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Biomedical subjects

J Mori

Publications and source records attributed to J Mori.

At least 19 recordsLinked to original sources

Change in concentrations of luteinizing hormone subunit messenger ribonucleic acids in the estrous cycle of beef cattle.

Changes in the concentrations of LH subunit messenger ribonucleic acids (mRNAs) and in the LH content of the anterior pituitary of beef cattle were studied during the estrous cycle. Japanese beef cows were classified according to the expected day of the estrous cycle: stage I (early-luteal phase, days 1-4; day 1=day of ovulation), stage II (early-mid-luteal phase, days 5-10), stage III (late-mid-luteal phase, days 11-17) and stage IV (follicular phase, days 18-20), according to the morphology of the ovaries. The anterior pituitaries of the cows were collected and the levels of alpha and LHbeta subunit mRNAs were determined by slot-blot analyses. The LH content of the anterior pituitary was measured by radioimmunoassay. The level of alpha subunit mRNA in the pituitary of cows was highest in stage I and decreased significantly by stage II (P<0.05); thereafter it tended to increase. The level of LHbeta subunit mRNA did not change significantly during the estrous cycle. The LH content of the pituitary of cows was low in stage I and tended to increase by stage II, then to decrease from stage II to III, and to increase significantly from stage III to IV (P<0.05). These results suggest that the highest levels of gene expressions of alpha subunit in the anterior pituitary occur in the early-luteal phase of beef cows, while the LH content is increased most in the follicular phase. The enhanced gene expressions of common alpha subunit in the early-luteal phase could be important in replenishing the bovine anterior pituitary with LH, which is depleted of hormone by the LH surge or the enhanced pulsatile release.

Animals↗

The role of hinge domain in heterodimerization and specific DNA recognition by nuclear receptors.

Four structural domains are characteristic of the members of the nuclear receptor superfamily. The hinge (D) domain which is located between the DNA binding (C) domain and the ligand binding (EF) domain, is less conserved among the nuclear receptors. In this study, we investigated the effects of the D domain on receptor function with regard to ligand binding, protein-protein interaction and DNA recognition. We found that EF domain of TR lacked T3 binding activity and additional D domain was required for its ligand binding. Using pull down assays and two-hybrid assays, we also demonstrated that the EF domain of TR did not dimerize with TR or RXR in solution, while the DEF domain was able to homo-and heterodimerize with RXR. In contrast, the RXR EF domain alone was able to heterodimerize with TR. The D domain of TR is required but that of RXR is not necessary for the interaction. We further demonstrated that the D domain was required for receptor specific DNA recognition. The ABC domain of vitamin D receptor (VDR) and TR(DEF) chimeric receptor could not bind to VDR response element (VDRE). Addition of own D domain of VDR to the ABC domain enables the chimeric receptor to bind VDRE and transactivate. The D domain of TR cannot substitute for that of VDR in context of specific DNA recognition. These data suggest that the D domain is important to maintain the integrity of the functional structure of the nuclear receptors.

Animals↗

[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size].

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

Aged↗

Silencing mediator for retinoid and thyroid hormone receptors interacts with octamer transcription factor-1 and acts as a transcriptional repressor.

Octamer transcription factor-1 (Oct-1) is a member of the POU (Pit-1, Oct-1, unc-86) family of transcription factors and is involved in the transcriptional regulation of a variety of gene expressions related to cell cycle regulation, development, and hormonal signals. It has been shown that Oct-1 acts not only as a transcriptional activator but also as a transcriptional repressor for certain genes. The mechanism of the repressive function of Oct-1 has not been well understood. Here we demonstrate by using the glutathione S-transferase pull-down assays and coimmunoprecipitation assays that the POU domain of Oct-1 directly interacts with a silencing mediator for retinoid and thyroid hormone receptors (SMRT). The interaction surfaces are located in the C-terminal region of SMRT, which are different from previously described silencing domains I and II or receptor interacting domains I and II. In transient transfection assays in COS1 cells, overexpression of SMRT attenuated the augmentation of Oct-1 transcriptional activity by OBF-1/OCA-B, activator for Oct-1. In pull-down assays, increasing amounts of SMRT could compete the binding of OCA-B to Oct-1 POU domain. The activity of Oct-1 could be determined by a regulated balance between SMRT and OCA-B. Furthermore, cotransfected unliganded thyroid hormone receptor enhanced the transactivation by Oct-1, and addition of 3,3',5-tri-iodo-l-thyronine obliterated the stimulatory effects. Consequently, in the presence of cotransfected thyroid hormone receptor, the octamer response element acts as an element negatively regulated by 3,3',5-tri-iodo-l-thyronine. The results suggest that the transcriptional activity of Oct-1 can be modulated by interaction through its POU domain by a silencing mediator SMRT resulting in the cross-talk between Oct-1 and nuclear receptors.

