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Biomedical subjects

M Sone

Publications and source records attributed to M Sone.

At least 19 recordsLinked to original sources

GAL4/UAS-WGA system as a powerful tool for tracing Drosophila transsynaptic neural pathways.

Visualization of specific transsynaptic neural pathways is an indispensable technique for understanding the relationship between structure and function in the nervous system. Here, we demonstrate the application of the wheat germ agglutinin (WGA) transgene technique for tracing transsynaptic neural pathways in Drosophila. The intracellular localization of WGA was examined by immunoelectron microscopy. WGA signals were detected in granule-like structures in both the outer photoreceptor cells expressing WGA and the second-order laminar neurons. Misexpression of tetanus toxin (TNT), which inactivates N-synaptobrevin, in the outer photoreceptor cells resulted in the elimination of on/off transients in electroretinogram (ERG) recordings and in a great reduction in WGA transfer into laminar neurons, suggesting that anterograde WGA transsynaptic transfer is dependent mainly on synaptic transmission. Retrograde WGA transfer was also detected upon its forced expression in muscle cells. WGA primarily expressed in muscle cells was taken up by motoneuron axons and transported to their cell bodies in the ventral nerve cord, suggesting that WGA can trace motoneuronal pathways in combination with the muscle-specific GAL4 driver. Thus, the GAL4/UAS-WGA system should facilitate the dissection of the Drosophila neural circuit formation and/or synaptic activity in various regions and at various developmental stages.

Animals↗

Histopathologic features of the temporal bone in patients with cystic fibrosis.

OBJECTIVES: To investigate the lower than expected incidence of otitis media in patients with cystic fibrosis (CF) through histopathologic evaluation of temporal bones and to document pathologic findings in the inner ears of patients with CF who received long-term administration of antibacterial and diuretic agents. DESIGN: Clinical records of patients who died of CF were reviewed. Their temporal bones were sectioned, stained with hematoxylin-eosin, and examined histologically. Additional sections were stained with Alcian blue and periodic acid-Schiff for comparison of goblet cell densities from middle ears and auditory tubes of patients with CF with those of control temporal bones. Results were analyzed using the t test. SUBJECTS: Twenty-one temporal bones from 11 patients with CF and 13 bones from 8 age-matched patients without CF were selected. RESULTS: All temporal bones with CF had well-pneumatized mastoids. Temporal bones from 2 patients (3 ears) revealed histological findings of chronic otitis media with effusion. There was a statistically significant reduction in the density of goblet cells in the medial (P = .002) and lateral (P = .05) walls in patients with CF who had no otitis media histologically compared with control temporal bones. Two patients with CF who had otitis media had increased densities of goblet cells. Inner ear damage, due to ototoxic drugs, was seen in most of the temporal bones from patients with CF. CONCLUSION: Low densities of goblet cells in temporal bones with CF may contribute reduced amounts of viscous mucus, which can lead to a low incidence of otitis media.

Adolescent↗

Orexin-A in the human brain and tumor tissues of ganglioneuroblastoma and neuroblastoma.

Regional distribution of orexin-A-like immunoreactivity in the human brain and pituitary, and the presence of orexin-A-like immunoreactivity in the tumor tissues of pheochromocytomas, ganglioneuroblastomas and neuroblastomas were studied by radioimmunoassay. Expression of orexin mRNA was studied by reverse transcriptase polymerase chain reaction (PCR) method. Orexin-A-like immunoreactivity was detected in every region of human brain, but not in the pituitary. The highest concentration of orexin-A-like immunoreactivity in the human brain was found in hypothalamus (17.8 +/- 4.3 pmol/g wet weight, mean +/- SEM, n = 7), followed by thalamus, medulla oblongata, and pons. Orexin-A-like immunoreactivity was detected in the tumor tissues of ganglioneuroblastoma and neuroblastoma, but not in the tumor tissues of pheochromocytoma. Reverse phase high performance liquid chromatographic analyses of the orexin-A-like immunoreactivity in the human brain extracts and neuroblastoma extracts showed a single immunoreactive peak, which was eluted in an identical position to synthetic human orexin-A. Orexin mRNA was expressed in the hypothalamus and in the tumor tissues of ganglioneuroblastoma and neuroblastoma. These findings suggest that orexin-A is produced in the hypothalamus and transported to various brain regions via axons. In addition, this study has shown for the first time the production of orexin-A by ganglioneuroblastomas and neuroblastomas.

Adrenal Gland Neoplasms↗

Binding sites for melanin-concentrating hormone in the human brain.

