Search PubMed⌕ Search

Biomedical subjects

Y Honma

Publications and source records attributed to Y Honma.

At least 73 records · Page 4Linked to original sources
PubMed1999

Inhibitory effects of diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells.

BACKGROUND: Benzodiazepines have a direct bronchodilator action in airway smooth muscle, but the mechanisms by which these agents produce muscle relaxation are not fully understood. The current study was performed to identify the effects of the benzodiazepines diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells. METHODS: Whole-cell patch-clamp recording techniques were used to evaluate the effects of the benzodiazepines diazepam (10(-8) to 10(-3) M) and midazolam (10(-8) to 10(-3) M) on inward Ca2+ and outward K+ channel currents in dispersed canine tracheal smooth muscle cells. The effects of the antagonists flumazenil (10(-5) M) and PK11195 (10(-5) M) on these channels were also studied. RESULTS: Each benzodiazepine tested significantly inhibited Ca2+ currents in a dose-dependent manner, with 10(-6) M diazepam and 10(-5) M midazolam each causing approximately 50% depression of peak voltage-dependent Ca2+ currents. Both benzodiazepines promoted the inactivated state of the channel at more-negative potentials. The Ca2+-activated and voltage-dependent K+ currents were inhibited by diazepam and midazolam (> 10(-5) M and > 10(-4) M, respectively). Flumazenil and PK11195 had no effect on these channel currents or on the inhibitory effects of the benzodiazepines. CONCLUSIONS: Diazepam and midazolam had inhibitory effects on voltage-dependent Ca2+ channels, which lead to muscle relaxation. However, high concentrations of these agents were necessary to inhibit the K+ channels. The lack of antagonized effects of their antagonists is related to the non-gamma-aminobutyric acid-mediated electrophysiologic effects of benzodiazepines on airway smooth muscle contractility.

Anesthetics, Intravenous↗
PubMed1999

Detection of herpes simplex virus DNA in atypical epithelial keratitis using polymerase chain reaction.

AIM: To study herpes simplex virus (HSV) DNA in tears from patients with atypical epithelial keratitis of unknown aetiology. METHODS: Tear samples were collected from 17 affected eyes of 17 consecutive patients suffering from epithelial keratitis in whom HSV keratitis was suspected but whose diagnosis was difficult on the basis of clinical manifestations alone. Using reduced sensitivity polymerase chain reaction (PCR), tear samples were tested for HSV DNA. Tears from the unaffected eyes of the 17 patients were also examined, along with 38 tear samples from 19 normal volunteers. Southern blot analysis was performed to confirm that amplified DNA bands were specific for HSV. Clinical correlation with photographs of corneal lesions was also investigated. RESULTS: HSV DNA was detected in tears from the affected eyes of eight of the 17 patients with suspected HSV keratitis. Tears from the affected eyes of the other patients were PCR negative, as were tears from the unaffected eyes of all 17 patients, and from the 38 normal eyes. There was no correlation between PCR results and clinical manifestation of keratitis. CONCLUSIONS: Based on the sensitivity of the PCR system, eight of 17 suspected HSV keratitis patients were confirmed as suffering from HSV keratitis. HSV keratitis should therefore be considered as a possible diagnosis in atypical epithelial keratitis.

Adult↗
PubMed1999

Adenosine analogs as possible differentiation-inducing agents against acute myeloid leukemia.

Several adenosine analogs induce the functional and morphological differentiation of myelomonocytic leukemia cells. They can be classified into two types; i.e., those that do/do not require phosphorylation to induce the differentiation of leukemia cells. Neplanocin A, a potent S-adenosylhomocysteine hydrolase inhibitor, induces the differentiation of some leukemia cells without phosphorylation. On the other hand, deoxycoformycin (dCF), a potent adenosine deaminase inhibitor, also induces the myelomonocytic differentiation of leukemia cells when it is treated with deoxyadenosine (dAdo). This differentiation is inhibited by 5'-amino-deoxyadenosine, an inhibitor of (deoxy)adenosine kinase, suggesting that kinase-dependent phosphorylation is involved in the differentiation-inducing effect of dCF plus dAdo. Retinoids induce the differentiation of NB4 cells, a cell line derived from human promyelocytic leukemia. When used in combination with all-trans retinoic acid (ATRA), both NPA and dCF plus dAdo greatly enhance the granulocytic differentiation of NB4 cells. This enhancing effect is greatest when the cells are pretreated with NPA and then with ATRA. On the other hand, pre-exposure of NB4 cells to ATRA greatly potentiates the differentiation induced by dCF plus dAdo, while pretreatment with dCF plus dAdo before exposure to ATRA is less effective. The ATRA-induced differentiation of NB4 cells is effectively augmented by clinically applicable concentrations of these analogs. A clinical strategy that combines intermittent treatment with these analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.

