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Biomedical subjects

H Watabe

Publications and source records attributed to H Watabe.

At least 55 records · Page 3Linked to original sources

Noninvasive quantification of rCBF using positron emission tomography.

This study proposes a new method for the pixel-by-pixel quantification of regional CBF (rCBF) with positron emission tomography and H(15)(2)O by using a reference tissue region. No arterial blood is required. Simulation studies revealed that the calculation of rCBF was fairly stable provided that the frame time was relatively short compared with total scan time. In practice, calculated CBF images correlated significantly with those obtained with the dynamic/integral method. Because the method accurately detects changes in CBF, it is particularly suitable for brain activation studies.

Adult↗

Modulatory effect of antibiotics on cytokine production by human monocytes in vitro.

Some antimicrobial agents have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. Fosfomycin (FOM) and clarithromycin (CAM) have immunomodulatory activity on human lymphocyte function. In the present study, we examined the effects of FOM and CAM on cytokine synthesis by lipopolysaccharide (LPS)-stimulated human monocytes in comparison with that of dexamethasone in vitro. The three drugs demonstrated positive or negative effects on the synthesis of various cytokines by LPS-primed monocytes. They suppressed the synthesis of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), IL-1 beta, the IL-1 receptor antagonist, and granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner at concentrations between 1.6 and 40 micrograms/ml. On the contrary, the drugs showed different actions on the synthesis of IL-6 and IL-10. Namely, FOM enhanced both IL-6 and IL-10 synthesis, CAM enhanced only IL-10 synthesis, but dexamethasone deeply suppressed the synthesis of both cytokines. These data indicate that antibacterial agents may modify acute-phase inflammatory responses through their effects on cytokine synthesis by monocytes.

Anti-Bacterial Agents↗

Antifungal antibiotic benanomicin A increases susceptibility of Candida albicans to phagocytosis by murine macrophages.

Benanomicin A is an antifungal antibiotic produced by Actinomadura spadix. In the present study, we investigated the effect of benanomicin A on the phagocytosis of Candida albicans by murine peritoneal macrophages and on the cell-surface hydrophobicity (CSH) of C. albicans. Although pretreatment of macrophages with benanomicin A had no effect on the phagocytosis, addition of benanomicin A to the culture of macrophages and Candida cells increased the susceptibility of Candida cells to the phagocytosis by the macrophages. Pretreatment of Candida cells with benanomicin A also increased the susceptibility of Candida cells to the phagocytosis. When Candida cells were mixed with benanomicin A, the antibiotic bound irreversibly to Candida cells. These data suggest the possibility that the increased susceptibility of Candida cells to the phagocytosis is mediated by the binding of benanomicin A to Candida cells. Examination of physicochemical property of Candida cell surface showed that the CSH of Candida cells significantly decreased by the treatment with benanomicin A. Thus, binding of benanomicin A to Candida cells may induce biochemical/physicochemical alternation of the surfaces, so that they become more susceptible to phagocytosis by murine macrophages. These properties of benanomicin A, along with its antifungal activity, seem to be beneficial in the treatment of fungal infections.

Animals↗

Smooth pursuit eye movements elicited by pseudorandom target motion in normal subjects.

The purpose of this study was to determine which test conditions are appropriate for clinical examination of predictive control ability in smooth pursuit eye movements (SPEM). A combination of sinusoidal and pseudorandom target motion was employed to examine SPEM. Pseudorandom waves were generated by summing sinusoidal components spaced at 0.05 Hz intervals over three frequency ranges: 0.05 to 0.5 Hz, 0.05 to 1 Hz and 0.05 to 1.5 Hz. The peak amplitude of the resultant target waveform was set at 30 degrees. Testing was performed with 8 normal subjects. The results indicate a SPEM gain of 0.9 for 0.05-0.5 Hz, 0.7 for 0.05-1 Hz and 0.3 for 0.05-1.5 Hz. It is concluded that the pseudorandom wave of 0.05 to 1 Hz in frequency range is most suitable for clinical use.

Adult↗

Voluntary suppression of caloric nystagmus under fixation of imaginary or after-image target.

