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Biomedical subjects

Y Fujino

Publications and source records attributed to Y Fujino.

At least 109 records · Page 6Linked to original sources

[Treatment of cytomegalovirus retinitis in AIDS with an intraocular sustained-release ganciclovir implant].

Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.

AIDS-Related Opportunistic Infections↗

Effects of endometrial stromal cells and peritoneal fluid on fertility associated with endometriosis.

Endometriosis is one cause of infertility. The disease causes severe non-bacterial inflammation and adhesion in the ovarian tubes and/or referred reproductive organs, but a number of types of unexplained infertility without severe organic disorders also exist. In the present study, we investigated the effects of endometrial stromal cells (SC) and peritoneal fluid (PF) in endometriosis on the fertilization and embryonic development rates using mouse ova and embryos. In addition, we prepared endometriosis artificially in rats and investigated the effects of peritoneal perfusate on the fertilization and embryonic development rates. We also investigated the in vitro fertilization rate in these rats. The mouse ova, sperm, and two-cell embryos were cultured on SC isolated surgically from patients with uterine myoma (M) or endometriosis (E), and 24 hours later, the fertilization and embryonic development rates were investigated. To this co-culture system, PF from M or E patients was added, at varying concentrations, and the fertilization and embryonic development rates were investigated. Then, rats with experimental endometriosis were prepared. After confirmation of the presence of lesions, peritoneal perfusate was added, at varying concentrations, to the co-culture system, and the fertilization and embryonic development rates were investigated. In addition, the in vitro fertilization rate was investigated in these rats. Both the fertilization rate and the embryonic development rate were significantly lower for the co-culture system in the E group. In the PF addition system, PF decreased the fertilization and embryonic development rates at lower concentrations in the E group. In rats with artificial endometriosis, peritoneal perfusate from rats with lesions significantly decreased the fertilization and embryonic development rates at lower concentrations. The in vitro fertilization rate was significantly lower in rats with lesions. The above results strongly suggested that inhibitions of fertilization and embryonic development induced by SC and PF, and altered quality of the ovum itself, might be responsible for infertility in endometriosis.

Animals↗

Human T-cell lymphotropic virus type 1 can infect primary rat retinal glial cells and induce gene expression of inflammatory cytokines.

PURPOSE: To examine whether or not retinal glial cells can be infected by human T-cell lymphotropic virus type 1 (HTLV-1) and test the possibility that HTLV-1-infected retinal glial cells are involved in the pathogenesis of HTLV-1 uveitis (HU). METHODS: We tested infection of HTLV-1 by a standard coculturing method using WKAH rat retinal glial cells and irradiated MT-2, a human T cell line that produces HTLV-1. Infection was confirmed by detecting the integrated HTLV-1 provirus, using polymerase chain reaction (PCR), viral gene expression, using reverse transcriptase-PCR (RT-PCR) and HTLV-1 p19 ELISA, and by identifying the HTLV-1-infected glial cells by immunofluorescence cytochemistry and in situ hybridization. Changes in cytokine gene expression were studied by RT-PCR. RESULTS: Using a semiquantitative PCR of HTLV-1 provirus sequence, we found that 2.6% of the retinal glial cells were infected at 3 days after infection, followed by a gradual decrease in the percentage with an extended period of culture up to 4 weeks. This time course of infection was also verified by RT-PCR and ELISA studies that detect viral mRNA expression and protein production, respectively. Expression of HTLV-1 gag protein and tax mRNA was detected in a part of glial cells by indirect immunofluorescence cytochemistry and in situ hybridization, respectively. RT-PCR analysis of cytokine gene expression revealed that gene expression of IL-6, CINC-1 (Gro, KC), and TNF-alpha were induced in these cells, with a peak at 3 weeks after infection. CONCLUSION: These results provided supportive evidence for the theory that the infection of retinal glial cells by HTLV-1 and subsequent production of inflammatory cytokines could be one contributing factor for the development of the unique clinical features of HU. A better understanding of the specific roles of the inflammatory cytokines in the pathogenesis of HU would be beneficial in the treatment and control of this disease.