Binding sites for melanin-concentrating hormone (MCH) in human brain were investigated and characterized by radioligand binding. Specific binding sites for MCH were present in every region of human brain (cerebral cortex, cerebellum, thalamus, hypothalamus, pons, and medulla oblongata) obtained at autopsy. alpha-Melanocyte stimulating hormone or ACTH was a poor inhibitor of (125)I-MCH binding (IC(50) 1 microM) compared with MCH (IC(50) = 0.3 +/- 0.07 nM, mean +/- SEM, n = 3). Scatchard plots of (125)I-MCH binding in human brain (thalamus) gave a dissociation constant of 0.2 +/- 0.06 nM and maximal binding of 5.8 +/- 0.3 fmol/mg protein (n = 3). These findings suggest that specific MCH binding sites that differ from the melanocortin receptors exist in human brain.

Adrenocorticotropic Hormone↗

Bilateral same day surgery for bilateral perforated chronic otitis media.

OBJECTIVE: Bilateral same day surgery has been performed rarely because of the risk of postoperative sensorineural hearing loss following conventional myringoplasty or tympanoplasty (CMT). Simple underlay myringoplasty (SUM) through the ear canal has been developed by Yuasa R, Saijo S, Tomioka Y, et al. Office closure of eardrum perforation with fibrin glue (in Japanese), Otolaryngol Head Neck Surg (Tokyo) 1989;61:1117-1122, which has little risk of sensorineural hearing loss. We tried bilateral same day surgery using this technique and evaluated its outcome. METHODS: Of 86 cases with bilateral perforated chronic otitis media that we treated between 1995-1997, 25 cases underwent bilateral same day surgery. Bilateral SUMs was performed on seven patients, SUM and CMT on 16 patients, and bilateral CMTs on two patients. RESULTS: Closure of perforation was successful in 18 patients (72%) on both sides and in seven patients (28%) on one side. Postoperative air-bone gap of less than 20 dB was achieved in 15 cases (60%) on both sides and in 23 cases (92%) on one side. CONCLUSION: Bilateral same day surgery for bilateral perforated chronic otitis media is possible if the operative indications are considered.

Adolescent↗

Long-term observation on hearing change in patients with chronic otitis media.

OBJECTIVE: Very few reports are available in the literature to clarify the natural long course of hearing change in an individual patient with chronic otitis media (COM). We reviewed hearing change in patients suffering from perforated COM without an operation. METHODS: Eighty-seven ears of 70 patients had COM with tympanic perforation and were observed without an operation. The mean follow-up period was 10.7 years (5-22 years) and the mean age at the first examination was 51.3 years. To minimize the effect of aging, 23 patients with normal ear drums on the other side were further analyzed. RESULTS: All 87 ears tended to show deterioration of hearing gradually under long observation. In 23 patients, hearing deterioration was 0.13 dB/year in the control side and 0.61 dB/year in the COM side (P < 0.02). Although elevation of bone conduction hearing level tended to be larger at high frequencies than at low and middle frequencies, there was no significant difference between COM and normal ears. CONCLUSIONS: Air conduction hearing levels deteriorated with the passage of time and surgery is recommended at the early stage of COM to prevent progress of hearing loss.

Adult↗

The Drosophila trio plays an essential role in patterning of axons by regulating their directional extension.

We identified the Drosophila trio gene, which encodes a Dbl family protein carrying two Dbl homology (DH) domains, each of which potentially activates Rho family GTPases. Trio was distributed along axons in the central nervous system (CNS) of embryos and was strongly expressed in subsets of brain regions, including the mushroom body (MB). Loss-of-function trio mutations resulted in the misdirection or stall of axons in embryos and also caused malformation of the MB. The MB phenotypes were attributed to alteration in the intrinsic nature of neurites, as revealed by clonal analyses. Thus, Trio is essential in order for neurites to faithfully extend on the correct pathways. In addition, the localization of Trio in the adult brain suggests its postdevelopmental role in neurite terminals.

Animals↗

Increased secretion of adrenomedullin from cultured human astrocytes by cytokines.

