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Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 127 records · Page 7Linked to original sources

Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.

The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity. However, the addition of ONO-2235 (100 microM) prevented the inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition of NO production in HUVEC. this agent might ameliorate endothelial function associated with diabetes.

Aldehyde Reductase↗

Responses of catecholamines, renin-angiotensin system, and atrial natriuretic peptide to exercise in untrained men and women.

1. Plasma norepinephrine (NE), epinephrine (E), renin activity (PRA), angiotensin II (ATII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured in 20 male and 15 female subjects during submaximal treadmill test. 2. Exercise duration was not different between the two groups (male vs. female: 13.4 +/- 0.8 min vs. 11.6 +/- 0.7 min, ns). Female subjects had higher heart rate during exercise, while systolic blood pressure at peak exercise was higher in male subjects. 3. Plasma NE, E, ANP, and ATII responses were comparable between male and female subjects, but PRA both at rest and during exercise and ALD at rest were significantly higher in male subjects. 4. Cardiac responses to submaximal exercise were different between male and female subjects, but neurohormonal responses were comparable between the two groups except for the high PRA at rest and during exercise and high plasma ALD at rest in male subjects.

Adult↗

Changes in cochlear function after double-membrane rupture in the guinea pig.

We measured the transiently evoked otoacoustic emissions (TEOAEs), compound action potentials (CAPs) and cochlear microphonics (CMs) in guinea pigs after rupture of the round window membrane alone (n = 5) or of the round window membrane with localized cochlear damage (n = 10). The localized cochlear damage entailed rupture of Reissner's membrane with damage to the stria vascularis. We determined the time course of changes in the total echo power (TEP) in TEOAEs and the minimal detectable levels of CAPs and CMs. The endocochlear potential (EP) was measured in the cochlea with localized damage. There were no changes in TEOAEs, CAPs or CMs in the guinea pigs subjected to round window membrane rupture alone, but the minimal detectable levels of CAPs and CMs were increased in all the guinea pigs in which TEOAEs were absent after rupture of the round window membrane with localized cochlear damage. Our results suggest that double-membrane rupture (rupture of the round window membrane with localized cochlear damage) produces acute sensorineural hearing loss. The hearing loss appeared to be related to damage to the cochlea, which may be induced by influx of potassium-rich endolymph into the perilymph, and by morphological damage to the scala media.

Acoustic Stimulation↗

Changes in the expression of gap junction proteins (connexins) in hamster tongue epithelium during wound healing and carcinogenesis.

We examined changes in the expression and localization of connexin proteins and transcripts by means of immunofluorescence and in situ hybridization in normal conditions, wound healing and carcinogenesis using hamster tongue epithelium, in which differentiation, migration and growth of keratinocytes takes place physiologically and pathologically. In normal hamster tongue epithelium, immunofluorescent staining showed that Cx26 and Cx43 proteins were localized differently during differentiation of keratinocytes, but in in situ hybridization, the localization of Cx26 and Cx43 transcripts overlapped considerably, suggesting that the different localization of Cx26 and Cx43 proteins in squamous epithelium is largely regulated at post-transcriptional levels. During wound healing, the expression and localization of connexin proteins and transcripts were changed drastically. Shortly (6 h) after injury the expression of Cx26 and Cx43 proteins decreased at wound edges, but by 1-3 days after injury the expression of both proteins increased and both proteins co-localized to the same spots in the epithelium near wound edges. During carcinogenesis, the increased expression of Cx26 and Cx43 proteins and their transcripts and co-localization of both proteins occurred in papillomas, and the expression of Cx26 was reduced as cancer cells became morphologically less differentiated. We also found, that during wound healing in papillomas, squamous cell carcinomas and keratinocytes, Cx26 and Cx43 proteins were localized aberrantly in the cytoplasm, especially around nuclei, rather than on plasma membranes. These results indicate that quantitative and qualitative changes in connexin expression are associated with differentiation, migration and proliferation of keratinocytes in squamous epithelium.

Animals↗

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Japanese patients.

