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Biomedical subjects

S Yamano

Publications and source records attributed to S Yamano.

At least 37 records · Page 2Linked to original sources

[CHF arising after low dose THP-COP chemotherapy in an elderly patient with malignant lymphoma].

A 76-year-old woman was admitted with a one-month history of low grade fever and dizziness. She had a palpable right supraclavicular lymph node. Abdominal ultrasonography showed swollen lymph nodes around the abdominal aorta. A specimen from the right supraclavicular lymph node showed malignant lymphoma (diffuse large B cell type). We started chemotherapy according to the low-dose THP-COP protocol (pirarubicin, cyclophosphamide, vincristine and prednisolone) on the 31st hospital day. Since no adverse effects were detected after two low-dose cycles, the patient received a third course with standard doses on the 87th hospital day. The total dose of pirarubicin was 72 mg/m2. Two days after the third course started, she suffered from dyspnea caused by congestive heart failure. A chest X-ray showed advanced cardiomegaly, severe congestion and bilateral pleural effusion. These conditions improved with transvenous administration of diuretics, a vasodilator and phosphodiesterase inhibitor. In this case, congestive heart failure developed even though the total dose of pirarubicin was lower than in previous reports of this complication. When the THP-COP protocol is indicated in elderly patients, cardiotoxicity should be monitored even if the total dose of pirarubicin is very low.

Aged↗

Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations.

Liddle's syndrome is a rare form of hereditary hypertension caused by mutations of the epithelial sodium (Na(+)) channel (ENaC). Analysis of the diseased pedigrees indicates an autosomal dominant inheritance, and the identified mutations are heterozygotes of gain-of-function mutations. However, sporadic cases of Liddle's syndrome have been reported in the literature, including one recently reported case caused by a de novo mutation of ENaC. We identified two patients with Liddle's syndrome who did not have family histories of hypertension. Sequence analysis showed a mutation in each case (P616L in betaENaC and W576X in gammaENaC), both confirmed to be de novo mutations. These data indicate that Liddle's syndrome should be considered even in patients without a family history of hypertension.

Adult↗

[Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia].

Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.

Acute Kidney Injury↗

Penetrating capacity of human spermatozoa cool preserved in electrolyte-free solution.

OBJECTIVE: To evaluate whether human spermatozoa preserved in electrolyte-free (EF) solution at 4 degrees C possess normal penetrating capacity. STUDY DESIGN: The acrosomal status of human spermatozoa cool preserved in EF solution was evaluated before preservation and before and after reinitiation by using chlortetracycline staining. The zona-free hamster egg sperm penetration test was performed using spermatozoa cool preserved in EF solution. RESULTS: The percentages of capacitated and acrosome-reacted spermatozoa cool preserved in EF solution before reinitiation were similar to those of fresh spermatozoa, but they significantly increased after reinitiation. The penetration rate and fertility index of spermatozoa cool preserved in EF solution were comparable to those of fresh spermatozoa (48.3% vs. 50.8% and 1.37 +/- 0.15 vs. 1.29 +/- 0.10, respectively). CONCLUSION: Human spermatozoa cool preserved in EF solution for one week can possess as much penetrating capacity as fresh spermatozoa.

Acrosome↗

Hormonal control of mRNA expression of immunoglobulin binding factor in uterine cervix.

Uterine cervical mucus contains an immunoglobulin binding factor (IgBF). It may play a role in preventing antibody production against sperm in the female reproductive tract. To elucidate the mechanism involved in the production of activated IgBF, we determined the effects of hormones on the expression of mRNAs of IgBF and of protein disulfide isomerase (PDI), activating enzyme, in uterine cervix by quantitative RT-PCR. The uterine cervices of female rats were excised at preovulatory, ovulatory, and postovulatory phases. The human uterine cervical adenocarcinoma cells (TCO-2) were cultured for 24 h in serum-free medium containing 17beta-estradiol or progesterone. Expression of IgBF and PDI mRNAs was significantly highest during the ovulatory phase. 17beta-estradiol stimulated the expression of both mRNAs in TCO-2; whereas progesterone was ineffective. In conclusion, estrogen regulates the production of IgBF by the endocervix and PDI in vivo, thereby increasing the level of activated IgBF in the female reproductive tract during the ovulatory phase, allowing sperm to enter the uterine cavity.

Animals↗

Purification and characterization of NAD-dependent morphine 6-dehydrogenase from hamster liver cytosol, a new member of the aldo-keto reductase superfamily.

