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Biomedical subjects

T Ishimaru

Publications and source records attributed to T Ishimaru.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig.

The effects of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8, 9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2 , 1-g][1,7]naphthyridine-6,13-dione), a novel tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs were studied in comparison with those of anti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0.03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethane-anesthetized guinea pigs, but they decreased voiding pressure, although the effect of propiverine was not statistically significant. A structurally unique tachykinin NK(1) receptor antagonist, (+/-)-CP-99,994 ((+/-)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a minimum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the volume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties.

Animals↗
PubMed1999

Axially chiral 1,7-naphthyridine-6-carboxamide derivatives as orally active tachykinin NK(1) receptor antagonists: synthesis, antagonistic activity, and effects on bladder functions.

Cyclic analogues of N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1) having a 6-9-membered ring (6-9) were synthesized and evaluated for NK(1) antagonistic activities. The 8-membered ring compound with a beta-methyl group at the C((9))-position, (aR,9R)-7-[3, 5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione [(aR,9R)-8b], was atropodiastereoselectively synthesized by cyclization of a chiral intermediate, 10g. On the other hand, the 7-membered ring compound with a beta-methyl group at the C((9))-position [(9S)-7b] was obtained as an equilibrium mixture of atropisomers with a ratio of ca. 3:2 in solution at room temperature (measured by NMR in CDCl(3)). Compounds (9S)-7b and (aR,9R)-8b exhibited excellent antagonistic activities both in vitro [IC(50) (inhibition of [(125)I]BH-SP binding in human IM-9 cells) = 0.28 and 0.45 nM, respectively] and in vivo (iv and po). Significantly, the in vitro activity of (aR, 9R)-8b was ca. 750-fold higher than that of its enantiomer (aS, 9S)-8b, ca. 40-fold higher than its atropisomer (aS,9R)-8b, and ca. 20-fold higher than its diastereomer (aR,9S)-8b. The structure-activity relationships in this series, along with the X-ray analysis of (aR,9R)-8b, indicated that the stereochemistry around the -C((6))(=O)-N((7))-CH(2)Ar moiety is important for NK(1) receptor recognition. The NK(1) antagonists showed effects on bladder functions in guinea pigs upon intravenous injection: i.e., the antagonists increased the shutdown time of distension-induced rhythmic bladder contractions and the bladder volume threshold, and the effects on the shutdown time were found to correlate well with the NK(1) antagonistic activities. Compound (aR,9R)-8b has been identified as a potential clinical candidate for the treatment of bladder function disorders.

Animals↗
PubMed1999

TrkA expression in olfactory epithelium and bulb during development.

The purpose of the present study was to examine immunohistochemically the expression of high-affinity nerve growth factor receptor (trkA) in the olfactory nervous system of developing mice and of colchicine-treated adult mice. Olfactory epithelia of embryos and neonates showed trkA immunoreactivity not only in basal cells but in receptor cells, with trkA-immunoreactive olfactory nerve fibers in the subepithelium and the bulb. In adults, trkA immunoreactivity was found only in basal cells of olfactory epithelia. Olfactory epithelia of colchicine-treated adult mice, however, exhibited appearance of trkA-immunoreactive receptor cells and increased trkA immunoreactivity in olfactory nerve fibers. These findings indicate that expression of trkA continually occurs in the olfactory nervous system during life and that trkA can be highly expressed during development.

Animals↗
PubMed1999

Repeat-directed isolation of a novel gene preferentially expressed from the maternal allele in human placenta.

Using a repetitive sequence of tandemly arrayed pentanucleotides in the human H19 3'-flanking region, we isolated a phage clone (lambda PEN11) which localized to chromosome 11p15.5. The lambda PEN11 phage encodes a 2.3-kb cDNA consisting of seven exons at least. The gene was mainly expressed in brain and pancreas (and less abundantly in testis), and demonstrated differential allele usage, with maternal expression being predominant in placenta, which indicates the gene is an atypical imprinted gene. While the pentamer repeat might contribute to this effect, it is also possible that the differential allele usage might reflect the local chromosomal structure known as the imprinting domain.

