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Biomedical subjects

S Hirano

Publications and source records attributed to S Hirano.

At least 19 recordsLinked to original sources

Morphological analysis of the early development of the chick neural tube separated from the floor plate and notochord.

When the neural tube of avian embryos is separated from the notochord and floor plate, motoneurons in the spinal cord fail to develop. In order to investigate the factors involved in this phenomenon, cell proliferation activity and cell death were observed following paramedian incision of the neural tube at the level of the segmental plate using colchicine, BrdU, and TUNEL methods. If the notochord and/or floor plate produces a substance(s) that promotes cell division in the basal plate neuroepithelium or that supports the survival of the motoneuron's neuroblasts, mitotic figures should not be present in the neuroepithelium nor should substantial cell death be observed in the ventral aspect of the notochord- and floor plate-deprived neural tube. Surprisingly, however, neither result was observed in the present experiments, with the exception of a considerable amount of homogeneously distributed cell death. Neuroepithelial cells continued to proliferate and gave rise to neuroblasts. Nevertheless, motoneurons failed to develop, and the neural tube was enveloped by only the basement membrane of the alar plate (S. Hirano and H. Tanaka, 1994, Dev. Growth Differ: 36, 481-488). These morphological results revealed that the cause of the development of the anterior horn lacking a neural tube in the notochord- and neural tube-eliminated embryos is not the elimination of the source of the surviving factor(s) of the motoneuron's neuroblasts, but rather the elimination of the signals to induce the motoneurons, derived from the notochord and/or floor plate. The larger amount of cell death in the neural tube on the experimental side suggests that a nonspecific survival factor(s), necessary for the survival of a variety of types of neuroblasts, is also produced by the notochord and/or floor plate.

Animals

Solitary mastocytoma treated with tranilast.

Two infants with solitary mastocytoma were treated with 5 mg/kg/day of tranilast [N-(3',4'-dimethoxycinnamoyl)anthranilic acid], a mast cell stabilizing compound extracted from Nandina domestica. Tranilast was administered orally in three divided doses. In one infant, a topical corticosteroid was also applied in combination with the oral tranilast. Patients experienced symptomatic relief, and nodules resolved almost completely after eight weeks of treatment. Tranilast therapy was continued for six months. No relapses were observed after discontinuation of therapy. We speculated that tranilast not only inhibited mast cell degranulation but also reduced the number of mast cells.

Cell Degranulation

Vocal fold atrophy and its surgical treatment.

The effectiveness of surgical treatment for vocal fold atrophy of various causes was examined. Type I thyroplasty was performed on 31 patients with vocal fold atrophy, often bilaterally and occasionally combined with type III thyroplasty. Of these 31 patients, 3 patients underwent the operation twice, for a total of 34 operations. The surgery was found to be effective in improving the voice quality and the ease of phonation. When a scar or sulcus was present, the results were not as satisfactory. The intraoperative decision-making process as to which procedure to perform is extremely important for achieving an optimal voice, and should be based on the intraoperative voice quality, fiberoptic findings, and manual tests. In operations for vocal fold atrophy in which the vocal folds are mobile, a silicone shim should be firmly fixed to prevent migration. Overcorrection is generally recommended. No complications were encountered. It was often the increased ease of phonation rather than the improved voice quality that patients appreciated after surgery.

Adult

Omohyoid muscle transposition for the treatment of bowed vocal fold.

Imperfect glottal closure is usually the most important factor causing dysphonia in patients with bowing of the vocal folds. We have performed laryngeal framework surgery, which allows the medialization of the vocal folds from the outside without creating any scar tissue on them. Over the past 6 years, however, we encountered three cases with marked bowing of the vocal folds that could not be cured by laryngeal framework surgery alone. We used an open laryngeal procedure in these cases, even though such procedures had been considered contraindicated in the treatment of hoarseness. After performing a laryngofissure, we made a small pocket beneath the vocal fold mucosa at the anterior commissure. The superiorly based omohyoid muscle flap was then transposed into the mucosal pocket and sutured to the vocal process. This procedure should be considered an option in treating highly bowed vocal folds.