Animals↗

Effects of serum from pregnant versus non-pregnant women on natural killer cell activity.

PROBLEM: To test the effect of serum obtained from in vitro fertilization-embryo transfer (IVF-ET) patients on the healthy volunteers natural killer (NK) cell activity. METHOD OF STUDY: Retrospective non-randomized clinical study. Suppressive effect on NK cell activity was measured with serum obtained from 25 pregnant and 24 non-pregnant women during IVF-ET procedure. RESULTS: Suppressive serum effect of volunteers' NK cell activity was significantly higher in pregnant than in non-pregnant women (P < 0.01). CONCLUSIONS: The suppressive activity of serum from pregnant women on NK cell suppression activity was useful in predicting the establishment of a successful pregnancy.

Adult↗

Tension pneumopericardium following tracheoplasty for congenital tracheal stenosis.

Tension pneumopericardium is a rare complication of mechanical ventilation following tracheoplasty for congenital tracheal stenosis. This case report describes fatal tension pneumopericardium in a three-month-old male infant some 24 hours following tracheoplasty for this condition. Because of persisting stenosis of the left main bronchus, ventilation pressures of PIP 23 cm H2O and PEEP 5 cm, progressing to PIP 28 cm and PEEP 7 cm were needed to maintain adequate respiratory exchange. Partial relief of the pneumopericardium was achieved by vigorous cardiac massage, but three days later the infant died of massive airway haemorrhage.

Acidosis, Respiratory↗

[Antihypertensive effects of a novel calcium antagonist, AE0047, in various hypertensive models].

The antihypertensive effects of oral or intravenous administration of AE0047, a novel 1,4-dihydropyridine-type calcium antagonist, were investigated in spontaneously hypertensive rats (SHR/crj), one kidney-one clip renal hypertensive rats (RHR), deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DHR) and two kidney-one clip renal hypertensive dogs (RHD). AE0047 (1, 3, 10 mg/kg, p.o.) caused a dose-related reduction of systolic blood pressure (SBP) with low reflex tachycardia in SHR/crj and RHR. The effect reached its maximum at 2-4 hr after administration and was sustained for a long time. In DHR, AE0047 (0.3, 1, 3 mg/kg, p.o.) similarly showed the antihypertensive effects at 2-7 hr with no significant changes in heart rates (HR). The doses (ED30) of AE0047 required to decrease SBP by 30% were 2.6, 3.4 and 0.68 mg/kg in SHR/crj, RHR and DHR, respectively. In RHD, and AE0047 capsule (GJ-0956: 4, 8, 16, 32 mg/body, p.o.) produced dose-dependent and long lasting effects with a transient and slight increase in HR. Furthermore, the intravenous administration of AE0047 (10, 30, 100 micrograms/kg) produced the antihypertensive action slowly, reached a plateau 10 min later and then maintained for many hours. In contrast, nitrendipine (3-100 mg/kg, p.o., 3-30 micrograms/kg, i.v.) and nicardipine (1-30 mg/kg, p.o., 3-30 micrograms/kg, i.v.) exhibited a similar potency to AE0047, but these maximal effects were produced at 1-2 hr and 0.5-1 min in the case of oral and intravenous administration, respectively, with a rapid recovery in the above hypertensive rats. These results indicate that AE0047 exhibits an antihypertensive effect with a slow onset and long-lasting profile.

Administration, Oral↗

Low sensitivity of adrenal chromaffin cells to acetylcholine, neostigmine and oxotremorine in 21-day-old rats.