Adenosine↗
PubMed1999

Relation between hemoglobin discordance and adverse outcome in monochorionic twins.

BACKGROUND: The effects of discrepancies in the birth weight and hemoglobin concentration ([Hb]) at the birth on infant outcome have not been fully investigated in monochorionic (MC) and dichorionic (DC) twins. METHODS: A retrospective study of 95 twin pregnancies. All 190 neonates (68 MC twins and 122 DC twins) were admitted to the neonatal intensive care unit, and the [Hb] was determined soon after birth. The [Hb] discordance represents the [Hb] of the smaller twin expressed as a percentage of the [Hb] of the larger twin. Infants were followed-up until 1 year of corrected age and their psychomotor development was evaluated between 12 and 18 months. RESULTS: One DC infant died by 1 year of age. Twelve MC infants and eight DC infants had disabilities by 1.5 year of age. In the MC group, 11 infants (28%) of 20 pairs with an intertwin [Hb] discordance >100 had disabilities compared with one (3.6%) of 14 pairs with an [Hb] discordance < or = 100 (p<0.05). A similar trend was observed in the DC group, but the difference was not significant. The incidence of disabled infants increased as the intertwin birth weight discordance increased in MC twins. CONCLUSIONS: An adverse outcome at 1 year of age in MC twins was associated with a greater birth weight discordance and an [Hb] disordance that indicated polycythemia in the smaller twin.

Adult↗
PubMed1999

Effects of placental chorionicity on outcome in twin pregnancies. A cohort study.

OBJECTIVE: To examine the effects of the chorionicity of the placenta on infant outcome at 1 year of age in twin pregnancies. STUDY DESIGN: Cohort study and retrospective review of the medical records of 44 monochorionic (MC) and 164 dichorionic (DC) twin gestations that had been followed at our institution since < 20 weeks' gestation. Physical and neurologic status was assessed at 1 year of corrected age in infants born to these 208 women. RESULTS: Adverse infant outcomes, such as death, cerebral palsy and mental retardation, occurred in 9 (10%) of 88 MC infants (4 deaths and 5 disabled infants) as compared with 12 (3.7%) of 328 DC infants (6 deaths and 6 disabled infants) (P < .05). Although delivery occurred one week earlier in MC than in DC twins (34.7 +/- 2.8 vs. 35.7 +/- 2.3 weeks, P < .01), there was no significant difference in gestational age at birth or birth weight between the 9 MC and 12 DC infants with adverse outcomes. A presumptive antenatal diagnosis of twin-twin transfusion syndrome (TTTS) was made in 14 (32%) of the 44 MC twin gestations. TTTS was considered to be responsible for adverse outcome in 7 MC infants. All 9 MC infants with adverse outcomes and 4 (33%) of 12 DC infants with adverse outcomes belonged to pairs that had weight discordance > or = 25% (P < .01). CONCLUSION: MC twins had an increased risk of adverse outcomes as compared with DC twins, mainly because of TTTS. In both MC and DC twins, a birth weight discordance > or = 25% was associated with adverse infant outcomes. The number of infants with disabilities at 1 year of age was equal to the number of deaths.

Adult↗
PubMed1999

Effect of metalloproteinase inhibitor on corneal cytokine expression after alkali injury.

PURPOSE: Interleukin (IL)-1alpha and IL-6 levels in the cornea are greatly elevated during the early stages after an alkali burn in mice. The authors investigated the effect of synthetic inhibitor of matrix metalloproteinase (SIMP) on the expression of inflammatory cytokines in alkali-burned murine corneas and evaluated the clinical appearance of the eyes. METHODS: After 0.5N NaOH-alkali burns to 400 corneas of ICR mice, 200 received 400 microg/ml of SIMP topically 4 times a day while 200 corneas were similarly treated with vehicle only. At days 4, 7 and 14 after injury, each cornea was assigned a clinical score for corneal opacity, corneal epithelial defect, hyphema and cataract. Extracts of injured corneas in each group were then assayed for cytokine production using ELISA systems for IL-1alpha, IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha). RESULTS: The levels of IL-1alpha, IL-1beta and IL-6 were significantly lower in the SIMP-treated group than in the vehicle-treated group 7 days after the burn. However, levels of these cytokines were similar in the SIMP and non-SIMP groups at days 4 and 14. Levels of TNF-alpha did not differ between both groups at any postinjury time. In the SIMP-treated corneas, there was less opacification and hyphema formation and epithelial regeneration was faster. CONCLUSIONS: Topical application of SIMP in alkali-burned murine corneas reduced the expression of IL-1alpha, IL-1beta, and IL-6 and lessened the severity of the injury.

