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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 649 records · Page 36Linked to original sources

Establishment and characterization of a CD95 (Fas/Apo-1)-negative myeloma cell line.

Although expression of CD95 (Fas/Apo-1) on myeloma cells has been reported, its significance is not clearly understood. We established a myeloma cell line, KHM-11ad (11ad), from a parental cell line, KHM-11, by collecting cells adhered to a plastic dish. KHM-11 cells have been reported to be positive for CD45 and CD95 (Fas/Apo1), and negative for a myelomonocytic antigen, CD13. Interestingly, CD95 was not detected in 11ad. Expression of CD45 was also significantly decreased in 11ad cells while expression of CD13 was detected in these cells. The growth rate of 11ad cells was 1.7 times lower than that of KHM-11 cells. Analysis of adhesion molecules showed that expression of VLA4 and CD44 was significantly suppressed in 11ad. The IC50 of melphalan (L-PAM) for 11ad cells was 50 times higher than that for KHM-11, indicating that 11ad is significantly refractory to L-PAM than KHM-11 cells. Induction of apoptosis by doxorubicin and cycloheximide was suppressed in 11ad cells compared with those in KHM-11 cells. Western blot analysis for Bcl-2 family of proteins showed that Bax was expressed at a 2.2 times lower level in 11ad cells than in KHM-11 cells while there was no difference in expression of Bcl-2, Bcl-Xs nor Bcl-XL. These results suggest that CD95-negative myeloma cells may have characteristics as follows: (1) slow proliferation; (2) low sensitivity to apoptosis; (3) low expression of VLA4, CD44 and Bax. Although these intraclonal variations were based on the findings of cell lines, these may reflect similar variations in vivo. The 11ad line may be a suitable model for analyzing intraclonal variation of myeloma cells.

Antigens, Surface↗

Usefulness of cardiopulmonary bypass in reconstruction of inferior vena cava occupied by renal cell carcinoma tumor thrombus.

UNLABELLED: Aggressive surgical treatment in renal cell carcinoma is still controversial. The aim of this paper is to assess inferior vena caval (IVC) reconstruction for suprahepatic vena caval renal cell carcinoma (RCC) tumor thrombus. Twelve patients with suprahepatic vena caval thrombus from renal cell carcinoma who underwent surgical repair with cardiopulmonary bypass were evaluated. The vena caval defect was reconstructed by direct suture, patch repair, or graft replacement. Of 12 patients undergoing partial cardiopulmonary bypass, tumor thrombus extended to the junction of the hepatic vein in three patients and to the right atrium in one. Tumor thrombus was removed manually or with balloon catheter. Tumor thrombus in the right atrium was removed during electrical ventricular fibrillation. Repair of the IVC was performed by direct suture of the IVC wall in two patients, patch repair with expanded polytetrafluoroethylene (EPTFE) graft in seven, and graft replacement with an EPTFE graft in three. There were no operative deaths and the only postoperative complication was one patient death from pulmonary emboli. The four patients with nonlocalized disease died within 2 years, but four patients lived for more than 3 years postoperatively. Survival was 37.5% at 3 years and 18.8% at 5 years by the Kaplan-Meier's method. CONCLUSIONS: (1) Partial cardiopulmonary bypass is useful for the control of bleeding when tumor thrombus in the IVC extends to the junction of the hepatic vein. (2) Nephrectomy with tumor thrombectomy of the IVC is valuable, and long-term survival is possible in patients without distant metastases or regional lymph node metastases.

Adult↗

A highly sensitive ELISA for the quantification of polymyxin B sulfate in human serum.