Voluntary suppression of caloric nystagmus was investigated in 10 normal subjects under the following three conditions; i) with visible, earth-fixed target in the dark ("visual"), ii) with imaginary target in the dark ("imaginary"), and iii) an after-image on the fovea in the dark ("after-image") Subjects were able to suppress caloric nystagmus with a visible target very well, but they could only partially suppress caloric nystagmus with imaginary target and with after-image. The degree of suppression in the "imaginary" and "after-image" conditions was significantly less than that in "visual", but was not zero. These results are consistent with those of many reports about visual-vestibular interaction and VOR voluntary modification during rotation, and suggest that smooth pursuit eye movements (SPEM) system plays a major role in visual suppression during caloric nystagmus.

Adult↗

Influence of foveal afterimage on non-visually induced pursuit eye movements.

Smooth pursuit eye movements (SPEMs) were measured during trials with an acoustic target, a somatosensory target (finger tip), and an imaginary target. Under these non-visual conditions the induced SPEMs were investigated both with and without a foveal afterimage. Ten normal subjects were examined. Considerable inter-individual differences were observed in performance of the non-visual SPEMs. However, the presence of an afterimage did not influence SPEMs during acoustic or somatosensory pursuit. It is concluded that the capacity for "visualization" may not involve the ability for non-visual SPEMs. As in imaginary target condition the subjects could not elicit SPEM without the afterimage, clearly the memory of target motion alone cannot generate SPEMs. The afterimage may help the subject to convert the memory of target motion into the perception of virtual target motion.

Acoustic Stimulation↗

Influence of superimposed optokinetic stimulus on smooth pursuit eye movements elicited by sinusoidal spot target oscillation.

In 6 healthy subjects, smooth pursuit eye movements (SPEMs), elicited by sinusoidal spot target oscillation, were measured against three different backgrounds: dark, stationary texture (texture), and texture background movement in-phase with the spot target (coupled). Spot-target oscillation frequencies ranging between 0.2 to 1.6 Hz and peak velocities ranging between 19 to 75 degrees/s were employed. SPEM gain did not differ significantly among the three backgrounds below 0.8 Hz. However when at 1.6 Hz it responded to a peak velocity of 75 degrees/s, the gain for the "coupled" background condition was greater than that for the "dark" condition, which in turn was greater than the gain for "texture". However, SPEM phase delays were found to be similar for the three background conditions. Since the responses during "coupled" and "texture" backgrounds are most likely elicited by rapid-rise optokinetic reflex (OKR) interaction it can be concluded that SPEMs and the rapid-rise OKR system have the same latency (response) time.

Adult↗

Establishment and evaluation of MRK16-magnetic cell sorting assays for detecting low expression of multidrug resistance P-glycoprotein using human leukemia cell lines and peripheral blood cells from healthy donors.

Two types of magnetic cell sorting assays, termed MRK16-MACS and MRK16-MACS-FACS, have been established to detect low expression level of P-glycoprotein (P-gp) using a monoclonal antibody MRK16, which recognizes a cell surface epitope of P-gp. With K-562 and U-937 cell lines, which are known to express low levels of P-gp and hence routinely used as negative control cell lines in conventional flow cytometry, both assays gave significantly positive reactivities indicating improved specificity and sensitivity of these assays. The findings in the dilution test, where P-gp-positive cells were added to P-gp-negative cells at various ratios, demonstrated that the MRK16-MACS assay is quantitative and capable of detecting small numbers of P-gp-positive cells as few as 2.5% of the total cells tested. Furthermore, specific enrichment of P-gp-expressing cells in magnetic cell sorting assays was verified by reverse transcription-polymerase chain reaction (RT-PCR) analysis and functional assay for P-gp with Rhodamine 123. The availability of such magnetic cell sorting assays may offer an approach to quantitate low level of P-gp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Enhancement by recombinant human interferon alfa of the reversal of multidrug resistance by MRK-16 monoclonal antibody.

