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Biomedical subjects

J Saito

Publications and source records attributed to J Saito.

At least 55 records · Page 3Linked to original sources
PubMed2000

Octreotide improved ventricular arrhythmia in an acromegalic patient.

We saw a remarkable effect of octreotide, the long-acting somatostatin analogue, in reducing the number of ventricular premature complexes (VPCs) in a 59-year-old woman with acromegaly. Her basal GH and IGF-1 levels were up to 22.9 ng/ml and 934.9 ng/ml respectively. MRI revealed a 14 x 12 x 10 mm mass lesion in the pituitary gland. She had hypertension and echocardiography showed an increase in left ventricular wall thickness. Electric cardiography showed the presence of frequent VPCs and 24-h Holter monitoring revealed 24,277 beats of multifocal VPCs/24 h. She was treated with 300 microg/day of octreotide for four weeks before transsphenoidal surgery. After octreotide treatment, GH and IGF-1 were suppressed to 1.8 ng/ml and 145.3 ng/ml respectively, and the tumor size was remarkably reduced. Furthermore, the number of VPCs was also dramatically reduced to 2062 VPCs/24-h (8.5% of pretreatment) with 24-h Holter monitoring. This case shows that VPCs of acromegalic patients can be controlled by suppressing GH and IGF-1 with octreotide, and this agent is useful for reducing both tumor size and frequency of VPCs prior to surgery.

Acromegaly↗
PubMed2000

Primary intracerebral and aneurysmal subarachnoid hemorrhage in Izumo City, Japan. Part I: incidence and seasonal and diurnal variations.

OBJECT: The purpose of this community-based study was first to estimate the incidence rates of primary intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH) in Izumo City, Japan, and second to investigate whether there were seasonal and diurnal periodicities in their onset. METHODS: During 1991 through 1996, 267 patients with primary ICH and 123 with aneurysmal SAH were treated in Izumo City. The crude and the age- and sex-adjusted annual incidence rates per 100,000 population for all ages were 52 and 48 for ICH and 24 and 23 for SAH, respectively. These incidence rates were higher than those previously published for any other geographical region. The incidence rates of both ICH and SAH increased almost linearly with age. For ICH, a significant seasonal pattern was observed in men and in patients younger than 65 years, with a peak in winter and a trough in summer. However, no significant seasonal fluctuation was found in women or in individuals aged 65 years or older. There was no significant seasonal periodicity for SAH, even when patients were analyzed according to sex and age. Diurnal variations in the onset of both ICH and SAH were significant (except in men with SAH), with a nadir between midnight and 6:00 a.m. CONCLUSIONS: The actual incidence rates of both primary ICH and aneurysmal SAH seem to be much higher than have been reported so far. In addition, the data indicate the existence of seasonal periodicity for men and younger patients with ICH, and that the risk of both ICH and SAH is lower during nighttime.

Adult↗
PubMed2000

[Problems in the assessment of care grade].

We were involved in assessing the care grade of 238 people. The assessed care grade did not clearly correspond to the degree of handicap. Twenty-four people want a review of their assessed care grade. The reason for this discrepancy was that the home visiting assessment was performed incorrectly.

Persons with Disabilities↗
PubMed1999

Crystal structure of chitosanase from Bacillus circulans MH-K1 at 1.6-A resolution and its substrate recognition mechanism.

Chitosanase from Bacillus circulans MH-K1 is a 29-kDa extracellular protein composed of 259 amino acids. The crystal structure of chitosanase from B. circulans MH-K1 has been determined by multiwavelength anomalous diffraction method and refined to crystallographic R = 19.2% (R(free) = 23.5%) for the diffraction data at 1.6-A resolution collected by synchrotron radiation. The enzyme has two globular upper and lower domains, which generate the active site cleft for the substrate binding. The overall molecular folding is similar to chitosanase from Streptomyces sp. N174, although there is only 20% identity at the amino acid sequence level between both chitosanases. However, there are three regions in which the topology is remarkably different. In addition, the disulfide bridge between Cys(50) and Cys(124) joins the beta1 strand and the alpha7 helix, which is not conserved among other chitosanases. The orientation of two backbone helices, which connect the two domains, is also different and is responsible for the differences in size and shape of the active site cleft in these two chitosanases. This structural difference in the active site cleft is the reason why the enzymes specifically recognize different substrates and catalyze different types of chitosan degradation.

Amino Acid Sequence↗
PubMed1999

Optical monitoring of the neural activity evoked by mechanical stimulation in the earthworm nervous system with a fluorescent dye, FM1-43.