Adult

Early detection of prostate cancer. Results of a prostate specific antigen-based detection program in Japan.

BACKGROUND: Prostate cancer increasingly is becoming a medical problem in Japan. To maximize the chance for cure, extensive effort is being made to detect prostate cancer while confined to the gland. METHODS: Determination was made of serum prostate specific antigen (PSA) in the early detection of prostate cancer in an Asian male population aged 55 years or older. Recommendation for biopsy was based solely on this parameter when its value exceeded 2.0 ng/ml in IMx immunoenzymetric assay. RESULTS: Of 1189 men, 150 (12.6%) had elevated values. The proportion of males with serum PSA greater than 4.0 ng/ml was only 3.4%. Of the 99 males who underwent ultrasound-guided biopsies, 16 cancers were detected, a cancer detection rate of 1.3%. Most of these (81.3%) were clinically localized cancers. Seven patients with cancer had serum PSA levels below 4.0 ng/ml including 5 less than 3.0 ng/ml. These tumors would have been overlooked if the conventional cutoff levels of 4.0 ng/ml had been applied. Radical prostatectomy was conducted on 13 patients. All had histologic features of clinically significant cancer and 69.2% were pathologically confined within the gland. CONCLUSIONS: Elderly Asian males appear to have lower serum PSA than their Western counterparts. The optimal cutoff of serum PSA for early detection should be examined further in Asian male populations. Differences in the incidence of prostate cancer between ethnic groups may have been overestimated in previous studies owing in part to unawareness by the physician and general public. Though the frequent use of more sophisticated diagnostic modalities will likely disclose greater numbers of prostate cancers in Japan, whether early detection reduces mortality by minimizing risk of death from cancer remains a point to be determined.

Aged

Altered expression and function of E-cadherin in cervical intraepithelial neoplasia and invasive squamous cell carcinoma.

HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium-dependent cell-cell adhesion molecule, in microwave-treated, paraffin-embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C4I, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative cell line which showed a significant degree of cell-cell aggregation. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer.

Blotting, Western

Effects of gadolinium chloride on the rat lung following intratracheal instillation.

The metabolic behavior, clearance, and pulmonary effects of gadolinium (Gd), one of the rare earth elements, were investigated after single intratracheal instillation of gadolinium chloride (GdCl3) in male Wistar rats. There was a dose-related increase in Gd content of lung tissue. Gd content in the supernatant of bronchoalveolar lavage fluid (BALF) did not exceed 5 micrograms Gd/BALF even at a dose of 100 micrograms Gd/rat. Gd in the lung tissue decreased very slowly with a biological half-life of 136 days at a dose of 50 micrograms Gd/rat. On the other hand, Gd content in the supernatant of BALF was not detectable after 31 days. These results suggest that intratracheally instilled Gd can be retained in epithelial lining fluid only to a limited extent as soluble forms and is deposited in the lung tissue probably in insoluble forms which are metabolized very slowly. Calcium (Ca) content in BALF increased more rapidly than other toxicological indices such as lactate dehydrogenase activity, protein concentration, and inflammatory cell counts. In the lung tissue, levels of Ca in Gd-instilled groups did not differ from the control value. Although these data suggest that the origin of Ca may be blood plasma, biological and/or toxicological significance of increased Ca is not known. The number of neutrophils reached the maximum at 12 hr after instillation, indicating that Gd has the potency to cause acute lung toxicity. Summarizing the observation, Gd instilled intratracheally into rats was deposited in the lung tissue in nonsoluble forms with an extremely long half-life, while the metal caused a rapid and selective infiltration of serum Ca before acute lung toxicity.

Animals

Morphological analysis of the role of the neural tube and notochord in the development of somites.

