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Biomedical subjects

Y Furuya

Publications and source records attributed to Y Furuya.

At least 145 records · Page 8Linked to original sources

5-Fluorouracil attenuates an oncostatic effect of melatonin on estrogen-sensitive human breast cancer cells (MCF7).

The pineal hormone, melatonin, has been reported to have an inhibitory effect on the cell growth of human breast cancer. We have now assessed the interaction of melatonin with 5-fluorouracil (5-FU) on estrogen-sensitive MCF7 and estrogen-insensitive HBC4 cell lines. Melatonin inhibited MCF7 cell growth dose-dependently, reaching a maximum inhibition of growth of 39% that of control at a concentration of 0.3 nM (this is about equivalent to the physiological concentration of melatonin secreted at 0200 h in humans). 5-FU also demonstrated an inhibitory effect on MCF7 cell growth and a maximal inhibition of growth by 24% was acquired at a concentration of 500 ng/ml. By contrast, the inhibitory effect of melatonin was reduced by the co-administration of 5-FU, independently of 5-FU concentration. Melatonin and/or 5-FU exhibited no effect on HBC4 cells. This preliminary study indicates that 5-FU should be handled with care for treatment of estrogen sensitive-breast cancer.

Breast Neoplasms↗

[Calcified false channel wall in aortic dissection].

Chest radiographs and computed tomographic images of 110 patients with chronic aortic dissection were retrospectively reviewed. Among these, calcification of false channel wall was observed in 12 cases (about 10%). Stanford type A dissection was noted in 5 cases and type B in 7 cases. Calcified false channel wall may closely simulate intimal calcification of atherosclerotic aneurysm on chest radiographs and sometimes even on CT. Careful observation of CT images with and without contrast enhancement is helpful to correctly identify the site of calcifications in the false channel wall, true channel wall, and intimal flap in the individual cases. In 3 cases calcification was present mainly in the false channel wall with no or only minimal calcification in the true channel wall. These cases may suggest that the endothelialized false channel lumen may develop atheromatous changes much more rapidly than the true lumen. According to advances in surgical and medical treatment of acute aortic dissection, radiologists may encounter cases of chronic aortic dissection with increasing frequency. Full recognition of this potential pitfall in the diagnosis of aortic dissection is important to avoid confusion.

Aged↗

Proliferation-dependent vs. independent programmed cell death of prostatic cancer cells involves distinct gene regulation.

Androgen-independent Dunning R-3327 AT-3 rat prostatic cancer cells can be induced to undergo programmed cell death in either a proliferation-dependent or independent manner depending upon the therapeutic agent used. In the present study, 5-fluorodeoxyuridine (5-FrdU) was used to induce proliferation-dependent death of the AT-3 cells via its ability to inhibit thymidylate synthetase. Ionomycin and thapsigargin were used to induce proliferation-independent death of these cells via their ability to sustain an elevation in intracellular free Ca2+. Based upon the temporal sequence of DNA fragmentation, morphologic changes, and loss of cell viability, each of the three test agents, at the doses used, induces the programmed death of AT-3 cells with essentially identical kinetics. Based upon these similarities, comparisons of the pattern of gene expression during the proliferation-dependent (i.e., 5-FrdU-induced) vs. proliferation-independent (i.e., ionomycin and thapsigargin-induced) programmed death of AT-3 cells allow identification of genes whose enhanced expression is involved in the initiation vs. completion of programmed cell death. Based upon this approach, enhanced H-ras and TRPM-2 expression is associated with initiation of proliferation-dependent programmed death of AT-3 cells while enhanced c-myc, calmodulin, and alpha-prothymosin expression is associated with initiation of proliferation-independent programmed death of these cells. In contrast, enhanced expression of glucose-regulated 78 kilodalton and tissue transglutaminase genes are associated with the completion of programmed cell death, since their expression is enhanced in both proliferation-dependent and independent programmed cell death of AT-3 cells.

Animals↗

The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases.

The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4B3). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin-embedded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4B3, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P < 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P < 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones.

Antibodies, Monoclonal↗

Cyclic ADP-ribose modulates Ca2+ release channels for activation by physiological Ca2+ entry in bullfrog sympathetic neurons.