In the central nervous system of the earthworm, sensory and motor neurons have direct synapses on three giant fibers. To determine the locations of synapses and neural network activated by mechanical stimuli, we optically monitored the activity-dependent staining in the earthworm ventral nerve cord with a styryl dye, N-(3-triethylammoniumpropyl)-4- (4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. When scratch stimulus was applied to the body wall of the earthworm, bright fluorescent spots with 3-10 microns in diameter localized only in the stimulated segmental ganglion of the ventral nerve cord. The fluorescent intensity of these spots decreased during dye-free high K+ saline incubation. These results suggest that FM1-43 is useful for activity-dependent staining of invertebrate neurons and their synaptic regions as well as vertebrate nervous system.

Animals↗
PubMed1999

Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides.

Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gammaIFN), i.e., ds polynucleotides increase class I much more than class II, whereas gammaIFN increases class II more than class I. The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the class II transactivator, RFX5, and the IFN regulatory factor 1 differently from gammaIFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene therapy.

3T3 Cells↗
PubMed1999

Thyroglobulin regulates follicular function and heterogeneity by suppressing thyroid-specific gene expression.

Thyroglobulin (TG) is the primary synthetic product of the thyroid and the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and lysosomal degradation can each modulate thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (the TSHR), increases thyroid hormone levels by upregulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of the thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex (MHC) class I gene expression, which is also regulated by TTF-1 and Pax-8 in the thyroid, is simultaneously decreased; this maintains self tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. We now show that follicular TG, 27S > 19S > 12S, counter-regulates TSH-increased thyroid-specific gene transcription by suppressing the expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS and TSHR genes, but increases class I expression. TG action involves an apical membrane TG-binding protein; however, it acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the start of TTF-1 transcription. TG does not affect ubiquitous transcription factors regulating TG, TPO, NIS and/or TSHR gene expression. TG activity is not duplicated by thyroid hormones or iodide. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism which regulates follicular function, regulates thyroid hormone secretion, and contributes to follicular heterogeneity.

Animals↗
PubMed1999

Unilateral papilledema after bone marrow transplantation.

We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation.

Adult↗
PubMed1999

Glucocorticoid receptor-mediated post-ceramide inhibition of the interleukin-1beta-dependent induction of ovarian prostaglandin endoperoxide synthase-2 in rats.

Ovulation may constitute a cyclic, inflammatory-like process, wherein interleukin (IL)-1 induction and increased biosynthesis of prostanoids may feature prominently. In excess, glucocorticoids, potent anti-inflammatory agents, may exert an antiovulatory effect. This paper addresses the possibility that the antiovulatory action of glucocorticoids may be partly due to interference with ovarian prostanoid biosynthesis. Specifically, we examined the effect of treatment with dexamethasone, a synthetic glucocorticoid, on the IL-1-induced expression and activity of ovarian prostaglandin endoperoxide synthase (PGS)-2, the inducible variety of the rate-limiting enzyme in the prostaglandin cascade. Treatment of cultured whole ovarian dispersates from immature rats with dexamethasone for 48 h produced a significant decrease (98.9% inhibition) in the IL-1-supported expression of PGS-2 transcripts. Comparably marked inhibition was also noted for the corresponding immunoreactive protein. The dexamethasone effect was not limited to the IL-1-mediated induction of PGS-2 transcripts, comparable suppression being noted for the IL-1-mediated up-regulation of ovarian transcripts corresponding to IL-1beta, the IL-1 receptor antagonist, and the type I IL-1 receptor. The order of potency of the glucocorticoids studied was dexamethasone > prednisolone = cortisol. Dexamethasone proved equally effective in suppressing the induction of PGS-2 transcripts by congeners of the sphingomyelin-ceramide cycle (e.g., C-2 ceramide, sphingomyelinase, and sphingosine). The dexamethasone effect proved glucocorticoid-specific, as synthetic agonists representative of the progestin (R-5020), androgen (R-1881), and estrogen (diethylstilbestrol) steroid series proved to be without effect. Cotreatment with RU-486 resulted in reversal of the ability of dexamethasone to suppress PGS-2 activity or expression. Taken together, these observations suggest that dexamethasone is capable of glucocorticoid receptor-mediated/post-ceramide suppression of IL-1-supported ovarian PGS-2 transcript, protein, and activity. These findings are compatible with the view that the chronic anovulatory state associated with adrenal hyperactivity or glucocorticoid excess may be due in part to inhibition of ovarian prostaglandin biosynthesis.

Animals↗
PubMed1999

High-risk types of human papillomavirus associated with the progression of cervical dysplasia to carcinoma.

