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Biomedical subjects

T Hirose

Publications and source records attributed to T Hirose.

At least 469 records · Page 26Linked to original sources

Non-classical androgenic actions of RU38486 in androgen-responsive Shionogi carcinoma 115 cells in serum-free culture.

Antiglucocorticoid and antiprogestin RU38486 (RU486) stimulated the growth of highly androgen- and moderately glucocorticoid-sensitive SC-3 cells (a cloned cell line from Shionogi mouse mammary carcinoma 115) in a dose-dependent manner. A maximal 8-fold stimulation of growth by RU486 has been observed at 10(-7) M in a serum-free medium and its potency has been found to be almost the same as that of dexamethasone (Dex). The growth rate of SC-3 cells treated by triamcinolone acetonide (TA) or Dex combined with RU486 at 10(-9)-10(-7) M was enhanced compared to cells treated by TA or Dex alone, indicating that RU486 had additive rather than antagonistic effects. Our previous study revealed that RU486 could compete with the specific uptake of [3H]testosterone in intact SC-3 cells at relatively low affinity and the present study showed that the stimulatory effect of RU486 on the growth of SC-3 cells was significantly inhibited by pure antiandrogen flutamine and that half-maximal inhibition by flutamine was achieved at 10(-6) M. Moreover, we demonstrated that the conditioned medium from RU486-stimulated SC-3 cells contained growth-promoting activity which caused a 3.5-fold increase in DNA synthesis by SC-3 cells in the absence of RU486 and which was abolished by treatment with heparin-Sepharose. These results indicate that RU486-induced growth of SC-3 cells may be expressed as an androgenic activity through androgen receptor and mediated by a heparin-binding growth factor.

Animals↗

Functional abnormality of glucocorticoid receptor in Shionogi carcinoma 115 cells as evidenced by gene transfer experiments.

The assay systems for steroid receptor functions in steroid-sensitive cells (SC-3 cells) were developed in which hormone-responsive element linked to a reporter gene [chloramphenicol acetyl transferase (CAT) gene] was transfected by the electroporation technique. Stimulation with androgen of SC-3 cells transfected with mouse mammary tumor virus promoter-CAT gene (MMTV-CAT) resulted in clear enhancement of CAT activity, whereas glucocorticoid required abnormally high concentrations to obtain significant stimulation. The simultaneous addition of glucocorticoid surprisingly inhibited androgen-induced CAT activity in SC-3 cells, whereas glucocorticoid and androgen acted together synergistically to activate CAT activity in T 47D cells. When SC-3 cells were cotransfected with the expression vector of human glucocorticoid receptor (GR) gene, inhibition with glucocorticoid of androgen-enhanced CAT activity was abolished. These results would suggest that SC-3 cells contain functionally abnormal GR.

Animals↗

Interleukin 5 up-regulates high-affinity interleukin 2 receptor expression by human resting peripheral T cells: a comparison with the effect of interleukin 4 on B cells.

The separate regulation mechanisms of cytokines on two classes of interleukin 2 receptors (IL-2R) on human peripheral T and B cells were analyzed by a flow cytometer using a double stain with IL-2R alpha (55 kilodalton Tac) and IL-2R beta (75 kilodalton mik beta 1, mik beta 3). Although the expression of IL-2R alpha by T cells was slightly enhanced by IL-2 and IL-4, expression of the beta chain was diminished by both cytokines. IL-5 by itself did not alter the expression of either IL-2R alpha or beta, but preculturing with IL-2 for 24 h followed by IL-5 for another 24 h induced an increase in IL-2R alpha expression and in simultaneous alpha/beta chain expression. Increased numbers of high-affinity IL-2R were confirmed by 125I binding assays. On B cells, IL-4 increased alpha, beta, and simultaneous alpha/beta chain expression, but IL-4-treated B cells did not show an increased number of high-affinity IL-2R.

B-Lymphocytes↗

Novel cerebroprotective agents with central nervous system stimulating activity. 2. Synthesis and pharmacology of the 1-(acylamino)-7-hydroxyindan derivatives.