Animals↗
PubMed1999

[Physio-social activities and active life expectancy, life expectancy in Japanese elderly].

PURPOSE: Incidence of loss of activity and death in elderly people living at home were investigated to attempt to determine their relationship to physio-social activities in elderly. METHOD: This longitudinal study of life expectancy and active life expectancies is a thirty-six months follow up study. Loss of activities were classified as follows: Long term (over six months) treatment at home, long term (over six months) admission to hospital or intermediate institute for the elderly, admission to nursing home, and death. Subjects were persons living at home in Ogi, Saga prefecture, aged 70 years or older not requiring help in active daily living (ambulating, bathing, dressing, discharging, eating). RESULTS: 6,274 (male = 2,383, female = 3,891) subjects were followed for thirty six months, and 178 people experienced long term treatment at home, 310 people had long term admission to a hospital or intermediate institute for elderly, 28 people were admitted to a nursing home and 449 people experienced death. The main results were as follows: (1) From the Cox proportional hazards model using the likelihood-ratio method of survival and active life loss, significant hazard ratios for reduction active life expectancy for male were found for age, disability score for ADL, speech disorder, inconvenient bathroom design, with attention to health, and daily activity were associated with extension of active life expectancy. Age, disability score for ADL, speech disorder, inconvenient bathroom design were associated with reduced life expecting, while, attention to health, choosing to undergo regular health examinations, and daily were associated with increased activity in life expectancy. (2) Hazard ratios for reduction active life expectancy for females were age, disability score for ADL, defect of memory deficits, inconvenient design for hallway and stairs. Participating in health examinations, Purpose in life were associated with life expectancy increase. For females were age, disability score for ADL, speech disorder, inconvenient design of bathroom were associated with decrease in life expectancy, while having a person in life was associated with increase in life expectancy. DISCUSSION: Relationship between physio-social activities in elderly is a significant factor in many studies on elderly health. This study suggests that age, disability score for ADL, inconvenient for housing design, active health behavior, daily activities, and Losing a sense of worth in living, affect active life expectancy and life expectancy.

Activities of Daily Living↗
PubMed1999

Role of CD14 expression in the differentiation-apoptosis switch in human monocytic leukemia cells treated with 1alpha,25-dihydroxyvitamin D3 or dexamethasone in the presence of transforming growth factor beta1.

Transforming growth factor beta (TGF-beta) enhanced the growth-inhibitory activities of dexamethasone (Dex) and 1alpha,25-dihydroxyvitamin D3 (VD3) on human monocytoid leukemia U937 cells. TGF-beta and VD3 synergistically increased the expression of differentiation-associated markers such as the CD11b and CD14 antigens, whereas TGF-beta and Dex did not. On the other hand, TGF-beta and Dex synergistically increased the number of Apo2.7-positive cells, which represents the early stage of apoptosis, whereas TGF-beta and VD3 did not, suggesting that TGF-beta enhanced apoptosis with Dex and enhanced monocytic differentiation with VD3. In the presence of TGF-beta, the retinoblastoma susceptibility gene product, pRb, was synergistically dephosphorylated by Dex as well as VD3. TGF similarly enhanced the expression of the p21Waf1 gene in U937 cells treated with Dex and VD3. TGF-beta dose-dependently increased the expression of Bcl-2 and Bad and decreased the expression of Bcl-X(L) in U937 cells. Dex enhanced the down-regulation of Bcl-X(L) expression in TGF-beta-treated cells, whereas VD3 blocked this down-regulation of Bcl-X(L). However, the down-regulation of Bcl-X(L) by treatment with the antisense oligomer did not affect the apoptosis or differentiation of U937 cells. The apoptosis of CD14-positive cells was suppressed in the VD3 plus TGF-beta-treated cultures. These results suggest that the expression of CD14 is involved in the survival of differentiated cells.

Apoptosis↗
PubMed1998

Human monocytoid leukemia cells are highly sensitive to apoptosis induced by 2'-deoxycoformycin and 2'-deoxyadenosine: association with dATP-dependent activation of caspase-3.

The adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) significantly inhibits the proliferation of leukemia and lymphoma cell lines. When cells were incubated in the presence of both dCF and 2'-deoxyadenosine (dAd), the concentration of dCF required to induce apoptosis of monocytoid leukemia cells was much lower than that required for myeloid, erythroid, or lymphoma cell lines. Among the cell lines tested, U937 cells were the most sensitive to this treatment. The concentration of dCF that effectively inhibited the proliferation of U937 cells was 1/1,000 of that required for lymphoma cell lines, on a molar basis. However, the uptake of dCF or dAd in U937 cells was comparable with that in other leukemia and lymphoma cell lines. The intracellular accumulation of dATP in U937 cells was only slightly higher than that in other leukemia cells in dCF-treated culture. Treatment with dCF plus dAd induced apoptosis in U937 cells at low concentrations, and this apoptosis was reduced by treatment with caspase inhibitors. Induction of caspase-3 (CPP32) activity accompanied the apoptosis induced by dCF plus dAd. No activation of CPP32 was observed in cytosol prepared from exponentially growing leukemia and lymphoma cells. However, dATP effectively induced CPP32 activation in cytosol from monocytoid cells, but not in that from nonmonocytoid cells, suggesting that dATP-dependent CPP32 activation is at least partly involved in the preferential induction of apoptosis in monocytoid leukemia cells. The combination of dCF and dAd may be useful for the clinical treatment of acute monocytic leukemia.

Apoptosis↗
PubMed1998

Identity of human normal counterpart (MmTRA1b) of mouse leukemogenesis-associated gene (MmTRA1a) product as plasma membrane phospholipid scramblase and chromosome mapping of the human MmTRA1b/phospholipid scramblase gene.

We recently cloned a new leukemogenesis-associated gene MmTRA1a (Mm-1 cell derived transplantability-associated gene 1a, former name "TRA1") from a mouse leukemogenic and monocytic Mm-P cell cDNA library and also cloned its normal counterpart MmTRA1b (former name "NOR1") from a normal mouse kidney cDNA library. The mouse MmTRA1a is a truncated form of mouse MmTRA1b. Here we report the cloning of a cDNA (human MmTRA1b) homologous to the mouse MmTRA1b from a human monocytic U937 cell cDNA library. The human MmTRA1b cDNA predicts a peptide containing 318 amino acids with a calculated molecular weight of 35,047 Da. The predicted human MmTRA1b protein sequence shared 78% amino acid identity with the mouse counterpart (328 amino acids). Both the human homologue and mouse MmTRA1b protein but not MmTRA1a protein possess a proline-rich domain at the N-terminal end. The human MmTRA1b gene was mapped to chromosome 3q23. Expression of the human homologue was increased during differentiation of U937 cells induced by most typical differentiation inducers. Moreover, predicted amino acid sequence analysis of human MmTRA1b cDNA revealed perfect identity with the human plasma membrane phospholipid scramblase that is required for transbilayer movement of membrane phospholipids. These results provide new information on the possible roles of MmTRA1b/phospholipid scramblase and the truncated MmTRA1a in the leukemogenesis and differentiation of monocytic leukemia cells.

Amino Acid Sequence↗
PubMed1998

Induction of differentiation in acute promyelocytic leukemia cells by 9-cis retinoic acid alpha-tocopherol ester (9-cis tretinoin tocoferil).

Acute promyelocytic leukemia (APL) has a specific genetic rearrangement between the retinoic acid receptor (RAR)-alpha gene and the pml nuclear protein gene. All-trans retinoic acid (ATRA) induces granulocytic differentiation of APL-derived cells and is used to treat APL patients. However, ATRA interacts with normal cells with RAR throughout the entire body, and when used at high doses or over a long duration, it induces several adverse effects. The development of drugs that selectively act on APL cells may contribute to increasing the therapeutic efficacy of APL treatment as well as elucidating the mechanisms of response to ATRA. In this study, 9-cis retinoic acid alpha-tocopherol ester (9CTT) inhibited the proliferation of APL-derived NB4 and HT93 cells and induced differentiation markers, such as granulocytic maturation, nitroblue tetrazolium reduction, and CD11b expression, in these cells. The effects of 9CTT on non-APL cells, including HL-60 and U937 cells, were much weaker than those on APL cells, and tretinoin tocoferil (TT), which is an alpha-tocopherol ester of ATRA, did not induce the differentiation of APL cells as effectively as 9CTT. The differentiation-inducing effects of 9CTT were inhibited by RAR antagonists. 9CTT and TT similarly induced the transactivating activity of RARs, but were not effective on RXRs. 9CTT downregulated the expression of PML/RAR-alpha protein more effectively than TT, which suggests that it may be involved in the selectivity of 9CTT against APL cells. Interestingly, 9CTT enhanced the differentiation of APL cells induced by ATRA, 9-cis retinoic acid, and synthetic retinobenzoic acids. Combined with 1alpha,25-dihydroxyvitamin D3 (VD3), 9CTT also more than additively induced the differentiation of APL cells. Thus, 9CTT, alone or in combination with other retinoids or VD3, may be useful for the treatment of APL.