In the previous study, we have demonstrated that nicotine hardly induces catecholamine release from adrenal medulla of 21-day-old rats. The present study examined the responsiveness of the adrenal chromaffin cells to acetylcholine in vitro and neostigmine and oxotremorine in vivo in 21-day-old and 8-week-old rats. As assessed by electron microscopy, the number of the chromaffin granules was markedly decreased and the content of adrenaline in adrenals was diminished significantly by oxotremorine treatment in 8-week-old rats, whereas these changes did not occur in 21-day-old rats. Morphological changes of the adrenal chromaffin cells, with respect to exocytosis, were not observed in neostigmine-treated 21-day-old rats and acetylcholine-treated adrenal slices prepared from 21-day-old rats. Catecholamine release was hardly evoked by acetylcholine in these slices as judged by measuring the catecholamine content in the medium. These results indicate that the sensitivity of the chromaffin cells to these secretagogues in 21-day-old rats is very low when compared to that in young adult rats.

Acetylcholine↗

CD8+ T lymphocyte counts as an adjunctive predictor of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

We encountered a case of cytomegalovirus (CMV) retinitis with spontaneous regression in association with an increased number of CD8+ but not CD4+ T lymphocytes in a patient with acquired immunodeficiency syndrome (AIDS). Thus, we examined the number of CD4 and CD8 counts at the diagnosis of CMV retinitis and compared with those of Pneumocystis carinii pneumonia (PCP). All 21 patients with a confirmed diagnosis of PCP (22 episodes) and 14 CMV retinitis patients were included in this study. Although PCP occurred after depletion of CD4 count to below 200/microl, CD8 count at that time varied widely and remained normal in some patients (median: 276.5/microl, range: 133-900/microl). In contrast, as CMV retinitis occurred after further depletion of CD4 count to below 50/microl, CD8 count decreased to below 500/microl (median: 238/microl, range: 43-448/microl) (p<0.05; PCP vs CMV retinitis). The values of the sensitivity and specificity for CMV retinitis obtained at the cutoff point of either 400/microl in CD8 count and 50/microl in CD4 count were similar. When these two cutoff points were combined, the positive predictive value was 46%. Monitoring of CD8 count may prove valuable as an additional predictor of CMV retinitis in patients with AIDS after CD4 depletion.

AIDS-Related Opportunistic Infections↗

[Human leukocyte antigens and episcleritis in leprosy (Hansen's disease)].

Human leukocyte antigens (HLA) were analyzed in Japanese leprosy patients to ascertain whether immunogenetic differences exist between leprosy patients with episcleritis (ES) and those without it. The subjects were 79 Japanese leprosy patients, including 33 patients with a past history of ES, and 49 patients without ES. Controls were 114 healthy subjects. A standard microcytotoxicity test was used for typing HLA-A, -B, -C, -DR and -DQ antigens. HLA-DRB1 and DQB1 genotypings were performed by using the polymerase chain reaction (PCR)-single strand conformation polymorphism and PCR-restriction fragment length polymorphism methods. The occurrence of HLA-Cw3 was significantly greater in the patients with ES (66.7%) than in those without ES (43.5%; odds ratio = 2.6, p < 0.05). The occurrence of HLA-DR4 was significantly lesser in the patients with ES (15.2%) than in those without ES (39.1%; odds ratio = 0.28, p < 0.05) and the controls (46.5%; odds ratio = 0.21, p < 0.005). At the genomic level, the occurrence of HLA-DRB1*0405, DQB1*0401, and DQB1*0302 was significantly lesser in the patients with ES (0%, 0% and 6.1%, respectively) than in those without ES (15.2%, 13.0%, and 26.1%, respectively; odds ratio = 0.07, 0.09 and 0.18, p < 0.05). HLA-DRB1*0405 and DQB1*0401 were also significantly lesser in the patients with ES than in the controls (29.8% and 29.8%; odds ratio = 0.04, p < 0.0001). Our results suggest that HLA-Cw3 causes susceptibility to episcleritis in Japanese patients with leprosy, whereas DR4 (DRB1*0405), DQB1*0401, and DQB1*0302 provide some protection against leprous episcleritis.

