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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 19 recordsLinked to original sources

The strain-dependent constitutive expression of murine serum amyloid-P component is regulated at the transcriptional level.

The strain-dependent expression of murine serum amyloid P-component (SAP) has been known to be linked to the Sap locus. We have quantified the SAP mRNA in several inbred strains including DBA/2 and C57BL/6 mice which represent high and low producers of SAP at resting state, respectively, and found that the mRNA levels correlated well with the amount of SAP protein. Interestingly, the SAP mRNA level of F1 mouse between DBA/2 and C57BL/6 was low and similar to that of C57BL/6. Primer extension and ribonuclease (RNAase) protection analyses demonstrated that a single type of transcript was generated from the SAP gene and that the cap sites were identical regardless mouse strains tested under unstimulated and stimulated (by lipopolysaccharide (LPS) or interleukin-6 (IL-6)) conditions. To investigate possible structural difference of the SAP gene including 5' flanking region, we have cloned, sequenced and compared the SAP genes from DBA/2 and C57BL/6 mice. Sequence analyses revealed that the 5' flanking regulatory regions, as well as the coding regions, were well-conserved between the two strains. These results demonstrate that the strain-dependent SAP expression occurs at the transcriptional level but seems to be affected by neither different type of the transcripts nor structural difference of the 5' flanking and coding regions of the SAP gene. It was suggested that a possible transcription factor with suppressive activity, which is encoded by a gene linked to Sap, may be involved.

Animals

Establishment and characterization of a thymic carcinoma cell line (Ty-82) carrying t(15;19)(q15;p13) chromosome abnormality.

A new human cell line, designated Ty-82, was established from the pleural effusion of a 22-year-old woman with undifferentiated thymic carcinoma. This cell line consisted of primitive cells that were positive for alpha-naphthyl butyrate esterase and acid phosphatase. The cells were shown to express epithelial membrane antigen, but were completely negative for cytokeratin, carcinoembryonic antigen, glial fibrillary acidic protein, desmin, S-100 protein, lysozyme, Leu-7, HLA-DR (Ia), leukocyte common antigen, Ki-I antigen, T-cell antigens, B-cell antigens, myelomonocyte antigens, and Epstein-Barr-virus nuclear antigen. Electron microscopy showed that the cells were highly anaplastic, with no sign of cellular differentiation to any lineages. The Ty-82 cell line was found to have a karyotype of 46,XX,t(15;19)(q15;p13), being identical to that of the patient's tumor cells. Four of 5 nude mice inoculated sub-cutaneously with Ty-82 cells developed tumors which displayed a histological picture similar to the original tumor. Thymic carcinoma is a recently recognized entity, and its cellular and clinical behavior are poorly understood. The newly established thymic carcinoma cell line would provide a useful tool for the better understanding of this rare disease.

Adenocarcinoma

Possible mechanisms of age-associated reduction of vascular relaxation caused by atrial natriuretic peptide.

We investigated the effect of aging on atrial natriuretic peptide (ANP)-induced relaxation and cyclic GMP (cGMP) formation in the rat thoracic aorta. In the aorta from young rats (4 weeks old), removal of the endothelium, and treatment with the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), the radical scavenger, hemoglobin (Hb), and the soluble guanylate cyclase inhibitor, methylene blue (MB), attenuated ANP-induced relaxation and considerably reduced ANP-stimulated cGMP formation. With increasing age of the rats, the ANP-induced relaxation and cGMP formation in endothelium-intact aorta decreased, and Hb, L-NAME and MB no longer inhibited the ANP-induced effects, irrespective of whether the endothelium was present or absent. In the arteries without endothelium, the age-associated reduction in ANP-induced relaxation was less than in arteries with endothelium. Aging also decreased the relaxation induced by the soluble guanylate cyclase activator, nitroprusside. Potentiation due to the cGMP-phosphodiesterase (cGMP-PDE) inhibitor, M&B 22948, of the ANP-induced relaxation was greater in aortas from old rats than in those from young rats, suggesting that the degradation of cGMP may be accelerated in old rats. These results suggest that the relaxant action of ANP on the thoracic aorta from young rats is in part modulated by endothelium-derived relaxing factor (EDRF/nitric oxide), which in turn activates soluble guanylate cyclase, thus elevating the cGMP level. Aging may decrease the ANP-induced relaxation and ANP-stimulated increase in cGMP level by decreasing the ability of endothelial cells to produce EDRF, by decreasing guanylate cyclase activity, and by enhancing cGMP-PDE activity.