Adrenomedullin, originally discovered from pheochromocytoma, is a member of the calcitonin gene-related peptide family. The production and secretion of adrenomedullin by cultured human astrocytes were studied by northern blot analysis and radioimmunoassay. Northern blot analysis showed the expression of adrenomedullin mRNA in cultured human astrocytes. Immunoreactive adrenomedullin concentrations in the culture medium were 29.6+/-1.2 fmol/10(5) cells/24 h (mean +/- SEM, n = 4). Treatment with interferon-gamma (100 U/ml), tumor necrosis factor-alpha (1 and 10 ng/ml), or interleukin-1beta (1 and 10 ng/ml) for 24 h caused >20-fold increases in immunoreactive adrenomedullin levels in the culture medium of human astrocytes. On the other hand, northern blot analysis showed only small increases (approximately 40%) in the adrenomedullin mRNA expression of human astrocytes with either 100 U/ml interferon-gamma or 10 ng/ml interleukin-1beta and no noticeable change with tumor necrosis factor-alpha. Reverse phase HPLC of the medium extracts of human astrocytes treated with interferon-gamma, tumor necrosis factor-alpha, or interleukin-1beta showed that most of immunoreactive adrenomedullin was eluted in the position of adrenomedullin-(1-52). On the other hand, immunoreactive adrenomedullin in the medium of human astrocytes without cytokine treatment was eluted earlier than the adrenomedullin standard, suggesting that this immunoreactive adrenomedullin represents adrenomedullin with some modifications or fragments of the adrenomedullin precursor. The present study has shown the production and secretion of adrenomedullin by human astrocytes and increased secretion of adrenomedullin by cytokines.

Adrenomedullin↗

Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1.

The Rho family GTPases are involved in a variety of cellular events by changing the organization of actin cytoskeletal networks in response to extracellular signals. However, it is not clearly known how their activities are spatially and temporally regulated. Here we report the identification of a novel guanine nucleotide exchange factor for Rac1, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosophila SIF proteins. STEF protein contains two pleckstrin homology domains, a PDZ domain and a Dbl homology domain. The in vitro assay showed that STEF protein specifically enhanced the dissociation of GDP from Rac1 but not that from either RhoA or Cdc42. Expression of a truncated STEF protein in culture cells induced membrane ruffling with altered actin localization, which implies that this protein also activates Rac1 in vivo. The stef transcript was observed in restricted parts of mice, including cartilaginous tissues and the cortical plate of the central nervous system during embryogenesis. These findings suggested that STEF protein participates in the control of cellular events in several developing tissues, possibly changing the actin cytoskeletal network by activating Rac1.

Amino Acid Sequence↗

Extracellular signal-regulated kinase mediates renal regeneration in rats with myoglobinuric acute renal injury.

In vitro data support that extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), members of mitogen-activated protein (MAP) kinases, mediate the signal transduction pathways responsible for the cell proliferation. However, in vivo role of these MAP kinases is poorly understood. Intramuscular injection of 50% glycerol solution induces acute renal failure in rats. This injury is known as a model of rhabdomyolysis in human. To investigate the molecular mechanism of the signaling pathway in this injury, we examined the role of ERK and JNK. After the glycerol injection JNK was rapidly and transiently activated at about 4 h, while the activation of ERK was gradually increased and the levels were sustained at least to 24 h. Next, we examined the expression of cell-cycle related proteins after the glycerol injection using Western blot analysis. The levels of proliferating cell nuclear antigen (PCNA) protein as a marker for cell proliferation were induced at 2 h and significantly increased to 24 h after the injection. In addition, cyclins D1, D2, and D3 as markers for G1 phase also increased with similar time courses. To examine whether activation of ERK and/or JNK are involved in the renal regeneration after the glycerol injection, we examined the effect of genistein, which is an inhibitor of tyrosine kinase, on the activation of ERK and JNK. Administration of genistein to rats with this injury decreased the activation of ERK, but not JNK. The induction of PCNA and cyclin D1 was also prevented by this treatment. In this condition, renal function was further worsened as compared to control rats. These results provide the first evidence that ERK may be involved in the repair process of renal tubules damaged by this injury.

Animals↗

Neural expression of hikaru genki protein during embryonic and larval development of Drosophila melanogaster.

Hikaru genki (HIG) is a putative secreted protein of Drosophila that belongs to immunoglobulin and complement-binding protein superfamilies. Previous studies reported that, during pupal and adult stages, HIG protein is synthesized in subsets of neurons and appears to be secreted to the synaptic clefts of neuron-neuron synapses in the central nervous system (CNS). Here we report the analyses of distribution patterns of HIG protein at embryonic and larval stages. In embryos, HIG was mainly observed in subsets of neurons of the CNS that include pCC interneurons and RP5 motorneurons. At third instar larval stage, this protein was detected in a limited number of cells in the brain and ventral nerve cord. Among them are the motorneurons that extend their axons to make neuromuscular junctions on body wall muscle 8. Immunoelectron microscopy showed that these axonal processes as well as the neuromuscular terminals contain numerous vesicles with HIG staining, suggesting that HIG is in a pathway of secretion at this stage. Some neurosecretory cells were also found to express this protein. These data suggest that HIG functions in the nervous system through most developmental stages and may serve as a secreted signalling molecule to modulate the property of synapses or the physiology of the postsynaptic cells.