Although Ca(2+)-induced Ca2+ release (CICR) via ryanodine receptors has been found to occur in intact neurons, little is known about the physiological processes that regulate it. We studied the effects of cyclic ADP-ribose (cADPR) on CICR in cultured bullfrog sympathetic neurons by fura-2 fluorescence recording and patch-clamp techniques. cADPR applied through a patch pipette augmented action potential- or depolarizing pulse-induced rises in intracellular Ca2+ without a change in Ca2+ entry initiating the responses, but not in the presence of ryanodine. Likewise, cADPR enhanced a single or oscillatory rise(s) in intracellular Ca2+ induced by caffeine. These results strongly suggest that cADPR can be an endogenous modulator of ryanodine receptors in neurons.

Adenosine Diphosphate Ribose↗

[Serotype-specific amplification of Rickettsia tsutsugamushi DNA from clinical specimens by nested polymerase chain reaction].

Polymerase chain reaction (PCR) with nested primer pairs was used to diagnose Tsutsugamushi disease and identify the Rickettsia tsutsugamushi serotype. The primer pairs used for PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen. Five serovariants, the Gilliam, Karp, Kato, Kawasaki, and Kuroki strains of Rickettsia tsutsugamushi were detected and identified by nested PCR. The serotypes of patients registered during 1990 to 1992 in Kanagawa Prefecture were identified by nested PCR. Sixty percentage of patients showed Kawasaki types, 20% Karp types, and 20% Kuroki types. This result suggested that the recent Tsutsugamushi disease were mostly caused by Kawasaki types in Kanagawa Prefecture.

DNA Primers↗

Immunohistochemical microquantitation method for type I collagen in kidney histological section of the rats.

An immunohistochemical micromethod for quantitation of type I collagen in frozen histological section of rat kidney was developed. A principle of this method is enzyme-linked immunosorbent assay (ELISA). The intensity of immunoreactivity of the section to an anti-type I collagen antibody was quantitated, and then the total protein content in the same section was measured colorimetrically. Type I collagen content was expressed as mg of type I collagen per g of total protein. In this micromethod, the minimum area and optimum thickness of the section were 5 mm2 and 10 microns, respectively. Type I collagen content in the rat kidney section was 3.02 +/- 0.12 mg/g. This method should be useful for diagnosis of renal failure.

Animals↗

A new immunohistochemical method for quantification of fast-myosin in frozen histologic sections of the rat skeletal muscles.

An immunohistochemical micromethod for quantification of fast-myosin in frozen histologic sections of rat skeletal muscles was developed. The principle of this method was enzyme-linked immunosorbent assay (ELISA). We used frozen tissue sections as models of the antigen-coated wells of ELISA plate. The intensity of immunoreactivity of the frozen section to an anti-fast-myosin monoclonal antibody was quantified directly from the color developed with the second antibody coupled with peroxidase using phenol-4-aminoantipyrine as a substrate. Then, the same section was incubated in 0.01 M acetic acid solution to cleave antigen-antibody complexes, followed by colorimetric measurement to obtain the absolute value of total protein per section. Fast-myosin content in the frozen tissue section was expressed as mg of fast-myosin per g of total protein. In this micromethod, the minimum area and the optimum thickness of the section were 5 mm2 and 10 microns, respectively. Fast-myosin contents in the extensor digitorum longus and soleus muscles were 185.0 +/- 6.1 and 17.5 +/- 2.4 mg/g, respectively. The results obtained by this micromethod were in good agreement with those obtained by two conventional methods, immunohistochemical morphometry and biochemical determination. This micromethod is useful for a quantitative evaluation of the contractile function of the mammalian skeletal muscles.

Actins↗

A family with complete deficiency of plasma cholesteryl ester transfer protein activities.

A 43-year-old male with a high value of high density lipoprotein cholesterol (151 mg/dl) was found among subjects receiving annual health checks. We investigated the cholesteryl ester transfer protein (CETP) activity and conducted a family study. There was complete deficiency of CETP activities in the proband and his sister, and partial deficiency of CETP activities in his mother and daughter. Genetic analysis revealed a splicing defect (G to A point mutation) in intron 14 of the CETP gene.