BACKGROUND: The anti-P-glycoprotein monoclonal antibody MRK-16 mediates the reversal of multidrug resistance. Recombinant human interferon alfa (rHuIFN alpha) enhances the cytotoxic activity of diverse chemotherapeutics and may modulate multidrug resistance. PURPOSE: Our purpose was to determine the outcome of combination treatment with MRK-16, rHuIFN alpha-2a, and cytotoxic agents on tumor cells that express P-glycoprotein (Pgp). METHODS: Three Pgp-expressing, multidrug-resistant human tumor cell lines were used: the MDR1 retrovirus-infected HT-29 colon adenocarcinoma (HT-29mdr1), the doxorubicin (Adriamycin)-resistant MCF-7 (AdrR MCF-7) breast carcinoma, and the de novo Pgp-acquired, HCT-15 colon carcinoma. The parental cell lines HT-29par and MCF-7 were used as controls. The in vitro effects of MRK-16 and rHuIFN alpha-2a were studied on: (a) chemosensitivity of parental and multidrug-resistant cell lines to vincristine, doxorubicin, or paclitaxel (Taxol); (b) intracellular drug concentrations; and (c) Pgp expression. The efficacy of vincristine alone or in combination with MRK-16 and/or rHuIFN alpha-2a was assessed against HT-29mdr1 cells in female, athymic NCr-nu/nu mice. RESULTS: For vincristine, the IC50 (i.e., the concentration that causes 50% inhibition of cell growth) was 7.0 ng/mL in HT-29mdr1 cells. Pretreatment of HT-29mdr1 cells with MRK-16 partially restored vincristine sensitivity (IC50 = 4.8 ng/mL), which was enhanced by noncytotoxic concentrations of rHuIFN alpha-2a (IC50 = 2.9 ng/mL) via a mechanism independent of Pgp modulation or [3H]vincristine efflux. rHuIFN alpha-2a potentiated MRK-16 reversal of multidrug resistance with both doxorubicin and paclitaxel on HT-29mdr1 cells and with vincristine on AdrR MCF-7 and HCT-15 tumor cells. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, significantly increased the median survival times of the HT-29par tumor-bearing mice (60 days versus 35 days; P < .0001) but was only marginally therapeutic for HT-29mdr1 tumor-bearing mice (52 days versus 46 days). Pretreatment with MRK-16 (500 micrograms) and rHuIFN alpha-2a (5 x 10(4) U), alone or in combination, 24 hours before vincristine therapy did not affect the survival of HT-29par tumor-bearing mice. In contrast, the survival of mice bearing HT-29mdr1 tumors was significantly increased following treatment with MRK-16 before vincristine (80 days; P < .0001). Administration of a nontherapeutic dose of rHuIFN alpha-2a (5 x 10(4) U) with MRK-16 before vincristine treatment further increased the median survival times of HT-29mdr1 tumor-bearing mice (116 days; P < .0001). CONCLUSIONS: MRK-16 used in combination with rHuIFN alpha-2a was significantly more effective than MRK-16 in overcoming multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Validation of noninvasive quantification of rCBF compared with dynamic/integral method by using positron emission tomography and oxygen-15 labeled water.

This study proposes a new solution for the quantification of rCBF pixel-by-pixel using PET and 15O-H2O. The method represents an application of weighted integration that used PET image only, requiring no input function of arterial blood. It generates the rCBF image quickly and automatically. Simulation studies revealed that the calculation of rCBF was fairly stable as long as a relatively shorter scan frame time and longer scan time were selected. Calculated images of actual PET study by this method correlated significantly with those identified by the dynamic/integral method. Because this procedure could detect whole brain CBF change between different studies as accurately as by the dynamic/integral method, this procedure may be the most suitable for brain activation studies.

Cerebrovascular Circulation↗

Occurrence of the antibody against human papillomavirus type 16 virion protein L2 in patients with cervical cancer and dysplasia.

Infection with HPV 16 is believed to be a major risk factor for cervical cancer. To correlate HPV 16 infection and carcinogenesis in the cervix, we examined by ELISA 326 sera from healthy females and patients with cervical cancer, cervical intraepithelial neoplasia, or dysplasia, for the presence of IgG antibodies against HPV 16 virion protein L2 expressed in Escherichia coli. Whereas 2 of 208 were positive in the healthy females, 4 of 23 and 6 of 90 were positive in the patients with cervical cancer and dysplasia, respectively. The findings indicate that infection with HPV 16 is related to cancer and dysplasia of the cervix. The anti-L2 antibody did not occur coincidentally with the antibodies against the HPV 16 early proteins E4 and E7, which are specifically but independently associated with patients with cervical cancer.