Morphine 6-dehydrogenase, which catalyzes the dehydrogenation of morphine to morphinone, was purified 815-fold to a homogeneous protein from the soluble fraction of hamster liver with a yield of 15%. The enzyme was a monomeric protein with a molecular weight of 38 kDa and an isoelectric point of 5.6. Although both NAD and NADP served as cofactors, the enzyme activity with NADP was less than 5% that found with NAD at pH 7.4. With NAD, the enzyme gave the maximal activity at pH 9.3, and the K(m) and V(max) values toward morphine were 1.0 mM and 0.43 unit/mg protein, respectively. Among morphine congeners, normorphine exhibited higher activity than morphine, but codeine and ethylmorphine were poor substrates, and dihydromorphine and dihydrocodeine showed no detectable activity. The enzyme also exhibited significant activity for a variety of cyclic and alicyclic alcohols. In addition to xenobiotics, the enzyme catalyzed the dehydrogenation of 17beta-hydroxysteroids with much higher affinities than morphine. In the reverse reaction, the enzyme exhibited high activity for o-quinones, but morphinone, naloxone, and aromatic aldehydes and ketones were reduced at slow rates. Sulfhydryl reagents and ketamine strongly inhibited the enzyme, whereas pyrazole, barbital, and indomethacin had little effect on enzyme activity. 17beta-Hydroxysteroids inhibited the enzyme in a competitive manner against morphine. A total of 302 amino acid residues, which comprised approximately 94% of whole protein, were identified by sequencing of the peptides obtained by proteolytic digestion. This amino acid sequence of the enzyme showed significant homology to members of the aldo-keto reductase (AKR) superfamily and shared 63-64% identity with members of the AKR1C subfamily. These findings indicate that the enzyme is a new member of the AKR superfamily that is involved in steroid metabolism as 17beta-hydroxysteroid dehydrogenase as well as xenobiotic metabolism.

Alcohol Oxidoreductases↗

Effective activation method with A23187 and puromycin to produce haploid parthenogenones from freshly ovulated mouse oocytes.

Freshly ovulated mouse oocytes exposed to 5 mM calcium ionophore A23187 for 5 min and controls (not exposed) were cultured in TYH medium with 10 microg/ml puromycin (the puromycin group) or 2 mM 6-dimethylaminopurine (DMAP; the DMAP group) for 4 h. Among the controls, few oocytes were activated even if they were treated with DMAP or puromycin. In the oocytes exposed to A23187, in contrast, the activation rate, i.e. the rate of oocytes showing at least one pronucleus (PN) after the treatment, was 46.2% (48/104) in the DMAP group and 90.0% (118/131) in the puromycin group. Activation rate in the puromycin group was significantly higher than in the DMAP and control groups (p < 0.0001, respectively). Furthermore, 82.4% (108/131) of the activated oocytes in the puromycin group showed one PN with extrusion of the second polar body (PB). In the puromycin group, the DNA content of the PN of parthenogenones with 1PN2PB was half that of a set of metaphase II chromosomes. Chromosomal analysis was possible in 14 parthenogenones with 1PN2PB in the puromycin group. The parthenogenones possessed a normal set (n = 20) of haploid chromosomes. The combination of A23187 and puromycin proved to be an effective method of producing haploid parthenogenones.

Animals↗

Effects of preservation of mouse spermatozoa in electrolyte-free solution at 4 degrees C on the outcome of mouse in vitro fertilization.

PURPOSE: The aim was to assess the fertilizing capacity of spermatozoa cool-preserved in electrolyte-free (EF) solution. METHODS: Mouse spermatozoa were cool-preserved in EF solution and the acrosomal status of the spermatozoa was compared before and after preservation using chlortetracycline stain. Mouse oocytes were inseminated by spermatozoa cool-preserved in EF solution for 2, 4, or 7 days and fertilization and blastocyst rates were evaluated. RESULTS: Acrosomal status of spermatozoa cool-preserved in EF solution was not different from spermatozoa before preservation, but the capacitated and acrosome-reacted spermatozoa significantly increased after reinitiation. Cool-preservation in EF solution for up to 4 days did not affect fertilization rate. Blastocyst rate of embryos derived from spermatozoa cool-preserved for 4 or 7 days in EF solution was significantly lower than that of embryos derived from fresh spermatozoa. CONCLUSIONS: Mouse spermatozoa cool-preserved in EF solution possesses as much fertilizing capacity as fresh spermatozoa. However, prolonged preservation affects the embryonic development.

Acrosome Reaction↗

Adenoviral-mediated gene transfer to mouse salivary glands.