Adolescent↗

[Use of intravitreal ganciclovir for cytomegalovirus retinitis in a patient with systemic lupus erythematosus].

A patient with systemic lupus erythematosus (SLE) developed bilateral cytomegalovirus (CMV) retinitis and was treated with a total of 9 intravitreal ganciclovir injections at a dose of 400 micrograms/50 microliters in each eye under topical anesthesia. She was unable to receive systemic antiviral therapy because of bone marrow suppression and renal failure. The condition of both eyes improved after the intravitreal injections. Recurrence of CMV retinitis was not seen until death. Intravitreal injections of ganciclovir are useful even for the non-acquired immunodeficiency syndrome (AIDS) immunocompromised patients with CMV retinitis when the patients can not receive intravenous medications because of systemic complications.

Antiviral Agents↗

[Clinical aspects of Behçet's disease--epidemiological features and visual prognosis].

Behçet's disease patients who visited the eye clinic of Tokyo University Hospital during the past 20 years were surveyed retrospectively, and their epidemiological features and visual prognosis were demonstrated. We evaluated the number of patients, sex ratio, age of onset, ratio of complete type to incomplete type, and ratio of major symptoms other than the ocular manifestation. The results showed a tendency similar to the results of the nationwide hospital survey in Japan. We also evaluated the visual prognosis of Behçet's disease patients in our clinic by the least square method. In the groups of patients whose visual acuity at the initial visit was over 0.4, the visual prognosis of those who visited from 1984 till 1993 was significantly better than that of those who visited from 1974 till 1983. The use of cyclosporine was presumed to be one of the most important factors in the improved visual prognosis of Behçet's disease patients in our clinic.

Adolescent↗

Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response.

This study examines whether genetic susceptibility vs genetic resistance to experimental autoimmune uveoretinitis (EAU) are connected to a predisposition to mount a Th1-dominated (IFN-gamma high, IL-4 low) vs a Th2-dominated (IL-4 high, lFN-gamma low) response. Lewis rats developed disease with high incidence after immunization with the uveitogenic peptide R16, whereas F344 rats were resistant. Primed lymph node cells from both strains proliferated in culture in response to R16. However, while the Lewis cultures transferred EAU to syngeneic recipients, those of F344 did not. The Lewis cultures produced substantially more IFN-gamma mRNA and protein in response to R16, than did those of F344. Both strains made low levels of IL-10 mRNA and IL-4 mRNA. Unlike the primary cultures, long-term (R16-specific) T cell lines derived from each of the strains transferred EAU equally well to their respective recipients, and produced similar, high levels of IFN-gamma mRNA and protein. Treatment of F344 with Bordetella pertussis toxin concurrently with immunization abrogated its resistance, enhanced Ag-specific IFN-gamma production in culture, and yielded a primed cell population capable of transferring EAU. Conversely, immunization of Lewis rats with R16 in IFA induced little or no disease; the primed cells produced minimal amounts of IFN-gamma and did not transfer EAU. However, addition of IL-12 into the culture resulted in a highly pathogenic, IFN-gamma-producing cell population. We conclude that genetic susceptibility to ocular autoimmunity in this model is connected to an elevated Th1 response. Genetic resistance, however, does not seem to involve an elevated Th2 response, but rather an inhibited development of Th1-like effector cells.

Amino Acid Sequence↗

Differential distribution of three types of nociceptive neurons within the caudal bulbar reticular formation in the cat.

Nociceptive neurons within the reticular formation (RF) caudal to the obex were studied. 197 units recorded from the lateral part of subnucleus reticularis ventralis had receptive fields in the head, 72 units recorded from the medial RF in the body, and 160 units recorded from the middle third of RF in the head and body. About half of the units tested were antidromically excited by stimulation of nucleus centralis lateralis.

