RESULTS: 1. In the case of multiple scanning, average exposures in the field were uniform because all surfaces of the perpendicular object were oriented toward the incidence of the x-ray beam. At a minimum scanning speed of 1.8 second, however, a discrepancy of 3 times occurred in exposures observed reciprocally from the left and right sides of the object. This phenomenon indicates that only one-half of the object surface is oriented toward the x-ray beam and that the x-ray tube and detectors rotate in mutually opposite directions. In the case of multiple scannings, when slice thicknesses were 10 mm, 5 mm and 2 mm, average exposures were almost uniform. But with a slice thickness of 1 mm, average exposure was twice as great. This measurement indicates inadequate collimation in the case of a 1 mm slice thickness. These average exposures were roughly proportional to the mAs (product of tube current and scan speed) in the range between a minimum of 100 mAs and a maximum of 1200 mAs. 2. Noise increased in proportion to decrease of average exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiation Dosage↗

[Performance evaluation of the X-ray computed tomography "TCT-700 S" (Part 1)].

The performance of the Rotate/Rotate CT scanner "TCT-700 S" (Toshiba) was evaluated on the basis of the item entitled "User's initial acceptance tests (phase II)," set forth in "Standard of performance evaluation for X-ray computed tomography (second recommendation)" proposed by Takenaka et al. (1982). This report describes measurements for noise, contrast scale, spatial resolution, and high- and low-contrast resolution. Recommended phantoms were used to test performance. Results 1. Noise edepended on slice thickness and mAs. It increased as slice thickness decreased. No matter what the slice thickness, noise was great when mAs settings were small. Furthermore, short scan time caused considerable noise for each slice thickness. Reduction of mAs setting caused remarkable increased in noise when slice thickness were 1 mm or 2 mm Under routine examination, when thickness was 5 mm, at 120 kV, with an mAs setting of 440, scan field S(diameter 240 mm), and convolution filter FC-2, noise was 0.31%. When slice thickness was 10 mm at 120kv, 800mAs, with a scan field S (diameter 240 mm), and convolution filter FC-2, contrast scale was 1.84 x 10(-4) (cm-1/CT number). 2. When slice thickness was 5 mm, at 120 kV, with a mAs setting of 1200, scan field S(diameter 240 mm), and a convolution filter of FC-2, spatial resolution was 0.5LP/mm. 3. When slice thickness was 5 mm, at 120kV, with a mAs setting of 1200, scan field S (diameter 240 mm), and convolution filter of FC-2, minimum high-contrast resolution was 0.5 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

[Contact thermography as a prognostic indicator of breast cancer].

Ninety-seven primary, operable cancer patients were followed after surgery with a median follow-up of 44 months. Thermograms were classified into 3 categories: normal, equivocal and abnormal. There has been no recurrence in patients with normal thermographic pattern. Patients with abnormal thermographic pattern showed poor prognosis: 88% survival and 80% recurrence-free survival rate at 3 years. Normal thermographic pattern favored the survival curves and recurrence-free survival curves, even if stratified by nodal states. There seems to be no correlation between thermographic patterns and sites of recurrence, but patients with abnormal thermographic patterns tend to have recurrences at more than one site.

Breast Neoplasms↗

Evaluation of dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge as an adjunct in the diagnosis of early breast cancer. Research Group for Carcinoembryonic Antigen in Nipple Discharge.

We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. As an extension, a dot-immunobinding assay was developed to screen a large number of patients with nipple discharge for non-palpable breast cancer. The principle is as follows. CEA bound to a solid phase monoclonal anti-CEA antibody is detected by a second monoclonal anti-CEA antibody conjugated with horseradish peroxidase. The use of tetramethylbenzidine as a chromogen results in a stable color reaction that can be semiquantitively analyzed by the naked eye. The CEA levels determined by this dot assay correlated well with CEA levels determined using the former Elmotec assay. To determine whether or not the method could also be feasible in the detection of non-palpable breast cancer, a collaborative study from 12 Japanese institutes was organized. The CEA levels in nipple discharges from 155 patients were assayed. Thirteen of 30 patients with palpable breast cancer and 22 of 30 patients with non-palpable breast cancer exhibited CEA values higher than 400 ng/ml, a cut-off value determined using 89 benign controls. The specificity (91%) and sensitivity (73%) of this test were higher than those of mammography or cytology. The incidence of elevated CEA levels in nipple discharge correlated significantly with the incidence of intratumoral antigen expression. Thus, the system could prove useful in screening for early breast cancer.

Body Fluids↗

Inhibition of glycolysis induced by diethylstilbestrol in anaerobically grown yeast.

In anaerobically grown yeast cells which lack functional mitochondria, the presence of diethylstilbestrol (DES) depressed glycolysis. The addition of the inhibitor markedly increased the cellular concentration of glycolytic intermediates which are formed prior to the pyruvate kinase step as well as to bring about an increase in the [ATP]/[ADP] ratio. Under these conditions an 18 fold decrease in the mass action ratio for pyruvate kinase [( pyruvate] [ATP]/[phosphoenolpyruvate] [ADP]) was noted, however, there was little if any effect on the other glycolytic enzymes. These results suggest that the depression of anaerobic glycolysis caused by DES results from a blockage at the level of the regulatory enzyme pyruvate kinase through a modification of its intracellular environment.

Anaerobiosis↗