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Biomedical subjects

K Sugaya

Publications and source records attributed to K Sugaya.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Angiotensin II receptor subtype in human adrenal glands].

Although adrenal gland is one of the major target organs of angiotensin II (Ang II), the pathophysiological significance of the its receptor subtype has not been elucidated. We demonstrated by reverse transcription-polymerase chain reaction with Southern blot analysis mRNA expression of both AT1 and AT2 in human adrenal tissues of normal adrenocortical tissues, aldosterone-producing adenoma, Cushing's syndrome, and pheochromocytoma. Ang II-induced aldosterone secretion in vitro was suppressed only by 50% in the presence of selective AT1 antagonist CV-11974, while AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control. Ang II or CGP-42112 did not affect cortisol secretion. In addition, Ang II could stimulate aldosterone secretion in AT1a knockout mice both in the presence and absence of CV-11974. These results suggest that non-AT1 receptor subtype(s) including AT2, as well as AT1, is involved in the stimulation of aldosterone secretion from human adrenals.

Adrenal Gland Neoplasms↗
PubMed1999

[Giant prostatic hypertrophy: a case report].

Benign prostate hypertrophy weighing more than 200 g is defined as giant prostatic hypertrophy. An 81-year-old man presented with urinary retention and underwent retropubic prostatectomy. Blood loss was 1,850 ml and he received 800 ml of autologous blood. The removed specimen weighed 267 g and pathology revealed benign hyperplasia of the prostate. We collected 32 such cases from the Japanese literature.

Aged↗
PubMed1999

[Retroperitoneal schwannoma arising from the adrenal area: a case report].

A 67-year-old woman presented with upper abdominal pain and was found to have a suprarenal tumor by ultrasonography and CT scanning. Under a diagnosis of non-functioning adrenal tumor, we made an extraperitoneal approach via a lumbar incision and removed the tumor together with the left adrenal gland. There was minimal blood loss. The resected tumor was firm and had a yellowish-white cut surface. The lesion measured 60 x 40 x 35 mm and weighed 50 g. The pathological diagnosis was benign schwannoma, mainly of the Antoni type A. This is the 27th case of benign schwannoma in the adrenal area reported in the Japanese literature.

Adrenal Gland Neoplasms↗
PubMed1999

[Renal transplantation for patients with systemic lupus erythematosus: report of two cases].

Renal transplantation for patients with systemic lupus erythematosus (SLE) remains controversial. We performed living-tissue related renal transplantation on a 45-year-old woman with SLE and an eight-month history of hemodialysis. We also did cadaveric renal transplantation on a 41-year-old man with SLE and a 12-year history of hemodialysis. Serological tests including tests for antinuclear antibodies and complements were negative prior to surgery and throughout the course in both cases. The latter patients survived herpes-zoster virus infection in month 6 and bacterial pneumonia in month 9 after transplantation. Neither patient experienced any rejection or relapse of lupus nephritis after the procedure, and both maintained good renal allograft functions. The recurrence of lupus nephritis is reportedly extremely rare, i.e., with a possibility rate of less than 1% in transplant patients with burnt-out SLE. To the best of our knowledge, these cases are the 27th and 28th case reports of renal transplantation for SLE patients in Japanese literature.

Adult↗
PubMed1999

[Simultaneous and metachronous pelvic bone metastases from renal cell carcinoma necessitating hemipelvectomy: report of two cases].

Two patients, one with and one without a history of nephrectomy for renal cell carcinoma, presented with lower abdominal pain. One of them, a 49-year-old man, had tumors in the right kidney and the right ischiadic bone. He underwent nephrectomy and pathologic findings showed renal cell carcinoma (tubular type, granular cell subtype, INF-gamma, G2). The other patient, a 33-year-old man with a previous history of left nephrectomy for renal cell carcinoma (tubular type, granular cell subtype, INF-alpha, G2), was found to have a large tumor in the pelvis, extending from the pubic and iliac bones to the hip joint. Both patients underwent embolization of the hypervascular mass using a vascular coil followed by hemipelvectomy under general anesthesia. The pathology reports confirmed bone metastases from renal cell carcinoma. Both patients survived surgery and their postoperative courses were uneventful without urinary or bowel incontinence. However, impaired potency was noted in the latter case. Immunotherapy with INF-alpha was resumed immediately after surgery.