OBJECTIVES: In the past several years, much evidence has accumulated that strongly implicates human papillomavirus (HPV) as an etiological agent of cervical cancer. However, the natural history of HPV infection is not yet completely understood, and at present there is no good marker to predict progression to invasive cancer in individual patients with dysplasia. METHODS: Tissue specimens from 45 patients with cervical dysplasia were classified as showing progression to carcinoma (progression group; 26 women), spontaneous regression (regression group; 16 women), and persistence (persistence group; 3 women). The presence of HPV 16, 18, 33, and 52 DNA was examined in 90 formalin-fixed, paraffin-embedded surgical and biopsy specimens of dysplasia using the PCR method, and the relationship between the presence of HPV and cervical carcinogenesis was analyzed. The mean follow-up period was 25.8 months in the progressed group and 34.0 months in both the persistent and regressed groups. The mean ages were 46.4 in the progressed group and 46.8 in the persistent and regressed groups. RESULTS: HPV 16, 18, 33, and 52 DNA were detected in 19 of the 26 patients (73.1%) in the progressed group. All patients with HPV 16, 18, or 52 DNA showed progression to carcinoma. The HPV 33 DNA was detected in 5 of the 16 patients (31.3%) in the regressed group and in 2 of the 3 patients (66.7%) in the persistent group, while HPV 16, 18, and 52 DNA were not detected in the 19 patients that comprised the regressed and persistent groups. CONCLUSION: This retrospective study suggests that cervical dysplasia in patients with high-risk types of HPV possessed the potential to progress to carcinoma in situ and eventually to invasive carcinoma as well.

Adult↗
PubMed1999

Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene.

A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor ofthyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake ofradioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability.

Animals↗
PubMed1998

Dictyostelium TRFA homologous to yeast Ssn6 is required for normal growth and early development.

The TPR (tetratricopeptide repeat) family became widespread during evolution, having been found from bacteria to mammals. By means of restriction enzyme-mediated integration, we have identified a Dictyostelium gene (trfA) highly homologous to a Saccharomyces cerevisiae gene encoding a TPR protein, Ssn6 (Cyc8), which functions as a global transcriptional repressor for diverse genes. The deduced amino acid sequence of the Dictyostelium gene product, TRFA, contains 10 consecutive TPR units as well as Gln repeats, Asn repeats, and a region rich in Glu, Lys, Ser, and Thr. The sequences of some of the 10 TPR units in TRFA are more than 70% identical to the corresponding units in Ssn6. The trfA- cells produced smooth plaques on a bacterial lawn and failed to aggregate normally when starved on a plain agar plate. Individual trfA- cells also failed to correctly respond to cAMP, although the adenylyl cyclase of trfA- cells was expressed upon starvation and activated by stimulation with cAMP as in the wild-type cells. When cultured in a rich medium in suspension, they grew more slowly and stopped growing at a lower density than the wild-type cells. Furthermore, they divided into cells of various sizes and tended to be much smaller than the wild-type cells. These pleiotropic defects of the trfA- cells suggest the possibility that Dictyostelium TRFA may regulate the transcription of diverse genes required for normal growth and early development.

Amino Acid Sequence↗
PubMed1998

Autoregulation of thyroid-specific gene transcription by thyroglobulin.

Thyroglobulin (TG), the primary synthetic product of the thyroid, is the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and degradation control thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (TSHR), increases thyroid hormone levels by up-regulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of several thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex class I gene expression, which also is regulated by TTF-1 and Pax-8 in the thyroid, is decreased simultaneously. This helps maintain self-tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. In this report we show that follicular TG counter-regulates TSH-increased, thyroid-specific gene transcription by suppressing expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS, and TSHR genes, but increases class I expression. TG acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the 5' flanking region of TTF-1. TG does not affect ubiquitous transcription factors regulating TG, TPO, NIS, and/or TSHR gene expression. The inhibitory effect of TG on gene expression is not duplicated by thyroid hormones or iodide and may be mediated by a TG-binding protein on the apical membrane. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism that limits follicular function and contributes to follicular heterogeneity.

Animals↗
PubMed1998

Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen-activated protein kinase (MAPK) in cultured rat astrocytes.