Animals↗

Differential distribution of four types of tooth pulp neurons in the caudal medulla oblongata of the cat.

The medulla oblongata caudal to the obex was explored for neurons responsive to tooth pulp (TP) stimulation in cats. Four different classes of TP neurons were found. They were TP specific neurons, trigeminal wide dynamic range neurons with TP input, trigeminal subnucleus reticularis ventralis (SRV) neurons with TP input and convergent reticular formation with TP input. They were differentially distributed within the caudal medulla oblongata.

Animals↗

DNA fragmentation of oocytes in aged mice.

To investigate whether female fertility decreases with age due to poor oocyte quality, we examined the presence of DNA fragmentation in ovulated oocytes from young, mature and aged mice. Oocytes from three age groups of female mice (7-8, 20-24 and 40-48 weeks) were retrieved from the oviducts 15 h after human chorionic gonadotrophin (HCG) injection. Oocytes from each mouse were incubated in a CO2 incubator for 0-60 h in human tubal fluid (HTF). After incubation, each oocyte was stained with the terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) method. The rate of DNA fragmentation (interpreted as apoptotic changes) was significantly higher for oocytes from aged mice, and the fertilization rate was significantly lower, compared with oocytes from young and mature mice. Our results suggest that DNA fragmentation of oocytes might be one of the reasons for poor oocyte quality and lower fertility in the aged group.

Aging↗

Serum from endometriosis patients impairs the development of mouse embryos in vitro--comparison with serum from tubal obstruction patient and plasmanate.

BACKGROUND: The aim of this study was to evaluate the inhibitory effect of serum from endometriosis. To determine the effects of serum obtained from patients with endometriosis on mouse embryo development, we compared the fertilization and cleavage rates of mouse embryo in a standard mouse embryo culture system. METHODS: Sera were collected from 13 individuals who were diagnosed endometriosis and ten individuals who were diagnosed as having tubal obstruction. Mouse embryos were fertilized and cultured in vitro with serum supplement obtained from patients with endometriosis (n = 13) and tubal obstruction (n = 10), and plasmanate (n = 10). RESULTS: The fertilization rate was 26.6 +/- 14.9% in patients serum with endometriosis, and the cleavage rate was 21.2 +/- 9.1%, respectively. However, the fertilization rates were 60.9 +/- 12.5% (tubal obstruction group), and 77.3 +/- 14.7% (plasmanate group), the cleavage rates were 32.2 +/- 16.4% and 36.2 +/- 9.9%, respectively. CONCLUSIONS: Serum from patients with endometriosis revealed toxic effects on mouse embryos in vitro. The use of plasmanate instead of whole serum from patients with endometriosis will hopefully bring a better understanding of embryo development.

Adult↗

[Intravitreal injection of ganciclovir in AIDS patients with cytomegalovirus retinitis].

The therapeutic effects and safety of intravitreal ganciclovir injection were evaluated in 16 acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus (CMV) retinitis. The induction therapy was done in a total of 23 courses, i.e., in 14 eyes of 10 patients. Active lesions of CMV retinitis were suppressed by 3 to 7 injections over 21 to 42 days after the initiation of the induction therapy. Intravitreal injections once a week for maintenance suppressed the reactivation of the lesions for at least 6 weeks in 9 eyes of 7 patients among 10 eyes of 8 patients. As for the safety of intravitreal ganciclovir injections in the 16 AIDS patients with CMV retinitis, a total of 354 injections were given and two serious complications, that is, endophthalmitis and retinal detachment were observed in one eye each. During the course of intravitreal injection, 3 of 7 patients developed CMV retinitis in the contralateral eye and systemic CMV infections were suspected in 3 of 12 patients. Intravitreal injection of ganciclovir is thought to be effective for the treatment of CMV retinitis in AIDS patients, but careful procedure and examinations are needed.

AIDS-Related Opportunistic Infections↗