The differentiation of avian somites and skeletal muscles, which themselves are derived from somites, was studied in ovo after the isolation of the unsegmented segmental plate from the notochord and/or neural tube by surgical operations at the level of the segmental plate. In each experiment, the newly formed somites had a normal histological structure, with an outer epithelial somite and core cells in the somitocoeles. Thereafter, the three derivatives of the somites (dermatome, myotome and sclerotome) reacted differently to the different operations. When the somites developed without the notochord, only somitocoele cells showed massive cell death, and muscles developed regardless of the presence or absence of the neural tube. On the contrary, no cell death was observed in any part of the somites that were formed with the neural tube or the notochord present, and muscle cells developed. However, in those embryos that retained only the notochord, striated muscles developed only in the lateral body wall. In each of the experimental operations, the surface ectoderm always covered the somites, and, regardless of the state of sclerotome and/or myotome differentiation, the dermatome always survived. These histological observations indicate that the first step in somite formation is independent of axial structures. The results further suggest that the notochord may produce diffusible factors that are necessary for the survival and further development of sclerotomal cells, and that both the neural tube and notochord can support muscle differentiation. However, it is likely that each structure has a relationship to the development of epaxial muscles and hypaxial muscles respectively. Furthermore, an intimate relationship may also exist between the surface ectoderm and the development of the dermatome.

Animals

Establishment of normal values for flash visual evoked potentials (VEPs) in preterm infants: a longitudinal study with special reference to two components of the N1 wave.

To establish normal values for flash visual evoked potentials (VEPs) in the preterm period, we analyzed 356 records from 63 neurologically normal infants (26-35 weeks gestation) followed longitudinally. Using both sleep and drowsy state recording within the same session and a mean of 5.7 weekly recording sessions per infant, we hypothesized that the prominent negative wave (N1) consisted of 2 negative components, N1a (early) and N1b (late). This hypothesis could explain the previously reported variability in VEP indices. With a precise definition of the N1a peak, we were able to establish reference ranges for N1a peak latencies at various postmenstrual ages (PMA) which, unlike those previously reported, are narrow enough to be clinically useful. From a cross-sectional analysis we found that the N1a peak latency decreased with maturation at about 4.6 msec/week between 30 and 40 weeks PMA (P < 0.001). We also analyzed the N1 wave form and demonstrated its developmental maturation during this period. There were significant decreases in the amplitudes of both the N1a and N1b peaks with maturation (P < 0.001), but the decrease of the N1a amplitude was steeper than that of N1b. The N1 wave form changed from a wave in which the early peak (N1a) was higher than the late peak (N1b) into the reverse with N1b higher than N1a. This wave change may be related to developmental processes in the visual system. Longitudinal follow-up revealed that extra-uterine life may accelerate the maturation of the N1 wave form but has no effect on the decrease of the absolute values of peak latencies.

Electroencephalography

Effects of pirarubicin in comparison with epirubicin and doxorubicin on the contractile function in rat isolated cardiac muscles.

1. We have examined the effects of pirarubicin (THP), compared with epirubicin (EPI) and doxorubicin (DXR), on the contractile function in papillary muscles isolated from rats. 2. In in vivo experiments, in which the rat was treated once a week for 4 weeks with DXR (total dose 10 mg/kg) and thereafter once a week for 4 weeks with THP, EPI or DXR (total dose 10 mg/kg), a positive instead of negative force-frequency relationship was observed in the muscles treated with EPI and DXR, but not with THP, and an increase in contractile response to extracellular Ca2+ was observed more markedly in the muscles treated with DXR than in those treated with EPI and THP. 3. In in vitro experiments, in which the muscle preparations were incubated with the drugs at 100 or 200 microM for 2 hr, EPI and DXR caused a negative inotropic effect and a prolongation of tension duration, while THP caused a slight positive inotropic effect and a slight prolongation of tension duration. 4. Furthermore, a decrease in the potentiated postrest contraction was observed more markedly in the muscles incubated with EPI and DXR at 200 microM than in those with THP. 5. These results suggest that both EPI and DXR show a cardiotoxicity by impairing the function of cardiac sarcoplasmic reticulum, and that the switching of the treatment from DXR to THP produces less impairing effects.

Animals

Cortical activation with sound stimulation in cochlear implant users demonstrated by positron emission tomography.