In a continuous search for a novel cerebroprotective drug with a central nervous system (CNS) stimulating activity, a series of 1-(acylamino)-7-hydroxyindan derivatives has been synthesized and tested for its dual activities. The cerebroprotective activities of the compounds in this series were evaluated in terms of their effect on the survival of mice in hypoxic conditions (210 mmHg), and their CNS stimulating activities were examined by evaluating their promotional effects on the recovery from coma induced by cerebral concussion in mice. Several compounds prolonged the survival of mice in the hypoxic conditions at a dose of 30 mg/kg po. Four compounds in this series showed the CNS-stimulating effect at the same dose. Among them, 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4, 6-tetramethylindan (18, OPC-14117), which was active in the two tests with no side effect up to 500 mg/kg po daily for 2 weeks of administration to rats, was selected for preclinical investigations.

Animals↗

Undifferentiated carcinoma of the vulva mimicking epithelioid sarcoma.

We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma.

Aged↗

Lid margin reconstruction with an orbicularis oculi musculocutaneous advancement flap and a conchal cartilage graft.

A simple method to reconstruct the midlateral lid margin defect is described using an orbicularis oculi musculocutaneous advancement flap and a free conchal cartilage graft. This method is easy to perform not only in the lower eyelid, but also in the upper one, provides a natural gray line and a stable lid margin without postoperative eversion, and substitutes for the Leone and van Gemert procedure.

Adult↗

Congenital curved nail of the fourth toe.

Five cases of congenital curved nail of the fourth toe are reported. Patients included four males and one female; four cases were bilateral, and one was unilateral. There were no other significant associated anomalies of the extremities, and only the fourth toes were affected. The features of the deformity are a curved nail and hypoplasia of the soft tissue and bone of the distal phalanx of the fourth toe. This anomaly may be transmitted autosomally and is unique in that it may be of mesodermic origin.

Child↗

Tension lines of the auricular cartilage.

Utilizing Langer's technique for skin tension lines, we punctured the auricular cartilage of 10 human cadavers and 2 mature rabbits and 24 immature rabbits with a conical awl to determine their tension lines. Deformation of the holes into straight lines indicated the direction of maximum tension. A regular pattern was observed in adult rabbits and humans: Tension was at right angles to the long axis at the auricular base and parallel at the apex. This pattern was not present at birth, but developed at 1 to 2 weeks of age in rabbits. It is felt that these tension lines are responsible for the clinical results of auricular reconstruction. In children less than 1 week of age, tension lines are disorganized so that nonsurgical correction will be successful as long as hypoplasia is not present. In older children, correction will be successful when the deformity is parallel to the tension lines.

Animals↗

A rotational method of bilateral cleft lip nose repair.

Repairs of the bilateral cleft lip nasal deformity have focused on lengthening the lower columella by adding lip, nasal structure, or a piece of ear. In these methods, the raised true columella worsens the dorsal dislocation of the lateral crura of the alar cartilages and the lateral and dorsal displacement of the alar domes. We believe that lengthening the upper columella from above is more anatomic and reasonable than lengthening the lower columella. A method for reconstructing the upper columella by medial and ventral rotation of the dislocated alar domes is described. Figi's "flying bird" incision was extended to the columellar base along the nostril margin. Through this incision, the lower one-third of the nose, including the alae and nostril floors, was undermined widely. The inner layers, the nostrils, were freed from the surrounding tissues, except in the region of the columella and the septum, and rotated medially in the opposite direction of Cronin's technique. The resulting nasal shape, involving the columellar length and the concavity between the nasal tip and lateral ala, improved in 11 patients.

Adolescent↗

Reconstruction of the crus helicis in mild microtia using a preauricular tag.

A preauricular tag accompanying a mild microtia was utilized in reconstruction of the anterior aspect of the helix and the crus helicis. We believe that three-dimensional reconstruction of the crus helicis with a deep cymba conchae in microtia reconstruction is an important component in achieving a normal-looking auricle.

Child↗

Discrete association of CD3 and CD4 molecules in T-cell stimulation acting through the autologous mixed lymphocyte reaction and the CD3/T-cell receptor complex in human autoreactive T-cell clones.