Cell Differentiation↗
PubMed1998

Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies.

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.

Acute Disease↗
PubMed1998

Expression pattern of a novel death-promoting gene, DP5, in the developing murine nervous system.

We examined the expression patterns of the DP5 gene, which encodes a protein with apoptosis-inducing activity, in the developing nervous system of mice. This gene was primarily expressed in the spinal motor neurons and peripheral sensory ganglia of mouse embryos and transiently in the postnatal brain, particularly in the entorhinal cortex and hippocampus. These expression patterns suggest that the DP5 gene may be involved in the apoptosis, if not all, of the developing nervous system.

Amino Acid Sequence↗
PubMed1998

Significance of multimodal cerebral monitoring under moderate therapeutic hypothermia for severe head injury.

The therapeutic significance of moderate hypothermia and cerebral monitorings was assessed in the 10 patients with severe head injury. Cooling was begun as soon as possible after admission, using water blankets under general anesthesia. Jugular venous or tympanic temperature of patients was maintained at 32 degrees C for 3 to 5 days, then rewarming at the rate of 1 degree C a day was started. The intracranial pressure was controllable less than 20 mmHg under hypothermia. Moderate hypothermia reduced the jugular venous lactate (33.5%) as well as the cerebral blood flow velocity at M1 portion of middle cerebral artery (CBFV-M1) measured by transcranial Doppler (7.2%), while increase of the jugular venous oxygen saturation (SjO2) (17.9%) was observed in a majority of the patients. Our results demonstrated that moderate therapeutic hypothermia significantly reduced cerebral circulation and metabolism. Measurement of SjO2 and CBFV-M1 seems to be useful for estimation of cerebral circulation and metabolism in therapeutic hypothermia.

Adolescent↗
PubMed1998

Autosomal dominant cerebellar ataxia (SCA6): clinical, genetic and neuropathological study in a family.

We describe a family with dominantly inherited ataxia of late adult onset. Expansion of a CAG repeat in the gene encoding the alpha1A voltage-dependent calcium channel was identified at autopsy in one patient, a 65-year-old woman with a disease duration of 11 years. In this patient, pathological changes were confined to the cerebellar cortex and inferior olivary complex. The cerebellar cortex showed severe loss of Purkinje cells with proliferation of Bergmann's glia, being more pronounced in the superior parts of the vermis and hemispheres. In the inferior olivary complex, a reduced neuronal cell population, which could be interpreted as a change secondary to the cerebellar cortical lesion, was evident. We conclude that the pathological phenotype of this newly classified autosomal dominant cerebellar ataxia, SCA6, is cerebello-olivary atrophy, or more strictly cerebellar cortical atrophy.

Aged↗
PubMed1998

Gelatinous drop-like corneal dystrophy is not one of the beta ig-h3-mutated corneal amyloidoses.

PURPOSE: To discover if beta ig-h3 is mutated in gelatinous drop-like corneal dystrophy, as has been suggested. METHODS: Genomic DNA was isolated from unrelated individuals with lattice corneal dystrophy type I (n = 3), Avellino corneal dystrophy (n = 3), and gelatinous drop-like corneal dystrophy (n = 3) and used as a template for polymerase chain reaction to amplify all exons in beta ig-h3. The polymerase chain reaction product was then sequenced. RESULTS: Beta ig-h3 is mutated in lattice corneal dystrophy type I (Arg124Cys) and Avellino corneal dystrophy (Arg124His). In gelatinous drop-like corneal dystrophy, on the other hand, no mutation was detected in the entire coding region of beta ig-h3 (all 17 exons). CONCLUSION: Unlike the amyloidotic corneal dystrophies lattice type I and Avellino, gelatinous drop-like corneal dystrophy is not likely to be caused by a mutation in beta ig-h3.

Amyloidosis↗