Six postlingually deaf patients using multi-channel cochlear implants were examined by positron emission tomography (PET) using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during different sound stimuli. The stimulation paradigms employed consisted of two sets of three different conditions; (1) no sound stimulation with the speech processor of the cochlear implant system switched off, (2) hearing white noise and (3) hearing sequential Japanese sentences. In the primary auditory area, the mean rCBF increase during noise stimulation was significantly greater on the side contralateral to the implant than on the ipsilateral side. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area (P < 0.01), the bilateral auditory association areas (P < 0.01), the posterior part of the bilateral inferior frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P < 0.05). Activation of cortices related to verbal and non-verbal sound recognition was clearly demonstrated in the current subjects probably because complete silence was attained in the control condition.

Acoustic Stimulation

Antitumoral efficacy and pharmacokinetic properties of pirarubicin upon hepatic intra-arterial injection in the rabbit V x 2 tumour model.

To improve the efficiency of hepatic intra-arterial (h.i.a.) chemotherapy, we selected pirarubicin (THP) because it shows good properties for h.i.a. chemotherapy, such as fast and efficient cellular uptake, and used it for h.i.a. chemotherapy in rabbits with V x 2 tumour implanted in the liver. The anti-tumour effect of THP upon h.i.a. administration was compared with that upon intravenous (i.v.) injection and also with the anti-tumour activity of epirubicin (EPI) upon h.i.a. injection using optimal and maximal tolerated doses of each drug. When tumour growth rates and morphometric examinations were evaluated, it was found that THP and EPI were effective against V x 2 tumour when injected via the h.i.a. route. The activity of THP was stronger than that of EPI. As regards h.i.a. injection-related complication, plasma transaminase levels were temporarily elevated. To demonstrate higher anti-tumour activity and other advantages of h.i.a. injection of THP, plasma and tumour drug concentrations were determined by high-performance liquid chromatography after THP or EPI was administered at an equal dose to the rabbit V x 2 model. Hepatic intra-arterial injection of THP accomplished a selective and higher uptake into the tumour and lower effusion into the plasma than i.v. injection of THP or h.i.a. injection of EPL. Our findings indicate that THP is the better candidate of the two drugs tested for the h.i.a. chemotherapy because of its greater anti-tumour activity and the lower systemic drug exposure achieved upon h.i.a. injection.

Animals

Low molecular weight chitosan stimulation of mitogenic response to platelet-derived growth factor in vascular smooth muscle cells.

Low molecular weight chitosan (LMWC) (a mixture of chitooligosaccharides with high degrees of polymerization; an average degree of polymerization is 6.8) stimulated mitogenic response to platelet-derived growth factor (PDGF) in a dose-dependent manner in cultured rat vascular smooth muscle cells, and a maximum effect was observed at 100 micrograms/ml. However, the mitogenic response was not induced when cells were incubated with LMWC alone. This stimulatory effect of LMWC on the mitogenic response to PDGF (a competence factor) appeared to resemble the effect of insulin as a progression factor. Chitooligosaccharides with higher degrees of polymerization were more effective, but D-glucosamine, chitobiose, and chitotriose were barely active. LMWC as well as PDGF induced protein tyrosine phosphorylation in vascular smooth muscle cells.

Animals

Microcirculatory segments identified with monoclonal antibody against alpha-smooth muscle actin: comparison between Kimura's disease and angiolymphoid hyperplasia with eosinophilia.

Microcirculatory systems, which can be divided into several segments, have crucial physiological functions. We investigated whether monoclonal antibody against alpha-smooth muscle actin (alpha SMA) was useful for the identification of microcirculatory segments, according to the structure of their periendothelial cells, in two pathological cutaneous conditions. We examined skin specimens from patients with Kimura's disease and with angiolymphoid hyperplasia with eosinophilia, since little information is available on microvascular segments in these conditions. Immunostaining for alpha SMA revealed the morphological characteristics of the periendothelial cells clearly enough to identify five segments in the proliferative microvessels of Kimura's disease and angiolymphoid hyperplasia with eosinophilia. In Kimura's disease, postcapillary venules were predominant, while each vascular segment in angiolymphoid hyperplasia with eosinophilia was uniform. Vessels without periendothelial cells were detected to a greater extent in angiolymphoid hyperplasia with eosinophilia than in Kimura's disease. The antibody against alpha SMA appeared to be useful in the observation of periendothelial cells for the identification of vascular segments in pathological cutaneous conditions.

Actins