Adolescent↗

Conversion of cathepsin E to enzymatic unstable form in gastric cancer cells.

A new acid proteinase in human gastric cancer, named medium moving proteinase (Med.P), was found also in a gastric cancer transplanted into nude mouse. However, Med.P disappeared when the samples prepared from gastric cancer tissues were left for over 4 weeks at -80 degrees C, whereas the activity of cathepsin E (CE) increased. When these samples were reduced by dithiothreitol (DTT), Med.P appeared again and the CE activity decreased. These phenomena, revealed by electrophoretic analyses, indicated that Med.P is a monomeric form of CE (mono-CE). At weakly alkaline pH and after heating, mono-CE appeared to be more unstable than CE. These results indicated that CE assume an enzymatically unstable monomeric form in cancer cells.

Animals↗

Imaginary gaze effects on eye movements induced by linear acceleration: involvement of vestibular induced smooth pursuit eye movement.

We investigated smooth eye movements elicited i) by linear acceleration in a space-fixed imaginary gaze condition (smooth component of eye movement induced by linear motion: LSEM) and ii) during acoustic pursuit of a moving sound source (smooth component of eye movement induced by acoustic pursuit of a sound source: SSPEM). The two conditions were examined using the same test subjects. LSEM and SSPEM performance was found to be positively correlated across the subject population. From the comparison of LSEM and SSPEM we propose the following hypothesis: LSEM consists not only of a pure translational vestibular-ocular reflex (tVOR) component but also of a component based on the perception of otolithic information. Accordingly, this second component is instrumental in the pursuit of an imaginary visual target during linear self-motion.

Acceleration↗

[Quantitative analysis of smooth pursuit eye movement].

Abnormalities of smooth pursuit eye movement (SPEM) have been estimated, mainly using the wave form on an electro-oculogram, in a qualitative way. Many methods for quantitative analysis of SPEM have been designed, though most are still uncommon in present clinical use. Using a personal computer, we developed a method of automatic quantitative analysis of ocular tracking eye movement recorded by electro-oculography (EOG). The design concept of this method is based on the observation that eye movement during ocular tracking consists of two different kinds of eye movements, one is SPEM and the other is saccade. The combination of SPEM and saccade (composite eye movement: CEM) commonly appears during ocular tracking. These two kinds of eye movement are essentially different not only in behavior but also about involved neural pathway in the central nervous system. From this point of view, we believe that the two kinds of eye movements involved in ocular tracking should be evaluated separately. The analysis method is outlined as follows. A horizontal sinusoidally moving visual target was employed to elicit ocular tracking eye movements. The test frequencies were set at 0.1, 0.2, 0.4 and 0.8Hz, and the amplitude of target motion was 15 deg at each frequency. The 20 seconds of eye movement data measured by EOG were fed into the computer through a digital-analog converter for further analysis. Using our original saccade detection algorithm, based on the physiological behavior of saccades, the saccadic components were detected and removed from the eye movement wave. The remaining parts, fragments of SPEM, were connected by means of interpolating defective parts. The reconstructed wave was a slow cumulative eye position curve (SCEP). Sinusoidal target motion, CEM and SCEP were processed by the FFT (Fast Fourier Transformation) method. Bode plots were applied to summarize the gain and phase of responses to SCEP and the target motion wave. These processes enable us to estimate abnormalities of SPEM such as low gain, abnormal phase shift and large trends in tested duration. We conclude that the method described here is useful for quantitative estimation of SPEM in clinical neuro-otological examinations.

Adult↗

Electrophoretic analysis of a gastric cancer-associated acid proteinase using a highly sensitive detection system.

A highly sensitive detection system for acid proteinase separated on polyacrylamide gel was established. This system consisted of two-dimensional electrophoresis, combined with isoelectric focusing and polyacrylamide gel electrophoresis, and casein clotting (caseogram). Human urine, serum and gastric tissues obtained from normal individuals and gastric cancer patients were analyzed using this system. The previous electrophoretic method was not sufficiently sensitive to detected small amounts of pepsinogen (PG) C in normal urine. However, the new rapid and sensitive method clearly revealed its presence. In gastric tissue containing cancer cells, an additional proteinase, which was not present in normal tissue, was detected and named medium moving proteinase (MMP). MMP resembled PGs in alkaline stability rather than the non-PG proteinase, slow moving proteinase (SMP).