A highly sensitive ELISA for the determination of polymyxin B sulfate (PMB) was developed which is capable of measuring as low as 32 pg/ml. Anti-PMB antibody was obtained by immunizing rabbits with PMB conjugated with mercaptosuccinyl bovine serum albumin (MS. BSA) using N-(gamma-maleimidobutyryloxy) succinimide (GMBS) as a heterobifunctional coupling agent. An enzyme marker was similarly prepared by coupling PMB with horseradish peroxidase (HRP) employing GMBS. This ELISA showed very low reactivity with the PMB analogue, polymyxin E (0.05%). The values for PMB concentration detected by this assay were comparable with those detected by the bioassay. Moreover, the ELISA was about 10,000 times more sensitive in detecting PMB at lower concentrations. Serum PMB concentration after the oral administration of a PMB tablet to human subjects was determined by the ELISA. PMB was rapidly absorbed from the gastrointestinal tract after the administration, then slowly decreased. These results indicate that the ELISA may be a valuable tool for studies of the pharmacokinetics and pharmacodynamics of the anti-endotoxin drug, PMB.

Administration, Oral↗

Synthesis and antimicrobial characteristics of novel biocides, 4,4'-(1,6-hexamethylenedioxydicarbonyl)bis(1-alkylpyridinium++ + iodide)s.

Potent new biocides against both bacteria and fungi, 4,4'-(1,6-hexamethylenedioxydicarbonyl)bis(1-alkylpyridinium iodide)s (4DOCBP-6,n) (alkyl chain length, n = 8, 10, 12, 14, 16 and 18) were synthesized, 4DOCBP-6,n is a bis-quaternary ammonium compound (bis-QAC) and has a symmetrical dimeric structure which is composed of two alkylpyridinium iodides connected with a hexamethylenedioxydicarbonyl chain. 4DOCBP-6,10 and 4DOCBP-6,12 exhibited wide and effective antimicrobial spectra, compared with those of typical bactericides, N-dodecylpyridinium iodides (P-12) and benzyldimethyldodecylammonium chloride (BAC), or a popularly-used fungicide, 2-(4-thiazolyl)benzimidazole (TBZ). Their superior properties would be due to the unique dimeric structure which contains two active moieties in a molecule.

Anti-Bacterial Agents↗

Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity.

A series of 1-aminoalkyl-pyrrolo[2,3-c]azepin-8-one derivatives was synthesized and evaluated as alpha 1 adrenergic and serotonin 2 (5-HT2) receptor antagonists, with the aim of finding a novel antihypertensive agent potently exhibiting both activities. Some compounds with a 4-[4-(4-fluorobenzoyl)piperidino]butyl group at the 1-position exhibited both activities, and varied significantly in terms of the substituents at the 4-position of the pyrroloazepine ring. Among the compounds obtained in this study, (E)-1-[4-[4-(4-fluorobenzoyl)piperidino]-butyl]-4-hydroxyimino-7- methyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-c]azepin-8-one (15a, SUN9221) displayed potent alpha 1-adrenergic antagonistic activity (pA2 = 8.89 +/- 0.21) and 5-HT2 antagonistic activity (pA2 = 8.74 +/- 0.22) in isolated guinea pig arteries. This compound exhibited antihypertensive activity and a duration of action equivalent to orally administered prazosin or doxazosin, 3 mg/kg, in conscious spontaneously hypertensive rats, as well as potent antiplatelet aggregation activity.

Adrenergic alpha-1 Receptor Antagonists↗

Stress-induced gastric lesion formation is prevented in rats with daunomycin-induced nephrosis.

In the present study, we investigated the susceptibility to restraint plus water-immersion stress (RWIS) in rats with daunomycin-induced nephrosis in comparison to that in normal rats. The severity of RWIS-induced gastric lesions was significantly less in nephrotic rats on the 20th and 40th days after a single i.v. injection of daunomycin (12 mg/kg) than in the respective control rats. Acid secretion in pylorus-ligated rats significantly decreased under the 3-h stress. On the 20th day after treatment with daunomycin, acid secretion was significantly less in nephrotic rats than in control rats under both stress and unstressed conditions. Pretreatment of normal rats with methylene blue, a guanylate cyclase inhibitor, or phenylephrine, a vasoconstrictor, significantly prevented the stress-induced gastric lesions and decreased acid secretion. N(omega)-Nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor, prevented the stress-induced gastric lesion formation only. These results indicate that nephrotic rats are more resistant to RWIS-induced gastric lesions than normal rats. In addition, these results suggest that the decrease in acid secretion related to the decrease in the release of NO from endothelial cells may contribute, at least in part, to the prevention of the stress-induced gastric lesion formation in nephrotic rats.