Animals↗

Thyroid hormone regulation of apoptosis induced by retinoic acid in promyeloleukemic HL-60 cells: studies with retinoic acid receptor-specific and retinoid x receptor-specific ligands.

3,5,3'-Triiodo-L-thyronine (T3) potentiates apoptosis during the all-trans-retinoic acid-induced differentiation of promyeloleukemic HL-60 cells. We examined whether the retinoid receptor-specific thyroid hormone action is present during differentiation of HL-60 cells in this study. We used two distinct retinoid receptor agonists. T3 potentiates G1 arrest induced by Am80, a retinoic acid receptor (RAR)-specific agonist, but had no effect on G1 arrest induced by HX600, a retinoid x receptor (RXR)-specific agonist. Am80 alone induces the apoptosis, and T3 enhances it. Although HX600 alone fails to increase the apoptotic fraction, T3 enables the compounds to induce apoptosis. Am80-induced expression of CD11b, a marker for the differentiation, is enhanced by T3. However, T3 or HX600 or both do not affect the expression of CD11b. T3 does not alter the amount of mRNAs of various members of the bcl-2 family. T3, however, enhances the Am80-induced expression of bfl-1 and suppression of bcl-2. In contrast, T3 does not alter either bfl-1 and bcl-2 expression in the presence of HX600. Our observations suggest that cooperative action of T3 with an RXR-specific ligand is different from that with an RAR ligand in cellular apoptotic regulation and that thyroid hormone may be available as a chemotherapeutic agent in acute leukemia.

Apoptosis↗

Suppression of tumor growth and downregulation of platelet-derived endothelial cell growth factor / thymidine phosphorylase in tumor cells by angiogenesis inhibitor TNP-470.

We investigated the effects of the angiogenesis inhibitor TNP-470 on human lung squamous cell carcinoma cell lines H226B and H226Br both in vivo and in vitro. H226B was established from human lung squamous cell carcinoma and H226Br was established from a brain metastatic lesion of H226B in nude mice. Nude mice inoculated with these cells were treated with 30 mg / kg of TNP-470 subcutaneously every other day. At this dose, TNP-470 only significantly suppressed the growth of H226Br tumor, but not H226B tumor. Attempts to use a high dose of TNP-470 (100 mg / kg) resulted in a severe loss of body weight. Immunohistochemical studies showed marked tumor vascularization in H226Br tumor, but the formation of new blood vessels was suppressed by 30 mg / kg of TNP-470. Investigation of the mechanism of anti-angiogenic effects of TNP-470 in vivo showed that the expression and the activity of platelet-derived endothelial cell growth factor / thymidine phosphorylase (PD-ECGF / dThdPase) in H226Br tumor was significantly suppressed by 30 mg / kg of TNP-470. Furthermore, TNP-470 inhibited cell growth of cultured H226Br dose-dependently at concentrations of 1 microg / ml. Immunoblot analysis revealed H226Br cells gave a stronger PD-ECGF signal than H226B cells, and the expression of PD-ECGF / dThdPase in H226Br was also suppressed by treatment with TNP-470 at 0.1 microg / ml. No change in basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) was noted in these cell lines. Our results suggested that TNP-470 acts, at least in part, by downregulation of PD-ECGF / dThdPase in this cell line.

Angiogenesis Inhibitors↗

Mechanism of liver-selective thyromimetic activity of SK&F L-94901: evidence for the presence of a cell-type-specific nuclear iodothyronine transport process.