Adult↗

The role of androgen in the regulation of programmed cell death/apoptosis in normal and malignant prostatic tissue.

Cells possess within their repertoire of epigenetic programs the ability to undergo a process of cellular suicide, termed programmed cell death. This programmed cell death process involves an epigenetic reprogramming of the cell that results in an energy-dependent cascade of biochemical and morphologic changes within the cell (also termed apoptosis), resulting in its death and elimination. Although the final steps (i.e. DNA and cellular fragmentation) are common to cells undergoing programmed death, the activation of this death process is initiated either by sufficient injury to the cell induced by various exogenous damaging agents (e.g. radiation, chemicals, viruses, etc) or by changes in the levels of a series of endogenous signals (e.g. hormones and growth/survival factors). As an illustrative example, the role of androgen as a cell type specific endogenous regulator of the programmed death of normal and neoplastic prostatic cells will be presented.

Androgens↗

[Establishment and characterization of a human small cell lung carcinoma cell line (MT-428) derived from the patient who showed neurological paraneoplastic syndrome].

A new human small cell lung carcinoma (SCLC) cell line, designated MT-428, was derived from a patient who showed neurological paraneoplastic syndrome (combined with subacute cerebellar degeneration and peripheral sensory neuropathy) and was established in tissue culture. This cell line exhibited small cell (variant type) morphology as observed by phase contrast and electron microscopy. The MT-428 cells had a doubling time of 72 hours. Chromosomal analysis showed complicated rearrangements at short and long chromosomes with a modal number of 68. Several tumor markers, NSE, TPA and CPK-BB, were detected in culture medium. This cell line had a cloning efficiency of 1.3% in 0.8% methylcellulose. Finally, it should be noticed that autoantibody against MT-428 cell was demonstrated in serum of the patient. We concluded that the MT-428 cell line may provide a suitable model for studies of neurological paraneoplastic syndrome.

Animals↗

[Nocturnal infusion of 5-fluorouracil in advanced digestive tract cancer--two case reports].

Two patients, with terminal stage digestive tract carcinoma, are presented who received continuous nocturnal administration of intravenous 5-FU (300 mg/m2/day), between 9:00 pm and 8:00 am for more than 45 consecutive days. They showed improvement in general physical and functional status, and no side effects were observed. The first case is that of a patient with not only an early gastric cancer, but also a nonresectable esophageal cancer. After therapy, complete disappearance of the gastric cancer was noted by endoscopy. The second patient had advanced gastric cancer with carcinomatosis. He received intraperitoneal cisplatinum for intractable ascites without improvement. But after continuous nocturnal 5-FU therapy, a significant reduction in ascites was noted. Two cases did not experience leukopenia and no significant side effects were noted, even in the second patient who received nocturnal 5-FU for 122 days. The therapeutic effects of continuous nocturnal 5-FU administration generally appeared after 20 days, so a prolonged period of time seems to be important.

Adenocarcinoma↗

[Comparison between diltiazem and nicardipine used during anesthesia for coronary revascularization].

The effects of diltiazem (0.1 mg.kg-1 + 3 micrograms.kg-1.min-1) and nicardipine (0.01 mg.kg-1 + 2 micrograms.kg-1.min-1) on circulatory parameters were compared in 30 patients with ischemic heart disease, who underwent coronary revascularization. These drugs were administered intravenously via a Swan-Ganz catheter after induction of fentanyl anesthesia. The group injected with diltiazem showed significant decreases in heart rate, mean arterial pressure, cardiac output, left ventricular stroke work and rate-pressure product. The group injected with nicardipine showed significant decreases in mean arterial pressure, systemic vascular resistance, rate-pressure product and pressure-rate quotient. There were significant differences between the two groups in cardiac output, stroke volume, systemic vascular resistance and left ventricular stroke work. The results suggest that diltiazem protects the ischemic heart by slight cardiac suppression and that nicardipine reduces afterload by marked vascular dilatation during anesthesia for coronary revascularization. Both Ca-channel blockers were demonstrated to be useful.

Aged↗

Cell proliferation, DNA repair, and p53 function are not required for programmed death of prostatic glandular cells induced by androgen ablation.