We conducted molecular analysis of two candidate genes for spinal muscular atrophy (SMA), the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP), in 16 Japanese patients with SMA and compared the phenotypic features of SMA in these patients with the corresponding genotypes. Exons 7 and/or 8 of SMN were homozygously deleted in 11 SMA type I (Werdnig-Hoffmann disease) patients, two SMA type II patients and one SMA type III patient. Exons 5 and 6 of NAIP were homozygously deleted in six SMA type I patients. No patient had a deletion in NAIP without a deletion in SMN. Mechanical ventilation was required during the first 7 months of life in the SMA type I patients who had a deletion in both SMN and NAIP. Ventilatory support was initiated within 2 years after birth in patients who had a deletion in SMN but not in NAIP. We detected homozygous deletion of exon 5 of NAIP in the unaffected mothers of two SMA type I patients. In these families, the patients exhibited a deletion in both SMN and NAIP. The parents and unaffected siblings of these patients did not have a deletion in SMN. The present findings support the hypothesis that SMN deletion plays an important role in the development of SMA and suggest that combined deletion of both SMN and NAIP may be relevant for determining the disease severity.

Asian People↗

Distribution and ultrastructure of the stomata connecting the pleural cavity with lymphatics in the rat costal pleura.

We investigated the detailed distribution and ultrastructure of the stomata connecting the pleural cavity and the lymphatics in the rat costal pleura by scanning electron, transmission electron and light microscopy. The mesothelial cells lining the costal pleura appeared as both flattened and thick cell bodies. The thick cells possessed more rough endoplasmic reticula, Golgi complexes, mitochondria, and free ribosomes than the flattened cells. The thick cells were distributed in the intercostal regions each cephalic to the junction of the costal cartilage and bone, and in the band-like regions along the cephalic and caudal sides of each rib in the lateral and dorsal thoracic walls. In the regions lined with thick cells, there were stomata [12.9 +/- 10.3 microns2 (mean +/- SD) in area] consisting of prolongations of thick mesothelial cells and funnel-like projections of lymphatic endothelial cells that came up along the rims of the pores (5.9 +/- 3.2 microns2 in average area) in the submesothelial collagen fiber network. At the stomata, the basal lamina of the mesothelium was continuous with that of the endothelium. The mesothelial cells forming the stomata were mostly in close contact with the endothelial cells, but some gaps also existed between them. Valve-like endothelial flaps were frequently observed wherever endothelial cells constituting the stomata merged into the submesothelial lymphatics. Also present were lymphatic bulges that were either in close contact with the base of the thick mesothelial cells or exposed through the mesothelial pores. The lymphatic network was especially well developed in the submesothelial layer at and around the thick-cell regions. The initial lymphatics drained into the intercostal collecting lymphatics, which in turn led into either the parasternal or paravertebral lymphatic trunk. Our results suggest that the stomata play a major role in absorbing fluids and particulates in the pleural cavity. The thick mesothelial cells appear to secrete chemotactic substances to the endothelial cells. Understanding the heterogeneous distribution of the stomata could prove to be important clinically in inflammatory diseases and tumors in the chest.

Animals↗

Formation of actin filament networks in cultured rat hepatocytes treated with DMSO and glucagon.

Actin filament organization may play an important role in the maintenance of differentiated functions in epithelial cells. We previously reported our success in inducing and maintaining gap junctions, which are two kinds of differentiated function, in primary rat hepatocytes cultured with 2% DMSO and 10-7 M glucagon. In the present study, we demonstrated the formation of actin filament networks in the hepatocytes cultured with 2% DMSO and 10-7 M glucagon. Actin filaments in hepatocytes cultured in medium with only 2% DMSO added from 96 h after plating were concentrated under the plasma membrane and were observed to be circumferential. In hepatocytes cultured in the medium with both 2% DMSO and 10-7 M glucagon added from 96 h, not only the circumferential actin filaments but also the formation of actin filament networks were observed and the networks developed well with time in culture. The networks were observed as a dome-like structure under the cell face and terminated at the circumferential actin filaments. They were composed of electron-dense star-like vertices connected by microfilament bundles of varying length and were also very sensitive to the actin disruptor cytochalasin B. However, during the network formation, there were no significant increases in the amounts of actin protein and mRNA. The actin filament networks of the hepatocytes in this culture system might be closely related to the maintenance of differentiated functions.

Actins↗

Synthesis and nematocidal activity of aralkyl- and aralkenylamides related to piperamide on second-stage larvae of Toxocara canis.