The thyromimetic compound SK&F L-94901 shows more potent thyromimetic activity in the liver than in the pituitary gland or heart when administered to rats. The mechanisms of liver-selectivity of SK&F L-94901 were examined using cultured rat hepatoma cells (dRLH-84) and rat pituitary tumor cells (GH3), both of which showed saturable cellular uptake of tri-iodothyronine (T(3)). When isolated nuclei with partial disruption of the outer nuclear membrane were used, SK&F L-94901 competed for [(125)I]T(3) binding to nuclear receptors almost equally in dRLH-84 and GH3 cells. SK&F L-94901 also did not discriminate thyroid hormone receptors (TR) alpha1 and beta1 in terms of binding affinity and activation of the thyroid hormone responsive element. In intact cells, however, SK&F L-94901 was a more potent inhibitor of nuclear [(125)I]T(3) binding in dRLH-84 cells than in GH3 cells at an early phase of the nuclear uptake process and after binding equilibrium. These data suggest that SK&F L-94901 is more effectively transported to nuclear TRs in hepatic cells than in pituitary cells and therefore shows liver-selective thyromimetic activity. In conclusion, SK&F L-94901 discriminates hepatic cells and pituitary cells at the nuclear transport process. The cellular transporters responsible for this discrimination were not evident.

Animals↗

Chromogranin A expression in hepatocellular carcinoma in a patient with germline MEN1 gene mutation.

Hepatocellular carcinoma (HCC) was found in a patient with multiple endocrine neoplasia type 1 (MEN 1). The intriguing finding was that the HCC in the patient was positively stained for chromogranin A (CgA), a cellular marker for endocrine and neuroendocrine tumors. The patient had a pancreas endocrine tumor and type C hepatitis, that made pathological diagnosis of the origin of the tumor complicated.

Carcinoma, Hepatocellular↗

Cloning and characterization of a cDNA encoding serine palmitoyltransferase in Arabidopsis thaliana.

The first and committed step in de novo sphingolipid synthesis is catalysed by serine palmitoyltransferase (EC 2.3.1.50), which condenses serine and palmitoyl-CoA to form 3-ketosphinganine in a pyridoxal-5'-phosphate-dependent reaction. We have isolated and characterized a cDNA clone from Arabidopsis thaliana that is homologous to yeast and mammalian LCB2. For a functional identification, the A. thaliana homologous cDNA was expressed in Escherichia coli, which resulted in significant production of new sphinganine in E. coli cells.

Acyltransferases↗

1,25-Dihydroxyvitamin D3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells.

Very late antigen-4 (VLA-4) is the complex with alpha4 and beta1 integrins, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)2D3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha4 integrin is negatively regulated in the cell lines we studied. The expression of beta1 integrin is also decreased in HL-60 and U937 cells. The mRNA expression of alpha4 integrin is significantly decreased by the treatment with 1,25(OH)2D3, whereas 1,25(OH)2D3 does not alter the expression of beta1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1, 25(OH)2D3 is significantly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is highly expressed in the endothelial cells, it is possible that 1,25(OH)2D3 prevents the attachment of the cells from the endothelial cells in vivo.

Antigens, CD↗

Alkalinizing local anesthetic does not decrease pain during injection for dorsal penile nerve block.

STUDY OBJECTIVE: To evaluate whether alkalizing local anesthetic with sodium bicarbonate reduces pain related to infiltration of local anesthetic during dorsal penile nerve block for circumcision. DESIGN: Prospective, randomized, double-blind, controlled study. SETTING: E. Wolfson Medical Center, Holon, Israel. PATIENTS: 144 patients aged 15 to 54 years (mean +/- SD = 22.7 +/- 8.8 years), randomized before the block into four groups of 36 patients each. INTERVENTIONS: Group A (control) received a standard solution of 1 mg/kg lidocaine 2% mixed with 0.5 mg/kg bupivacaine 0.5% without epinephrine (pH = 6.3). Patients in Group B, Group C, and Group D received this mixture added with 8.4% sodium bicarbonate for a mean final pH of 6.90, 7.16, and 7.43, respectively. Penile block was performed using a 23-gauge needle by an anesthetist who was blinded to the pH of the solution. MEASUREMENTS AND MAIN RESULTS: Patients were questioned regarding pain suffered during injection of the anesthetic solutions by another physicians who also was blinded to the drug used. Pain was rated by a previously reported subjective pain scale. Mean pain scales were 2.0 +/- 0.17, 2.3 +/- 0.15, 2.2 +/- 0.16, and 1.94 +/- 0.15 for Groups A to D, respectively. The differences between these results were not statistically significant. CONCLUSION: Alkalinizing the acidic local anesthetic solution by sodium bicarbonate does not decrease pain related to infiltration during penile nerve block for circumcision.