Alleles↗
PubMed1999

Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography.

OBJECTIVE: The aim of the study was to determine the utility of ultrasonographically recorded blood flow waveforms of the pulmonary artery in the diagnosis of pulmonary hypoplasia. STUDY DESIGN: The normal values of the pulsatility index and peak systolic flow of pulmonary arterial blood velocity waveforms were determined in 300 uncomplicated single fetus pregnancies with well-established gestational ages between 24 and 40 weeks. We also measured the same parameters in 5 fetuses at high risk for development of severe pulmonary hypoplasia. We also determined the radial alveolar count and microvessel density, representing the extent of angiogenesis, in tissue specimens collected at autopsy from normal and hypoplastic lungs and stained both with hematoxylin and eosin and immunohistochemically for factor VIII. RESULTS: In healthy fetuses the pulsatility index values of both the right and left pulmonary arteries diminished significantly with advancing gestation, whereas the peak systolic velocity increased significantly with advancing gestation. In fetuses with pulmonary hypoplasia pulsatility index values were high and the peak systolic flow was significantly lower than in healthy fetuses. Histologic examination showed a lower radial alveolar count and poorer angiogenesis in fetuses with pulmonary hypoplasia than in healthy fetuses. CONCLUSION: Doppler ultrasonographic determination of pulmonary artery blood velocity waveforms is a useful tool for the diagnosis of pulmonary hypoplasia.

Blood Flow Velocity↗
PubMed1999

Virtual arthroscopy of the visible human female temporomandibular joint.

PURPOSE: This study was designed to obtain views of the temporomandibular joint (TMJ) by means of computed arthroscopic simulation (virtual arthroscopy) using three-dimensional (3D) processing. MATERIAL AND METHODS: Volume renderings of the TMJ from very thin cryosection slices of the Visible Human Female were taken off the Internet. Analyze(AVW) software (Biomedical Imaging Resource, Mayo Foundation, Rochester, MN) on a Silicon Graphics 02 workstation (Mountain View, CA) was then used to obtain 3D images and allow the navigation "fly-through" of the simulated joint. RESULTS: Good virtual arthroscopic views of the upper and lower joint spaces of both TMJs were obtained by fly-through simulation from the lateral and endaural sides. It was possible to observe the presence of a partial defect in the articular disc and an osteophyte on the condyle. Virtual arthroscopy provided visualization of regions not accessible to real arthroscopy. CONCLUSION: These results indicate that virtual arthroscopy will be a new technique to investigate the TMJ of the patient with TMJ disorders in the near future.

Arthroscopy↗
PubMed1999

MR imaging of the temporomandibular joint: a validation experiment in vitro.

RATIONALE AND OBJECTIVES: The authors compared magnetic resonance (MR) image quality obtained from 3- and 1-mm-thick sections in the depiction of the temporomandibular joint (TMJ) and its adjacent structures. MATERIALS AND METHODS: Eight TMJ specimens from four adult cadaver heads were depicted with MR imaging. Both 3- and 1-mm-thick sections were generated. One oral and maxillofacial radiologist, who was blinded to section thickness, evaluated the anatomic details of the images. Subsequently, the joints were surgically explored by two oral and maxillofacial surgeons, and the physical findings were recorded. RESULTS: Some statistically significant differences were found between the physical findings and the 3-mm-thick section images, while no significant differences were found with the 1-mm-thick sections. CONCLUSION: The TMJ and its adjacent structures were better depicted by thinner MR images.

Aged↗
PubMed1999

Reversible hyposmia caused by intracranial tumour.