3',5'-Cyclic-GMP Phosphodiesterases

Meningioma in a neonate: case report.

A 10-day-old female with a parasagittal meningioma presenting as a subcutaneous tumor is reported. Meningiomas within the 1st month of life are rare. The clinical and pathological characteristics of congenital meningioma are reviewed.

Female

Enhanced muscle sympathetic nerve activity during sleep apnea in the elderly.

To examine how muscle sympathetic nerve activity (MSNA) becomes modified during sleep apnea in the elderly, we analyzed polysomnographic recording simultaneously with microneurographically recorded MSNA. Subjects were three healthy elderly males aged 72, 75, and 76. MSNA was suppressed with deeper non-REM sleep stages in these elderly subjects. In all three subjects, sleep apnea for 10 s or longer was observed during sleep of 00:00-06:00. During sleep apnea, MSNA was enhanced concomitantly with a blood pressure fall and a reduction in saturation rate of oxyhemoglobin. With the termination of sleep apnea, MSNA was maximally enhanced with a transient elevation of blood pressure. We conclude that sleep apnea induces an enhancement of MSNA, which may be responsible for hypertensive episodes during sleep.

Aged

Ca(2+)-activated nonselective cation, maxi K+ and Cl- channels in apical membrane of marginal cells of stria vascularis.

Patch clamp recordings on the apical membrane of marginal cells of the stria vascularis of the gerbil were made in the cell-attached and excised configuration. Marginal cells are thought to secrete K+ into and absorb Na+ from endolymph. Four types of channel were identified; the most frequently observed channel was a small, nonselective cation channel which was highly similar to that found in the apical membrane of vestibular dark cells (Marcus et al., (1992) Am. J. Physiol. 262, C1423-C1429). The small nonselective cation channel was equally conductive (26.7 +/- 0.3 pS; N = 49) for K+, Na+, Rb+, Li+ and Cs+, 1.6 times more permeable to NH4+, but not permeable to Cl-, Ca2+, Ba2+ or N-methyl-D-glucamine. This channel yielded linear current-voltage relations which passed nearly through the origin (intercept: -2.2 +/- 0.4 mV, N = 49) when conductive monovalent cations were present on both sides of the membrane in equal concentrations. Channel activity required the presence of Ca2+ at the cytosolic face but not the extracellular (endolymphatic) face; there was essentially no activity for cytosolic Ca2+ less than or equal to 10(-7) M Ca2+ and full activity for greater than or equal to 10(-5) M. Cell-attached recordings had a conductance of 28.6 +/- 2.2 pS (N = 6) and a reversal voltage of -2.2 +/- 5.2 mV (N = 3) which was interpreted to reflect the intracellular potential of marginal cells under the present conditions. The three other types of channel were a Cl- channel (approximately 50 pS; N = 2), a maxi-K+ channel (approximately 230 pS; N = 1), and another large channel, probably cation nonselective (approximately 170 pS; N = 1). The 27 pS nonselective cation channel may be involved in K+ secretion and Na+ absorption under stimulated conditions which produce an elevated intracellular Ca2+; however, consideration of the apparent channel density in relation to the total transepithelial K+ flux suggests that these channels are not sufficient to account for K+ secretion.

Animals

Nitric oxide synthase responsible for L-arginine-induced relaxation of rat aortic rings in vitro may be an inducible type.