Adrenergic alpha-Agonists↗

An epidemic of parapoxvirus infection among cattle: isolation and antibody survey.

A disease characterized by papules, nodules, vesicles and, rarely, pustules and ulcers on teats was seen among cattle on a farm in Chiba Prefecture, Japan. A virus was isolated by inoculation of fetal bovine lung cell cultures from a vesicle on a teat of an infected cow. The virus was subsequently passaged in fetal bovine lung and muscle cells in which it produced complete cytopathic changes. The virus was identified by physicochemical examinations and electromicroscopic observation as a parapoxvirus. A seroepidemiological survey was performed on antibody to the isolated virus by the agar gel immunodiffusion test. The isolated virus formed a precipitation line which cross reacted with other parapoxviruses isolated previously in Japan. The positive rate was more than 50% among cattle in the Kanto district. The positive rate increased with age. It was suggested that parapoxvirus infection might have already been prevalent among cattle in Japan.

Age Factors↗

Involvement of parathyroid hormone-related peptide in cell proliferation activity of human uterine leiomyomas.

Uterine leiomyomas develop from uterine smooth muscle cells, which are known to be regulated by estrogen and other growth factors. The purpose of this study was to investigate the role of expression of parathyroid hormone related-peptide (PTHrP) in the growth of uterine leiomyomas treated or untreated with gonadotropin-releasing hormone agonist (GnRH-a). Thirty-nine leiomyoma tissues were obtained from 36 patients who had been treated with GnRH-a (n=10) or without GnRH-a (n=29). The intensity of PTHrP immunostaining was categorized into three grades; "negative", "weakly positive", and "positive". Leiomyoma cell growth was estimated by the proliferating cell nuclear antigen (PCNA) labeling index (LI) with an image analyser. We also investigated the correlation between PTHrP expression and cell proliferation or histopathological findings. In the GnRH-a-untreated group, LI of the PTHrP "positive" group was significantly higher than that of the PTHrP "negative" group, but the intensity of PTHrP immunostaining did not correlate with LI in the GnRH-a-treated group. PTHrP expression did not correlate with histological findings or clinical parameters (age and phase of menstrual cycle) in either the GnRH-a-treated or the -untreated group. In addition, the expression of mRNA for PTHrP and its receptor was detected in leiomyomas by reverse transcriptase-polymerase chain reaction (RT-PCR). Our results indicate that the expression of PTHrP in leiomyomas correlated positively with cell growth in the GnRH-a-untreated group, suggesting that PTHrP may act as a local cell growth modifier in an autocrine/paracrine fashion on uterine leiomyomas.

Adult↗

Inhibition of ovulation by tyrosine kinase inhibitors in the in vitro perfused rat ovary.

Protein tyrosine kinase activity, leading to tyrosine phosphorylation of the intracellular domains of receptors or non-receptor proteins, is an important feature of downstream signalling after receptor binding of a variety factors, such as growth factors and cytokines. Since several members of these classes of paracrine-autocrine mediator may be involved in the intraovarian events of ovulation, the present study was designed to evaluate the effect of protein tyrosine kinase inhibition on the in vitro perfused rat ovary. Immature rats were primed with 20 iu pregnant mares' serum gonadotrophin 48 h before surgical isolation of the right ovary with connecting vasculature. The ovary was placed in a perfusion system for either 10 h, to examine ovarian concentrations of the established ovulatory mediators plasminogen activator, prostaglandins E2 and F2 alpha, or for 20 h, enabling a complete ovulatory process to occur in vitro. Ovulation was induced by ovine LH (0.2 microgram ml-1) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mmol l-1) and the effects of two different protein tyrosine kinase inhibitors, genistein and tyrphostin A25, were studied. Unstimulated control ovaries did not ovulate and showed low secretion of progesterone and oestradiol. Addition of LH + 3-isobutyl-1-methylxanthine resulted in a marked stimulation of steroid release, and ovulations occurred in all ovaries (9.0 +/- 0.9; mean +/- SEM). The protein tyrosine kinase inhibitors, genistein and tyrphostin A25, significantly inhibited ovulation at the higher concentrations tested (3.0 +/- 0.3 at 100 mumol genistein l-1; 5.8 +/- 1.0 at 500 mumol tyrphostin A25 l-1) but no effect was seen at lower concentrations. The presence of genistein and tyrphostin A25 at any concentration used did not significantly decrease the LH + 3-isobutyl-1-methylxanthine-induced progesterone or oestradiol concentrations. The intraovarian concentrations of plasminogen activator activity, and prostaglandin E2 and F2 alpha were not altered by the presence genistein (100 mumol l-1). In conclusion, the results of the present study indicate that protein tyrosine kinase signalling pathways are integral parts of the mammalian ovulatory process but do not involve actions on the synthesis of steroids, plasminogen activator or prostaglandins.