Astrocytes, a subtype of glial cells, have been demonstrated to have an abundant number of receptors for pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide of the VIP/secretin family which stimulates cAMP accumulation 1000 times more potent than VIP in astrocytes. PACAP is reported to stimulate the proliferation of astrocytes at low concentrations at which it does not yet stimulate the cAMP accumulation. In the present study, we examined the effect of PACAP on the activation of mitogen-activated protein kinase (MAPK), one of the important intracellular signals for the proliferation, and compared it with that of epidermal growth factor (EGF). To investigate the activation of MAPK, we focused on ERK2, one of MAPK, in cultured rat astrocytes. The activation of ERK2 was determined by immunoblotting and measurement of the activity in terms of the phosphorylating activity of immunoprecipitates with MAPK antibody on myelin basic protein. One pM of PACAP38 temporarily activated ERK2 at 10 min. In contrast, EGF activated ERK2 from 10 min to 60 min continuously. As for the dose-response effect, PACAP stimulated ERK2 at as low a concentration as 10-14 M and peaked at 10-12 M. Thereafter, its activating effect gradually decreased at 10-10 M and returned to the basal level at 10-8 M, forming a bell-shaped dose-dependency. Neither an inhibitor of PKA (H89) nor inhibitors of PKC (staurosporine and calphostin C) had any effect on the ERK2 activation induced by 1 pM PACAP38. Dibutyryl cAMP suppressed ERK2 activity in a dose-dependent manner. These data clearly demonstrated that PACAP stimulates MAPK in both a PKA- and a PKC-independent manner in cultured rat astrocytes.

Animals↗
PubMed1998

Characteristics of local electrograms with diastolic potentials: identification of different components of return pathways in ventricular tachycardia.

BACKGROUND: Diastolic potentials are often sought as a possible site for catheter ablation in post-infarct ventricular tachycardia. However, delivery of energy at such sites is often unsuccessful. The purpose of this study was to determine the characteristics of local electrograms with diastolic potentials and to identify activation pattern which might indicate the critical portion of the return path of the ventricular tachycardia reentry circuit. METHODS: In 17 patients with post-myocardial infarction ventricular tachycardia, 30 ventricular tachycardias were mapped with an 112 bipolar endocardial balloon at the time of surgery. Diastolic mapping of the return tract in ventricular tachycardia was performed. Four activation patterns were observed (15 figure 8 patterns, 2 circular patterns, 2 biregional patterns and 11 monoregional patterns). Of 3,360 local electrograms, 207 (6.2%) demonstrated a diastolic potential in ventricular tachycardia. They were classified into following four categories, based on the appearance and timing of the systolic component. Type A-1 electrogram: systolic activation was of low amplitude (< 2 mV) and was prolonged (> or = 100 msec), but preceded the onset of the surface QRS in ventricular tachycardia. Type A-2 electrogram: systolic activation was of low amplitude, was prolonged, but followed the onset of the surface QRS. Type B electrogram: systolic electrogram was fractionated, but relatively normal amplitude (2.0-3.6 mV). Type C electrogram: systolic electrogram was almost normal. RESULTS: Of all electrograms with diastolic potentials, three type A-1 electrograms (1.4%) were located at the exit of the return pathway, 11 type A-1 electrograms (5.3%) were located at the pre-exit site. No type A-1 was found at an entrance/bystander area. 21 type A-2 electrograms (10.1%) were at the pre-exit and 83 type A-2 electrograms (40.2%) were located at the entrance/bystander area, but such electrograms were never found at the exit site. 71 type B electrograms (34.3%) and 18 type C electrograms (8.7%) were located at the entrance/bystander area. To distinguish the type A-2 electrograms at the pre-exit site from those at the entrance/bystander area, the diastolic potential to QRS interval was measured. This interval at the pre-exit was significantly shorter than that at the entrance/bystander area (-47.2 +/- 10.7 vs -96.3 +/- 31.3 msec, p = 0.0001). CONCLUSION: Type A-1 electrograms indicated the exit or pre-exit site of return pathway. Type A-2 electrograms with diastolic potential to QRS interval < -50 msec indicated the pre-exit site. However, the other types of local electrograms with diastolic potential did not indicate the critical portion of the ventricular tachycardia circuit. These observations may be helpful during catheter mapping and ablation of patients with post-infarct ventricular tachycardia. CONDENSED ABSTRACT: Diastolic potentials are often sought to direct catheter ablation in post-infarct ventricular tachycardia. We investigated the characteristics of local electrograms showing diastolic activity in an attempt to determine whether critical portions of the ventricular tachycardia circuit could be identified by a typical "signature." In 17 patients with a remote myocardial infarction, 30 ventricular tachycardias were mapped with 112 bipolar endocardial balloon at the time of surgery. Diastolic potentials in association with low amplitude (< 2 mV) and prolonged (> or = 100 msec) systolic electrograms preceding the onset of QRS were found at the exit site and pre-exit site of return pathway. A similar systolic electrogram occurring after QRS onset with a diastolic potential to QRS interval of < -50 msec was found at the pre-exit site. However, other local electrograms with diastolic activity were at sites remote from the exit or pre-exit of the return pathway. These observations may be helpful during catheter mapping and ablation in patients with ventricular tachycardia.

Body Surface Potential Mapping↗