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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Therapeutic efficacy of pirarubicin cyclophosphamide and doxifluridine in advanced and metastatic breast cancer].

Twenty-four eligible patients (23 of whom were evaluated) with advanced and metastatic breast cancer were treated at the Saitama Cancer Center every 4 weeks with pirarubicin (30 mg/m2 i.v., day 1 and 8), cyclophosphamide (200 mg/m2 div, day 1 and 8) and doxifluridine (800 mg/day po, day 1-14). The 23 evaluable patients had a median age of 49.7 years (range 35.3-72.1) and underwent a median number of 3 cycles (range 2-5). Grade 4 leukopenia (10/24 patients) was the dose-limiting factor and led to infection in one patient. Four complete responses and 7 partial responses with a median duration of 12.1 months (range 2.6-61.0) were achieved, resulting in an overall response rate of 47.8%. The 50% survival duration was 22.9 months.

Adult↗
PubMed1998

Telomerase activity in renal cell carcinoma.

BACKGROUND: Telomerase activity has been shown to be increased in numerous tumors and cell lines, although to the authors' knowledge there has been no previous assessment of telomerase activity in renal cell carcinoma (RCC). To examine whether telomerase activity could be used as a biochemical parameter for predicting the behavior of RCC, telomerase activity was quantified in RCC samples and correlated with clinicopathologic findings. METHODS: Telomerase activity was quantified in 50 RCC samples and 21 samples of normal renal tissue using fluorescence-based telomeric repeat amplification. RESULTS: Telomerase activity was detected in 28 of 50 RCC samples (mean +/- standard deviation, 35.03 +/- 18.47 U/microg protein), whereas there was no telomerase activity in 21 normal renal tissue specimens. Telomerase activity in tumors classified as pT4 was significantly higher than in tumors classified as pT1 to pT3. Telomerase activity also correlated with patient age. CONCLUSIONS: Telomerase activity was increased in RCC samples compared with normal renal tissues. Although significant associations were observed between telomerase activity and clinicopathologic parameters, further study is required to determine whether telomerase activity affects the biologic and clinical behavior of RCC.

Adult↗
PubMed1998

A new water-cooled and doubly bent crystal monochromator for Compton scattering experiments.

The design and performance of a new water-cooled and doubly bent crystal monochromator for Compton scattering experiments are described. Its mechanical system is similar to that of a usual bent cylindrical X-ray mirror. A monolithic Si (111) crystal is mounted on a water-cooled and cylindrically polished copper crystal holder with liquid Ga-In alloy between them in order to obtain good thermal and mechanical contact. The sagittal bending radius of the holder, R(s), is 508 mm. The holder is mounted on a mechanical bender making a meridian radius, R(m), of 596 m. The performance of the monochromator, which has been installed at the Photon Factory Accumulator Ring beamline NE1, is as follows. The focused beam size, flux and energy resolution for 60 keV X-rays are 0.5 mm in height and 2.0 mm in width, 5 x 10(12) photons s(-1) and about 60 eV, respectively. The new monochromator gives one order higher brightness at the sample position and also better energy resolution than the previous monochromator. The overall momentum resolution for high-resolution Compton scattering experiments becomes 0.08 atomic units, and the background can be reduced by a third, because it is possible to insert a fine slit after the analyser crystal without losing any Compton scattering signal.

Journal Article↗
PubMed1998

Multidrug-resistant recurrent breast cancer which responded to medroxyprogesterone acetate showing a remarkable improvement in the quality of life: report of a case and the role of team medical care.

We herein report the case of a patient with recurrent breast cancer who showed a remarkable improvement in her quality of life (QOL) as a result of a good response to medroxyprogesterone acetate (MPA). A 43-year-old Japanese woman developed bone metastases 3 years after surgery. Subsequent radiotherapy and chemoendocrine therapy with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and tamoxifen all failed, and she could not sit up because of bone metastases. The performance status (PS) on admission was grade 4. After admission, delirium accompanied with sensory and visual hallucination caused by intense anxiety occurred, and a continuous consultation by psychiatrists was necessary. MPA treatment at the dose of 1200 mg/day alleviated the bone pain, thus improving her PS to grade 1. Her appetite also improved, while her mental state stabilized. A bone scintigram revealed an improvement of bone metastases, and the tumor markers also returned to normal values. The patient thus showed a pronounced improvement in her QOL due to both MPA treatment and team medical care. The role of the medical staff as well as the importance of their cooperation in achieving an improvement in the QOL of cancer patients is also discussed.

Adult↗
PubMed1998

In situ gradostat for the study of a natural phytoplankton community with an experimental nutrient gradient.