Animals↗

Renal nerve stimulation induces alpha2-adrenoceptor-mediated antinatriuresis under inhibition of prostaglandin synthesis in anesthetized dogs.

The interaction between prostaglandins and alpha-adrenoceptors in neural control of tubular sodium reabsorption was examined in anesthetized dogs. Renal nerve stimulation (RNS; 0.5-1.0 Hz, 10 V, 1.0-milliseconds duration) reduced fractional excretion of Na+ (FENa) with minimal changes in hemodynamics and glomerular filtration. Intrarenal arterial infusion of prazosin (0.7 microg x kg(-1) x min(-1)), an alpha1-adrenoceptor antagonist, inhibited the RNS-induced reduction in FENa. However, the RNS-induced reduction in FENa was resistant to prazosin under pretreatment with indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor. Intrarenal arterial infusion of yohimbine (1 microg x kg(-1) x min(-1)), an alpha2-adrenoceptor antagonist, failed to inhibit the RNS-induced reduction in FENa in the absence or presence of indomethacin, but combined infusion of prazosin and yohimbine abolished the RNS-induced reduction in FENa in the presence of indomethacin. These results suggest that both alpha1- and alpha2-adrenoceptors mediate the RNS-induced antinatriuresis, but the alpha2-adrenoceptor-mediated portion is impaired by prostaglandins.

Adrenergic alpha-Antagonists↗

Functional analysis after auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration.

Recent transplantation studies indicate that subretinal space is not always an immunologically privileged site and non-autologous cells may be rejected in patients with exudative age-related macular degeneration (AMD). We performed autologous iris pigment epithelial (IPE) cell transplantation by cell suspension after autologous IPE cell culture in 8 patients with AMD. These patients were followed without immunosuppression between 1.5 and 8 months and the retinal function was analyzed. No cystoid macular edema or fluorescein leakage was observed. Six of the 8 patients improved visual acuity of more than two lines and the other two patients retained preoperative visual acuity. Five patients had increased visual field sensitivity, one patient retained pretransplantation sensitivity, and one patient showed a gradual decrease in sensitivity (one patient was not examined). Although 2 of the 8 patients showed decreased amplitude of flicker electroretinography (ERG) (about 60 to 70% as that of preoperative level), the average improvement of each amplitude of a single white flash (a wave), photopic, or flicker ERG was 123, 102, and 107%, respectively. No proliferative change in the submacular lesion or vitreous cavity was observed after transplantation. From this functional analysis, transplanted autologous IPE may have, in part, an alternative function in regard to the retinal pigment epithelium in the subretinal space.

Aged↗

Relationship between aging and recovery of the underlying mucosa immediately after removal of pressure: the first molar region in the mandible.