Animals↗

Cholesteatoma otitis media with intact ossicular chain.

Thirty-one cases of cholesteatoma with intact ossicular chain were reviewed to examine the extension of cholesteatoma, operation procedures, pre- and postoperative hearing levels, and postoperative condition of the ear drum. They were operated on at Departments of Hyogo College of Medicine and Osaka University Medical School from 1989-1996, which were 20.4% of all of the primary cholesteatoma cases (n = 152). Twelve cases located at attic were operated by atticotomy or canal wall up and scutumplasty, 17 cases located at attic/antrum were operated by canal wall down and reconstruction, and two cases located around stapes were operated through the ear canal. Preoperative hearing level was mild (34.2 +/- 18.4 dB) and postoperative one was slightly improved (28.7 +/- 11.2 dB). In ossicular reconstruction, modified Wullstein type III method showed better hearing gain than Wullstein type I method. Postoperative attic retraction and/or pocket occurred in 15 cases (48.4%), but no recurrent cholesteatoma was found during the present follow-up period. These findings suggested that cholesteatoma with intact ossicular chain showed good postoperative hearing results, but postoperative retraction of the ear drum should be followed up for a long time.

Adolescent↗

Study of systemic lupus erythematosus in temporal bones.

Despite some reports of sensorineural hearing loss with systemic lupus erythematosus (SLE), its pathologic correlate has remained unidentified due to the scarcity of human temporal bone studies. We here present findings in 14 temporal bones from 7 patients with SLE, examined histologically and immunohistochemically for pathologic conditions in the cochlea that might relate to their otologic histories. Blue-staining concretions were seen in the stria vascularis of 6 ears. Most of the cases showed a loss of spiral ganglion cells, with various degrees of hair cell loss and atrophy of the stria vascularis. One ear demonstrated formation of fibrous tissue and bone throughout the cochlea, with complete loss of the membranous labyrinth. Cochlear hydrops was found in only 1 ear. These findings in temporal bones from patients with SLE are discussed in relation to autoimmune disease of the inner ear.

Adolescent↗

Expression of intercellular adhesion molecule-1 in rat inner ear due to bacterial otitis media.

Expressions of anti-Streptococcus pneumoniae antibody and anti-intercellular adhesion molecule-1 (ICAM-1) antibody in the inner ear were studied immunohistochemically in rats following inoculation of S pneumoniae type 6A into the middle ear cavity. Positive staining with anti-S pneumoniae antibody was detected in the marginal cells of the stria vascularis of rats sacrificed 3 days after S pneumoniae inoculation, but almost no staining was detected in those sacrificed at 14 days. Strong ICAM-1 expression was detected in the basal cell layer of the stria vascularis of rats sacrificed 3 days after inoculation, but the intensity of the staining had decreased by 14 days. These results suggest that the stria vascularis may be a site of the inner ear damage that follows bacterial inoculation into the middle ear cavity. The up-regulated expression of ICAM-1 in the basal cell layer may represent a reaction of the inner ear to the bacterial otitis media.

Animals↗

Precocious estrus and reproductive ability induced by PG 600 in prepuberal gilts.

A total of 29 SPF Large White prepuberal gilts (mean age 152 days at treatment) were examined for estrous and ovulatory responses after PG 600 treatment. After treatment, 85.2% of the gilts showed standing estrus within 6 days. Whereas the treatment-to-estrus interval and duration were 3.7 and 1.9 days respectively. As ovulation occurred on Day 5 to 6, appropriate timing of artificial insemination would be about 4 days after treatment. Fertility of gilts revealed to be excellent, giving rise to a high percentage of normal embryos, 85.3%. Meanwhile, development and growth of fetuses were mostly normal. Other reproductive performances recorded were: mean litter size 6.8; mean birth weight 1.26 kg; weaning-to-return estrus interval 5 to 8 days. In conclusion, PG 600 was found to be useful in inducing fertile estrus in prepuberal gilts, a result which will be of interest for commercial pig farms.

Animals↗

Elevated plasma immunoreactive neuropeptide Y concentrations and its increased urinary excretion in patients with advanced diabetic nephropathy.