To investigate autologous antigen recognition, we developed two autoreactive CD4+ T-cell clones, A2 and A10, maintained with non-T cells and IL-2. Autologous non-T-cell stimulation of the T-cell clones resulted in a decrease in cell surface expression of CD4, whereas the expression of CD2, CD3, and WT31 was unchanged. Activation of the autoreactive T-cell clones by cell surface binding anti-CD3 MoAb, as a specific antigen stimulator of the T-cell receptor complex, induced cell surface antigen comodulation of CD3, CD4, and WT31. These data suggest a discrete association of CD3 and CD4 molecules in T-cell stimulation, acting through the autologous mixed lymphocyte reaction and the CD3/T-cell receptor complex. PMA treatment resulted in concomitant down-regulation of CD3 and CD4 but calcium ionophore treatment did not. Thus, it appears that phosphorylation of CD3 leads to the down-regulation of surface antigens of CD4.

Antibodies, Monoclonal↗

Atypical primitive neuroectodermal tumors. Comparative light and electron microscopic and immunohistochemical studies on peripheral neuroepitheliomas and Ewing's sarcomas.

Recently, primitive neuroectodermal tumors (PNETs) have been shown to cover a wide spectrum of small round cell sarcomas, probably including some Ewing's sarcomas (ESs) and extraskeletal Ewing's sarcomas (EESs), in addition to classical peripheral neuroepitheliomas (PNs). In studies of small cell sarcomas, we found a group of undifferentiated tumors resembling PNETs with some features of neuroectodermal differentiation, but possessing areas of relatively large, pleomorphic cells. To clarify the nature of these tumors and their relationship to PNETs, we examined the variety of histological, immunohistochemical and ultrastructural features of 11 small cell sarcomas. Five of these tumors were composed of uniform, small round cells and were classified as PNs because of the presence of definite Homer-Wright rosettes and fibrillary processes. The presence of well developed neurite-like processes containing neurosecretory granules and immunoreactivities for various neural markers suggested that these PNs showed more advanced neuronal differentiation. Two tumors, with the classical features of ES, showed no ultrastructural evidence of neuronal differentiation, although only gamma-gamma neuron-specific enolase (NSE) positivity was detected. Four undifferentiated tumors with atypical features, included in this study as an atypical PNET group, showed certain neuroectodermal characteristics, such as ganglion cell differentiation, perivascular pseudorosettes, and gamma-gamma NSE reactivity. It is concluded from this study that PNETs may include small round cell tumors showing different degrees of neuro-ectodermal differentiation and some histological variations.

Adolescent↗

Effects of vasoactive intestinal polypeptide antagonists on cholinergic neurotransmission in dog and cat trachea.