Adolescent↗

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗

Atypical Wegener's granulomatosis with positive cytoplasmic antineutrophil cytoplasmic antibodies, ophthalmologic manifestations, and slowly progressive renal failure without respiratory tract involvement.

A 68-year-old woman had microscopic hematuria and proteinuria since the age of 50. She also had hearing impairment, arthralgia, retinal embolism, peripheral arterial occlusion of the right foot and chronic renal failure during the course. At the age of 68, she had progressive renal failure and nephrotic syndrome with high titers of serum cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). No evidence of respiratory tract involvement was found. Methylprednisolone pulse therapy and low dose cyclophosphamide therapy ameliorated the renal failure and reduced the serum c-ANCA level. She, however, died on July 19, 1998 due to pulmonary fungal and pneumocystis carinii infection.

Aged↗

Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P < 0.05) to 191 +/- 3 and 222 +/- 3 d, respectively, compared with 264 +/- 11 d in control bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

Anestrus↗

An epidemiological study of postviral olfactory disorder.

Postviral olfactory disorder develops after infection with the common cold, and is a relatively severe and prolonged disorder without rhino-sinusitis. This epidemiological study aimed to characterize its clinical pathology and determine the causative virus. Postviral olfactory disorder occurs most commonly in middle-aged women and is most prevalent in spring and summer. A comparison of the monthly frequency of the disorder with the incidence of isolation of various viruses suggest that the influenza virus, respiratory syncytial virus, and herpes virus are not causative viruses, while parainfluenza virus type 3 is most likely to be a causative virus. This conclusion is supported by immunological study and analysis of symptoms of the cold. All patients with postviral olfactory disorder had increased serum antibody titre for parainfluenza virus type 3. No prominent or specific symptoms of common cold were identified as a potential trigger of this syndrome in patient questionnaires.

Adult↗

Effect of zinc sulfate on sensorineural olfactory disorder.

We administered zinc sulfate to patients with sensorineural (post-viral, post-traumatic, or unknown aetiology) olfactory disorder and examined its effects. The patients were divided into three groups by method of treatment: zinc sulfate only, combination of zinc sulfate and the usual therapy, or the usual therapy. For disorders of post-viral and unknown aetiologies, there were no significant differences in improvement among the three groups. However, for post-traumatic olfactory disorder, the zinc sulfate groups had significantly higher improvement rates than did the group that received the usual therapy. The difference between post-traumatic and post-viral olfactory disorders in the effect of zinc sulfate therapy appeared to depend on the pathology of the associated lesions. In cases of post-traumatic olfactory disorder, regenerative capacity is retained in the olfactory epithelium because the blast cells of olfactory receptor cells remain intact. However, for post-viral olfactory disorder, the lack of olfactory receptor cells and blast cells due to viral infection results in loss of regenerative capacity. We also determined pre-treatment serum zinc concentrations in those patients who planned to be treated with zinc sulfate. Pre-treatment serum zinc concentration was not significantly related to improvement rates.

Craniocerebral Trauma↗

Efficacy of EMLA cream prior to dorsal penile nerve block for circumcision in children.

BACKGROUND: While circumcision may be performed solely with dorsal penile nerve block (DPNB), some painful steps in its use are skin needle penetration and infiltration of the anesthetic product. The objective of this study was to evaluate the efficacy of EMLA cream, prior to DPNB for circumcision in children. METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled study with 42 children undergoing circumcision with DPNB alone, as an ambulatory procedure. Overall efficacy of EMLA cream (Group A) during needle penetration and infiltration was assessed using a visual analog scale, compared with a placebo cream (Group B). Patients were asked to orally report any pain during skin needle penetration and infiltration of anesthetic, and were graded from 1 to 4 according to intensity of pain, as 1) none, 2) slight, 3) moderate, or 4) severe. The child graded the global discomfort of the entire procedure using the visual analog scale. RESULTS: When assessing needle penetration, none from Group A suffered any pain, whereas all from Group B suffered at least mild pain. Considering infiltration of the anesthetic, all children suffered at least slight-to-moderate pain. Based on the children's visual analog scale scores, EMLA cream has no beneficial effect for penile block. CONCLUSION: Since the dorsal penile nerves are located under the Buck's fascia, topical anesthesia may not reach them and other techniques may be necessary to anesthetize them. We found that although EMLA cream is efficient as a topical anesthesia during needle penetration for DPNB, it has no beneficial effect during infiltration.

Adolescent↗