Androgen ablation induces programmed death of androgen-dependent prostatic glandular cells, resulting in fragmentation of their genomic DNA and the cells themselves into apoptotic bodies. Twenty percent of prostatic glandular cells undergo programmed death per day between day 2 and 5 after castration. During this same period, < 1% of prostatic glandular cells enter the S phase of the cell cycle, documenting that > 95% of these die in G0. During the programmed death of these G0 glandular cells, a futile DNA repair process is induced secondary to the DNA fragmentation. This futile DNA repair is not required, however, since inhibition of this process by > 90% with an appropriately timed hydroxy-urea dosing regimen had no effect upon the extent of the programmed death of these cells after castration. Likewise, p53 gene expression is not required since the same degree of cell death occurred in prostates and seminal vesicles after castration of wild-type and p53-deficient mice.

Animals↗

[Androgen-dependent tumor].

Androgen receptor is necessary for the proliferation of androgen-dependent tumors including human prostatic cancer and murine androgen-sensitive tumors. However, androgen-independent tumor containing functional androgen receptor was observed in CS 2 cells, which is a subline of androgen-dependent mouse tumor (SC 115). CS 2 showed a new expression of hst-1, the product of which is a family of FGF. CS 2 secreted a growth factor which promotes growth of CS 2 and original SC 115 in an autocrine and paracrine manner. The role of oncogene(s) and suppressor gene(s) on the progression of the tumor is discussed.

Androgens↗

Influence of meals and night shifts on health.

(1) The effect of twice-daily meals on a body weight (BW) and blood pressure (BP), (2) the effect of working night shifts on BPs, and (3) a relationship between a meat diet and cedar pollinosis were statistically investigated with working men who had an annual medical examination. As a result, the effect of twice-daily meals on BW and BP was not different from thrice-daily meals on BW and BP. However, cases of twice-daily meals had larger percentages of alcohol drinkers and cigarette smokers. The night shift workers had almost the same frequency of hypertension as compared with day duty workers. A daily diet of meat including beef, chicken, and pork had a close relationship with cedar pollinosis.

Adult↗

[Epidemiology of Tsutsugamushi disease and typing of isolated Rickettsia in Chiba Prefecture].

In Chiba Prefecture, the first patient of Tsutsugamushi disease was found in the southern part in the 1950's, but after that no patient was detected until 1982. After 1982, patients have been noticed again, the number of patients has been increasing year by year. The number of serologically confirmed cases was 152 and 157 in 1989 and 1990, respectively with indirect immunofluorescence assay. About 90 percent of the patients were found in November and December, prevalently in the southern part of the prefecture. On the other hand, a few patients were found yearly in a harf of towns and villages in this prefecture. The number of isolated strains of Rickettsia tsutsugamushi from patients was 4, i.e., TR6030, TR6310, TR6311, and TR6324 in 1986 and 3, TR1811, TR1827 and TR1829, in 1991. Six isolates except TR6303 reacted with anti-Kawasaki monoclonal antibody but not with other strain specific monoclonal antibodies. Therefore, these 6 isolates were determined as Kawasaki type strain. An isolate. TR6303, reacted with anti-Kuroki monoclonal antibody at a titer of 1:2560 and anti-Karp monoclonal antibody at a titer of 1:320. This result suggested that the recent Tsutsugamushi disease is mostly caused by Kawasaki types in this prefecture.

Humans↗

Serotype-specific amplification of Rickettsia tsutsugamushi DNA by nested polymerase chain reaction.

Polymerase chain reaction (PCR) with nested primer pairs was used to diagnose scrub typhus and identify the Rickettsia tsutsugamushi serotype. The primer pairs used for PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen. Serotype-specific primers were used in the second PCR amplification. Five serovariants, the Gilliam, Karp, Kato, Kawasaki, and Kuroki strains of R. tsutsugamushi, were identified by nested PCR. In addition, the serotype identified by PCR with DNA from blood clots was the same as that of the strain isolated from five patients with scrub typhus. These findings indicate that this method is useful for diagnosis and identification of the rickettsial serotype in infected patients.

Base Sequence↗