1. The effects of vasoactive intestinal polypeptide (VIP) antagonists [AC-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were investigated by use of microelectrode, double sucrose-gap and tension recording methods. 2. In the dog trachea, repetitive stimuli at high frequency (20 Hz) markedly enhanced the amplitude of contraction, the amplitude of contractions evoked by 50 stimuli at 20 Hz relative to that evoked by 5 stimuli being 14.2 +/- 3.8 times (n = 7, +/- s.d.). In the cat, the summation was much less marked, the amplitude of contractions evoked by 50 stimuli relative to that evoked by 5 stimuli being only 2.1 +/- 0.6 times (n = 5, +/- s.d.). Neither VIP antagonist had any effect on the relationship between the number of stimuli at 20 Hz and the relative amplitude of contraction in the dog trachea, but did enhance the amplitude of contractions to 1.1-1.5 times control in the cat trachea. 3. VIP antagonists dose-dependently enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single stimulus in the cat trachea, without changing the resting membrane potential or input membrane resistance of the smooth muscle cells. However, neither antagonist had any effect on the amplitude of the e.j.p. in the dog trachea. 4. Neither VIP antagonist had any effect on the post-junctional response of smooth muscle cells to exogenously applied acetylcholine (ACh; 10(-9)-10(-5) M) in the dog or cat trachea.5. In the cat trachea, VIP (10-11 M) suppressed the ej.p. amplitude to 0.74 +/- 0.09 times the control value (n = 6). However, after pretreatment of the tissue with the VIP antagonists [Ac-Tyr', D-Phe2]-GRF(1-29)- H2 (10-8M) and [4-Cl-D-Phe6, Leu17]-VIP (10-8M), VIP (10-11 M) did not suppress the ej.p. amplitude, indicating that VIP antagonists block the presynaptic inhibitory action of exogenous VIP.6. In parallel with the enhancement of contraction, ej.ps showed marked summation when repetitive field stimulations were applied at high frequency (20 Hz) in the dog trachea. The relationship between the relative amplitude of the ej.p. and number of stimuli at 20 Hz was linear and the slope was 2.2 +/- 0.3 mV/stimulation. VIP antagonists did not affect this relationship. However, in the cat trachea, summation of ej.ps was not at all marked and a linear relationship was not observed with the double sucrose-gap method. Incubation of the cat tracheal tissue with either of the VIP antagonists (10-8 or 10-7M) markedly enhanced the summation of ej.ps evoked by repetitive field stimulation at 20 Hz, and after the treatment a linear relationship between the number of stimuli and the amplitude of ej.ps was observed, the slopes being 0.6 +/- 0.1 (n = 8) and 0.55 +/- 0.1 mV/stimulation (n = 5), respectively.7. These results indicate that both VIP antagonists, [Ac-Tyr', D-Phe2]-GRF(1-29)-NH2 and [4-Cl-DPhe6, Leu17]-VIP, have a prejunctional action accelerating the excitatory neuroeffector transmission, presumably by enhancing transmitter release from the vagus nerves in the cat, but not in the dog trachea.

Acetylcholine↗

Best's macular dystrophy with a macular hole.

The occurrence of a macular hole with Best's dystrophy is an extremely rare finding with only one reported case in the literature. We wish to report two cases with typical Best's dystrophy in one eye and a macular hole in the contralateral eye. In one case the Pattern Reversal VER (PVER) was also recorded and graphed as an amplitude-check size function curve. The PVER changes in this case were grossly subnormal in both the eyes, suggesting a significant degree of bilateral macular impairment. This implies that a significant amount of functional impairment occurs at the vitelliform stage itself, though how this stage progresses to a macular hole is unclear.

Adult↗

Gyrate atrophy of the choroid and retina in a 5-year-old girl.

A 5-year-old Asian-Indian female presented with bilateral cobblestone-like peripheral lesions, a single area of chorioretinal atrophy, infero-nasal to the disc, in her right eye and a non-recordable single flash ERG. Serum ornithine level was assayed at 841 mumol/l, ten times normal levels, and a diagnosis of gyrate atrophy, due to ornithine aminotransferase deficiency was made. The patient was refractory to any form of therapy and her clinical lesions spread rapidly in both eyes, showing both centrifugal and centripetal spread in her right eye. A rapid deterioration in her psychophysical tests was also seen over the 28 months follow-up. The presence of cobblestone-like peripheral lesions in a child should alert the clinician to the possibility of gyrate atrophy, and the rapid spread of the chorioretinal lesions coupled with non-recordable single flash ERGs, in a young patient may suggest a much poorer prognosis.

Child, Preschool↗

Retinal function in birdshot retinochoroidopathy.

The electroretinograms (ERGs) of 15 patients with birdshot retinochoroidopathy varied from super-normal to non-recordable, depending upon the severity and the stage of the disease. The abnormal ERGs were characterized by a disproportionate decrease of the b-wave amplitude compared with the a-wave amplitude, demonstrating the negative (-) type response. This distinct ERG pattern has not been observed in any other type of uveitis or chorioretinitis, and appears specific to birdshot retinochoroidopathy. ERG findings indicate that in birdshot retinochoroidopathy the neural layers of the retina are more diffusely and severely involved than the receptor-retinal pigment epithelium-choroid complex. In the most advanced stage, the patients becomes night blind with a non-recordable ERG, a situation that is essentially the same as retinitis pigmentosa, except that pigmentation is conspicuously absent in the fundus.

Adult↗