Adult↗

[Efficacy and endocrinological analysis of combined buserelin-pure FSH-hCG therapy in patients with polycystic ovary syndrome].

The study was designed to investigate the efficacy of combined buserelin-pure FSH-hCG therapy in patients with polycystic ovary syndrome (PCO) and to analyse its underlying hormonal changes. Buserelin was intranasally administered daily to 13 patients (35 cycles) for 4-10 weeks with a mean week of 5.4 +/- 1.6 (SD), followed by concomitant pure FSH administration. Out of the 13 patients, 8 were the ones who had experienced ovarian hyperstimulation syndrome (OHSS) using pure FSH alone. Hormonal analyses were performed on these 8 patients. This combined regimen resulted in a 97.1% ovulation rate (34/35) and a 37.1% incidence rate of OHSS (13/35). In 4 out of the 8 patients who had experienced OHSS, no OHSS was observed in the first cycle of the therapy. Eight patients became pregnant with the therapy. Excluding one patient whose husband had oligozoospermia, 7 patients conceived at the first cycle of the therapy and the pregnancy rate per cycle was 25.0% (7/28). No abortion or multiple pregnancy was observed in any of the 8 cases. Pretreatment with buserelin resulted in significantly decreased serum LH, FSH, LH/FSH ratio, estradiol (E2), testosterone (T), and androstenedione (ASD). Serum E2, T and ASD levels at both preovulatory and midluteal phases were significantly lower with the combined regimen than with pure FSH alone. These results indicate that this combined regimen improves the characteristic endocrine profile of PCO and enables pure FSH to achieve ovulation regularly with a high pregnancy rate, although it does not always inhibit OHSS.

Adult↗

Simplified nonlinearity correction of oxygen-15-water regional cerebral blood flow images without blood sampling.

UNLABELLED: A noninvasive method, the double-integration method, was developed to estimate regional cerebral blood flow (rCBF) by using 15O-water and PET. It relies on the acquisition of images with a correction of nonlinearity of brain tissue counts and can produce rCBF images on a pixel-by-pixel basis. METHODS: Oxygen-15-water PET studies were performed on five normal human volunteers, and continuous sampling from the radial artery was conducted to generate functional CBF images according to the invasive catheterization method. The method centers on a computer-based program elaborated to calculate an arterial input function with an assumption of the whole brain blood rate of 50 ml/dl/min and consequently does not require arterial catheterization or arterial input function sampled from other studies. RESULTS: The results indicate a good correlation between this method and the invasive method (r > 0.966, p < 0.001). CONCLUSION: This noninvasive method was demonstrated to provide an accurate estimation of rCBF and may simplify the activation studies.

Adult↗

[A clinical study on memory function in climacteric and periclimacteric women].

This study was designed to investigate memory function in climacteric and periclimacteric women who lived a normal, ordinary life. Two hundred women treated at the gynecological outpatient clinic of Koshigaya Hospital were divided into 7 groups: groups A(31-35 yr), B(36-40 yr), C(41-45 yr), D(46-50 yr), E(51-55 yr), F(56-60 yr) and G(61-65 yr). Each group consisted of 30 women except group G(n = 20). The memory function of each group was determined and the mean scores for 10 paired hard-associates after three trials of presentation were compared. The mean scores (+/- SD) for groups A and B were 8.0 +/- 2.0 and 8.2 +/- 1.7, respectively, which were not statistically different. The scores for both groups were significantly higher than those for the other groups (p < 0.01). The mean scores for groups C and D were 5.9 +/- 2.1 and 5.6 +/- 2.4, respectively, which were not statistically different. The score for group C was significantly higher than those for groups E(4.5 +/- 2.4), F(4.2 +/- 2.2), and G(3.3 +/- 1.6) (p < 0.05). The score for group D was significantly higher than those for groups F and G(p < 0.05). The score for group E was significantly higher than that for group G(p < 0.01). The decrease in memory function was the greatest in group C. In the climacterium, memory impairment was also observed in group E. The former corresponds to the climacteric commencement age group where cyclic changes in serum estrogen levels decrease or cease, and the latter corresponds to the age group for menopause.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