Seventy-nine aralkyl- and aralkenylamides related to piperamides were synthesized and their nematocidal activity against second-stage larvae of dog roundworm, Toxocara canis, was examined. The activity was greatly dependent on the alkyl chain length and the nature of the amine moiety, but was scarcely affected by the presence or absence of double bond(s) in the chain. The alkyl chain lengths which showed the strongest activity in a series of homologues were m = 11 for the pyrrolidine amides and m = 13 for the N-methylpiperazine amides. Although piperamides (3,4-methylenedioxyphenyl homologues) showed the strongest activity among the homologues tested, methoxy substituent(s) on the aromatic ring did not have much effect on the activity. However, conversion of the methoxy group to a hydroxy group greatly decreased the activity and shortened the chain length giving the strongest activity. Calculated log P values of non-phenolic aryl-piperamides fell in the range from 3.5 to 4.5, whereas those of hydroxyphenyl-piperamides were smaller, suggesting that different mechanisms are involved in the nematocidal activity of phenolic and non-phenolic compounds.

Amides↗

[Effects of adenosine and adenine on cold acclimation in mice].

The effects of adenosine (ADO) and adenine (ADE) on cold acclimation were studied in mice of the ddY strain. At 5 weeks of age, mice were maintained at 4 degrees C for 4 weeks. Test groups of mice were supplied with a 0.05% (w/v) solution of ADO or ADE as drinking water in addition to water. We measured changes in body weight, intake of water and food, rectal temperature upon acute exposure to -20 degrees C, weight of interscapular brown adipose tissue (BAT) and the levels of glucose, nonesterified fatty acids (NEFA) and 3H-butyrate in the blood prior to and after exposure to the lower temperature of -20 degrees C. Chronic exposure to cold (4 degrees C) reduced body-weight gain for the first two weeks but weight gain recovered within the next two weeks. ADO partially but selectively inhibited the gain in body weight. This effect was marked in mice maintained at room temperature. Such an inhibitory effect was the case of ADE in the room temperature. Exposure to cold stimulated the daily consumption of food. ADO further and selectively enhanced food intake, but ADE enhanced that in room temperature. Cold increased in daily intake of water. Both ADO and ADE accelerated the intake of water. This effect was marked in mice maintained at 4 degrees C and the effect of ADE was considerable. Mice chose to drink the water that contained ADO, while the choice of water that contained ADE was apparent only during exposure to cold. Exposure to cold rendered mice resistant to severe cold (-20 degrees C). ADO and ADE partially reduced this resistance. Exposure to cold increased the weight of BAT but ADO selectively prevented this increase. Cold did not change the levels of the various compounds measured in the blood. In mice exposed to 4 degrees C for 4 weeks, acute exposure to severe cold decreased the glucose level and increased the levels of NEFA and 3H-butyrate. ADO selectively prevented the changes in the levels of NEFA and 3H-butyrate. It remains to be confirmed whether the growth of brown adipocytes is always necessary when mice acclimate to cold.

Acclimatization↗

Transrectal ultrasonic planimetry of the prostate in relation to age and lower urinary tract symptoms among elderly men in Japan.

The aim of the present study is to correlate transrectal ultrasonic planimetric parameters of the prostate in relation to age and urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score for benign prostatic hyperplasia (BPH). In 647 examinees on a mass screening program for prostatic diseases using transrectal sonography (TRS) in Japan, prostatic volume, transition zone volume, transition zone index (transition zone volume/prostatic volume) and presumed circle area ratio (PCAR) were determined using transrectal ultrasonic planimetry and compared with age and AUA symptom score. Increase in age, prostatic volume, transition zone volume and PCAR were significantly correlated with AUA symptom score. However, multiple regression analysis demonstrated that age and PCAR were the only significant independent determinant of symptom score. In particular, PCAR was the only significant determinants of symptom score in men with an intermediately enlarged prostate (20-30 ml in volume). The most significant difference in AUA symptom score was found between subgroups divided by PCAR with a cutoff point of 0.8. Among the planimetric parameters obtained by TRS, PCAR was the most powerful for evaluating BPH in terms of the severity of lower urinary tract symptoms.

Aged↗

A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt's type (FAB-L3) leukemia.