Two patients with hyposmia caused by an intracranial tumour recovered olfactory functions after craniotomy. The first case was a 68-year-old male with a tumour metastasized from the lung to the right frontal lobe. The second case was a 75-year-old male with meningioma of the right frontal lobe. Results of T & T olfactometry and venous olfaction tests also indicated suspected central hyposmia. Magnetic resonance imaging (MRI) indicated compression of the frontal lobe by intracranial tumour. Pressure on the olfactory centre located in the frontal lobe produced hyposmia. Decompression of the frontal lobe by craniotomy improved the sense of smell. Therefore, some cases of olfactory disturbance caused by intracranial tumour may be reversible if they are the result of simple compression of the olfactory centre.

Aged↗
PubMed1999

Methylation imprinting of H19 and SNRPN genes in human benign ovarian teratomas.

In humans, studies of female germ cells are very limited by ethics. The current study investigated the usefulness of benign ovarian teratomas as a substitute for ova in analyses of imprinted genes. Twenty-five human benign ovarian teratomas were typed with 45 microsatellite DNA markers and classified according to their genotypic features. Two oppositely imprinted genes, H19 and SNRPN, were then chosen for analysis of their methylation states in these tumors. These analyses revealed that benign ovarian teratomas consist of a mixture of genetically and epigenetically heterogeneous cell populations. In contrast to previous reports, we could document only one case rising from germ cells by meiosis-II nondisjunction. H19 and SNRPN were methylated in individual teratomas to various degrees, ranging from normal somatic cell to expected ovum levels. The allele with residual methylation of H19 was consistent with that methylated in the patient's blood DNA, thus being of paternal origin. Degrees of H19 hypomethylation and SNRPN hypermethylation increased as the cellular origin of the tumors advanced in oogenesis and were closely correlated in individual teratomas. These results could be best explained by the assumption that the primary imprinting is a progressively organized process and suggest that the establishment of primary imprints on different genes might be mechanistically linked, even when those genes are oppositely imprinted.

Autoantigens↗
PubMed1999

Immunohistochemical study of angiogenic factors in endometrium and endometriosis.

The proliferative activity and angiogenic factors of pelvic endometriosis and uterine endometrium and their correlation with different pigmented lesions are important throughout the menstrual cycle. The proliferative activity and/or expression of angiogenic factors appears to be different between endometrium and endometriosis, and also different in each pigmented lesion. Immunohistochemical studies using computerized image analysis have shown that in normal endometrium, the PCNA index shows cyclic variation, but no cyclic change is observed in endometriosis. In the pelvic peritoneum, the PCNA index is higher in red lesions compared to black and white lesions. There is no difference in VEGF expression among different pigmented lesions. However, a cyclic variation of VEGF concentration was found in the peritoneal fluid of patients with endometriosis. As a newly determined angiogenic factor, the number of endoglin-positive cells and the mean endothelial area were higher in red lesions than in black or white lesions. These results suggest that the pathogenesis and activity of endometriosis possibly depends on internal angiogenesis. The cellular activity of endometriotic lesions may not necessarily coincide with the regulation of angiogenesis, and may not be synchronized in each pigmented pelvic lesion of endometriosis. Copyrightz1999S.KargerAG, Basel

Adult↗
PubMed1999

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

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

Adult↗
PubMed1999

The SHAP-HA complex in sera from patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To investigate serum derived hyaluronan (HA) associated protein-hyaluronan (SHAP-HA) complex in sera from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and determine levels of the complex in comparison with those of hyaluronan (HA), in order to assess the role of the complex as an indicator of joint inflammation. METHODS: ELISA and HA binding assays were used for quantitation of the SHAP-HA complex and HA levels in serum samples from 142 patients (114 with RA, 28 with OA) and 31 healthy controls. Clinical evaluations were also performed. RESULTS: In some RA sera, SHAP-HA complex levels were extremely high compared to control levels, but in OA sera no marked increase was observed compared to controls. This was also the case with the HA levels compared between RA and OA sera. However, in RA the levels of the SHAP-HA complex appear to be more related to clinical variables than are levels of HA, and the most significant correlations between levels of SHAP-HA complex and HA were found in the RA group. CONCLUSION: Quantitation of the SHAP-HA complex in sera may be useful as a joint marker that directly correlates to the degree of joint inflammation in RA, and offers new insight into the pathogenesis of arthritis. It may also serve as an independent criterion in the subsequent classification of RA and OA.