A new in situ gradostat was devised to study the dynamics of natural communities having nutrient gradients within aquatic habitats. This semi-enclosed mesocosm consisted of three components: i.e. three transparent, concentric cylindrical culture chambers, with diameters of 70, 60 and 40 cm, and 20 cm deep, supported by four flotation buoys, a medium reservoir, and a pump to supply the medium to the mesocosm. Water exchange between compartments was achieved via holes in the cylindrical walls, the number and size of the holes being chosen to regulate the rate of exchange. Sterile culture medium was pumped into the central (first) chamber and diffused outwards into the second and third chambers through the perforated walls. Suitable perforations could achieve a concentration gradient of up to 9.5 times between the first and third chambers within 12 h. The system was designed with the following characteristics: (1) an experimental semi-enclosed system in the natural environment; (2) to maintain equivalence with the external water except for the experimental factors; and (3) to form a manipulable gradient of experimental factors across the mesocosm. Using the in situ gradostat, the response of a natural phytoplankton community to a nitrate gradient was determined. A gradient from oligotrophic to eutrophic was maintained for 10 days in an oligotrophic pond. The mean growth rate of phytoplankton was lower in the eutrophic zone than that in the mesotrophic zone, where the highest mean growth rate was observed. The growth rate of each dominant phytoplankter showed its own pattern, but all rates were highest in the mesotrophic environment of the second chamber.

Journal Article↗
PubMed1998

Quantitative evaluation of nutritional pathways for the posterior cruciate ligament and the lateral collateral ligament in rabbits.

The cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from the synovial fluid. The contributions of these two routes as nutritional pathways are not known in detail. In this study, we injected [3H]methyl glucose as a tracer intravenously or directly into the knee of rabbits. Tracer concentrations in plasma, synovial fluid, the posterior cruciate ligament (PCL), and the lateral collateral ligament (LCL) were analysed by a pharmacokinetic compartment model. The contribution of [3H]methyl glucose permeation from the synovial fluid during steady state was calculated at 44.3% in the PCL and at 39.0% in the LCL. Although these results indicated that more than half the nutrition for both ligaments is provided by its vascular supply, synovial fluid permeation is also an important transport route for small molecules for the PCL and the LCL, which is an extra-articular structure.

Animals↗
PubMed1998

Effect of protein restriction on messenger RNA of insulin-like growth factor-I and insulin-like growth factor-binding proteins in liver of ovariectomized rats.

Effects of dietary protein restriction and ovariectomy on plasma concentrations and hepatic messenger RNA (mRNA) of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) were investigated in young female rats. Ovariectomy increased plasma IGF-I concentration in rats fed on either a 50 g casein/kg diet (protein-restricted diet) or a 200 g casein/kg diet (control diet), but it increased IGF-I mRNA in liver only in the rats fed on the control diet. On the other hand, by Western ligand blot analysis, we observed that ovariectomy increased plasma IGFBP-3 concentration, and decreased plasma IGFBP-4 concentration. Ovariectomy did not affect IGFBP-1 and IGFBP-2 mRNA in liver, but dietary protein restriction significantly increased them, which may correspond to their plasma concentrations. The present results show that ovarian hormones and dietary protein content affect the plasma concentrations of IGF-I, IGFBP-3 and IGFBP-4 and hepatic mRNA of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4 in different manners.

Analysis of Variance↗
PubMed1998

Random nuclear p53 overexpression pattern in tamoxifen-mediated endometrial carcinoma.

In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

Adult↗
PubMed1998

Influence of drinking green tea on breast cancer malignancy among Japanese patients.

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow-up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.

Adult↗
PubMed1998

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of delta-13CO2 using laser spectroscopy.

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified 13C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The 13C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of 13C-urea administration. The ratio of 13CO2 to 12CO2 was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of 13C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of delta-13CO2. In 32 H. pylori-negative patients (without therapy), the mean +/- 2SD of delta-13CO2 was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean +/- SD delta-13CO2 was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5-3.0 per mil (%0) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, and 94.1%, respectively. In conclusion, 13C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific 13C-UBT results.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Secondary treatment failure without anti-human chorionic gonadotropin antibody in a patient with Kallmann syndrome.

A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.

Adult↗
PubMed1998

Topical delivery of keloid therapeutic drug, tranilast, by combined use of oleic acid and propylene glycol as a penetration enhancer: evaluation by skin microdialysis in rats.

Topical delivery of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an inhibitor of collagen synthesis and a therapeutic drug for keloid and hypertrophic scar, was examined, in rats, with oleic acid alone or a combination of oleic acid and propylene glycol as penetration enhancer. Evaluation was by measurement of the concentration of tranilast in plasma and in the dialysate from skin microdialysis. When tranilast at a dose of 1.5 mg was applied topically as an ethanol solution containing 5% polyvinylpyrrolidone on a dorsal skin surface (2.25 cm2), the maximum concentration of tranilast in skin dialysate was approximately 2 microM. When 10 or 20% oleic acid was added to the same ethanol solution the maximum concentration of tranilast in the dialysate increased to 10-20 microM, and this value was further increased to 60 microM by the addition of a combination of oleic acid (10 or 20%) and propylene glycol (10%) to the solution. With the combination of oleic acid and propylene glycol the area under the plot of the concentration of tranilast in skin dialysate against time between 0 and 4 h (AUC0-4) was more than 400-fold that after intravenous administration. The transdermal bioavailability of tranilast as assessed by the AUC0-4 of tranilast in plasma, was 0.2% of the dose applied in the ethanol solution, 3-5% of that applied in the ethanol solution containing oleic acid, and 14-16% of that applied in the ethanol solution containing both oleic acid and propylene glycol. These results suggest that the topical delivery of tranilast with an absorption enhancer such as a mixture of oleic acid and propylene glycol might be a more effective medication than oral administration of tranilast for the treatment of keloid and hypertrophic scar.