To investigate changes in the characteristics of edentulous mucosa in the alveolar ridge with aging, we applied pressure to the mucosa of the alveolar ridge in subjects of various ages and evaluated the recovery amount and time after the pressure was removed. Twenty-three subjects ranging from 23 to 79 years of age, who had lost the first mandibular molar tooth, were selected. Displacing pressure was applied to the mucosa corresponding to the mandibular first molar region. After release the pressure, we measured the recovery amount of mucosa from its displacement, which was expressed as the movement of a target which had been placed on the mucosa as measured by an indirect displacement measurement device. The levels of displacement were set at 0.1 mm, 0.2 mm and 0.3 mm, and the time to achieve the selected displacement level was set at 1 second. The initial recovery of the mucosa immediately after the pressure has been released was designated as the initial recovery amount, and the time needed for recovering to 90% of the previous state was designated as the final recovery time. Then we investigated the relationships between the measures of the initial recovery amount, the final recovery time, and the subjects' ages. The initial recovery amount of mucosa was lower and the final recovery time was longer in older subjects, and this tendency was exaggerated when the displacement was increased.

Adult↗

Mandibular-position sensation during sedation by administration of nitrous-oxide (N2O) gas.

Our aim was to confirm the influence of N2O gas on mandibular-position sensation. The subjects in this study were eight healthy adults. Each subject was asked to hold the reference stick for five seconds between the central tooth in his or her upper and lower jaws. Then, the reference stick was replaced by the test sticks with different thickness, each of which the subjects were again asked to hold at the same position for five seconds. The subjects were instructed to determine, based on judgement of the interincisal distance, whether the thickness of each test stick was larger or smaller than the reference stick. A series of trials was administered to each subject using all eight sizes of test sticks. We compared the ability of the subjects to discriminate mandibular position both before and after the application of a vibrating stimulus to the masticatory muscles, and before and during the administration of N2O gas. Discrimination ability was significantly decreased after the application of the vibrating stimulus. However, during the administration of N2O gas, no significant difference in discrimination ability was observed between before and after the vibrating stimulus. The results of this study indicated that N2O gas had an inhibitory effect on gamma-motor neuron activity, which is presumed to be mediated to some extent through the higher central nervous system. This is the case because the gamma-motor neurons are generally activated by vibrating stimuli applied to the muscle causing decreased discrimination ability of mandibular position. Thus, we conclude that mandibular-position sensation was influenced by N2O gas during the administration of N2O gas.

Adult↗

Adult T cell leukemia lymphoma (ATL) localized in the right tibial bone.

A 56-year-old man was admitted complaining of pain in the right tibia. He was diagnosed as having adult T-cell leukemia/lymphoma (ATL/L) in the right knee joint by roentgenographic and histological examination. Monoclonal integration of HTLV-I proviral DNA was demonstrated in the bone tumor cells, although polyclonal integration was observed in the peripheral blood. These results led us to make a diagnosis of ATL with localized growth in the right knee joint. The osteolytic bone change was progressive despite radiation therapy. Complete remission was achieved after amputation of his right lower leg and two courses of chemotherapy. Resection of the localized lesion might be useful in cases of ATL, but further studies are necessary to confirm this conclusion.

Bone Neoplasms↗

Uptake by hepatocytes and biliary excretion of intravenously administered polystyrene microspheres in rats.

The in vivo uptake by hepatocytes and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microsphere with a particle size of 50 nm (MS-50) after intravenous administration was studied in rats. It was confirmed by using confocal laser scanning microscopy that MS-50 was partially phagocytosed by the hepatocytes and that MS-50 taken up by the hepatocytes existed exclusively inside the cells 1 h after intravenous administration. Studies on the mechanism of the uptake of MS-50 by the hepatocytes using the liver perfusion technique revealed that a process mediated by apo-E was involved. After intravenous administration of MS-50, about 4% of dose was excreted into bile in 24 h. Pharmacokinetic evaluation of the excretion rate of MS-50 into bile showed that the process followed first-order kinetics. Qualitative evaluation of the fluorescence detected in the bile after intravenous administration of MS-50 revealed that the particles were certainly excreted into bile in an intact form. From these results, it was suggested that intravenously administered MS-50 would be partially phagocytosed by hepatocytes through a process mediated by apo-E and that MS-50 ingested by hepatocytes would be partially excreted into the bile.

Animals↗