1. Characteristics of L-arginine-induced non-endothelial nitric oxide (NO) formation in rat isolated thoracic aorta were investigated. 2. Relaxation to L-arginine in arterial rings devoid of endothelium developed about 2 h after the first challenge with L-arginine and reached a maximum after a further 4 h of incubation. 3. After the arteries had relaxed in response to L-arginine, guanosine 3':5'-cyclic monophosphate (cyclic GMP) production was stimulated. In fresh arteries that had not yet relaxed in response to L-arginine, L-arginine failed to elevate cyclic GMP levels. 4. Glucocorticoids, actinomycin D and polymyxin B prevented the development of L-arginine-induced relaxation and L-arginine-stimulated increase in cyclic GMP formation. 5. Once L-arginine-induced relaxation developed, these agents no longer suppressed the relaxation and increase in cyclic GMP formation to L-arginine. 6. From these results, it is suggested that in the isolated thoracic aorta of the rat, endotoxin in the medium triggers induction of a non-endothelial NO synthase during prolonged incubation, which accelerates production of NO from added L-arginine to cause relaxation of the arteries via cyclic GMP. Glucocorticoids and protein synthesis inhibitors may prevent induction of NO synthase. It is suggested that the NO synthase mediating the production of muscle-derived NO from L-arginine is an inducible type.

Amino Acid Oxidoreductases

Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic aorta.

1. The mechanism of the vasorelaxant effect of platelet activating factor (PAF) on rat thoracic aorta and the effect of aging on the PAF-induced relaxation were investigated. 2. PAF at concentrations causing relaxation induced marked increases in guanosine 3':5'-cyclic monophosphate (cyclic GMP) production, but did not induce an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP). 3. Removal of the endothelium by mechanical rubbing, and treatment with the PAF antagonists CV-3988, CV-6209 and FR-900452, the nitric oxide biosynthesis inhibitor, NG-nitro L-arginine, the radical scavenger, haemoglobin, and the soluble guanylate cyclase inhibitor, methylene blue, inhibited PAF-induced relaxation and abolished or attenuated PAF-stimulated cyclic GMP production. 4. The relaxation was greatest in arteries from rats aged 4 weeks. With an increase in age, the response of the arteries to PAF was attenuated. 5. Endothelium-dependent cyclic GMP production also decreased with increase in age of the rats. 6. These results suggest that PAF stimulates production of nitric oxide from L-arginine by acting on the PAF receptors in the endothelium, which in turn stimulates soluble guanylate cyclase in the smooth muscle cells, and so increases production of cyclic GMP, thus relaxing the arteries. Age-associated decrease in PAF-induced relaxation may result from a reduction of cyclic GMP formation.

Aging

Effects of protein intake on immune parameters in mice surviving streptococcal infection.

Groups of mice were fed for 2 weeks on isocaloric diets containing 5, 7, 20 and 40% (w/w) casein, respectively, then injected intraperitoneally with group B streptococci, and observed for their survival rates. The mice fed 7% or 20% casein had lower mortalities than those fed 5% or 40% casein. In order to explain the different survival rates, other groups of mice were fed on the experimental diets and examined for the number of leukocytes in the blood, of spleen cells and thymocytes, for IgG and IgM antibody titres to the streptococci, for haemolytic titres of sera, the amount of complement component 3 (C3), for chemiluminescence and opsonic activity of peritoneal exudate cells (PEC) and spleen cells (SP), production of superoxide anion from PEC and SP, and production of immunoglobulins from cultured SP. After 2 weeks on a 7 or 20% casein diet mice showed increased serum levels of IgM antibodies reactive with the whole bacterial cells on days 3-5 when they were immunised with a sublethal dose of group B streptococci. The mice fed on the 7% casein diet also showed a higher C3 titre than the other diet groups when assayed by enzyme immunoassay. Furthermore, opsonophagocytic activity was highest when PEC or SP taken from mice on the 20% case in diet were incubated with radiolabelled microorganisms in the presence of fresh serum taken from the 7% casein group. The production of superoxide anions from PEC and SP was lowest in the mice fed on 5% casein when activity was expressed as nano-mol per animal. It is suggested from these results that the greater activity of phagocytic cells in the presence of increased amounts of C3 and IgM explains the heightened resistance in the mice fed on a 7% casein diet, and that suppressed opsonophagocytic activity resulting from the decreased number of leukocytes in the blood and other phagocytic cells explains the lowest resistance in the 5% casein group. However, mice fed on a 40% casein diet showed all these immunological parameters untouched, and their lowered resistance could not be explained. Different factors seem to be operative in them.