Adenoviral vectors effectively transfer genes to rat salivary glands. However, potent immune responses limit their use in vivo. Mice offer more opportunities than rats for the study of these immune processes. We first established conditions for infection of mouse salivary glands, with an adenoviral vector. The effects of time, viral dose, viral diluent buffer volume, and dexamethasone on expression of a transgene, luciferase, were determined by means of the recombinant vector AdCMVluc. Optimal luciferase expression was observed when the vector was suspended in 50 microL of buffer. This volume completely filled the gland parenchyma and slightly distended the capsule. Dexamethasone increased immediate transgene expression and reduced the acute inflammation one day following viral administration, but did not alter subsequent mononuclear inflammation or transgene expression 14 or 28 days later. An adenoviral vector encoding either anti-inflammatory cytokine IL-4 or IL-10 was co-administered with AdCMVluc to increase transgene expression at 14 and 28 days. While this strategy did not extend the duration of luciferase expression, co-administration of AdCMVIL-10 with AdCMVluc almost completely eliminated the chronic inflammatory infiltrate in the glands after 28 days. This study demonstrates that adenoviral-mediated gene transfer to mouse submandibular glands is possible by intraductal cannulation and that reduction of either the acute or chronic inflammatory infiltrates was insufficient to increase long-term transgene expression in this tissue.

Adenoviridae↗

Prospects for gene-based immunopharmacology in salivary glands.

The clinical potential of gene transfer is increasing. One likely major application of this emerging biotechnology will be for gene therapeutics, the use of a gene as a drug. Salivary glands provide an unusual but increasingly valuable target site for gene transfer. Studies in animal salivary glands from several laboratories, including our own, have provided proof of this concept. In this review, we provide a background and perspective on possible strategies for gene-based immunopharmacology in salivary glands. We use as a target disease model the autoimmune exocrinopathy Sjögren's syndrome.

Animals↗

Evidence that Toki-shakuyaku-san and its ingredients enhance the secretion of a cytokine-induced neutrophil chemoattractant (CINC/gro) in the ovulatory process.

We investigated the effects of Toki-shakuyaku-san and its crude ingredients in relation to the secretion of a cytokine-induced neutrophil chemoattractant, CINC/gro, interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) in the ovulatory process. Toki-shakuyaku-san significantly (p < 0.01) stimulated the secretion of 17 beta-estradiol but did not stimulate the secretion of progesterone in cultured whole ovarian dispersates. Toki-shakuyaku-san enhanced the secretion of CINC/gro in a dose-dependent manner and the production of CINC/gro at concentrations of 10 and 100 micrograms/ml of Toki-shakuyaku-san increased significantly (p < 0.01). Toki-shakuyaku-san also enhanced secretions of both IL-1 beta and TNF alpha, which are known to stimulate the secretion of CINC/gro in the ovulatory process. The production of TNF alpha increased significantly (p < 0.05) with 10 and 100 micrograms/ml of Toki-shakuyaku-san. Atractylodis Lanceae Rhizoma, Cnidii Rhizoma, Angelicae Radix, Paeoniae Radix and Alismatis Rhizoma, which are crude ingredients of Toki-shakuyaku-san, significantly (p < 0.01) enhanced the secretion of CINC/gro at concentrations of 100 micrograms/ml. The results of this study show that Toki-shakuyaku-san can stimulate the secretion of 17 beta-estradiol and stimulate the ovulatory process by stimulating the production of CINC/gro, IL-1 beta and TNF alpha in vitro. As a treatment for ovulatory disorders, Toki-shakuyaku-san may have stimulatory effects on both steroidogenesis and the ovulatory process.

Animals↗

Fertilization failure and oocyte activation.

Recent reports have suggested that when unfertilized oocytes with a spermatozoon after intracytoplasmic sperm injection (ICSI) are properly activated, the activated oocytes develop normally similar to fertilized oocytes. However, human oocytes do not easily respond to universal activators of mammalian oocytes like ethanol or calcium ionophore A23187, which induce a calcium transient in ooplasm. Puromycin activates human oocytes at a rate of 90%, but more than two thirds of the parthenogenesis possess 2 haploid pronuclei or 1 diploid pronucleus without extrusion of the second polar body. Therefore, the activation method which produces one pronucleus with extrusion of the second polar body in oocytes without a spermatozoon is necessary for producing embryos with normal karyotypes. Recently, we found the oocyte activation method which produced parthenogenesis displaying one pronucleus with extrusion of the second polar body. Using our method (a combination of calcium ionophore A23187 and puromycin), the activation rate was approximately 90% and the proportion of parthenogenesis displaying one pronucleus with extrusion of the second polar body was approximately 80% in human aged and mouse young oocytes. When human unfertilized oocytes following ICSI were activated by this method, two pronuclei were formed with extrusion of the second polar body in 30% of the oocytes. Four cleaved parthenogenesis (or embryos) showed normal karyotypes. However, the cytotoxic, teratogenetic and mutagenetic activity of Ca ionophore and puromycin should be approved prior to the clinical adaptation of the method.