We report a case of B-cell acute lymphocytic leukemia which showed histological transformation from an FAB-L2 into a Burkitt's type (FAB-L3). Both leukemias had identical immunoglobulin heavy-chain joining gene and kappa light-chain joining gene rearrangements, indicating the clonal identity of the two leukemias. A chromosomal analysis of leukemia cells on the onset indicated normal karyotype, whereas that of the transformed FAB-L3 showed t(8;14)(q24;q32). Furthermore, the proto-oncogene c-myc was in the germline configuration in the initial leukemia but in the rearranged configuration after transformation. Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.

Adolescent↗

[A pilot study of mass screening program for prostatic cancer by means of prostate specific antigen (PSA) filter paper method].

BACKGROUND: Mass screening program for prostatic cancer (PC) using prostate specific antigen (PSA) filter paper method was performed in an urban area of Kyoto in 1995. METHODS: In the primary study, males more than the age of 55 years were examined by PSA (Delfia PSA kit) with blood samples on a filter paper. The cut-off values were set at 4 and 10 ng/ ml. Subjects whose PSA level ranged from 4.1 to 10.0 ng/ml (gray zone) were examined by digital rectal examination (DRE), transrectal sonography (TRS) and PSA density (PSAD; more than 0.15) in the secondary study, then the suspected subjects of PC underwent 6 sextant biopsies under interventional ultrasound. Subjects whose PSA level were more than 10.1 ng/ml were biopsied directly. RESULTS: Of 3,749 males who took the annual health checkup system organized by the government, 2,387 males wished to submit this screening. Among them, 2,217 (92.9%) showed a negative PSA, 107 belonged to the gray zone and 43 had a PSA more than 10.1 ng/ml. Of these, 102 subjects underwent biopsy. PC was finally detected in 28 (1.2%). The positive predictive value for positive PSA and gray zone PSA was 46.3% and 8.4%, respectively. In the detected cancers, 17 cases (60.7%) belonged to Stage B, 5 (17.9%) to Stage C and 6 (21.4%) to Stage D. CONCLUSION: The results suggested that this system of mass screening program for PC combined with the annual health checkup was suitable for the future "national-level" screening.

Aged↗

Effects of tamsulosin metabolites at alpha-1 adrenoceptor subtypes.

We have investigated the affinity and selectivity of tamsulosin and its metabolites, M1, M2, M3, M4 and AM1, at the tissue and the cloned alpha-1 adrenoceptor subtypes in the radioligand binding and the functional studies. In the radioligand binding studies, the compounds competed for [3H]prazosin binding to the rat liver and kidney alpha-1 adrenoceptors, with the rank order of potency tamsulosin approximately M4 > M1 > M2 approximately M3 > > AM1 with the latter having a negligible affinity. All compounds differentiated cloned alpha-1 adrenoceptor subtypes with the rank order of potency of alpha-1A > or = alpha-1D > alpha-1B, except for M4 which had the highest affinity for the alpha-1D adrenoceptor. The compounds also concentration-dependently antagonized phenylephrine-induced contractions in the rabbit aorta and prostate. The resulting apparent pA2 values were very similar to those at the cloned rat alpha-1A adrenoceptor. We conclude that most tamsulosin metabolites are high potency antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha-1B adrenoceptor selectivity of tamsulosin.

Adrenergic alpha-Antagonists↗

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia in a patient who died of progressive peripheral polyneuritis and cerebral dysfunction].

We reported a 59-year-old woman who received a diagnosis of psoriasis vulgaris at the age of 35 and had been under medical treatment. She was admitted to our department on August 16, 1993 because of lymphadenopathy, arthralgia and neuralgia. We observed cervical and axillar lymphadenopathy 1-3 cm in diameter, anemia and leukothrombocytosis. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and immunoglobulin G (IgG), but not M-protein were observed by immunological analysis of the serum. Bone marrow aspiration biopsy revealed hypercellularity with myeloid hyperplasia and slight increase in plasma cells. Elevated levels of serum interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) were detected; IL-6 was 62.1 pg/ml and G-CSF was 66 pg/ml, but IL-1 alpha, IL-1 beta and TNF-alpha were within the normal range. Idiopathic plasmacytic lymphadenopathy (IPL) with polyclonal hyperimmunoglobulinemia was diagnosed by lymph-node biopsy and the patient received following treatment with prednisolone and hydroxyurea. Leukocytes, platelets and skin eruptions increased again when the steroid dose was tapered, so we changed treatments to MP (melphalan, prednisolone) therapy. In addition, various neurological abnormalities such as convulsions, loss of consciousness and peripheral polyneuritis were observed. Despite treatment her condition deteriorated and she finally died. Very few reports show these neurological abnormalities in IPL or Castleman's disease therefore we think this is a very rare case.