Adult↗
PubMed1999

[Bronchocutaneous fistula after treatment for breast cancer: a case report].

We describe a case of bronchocutaneous fistula that developed after surgery and radiotherapy for breast cancer. A 69-year-old woman presented with fever and the leakage, on expiration, of bubbles from a site on the left chest wall where a Halsted mastectomy and radiotherapy (60 Gy) had been performed 19 years earlier. Computed tomography and magnetic resonance imaging revealed a fistula bridging a bronchus and the skin. Repeated biopsies of the fistula failed to disclose any malignancy. The fistula closed after treatment with antibiotics, and has remained closed for 9 months, as disclosed by identical tomographic images. The paucity of literature describing the diagnostic imaging of bronchocutaneous fistula prompted this report.

Aged↗
PubMed1998

Axially chiral N-benzyl-N,7-dimethyl-5-phenyl-1, 7-naphthyridine-6-carboxamide derivatives as tachykinin NK1 receptor antagonists: determination of the absolute stereochemical requirements.

A potent and orally active NK1 antagonist, trans-N-[3, 5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N, 7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1t), was shown to exist as a mixture of separable and stable (R)- and (S)-atropisomers (1t-A and 1t-B) originating from the restricted rotation around the -C(6)-C(=O)- bond; the antagonistic activities of 1t-A were ca. 6-13-fold higher than those of 1t-B. Analogues of 1t (3), which have (S)- and (R)-methyl groups at the benzylic methylene portion of 1t, were prepared and separated into the diastereomeric atropisomers, 3a-A, 3a-B and 3b-A, 3b-B, in enantiomerically pure forms. Among the four isomers of 3, the (aR, S)-enantiomer (3a-A) exhibited the most potent antagonistic activities with an IC50 value of 0.80 nM (in vitro inhibition of [125I]BH-SP binding in human IM-9 cells) and ED50 values of 9.3 micrograms/kg (iv) and 67.7 micrograms/kg (po) (in vivo inhibition of capsaicin-induced plasma extravasation in guinea pig trachea), while the activity of the (aS,R)-enantiomer (3b-B) was the weakest with an IC50 value of 620 nM. The structure-activity relationships in this series of antagonists indicate that the (R)-configuration at the axial bond and the stacking (or stacking-like) conformation between the two phenyl rings as shown in 1t-A and 3a-A are essential for high-affinity binding and suggest that the amide moiety functions as a hydrogen bond acceptor in the interaction with the receptor.

Administration, Oral↗
PubMed1998

Retrograde transport of nerve growth factor from olfactory bulb to olfactory epithelium.

NGF is produced in the olfactory bulb and transported from the bulb to cholinergic neurons in the horizontal limb of the diagonal band. Although the expression of NGF receptors has been reported in olfactory epithelial cells, no correlation between NGF and olfactory epithelial cells has been found. This study aimed to define whether or not retrograde transport of NGF occurs in the olfactory neural system using the method of radioluminography. 125I-labeled NGF injected into the olfactory bulb was taken up and transported to the olfactory epithelium 18 h after injection. This finding suggests that bulbar NGF may act as a neurotrophic factor in olfactory epithelial cells.

Animals↗
PubMed1998

A HhaI/BstUI polymorphism in a novel gene at human chromosome 11p15.5.

We found a HhaI/BstUI polymorphism in the 3' untranslated region of a novel gene which was localized to 11p15.5. This region is one of prominent imprinting domains and contains multiple imprinted genes, such as H19, IGF2, KVLQT1, and p57KIP2, which suggests that regional factors might contribute to the imprinting. This polymorphism will be useful in the allelic analysis of expression and methylation of the novel gene.

Alleles↗