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide that is abundant in the brain and the peripheral sympathetic nervous system. In the present study we investigated possible changes in plasma immunoreactive (IR)-NPY concentrations and urinary IR-NPY excretion in patients with non-insulin dependent diabetes mellitus (NIDDM) and the relationship to diabetic complications, such as nephropathy and neuropathy. IR-NPY in plasma and urine was measured by radioimmunoassay in 69 patients with NIDDM. Plasma IR-NPY concentrations in patients with advanced nephropathy (creatinine clearance <30 ml/min) (100.5 +/- 10.3 pmol/l, n=9, mean +/- SEM) were higher than in the control subjects (55.0 +/- 6.8 pmol/l, n=15) (P<0.02). Urinary excretion of IR-NPY and fractional excretion of NPY were also increased in the patients with advanced nephropathy. Sephadex G-50 column chromatography of the urine extracts obtained from healthy subjects, diabetic patients with renal failure and non-diabetic patients with renal failure showed an immunoreactive peak eluting in the NPY position. On the other hand, neither plasma nor urinary IR-NPY was high in patients with retinopathy, or in patients with peripheral neuropathy. The present study has, for the first time, shown high plasma IR-NPY concentrations and urinary IR-NPY excretion in NIDDM patients with advanced nephropathy.

Adolescent↗

A population-based, case-control study of Taenia solium taeniasis and cysticercosis.

A two-phase study was conducted in a rural community in Honduras, to evaluate the association between neurocysticercosis (NCC) diagnosed by computed tomography (CT), epilepsy, seropositivity for antibodies to the cysticerci of Taenia solium [determined by enzyme-linked-immunoelectrotransfer-blot (EITB) assays], intestinal infection with this parasite, and various epidemiological factors. Of the 480 individuals studied in the first phase, 17% were seropositive and 2.5% supplied faecal samples which contained T. solium eggs. In the second phase, 148 individuals (74 of the seropositive subjects from the first phase and 74 matched controls from the seronegatives) underwent CT and neurological examinations. The CT results appeared normal in 110 (74%) of the 148, showed anatomical abnormality in seven (5%), and active or calcified lesions compatible with NCC in 31 (23% of the seropositives and 19% of the seronegatives). Only five of the latter had neurological symptoms (two being epileptics) and only five lived in households in which intestinal taeniasis had been detected. Subject age was significantly associated with NCC-compatible lesions but all the other factors investigated, including seropositivity, showed no significant association with the CT findings. The overall sensitivity of the EITB assays was found to be 55%. Taken together, the present results indicate that, even though it is a valuable tool in determining transmission levels in sero-epidemiological studies, the EITB assay should not be used to predict the existence of NCC or to estimate the prevalence of NCC. The results do provide further evidence that taeniasis and cysticercosis are widely prevalent in Honduras, and indicate that much larger studies of hyper-endemic communities may be necessary if the factors associated with the transmission of T. solium are to be elucidated.

Adolescent↗

[Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles].

We report an 80-year-old Japanese man with histologically-diagnosed Creutzfeldt-Jakob disease (CJD). The patient was admitted to our neurological unit because of sudden onset motor aphasia-like symptoms and right hemiparesis. His medical and family histories were unremarkable, and he had taken no medications. Urine, blood counts and blood chemistry were all within normal limits. Cerebrospinal fluid was normal except for elevation of neuron specific enolase (29.9 ng/ml). High-signal intensity was demonstrated in the cortex of the left temporal lobe on T2-weighted MRI images, and the lesion swelled during the initial stage of the disease. There was no enhancement with Gd-DTPA. Serial MRI showed that the high-signal lesion had spread into the bilateral cerebral cortex. The patient developed myoclonus followed by akinetic mutism within 6 months of onset. Consecutive EEGs revealed no periodic synchronous discharge (PSD). He died of pneumonia 21 months after of admission. Autopsy revealed spongiform changes in the cerebral cortex with Kuru plaques, confirming the diagnosis of CJD. The Cerebellar cortex was well preserved. The high-signal lesions corresponded to the spongiform changes in the cerebral cortex. Immunohistochemical analysis showed weak synaptic prion staining. Prion protein (PrP) gene analysis of genomic DNA isolated from the autopsied brain by polymerase chain reaction, the restriction fragment length polymorphisms, and direct sequencing revealed a point mutation (Val-->Ile) at codon 180 and a polymorphism (Met/Val) at codon 129 on different alleles. A few CJD patients with point mutations in codon 180 of the PrP gene have been reported. Combination of the codon 180 point mutation and codon 129 polymorphism may yield an atypical clinicopathological form of CJD that includes late onset, negative PSD, and atypical MRI findings, with preservation of the cerebellar cortex.

Aged↗