Animals

Phylogeny of regulatory regions of vertebrate tyrosinase genes.

Highly homologous DNA elements were found to be shared by the upstream regions of the mouse tyrosinase and tyrosinase related protein (TRP-1) genes. Several nuclear proteins were shown to bind to both of these upstream regions. Shared homologous DNA elements were also found in the 5' flanking sequences of Japanese quail and snapping turtle tyrosinase genes. Shared homologous nucleotide sequences were found to be scattered like an archipelago in the 5' upstream regions of mouse and human tyrosinase genes. Comparisons between Japanese quail and snapping turtle tyrosinase genes gave similar results. On the contrary, mammalian (mouse and human) and nonmammalian (quail and snapping turtle) tyrosinase genes did not show significant homology in their 5' upstream regions. In contrast, coding sequences in the first exons of vertebrate tyrosinase genes and their deduced amino acid sequences were found to be highly conserved except for their putative leader sequence-coding regions.

Amino Acid Sequence

[Long-term chemotherapy using erythromycin (EM) for chronic lower airway infection: effectiveness of clarithromycin in EM ineffective cases--the fourth report].

The effectiveness of long-term chemotherapy using Erythromycin (EM) for chronic lower airway infection has been practically proved. However, there still exist some ineffective cases, or cases in which the clinical effect was scarcely seen. In the present study was administered Clarithromycin (CAM) to such cases and found that CAM was effective in alleviating symptoms in some of them. The results were presented along with clinical findings and other basic studies. The subjects were 4 cases in which EM was either ineffective or low in its clinical effect. The subjects consisted of 1 case of DPB and 3 cases of bronchiectasis. EM was clinically ineffective in 2 cases and slightly effective in the two others. The pathogen was Pseudomonas aeruginosa in all cases. The dosage of EM was 200-1200 mg/day. The period of administration ranged from 2 years to 6 years 9 months. CAM was given orally after meals at a dose of either 200 or 400 mg/day. Chemotherapy had continued for 3-8 months at the time of final observation (Feb. 1992). Clinical effectiveness was evaluated on the basis of sputum volume and PaO2 examination, as well as evaluation by the patients themselves. As a result, in all 4 cases, reduction in sputum volume and improvement of PaO2 were observed. All subjects evaluated CAM therapy as being more effective than EM therapy. Moreover, it was found that CAM inhibited both the elastase and leucocidin produced in one of the ineffective cases by P. aeruginosa, whereas EM didnt.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[The 5th report on long-term chemotherapy using erythromycin (EM) for chronic lower airway infection--cases followed over 7 years].

Clinical studies were made over 7 years on 9 cases to whom long-term chemotherapy with EM was administered for chronic airway infection. 1) Clinical effectiveness: Highly effective in 8 cases; Improvement in QOL was observed in 8 cases. Bacteriological effect: In 7 cases, pathogenic bacteria disappeared. 2) No side effects were observed. 3) Changes in PaO2 levels with the passage of time: In most cases, PaO2 reached a plateau within 1 year. Although in some cases, there was subsequent elevation. 4) The frequency of catching cold over the 7 years period was low with an average of 1.2 times/year per subject. In only 2 cases were subject hospitalized due to acute exacerbation triggered by a cold. 5) Mucociliary transport improved in 7 out of 8 cases examined. However, only 4 of these recovered normal transport. The effect of EM in the other cases in which clinical improvement was not demonstrated was deemed slightly effective. On the basis of the above findings, it was suggested that long-term chemotherapy using EM was clinically efficacious. This is based on the fact that its efficacy, including amelioration of QOL appeared within one year of the initiation of therapy, and continued without decline for over 7 years.