Animals↗

Salivary glands as a model for craniofacial applications of gene transfer.

The potential applications of gene transfer technology to all branches of medicine are increasing. It is quite likely that within the next 10-20 years surgical practice routinely will utilize gene transfer, at least adjunctively. The purpose of this review is to familiarize the oral and maxillofacial surgeon with this technology. Studies performed with salivary glands in animal models are presented as examples of proof of concept.

Animals↗

Salivary gland cytokine expression in NOD and normal BALB/c mice.

The autoimmune diabetes-prone nonobese diabetic (NOD) mouse develops a chronic lymphocytic infiltration of endocrine and exocrine glands. The objectives of this study were to characterize the salivary immune infiltration and cytokine expression of NOD mice and compare these findings to those of normal BALB/c mice. A decline in salivary flow rates in NOD mice began between 8 and 12 weeks of age. At this same time lymphocytic foci are detectable in the salivary glands. Lymphocytic infiltration in the salivary glands of NOD mice increased with age and simultaneously salivary function declined. No lymphocytic infiltration was seen in BALB/c salivary tissues. Messenger RNA expression of several inflammatory cytokines, including interleukin-1beta (IL-1beta), IL-2, IL-10, interferon-gamma, and tumor necrosis factor-alpha was detected in the submandibular glands of both NOD and BALB/c mice by the reverse transcription polymerase chain reaction. IL-4 synthesis was also present in some tissues. Immunohistochemical analysis demonstrated the intense expression of inflammatory cytokines within lymphocytic infiltrates and epithelial cells of all NOD mice. Minimal expression of the same cytokines was detected only occasionally in BALB/c tissues stained in parallel. These results demonstrate cytokine expression in the salivary glands of normal mice and suggest that the overexpression of these inflammatory cytokines is likely involved in the development and progression of the organ-localized autoimmunity in the salivary glands of NOD mice.

Animals↗

Quality of embryo does not affect the implantation rate of IVF-ET in infertile women with antisperm antibody.

OBJECTIVE: To determine whether low quality score of embryos and advanced maternal age affect the implantation rate in infertile women with sperm-immobilizing antibody. DESIGN: A retrospective study. SETTING: The IVF Unit of the Department of Obstetrics and Gynecology at Tokushima University Hospital. PATIENT(S): Four infertile groups were studied: 20 women with sperm-immobilizing antibodies; 169 with tubal; 129 with male factor; and 72 with unexplained etiology. INTERVENTION(S): All women were hyperstimulated with GnRH analogue and scheduled ovarian stimulation with FSH and hMG for oocyte retrieval. MAIN OUTCOME MEASURE(S): Relationship of quality of transferred embryos, implantation rate and maternal age among four groups of infertile couples. RESULT(S): In the antisperm group, the fertilization rate (57.6%) and mean (+/- SD) score of transferred embryos (5.4+/-1.9) were significantly lower than those in the tubal group (72.4% and 6.2+/-1.9, respectively). However, the implantation rate in the antisperm group (23.6%) was significantly higher than those in other three groups (tubal, 8.6%; male factor, 9.5%; unexplained, 7.6%). With advancing maternal age, the implantation rate decreased in the three comparative groups. In contrast, the implantation rate in the antisperm group did not decrease with advancing maternal age. CONCLUSION(S): Women with antisperm antibodies have several disadvantages to overcome in order to achieve successful IVF-ET, such as a low fertilization rate and poor quality of transferred embryos. However, a high implantation rate was observed in this group, even in women at advanced age. The occurrence of a cellular or humoral immune reaction against sperm may augment the uterine receptivity for the implantation of fertilized ova or blastocyst.

Adult↗

Effect of lysophosphatidic acid on the ovum transport in mouse oviducts.

The effects of lysophosphatidic acid (LPA) on ovum transport in mouse oviducts were studied. When excised oviducts were incubated at 37 degrees C under 5% CO2 in humidified air for 24 hours, addition of LPA at 10 microM to the medium significantly accelerated the rate of ovum transport, and 1 microM LPA slightly increased the ovum transport rate. These increases were not inhibited by 10 microM indomethacin, a cyclooxygense inhibitor, but were suppressed by 260 ng/ml of pertussis toxin or 10 microM verapamil, a voltage-sensitive calcium channel blocker. These data suggested that LPA stimulates mouse ovum transport by contracting oviductual smooth muscle via a voltage-sensitive calcium channel mediated by a pertussis toxin-sensitive G-protein-linked receptor.

Animals↗