Brain Diseases↗

[Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis. After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320. Thereafter, the graft consisting of mononuclear cells was transplanted. TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT. Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause.

Adult↗

[Cerebral sinus thrombosis in a patient with protein S deficiency: a case report].

Cerebral sinus thrombosis associated with protein S deficiency is rare to the best of our knowledge. We report here a 22-year-old female who presented sudden onset of headache, vomiting and disturbance of consciousness. Neuroradiological studies including computed tomography scan, magnetic resonance imaging and cerebral angiography disclosed a huge cerebral sinus thrombosis in the territory of the superior sagittal sinus, torcular herophili, lateral sinus and straight sinus. Hematological studies confirmed the diagnosis of protein S deficiency. We summarize the reported cases of cerebral sinus thrombosis associated with protein S deficiency. For young patients presenting occlusive cerebrovascular disease, we stressed the importance of doing extensive hematological investigation to detect possible etiological factors, such as protein S deficiency, protein C deficiency, antithrombin III deficiency. Once we discover the etiology of a disease, we may be able to designate the precise treatment or regimen for each patient.

Adult↗

The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate.

PURPOSE: Our study was conducted to reveal quantitatively the relative effects of age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary symptoms as evaluated by the American Urological Association (AUA) symptom index score. MATERIALS AND METHODS: In 929 examinees (732 with a normal prostate and 197 with BPH) on a mass screening program for prostatic diseases using transrectal ultrasonography in Japan, the AUA symptom score was compared to age, prostatic volume and presumed circle area ratio using simple and multiple regression analyses. RESULTS: Simple regression analysis demonstrated the symptom score to correlate significantly with age (R = 0.162, p < 0.0001), prostatic volume (R = 0.072, p = 0.0281) and presumed circle area ratio (R = 0.150, p < 0.0001). However, multiple regression analysis demonstrated that age and presumed circle area ratio were significant independent determinants of the total symptom score. Among 7 symptoms included in the AUA symptom index weak stream and hesitancy scores were not influenced by age, prostatic volume or presumed circle area ratio. CONCLUSIONS: As a parameter representing the degree of BPH in terms of the severity of urinary symptoms, presumed circle area ratio was preferable to prostatic volume. Regression analyses confirmed again that the AUA symptom index was influenced considerably by age and was not specific to BPH.

Age Factors↗

[Mass screening for prostatic cancer].

Two mass screening programs for prostatic cancer (PC) have been conducted at our institution. The first program, based on transrectal ultrasonography (TRUS), was performed between 1975 and 1995 in a total of 16,313 men over 55 years of age. Those showing abnormal findings on TRUS were referred to the secondary urological examination including needle biopsy of the prostate. PC was detected in 93 men (0.6%) and 43 of them were in the early stage. In 1995, a new mass screening program for PC was performed in an urban area of Kyoto. Of 3,749 men over 55 years of age who took the annual health checkup organized by the government, 2,387 wished to receive this screening. The primary examination consisted of Delfia prostate specific antigen (PSA) assay of dried blood samples on a filter paper. Men with PSA levels > 4.0 and < or = 10.0 ng/ml showing abnormal findings on TRUS and/or digital rectal examination, or PSA density > 0.15, underwent 6 sextant biopsies under transrectal ultrasonography, as well as men with PSA levels > 10.0 ng/ml. PSA levels were < or = 4.0 in 2,217 men, > 4.0 and < or = 10.0 in 107, and > 10.0 in 43. Prostatic biopsy was performed in 102 men. PC was detected in 28 men (1.2%) and 17 of them were in the early stage. These findings suggest that the PSA-based mass screening program for PC combined with the annual health checkup is suitable for future "national-level" screening.

Adult↗