Administration, Oral

[A clinical study of respiratory tract infection due to Staphylococcus aureus detected by transtracheal aspiration].

A clinical study of 24 patients with respiratory tract infection due to S. aureus detected by transtracheal aspiration (TTA) was conducted, and the following results were obtained. 1) The detection frequency of S. aureus was relatively low (4.6%). 2) Pneumonia was the principal clinical manifestation. 3) Approximately one half of the patients had previously received antimicrobials. 4) Multiple organisms were frequently detected, particularly in cases of hospital-acquired infection. H. influenzae was the most frequently simultaneously detected organism. 5) On sputum examination, approximately 20 ml of purulent sputum was found in most cases, and S. aureus was detected in sputum specimens from 20 of the patients. 6) The largest number of cases was found in 1987. Onset was most common from autumn to spring. 7) Undernutrition was the most frequently associated host factor. As indicated by the above findings, the clinical expression of S. aureus infection is variable, and it is important that it be diagnosed accurately.

Adult

[The long-term chemotherapy with erythromycin (EM) in chronic lower respiratory tract infections--third report: clinical study of cases administered EM over 3 years].

An investigation was made of the use of EM therapy which began in 1986 or earlier in 31 cases with chronic lower respiratory tract infections. 1) Of the 20 cases in which EM (Erythromycin stearate) administration (600-1200 mg/day) was continued for 3 years or more and its usefulness could be evaluated, treatment with this agent was judged markedly effective in three, effective in 14, somewhat effective in two, and ineffective in one. This amounted to an effectiveness rate (effective or better) of 85%. 2) Improved QOL was observed in 15 of the 20 cases. 3) In the Pseudomonas infected cases, a discrepancy was seen between the effectiveness rate of 87.5% and the disappearance rate of the organism (12.5%), while in the Haemophilus cases no such discrepancy was found (75%). 4) EM administration was stopped in 11 cases because of side effects in two (stomatitis, gastrointestinal disorder) death in five, desire of the patient in three, and transfer to another hospital in one. The cause of death cases had no connection with administration of EM. 5) In the three patients who stopped EM on their own, the agent was again administered because of exacerbation of symptoms, although this readministration proved ineffective in two of the cases. The above results suggest that long term EM therapy is useful and that its continued administration is important.

Adult

[Three cases of lower respiratory tract infection worsened after rhinovirus infection].

We experienced three cases of lower respiratory tract infections worsened after Rhinovirus infection. Case 1: A 42-year-old male with diffuse panbronchiolitis was admitted to our hospital with the complaint of dyspnea on November 21, 1988. Rhinovirus was isolated from nasal washing and P. aeruginosa was cultured from transtracheal aspiration (TTA). Case 2: A 67-year-old male, whose underlying disease was pulmonary asbestosis, was admitted to our hospital complaining of pyrexia on June 12, 1990. Rhinovirus was isolated from TTA and H. influenzae and others were cultured from TTA. Case 3: A 64-year-old male with pulmonary emphysema was admitted to our hospital with a complaint of dyspnea on August 11, 1989. On December 17, 1989 the patient developed rhinorrhea and complained of purulent sputum, pyrexia and dyspnea after five days. Rhinovirus was isolated from nasal washing and TTA and S. nonhaemolyticus and others were cultured from TTA. As indicated in this report, it is interesting to study the relationship between viral infection of the upper respiratory tract and bacterial infection of the lower respiratory tract.

Adult

Ca(2+)-activated nonselective cation channel in apical membrane of vestibular dark cells.