Animals↗
PubMed1998

Effect of ointment bases on topical and transdermal delivery of salicylic acid in rats: evaluation by skin microdialysis.

Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 micromol salicylic acid were applied for 2 h to the surface of rat skin (1 cm2) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase << white petrolatum, poloid, hydrophilic poloid << absorptive ointment. The ratio of AUCskin (topical delivery) to the AUC of salicylic acid in plasma (AUCplasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUCskin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUCskin/AUCplasma for the different ointments was comparable, although the magnitudes of AUCskin and AUCplasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.

Animals↗
PubMed1998

N-acetyl-L-gamma-glutamyl derivatives of p-nitroaniline, sulphamethoxazole and sulphamethizole for kidney-specific drug delivery in rats.

Kidney-specific delivery of p-nitroaniline, sulphamethoxazole and sulphamethizole after either intravenous administration of the L-gamma-glutamyl or N-acetyl-L-gamma-glutamyl derivatives or the parent drugs has been examined in a rat model. All L-gamma-glutamyl derivatives were converted to the corresponding parent drugs within 60 min whereas the N-acetyl-L-gamma-glutamyl derivatives were fairly stable in the systemic circulation after parenteral administration. Concentrations of p-nitroaniline and sulphamethoxazole 20 min after administration of the parent drugs were somewhat higher in the kidney than in the liver and lung. The concentration of sulphamethizole in the kidney was dramatically higher than those in the hepatic and pulmonary tissue. Kidney-specific delivery of the drugs of interest was evaluated by determining the tissue concentrations of the released parent drug and the total drug levels (i.e. drug levels after hydrolysis of all conjugate to the parent drug). For L-gamma-glutamyl-p-nitroaniline released renal levels of p-nitroaniline and total p-nitroaniline concentrations were both higher than those obtained after p-nitroaniline dosing. Use of L-gamma-glutamylsulphamethoxazole resulted in higher total sulphamethoxazole concentrations in the kidney, but did not lead to an increase in released (unconjugated) sulphamethoxazole levels. In contrast, no kidney-selective distribution was observed for L-gamma-glutamylsulphamethizole. Markedly increased kidney distribution was observed for both N-acetyl-L-gamma-glutamyl-p-nitroaniline and N-acetyl-L-gamma-glutamylsulphamethoxazole and the liver and lung concentrations were correspondingly reduced in comparison with parent drug dosing. Use of the N-acetyl-L-gamma-glutamyl-p-nitroaniline conjugate increased the concentration of p-nitroaniline in the kidney to the same extent as did L-gamma-glutamyl-p-nitroaniline. In conclusion, N-acetyl-L-gamma-glutamyl derivatization of certain compounds seems to be useful for kidney-specific drug delivery and preliminary data suggests that lipophilic drugs are better substrates than hydrophilic compounds. Results related to the selectivity of tissue distribution of the derivatives and species differences are discussed.

Aniline Compounds↗
PubMed1998

Hepatic clearance of ONO-5046, a novel neutrophil elastase inhibitor, in rats and in the rat perfused liver.

The hepatic clearance of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)phenylsulphonylamino]benz oyl]aminoacetic acid), a low-molecular-weight neutrophil elastase inhibitor, has been investigated in rats and in the rat perfused liver. This ester was easily hydrolysed to its inactive metabolite EI-601 (N-[2-[(4-hydroxyphenyl)sulphonylamino]benzoyl]aminoacetic acid) in liver homogenate and in erythrocytes suspension in-vitro. On the other hand, it was stable in biological media such as plasma and whole blood, which contain plasma proteins. Scatchard plot analysis of ONO-5046 binding to bovine serum albumin (BSA) in-vitro indicated that the association constant (K) and number of binding sites (n) were 6.91 x 10(4) (M(-1)) and 4.33, respectively. Thus, ONO-5046 (100 microM) would bind to plasma proteins to an extent >99% at physiological plasma-protein concentrations. The total plasma clearance of ONO-5046 in rats was constant (approximately 9 mL min(-1) kg(-1)) under different steady-state plasma concentrations (5-50 microM) a value equivalent to the hepatic clearance. In the rat perfused liver, the hepatic extraction ratio of ONO-5046 was significantly reduced by adding BSA to the dosing solution. Thus, the relatively low hepatic clearance of ONO-5046, which has an ester linkage in its structure and is naturally susceptible to enzymatic hydrolysis, was found to be because of the extremely high protein-binding of the compound.

Animals↗
PubMed1998

In-vivo calibration of microdialysis probe by use of endogenous glucose as an internal recovery marker: measurement of skin distribution of tranilast in rats.

To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxy-cinnamoyl)anthranic acid), an anti-allergic agent, in rats. This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.

Animals↗