Patch-clamp recordings were made on cell-attached and excised apical membrane from dark cells of the semicircular canal of the gerbil. These cells are thought to secrete K+ and absorb Na+ from the luminal fluid (endolymph). Single-channel events were identified as being equally conductive (27.6 +/- 0.4 pS; n = 48) for K+, Na+, Rb+, Li+, and Cs+ and 1.4 times more permeable to NH4+ but not permeable to Cl-, Ca2+, Ba2+, nor to N-methyl-D-glucamine. The channels displayed linear current-voltage relations that passed nearly through the origin (intercept: -2.6 +/- 0.5 mV; n = 48) when conductive monovalent cations were present on both sides of the membrane in equal concentrations. Channel activity required the presence of Ca2+ at the cytosolic face; there was no activity at less than or equal to 10(-7) M Ca2+ and full activity at greater than or equal to 10(-5) M Ca2+. Cell-attached recordings had a mean reversal voltage of -36.4 +/- 7.9 mV (n = 7), which was interpreted to reflect the intracellular potential of dark cells under the present conditions. We have identified a nonselective cation channel in the apical membrane of vestibular dark cells that might participate in K+ secretion or Na+ absorption under stimulated conditions, but the density appears to be insufficient to fully account for the transepithelial K+ flux.

Animals

Maxi K+ channel in apical membrane of vestibular dark cells.

Recordings were made on excised apical membrane patches from vestibular dark cells from the semicircular canal of gerbils to determine if ion channels could be involved in the process of K+ secretion. Both nonselective cation channels [Am. J. Physiol. 262 (Cell Physiol. 31): C1430-C1436, 1992] and K(+)-selective channels were found. The K+ channels occurred in only 0.7% of the patches. In symmetrical 145 mM KCl solutions, the current-voltage (I-V) relation of the K(+)-selective channel was linear, indicating the absence of rectification, and the conductance was 240 +/- 8 pS (n = 8). The Goldman-Hodgkin-Katz equation for current carried solely by K+ could be fitted to the I-V relation in asymmetrical K+ and Na+ solutions and yielded a K+ permeability of 5.78 x 10(-13) cm3/s (n = 12). The channel was shown to be impermeable to Li+, NH4+, N-methyl-D-glucamine, and Cl-. Channel activity increased with depolarization and with increasing free [Ca2+]; for voltages between +40 and -60 mV, the strongest regulation occurred in the range 10(-6) to 10(-5) M Ca2+. Tetraethylammonium (2 x 10(-2) M) had from the cytosolic side no effect on the open probability (Po) but completely inhibited activity from the extracellular side. Po was reduced by Ba2+ (5 x 10(-3) M), verapamil (10(-4) M), quinine (10(-4) M), and quinidine (10(-4) and 10(-3) M), while lidocaine (5 x 10(-3) M) had no measurable effect on Po but decreased the amplitude. Rb+ and Cs+ were either poorly permeable or partially blocked the channel in a voltage-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Stimulation of Cl secretion by lactoferrin across canine airway epithelial cells in culture.

To investigate the effect of lactoferrin, an iron-binding glycoprotein in the respiratory tract, on ion transport function of airway epithelial cells, we measured bioelectric properties of canine cultured tracheal epithelium by Ussing's short-circuit technique. Addition of lactoferrin (60 micrograms/ml) to the mucosal side of epithelial sheet increased the short-circuit current (Isc) from 4.8 +/- 0.8 to 7.5 +/- 1.1 microA/cm2, and the submucosal addition likewise increased Isc from 3.8 +/- 0.6 to 5.6 +/- 0.7 microA/cm2 (p < 0.001, in each case). This effect was concentration dependent. The lactoferrin-induced increase in Isc was not altered by amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate or substitution of Cl with iodide in the medium. Intracellular cyclic AMP levels were not increased by lactoferrin. These results suggest that lactoferrin may selectively stimulate Cl secretion across the airway mucosa, an effect that may not be dependent on prostaglandins, beta-adrenergic receptor or intracellular cyclic AMP.

Animals