Adult↗
PubMed1998

Indicators of glial activation and brain oxidative stress after intraventricular infusion of endotoxin.

Glial activation and oxidative stress are both consequences of brain aging. To investigate whether glial activation causes oxidative stress or not, the immune activator, lipopolysaccharide (LPS), was intraventricularly injected into the rat brain. The expression of candidate genes were examined by in situ hybridization histochemistry (ISHH) combined with immunohistochemistry for glial markers over a period of time up to 24 h after the LPS injection. The mRNA for glial fibrillary acidic protein (GFAP) was elevated around the injection site by 2 h, and the volume of elevated expression spread to the entire brain after 6 h, with higher levels present in the injected hemisphere. The level of inducible isoform of nitric oxide synthase (i-NOS) mRNA increased in a punctate-like pattern in the region of the injection by 6 h and this response spread to the entire brain after 12 h. These results indicate that the glia are activated for at least 24 h after a single LPS injection. The mRNAs for a heat-shock protein (HSP70) and for the manganese-dependent superoxide dismutase (Mn-SOD) were elevated in the ipsilateral hemisphere as early as 2 h post-injection, but these responses subsided nearly to basal levels by 4 h. These levels of mRNAs for these genes increased again after 6 h of the LPS injection; thus, the earlier increases of the messages appeared to be associated with the survival surgery procedure. With microautoradiographic analysis, scattered OX-42 positive cells expressed i-NOS mRNA after 6 h post-injection, but elevation of Mn-SOD mRNA was not detected in either microglia or astrocytes at any time point examined. The level for Cu/Zn-SOD mRNA did not alter at any time point. The beta-amyloid precursor protein (betaAPP) mRNAs were elevated beginning at 6 h. These results indicate that chronic glial activation leads to a condition of oxidative stress in the brain. The data also suggest that LPS injection could be used to study the effects of chronic glial activation on the survival of neuronal populations that could be at risk from oxidative stress.

Animals↗
PubMed1998

An alternative procedure for the creation of an ileal conduit in patients undergoing pelvic exenteration: dextrotransmesenteric location.

Ileal conduits have long been accepted as a standard method for urinary diversion, but conventional ileal conduits are not always suitable for patients whose ureters are for the greater part compromised by neoplasm or preoperative irradiation, resulting in a shortening of the ureters. Bowel migration into the large cavity, which develops after pelvic organ removal, appears to cause tension on the ureteroileal anastomotic site. Dextrotransmesenteric placement of an ileal conduit may provide easy access to the shortened ureters without exerting pressure on the anastomosis. We employed this procedure in seven patients undergoing pelvic exenteration with relatively minimal morbidity.

Adult↗
PubMed1998

Alteration of the largest subunit of RNA polymerase II and its effect on chromosome stability in Schizosaccharomyces pombe.

A mutation in the RNA polymerase II largest subunit (RpII LS) that is related to abnormal induction of sister chromatid exchange has previously been described the CHO-K1 cell mutant tsTM4. To elucidate the molecular basis of this effect we introduced the mutation into the homologous site in the Schizosaccharomyces pombe rpbl gene, which encodes RpII LS. Since the tsTM4 mutant exhibited a decrease in the rate of DNA synthesis in cells arrested in S phase at the nonpermissive temperature, we focussed on the study of growth, the cell cycle, and chromosome stability at various temperatures. First, we examined the effects of the mutation on haploid yeast cells. The mutant showed slower growth than the wild type, but cell growth was not arrested at the nonpermissive temperature. When growing cells were shifted to the nonpermissive temperature, an accumulation of cells in G1 and/or G0 was observed. Tetrad analysis suggested that these phenotypes were associated with the mutation. In diploid cells, chromosome instability was detected by loss of intragenic complementation between two alleles of the ade6 gene. An abnormal fraction of cells containing an intermediate DNA content was also observed by FACS analysis. The accumulation of this fraction may reflect the fact that a large number of cells are in S phase or have an abnormal DNA content as a result of chromosome instability. These observations demonstrate that the S. pombe rpb1 mutant exhibits a phenotype very similar to that of the CHO-K1 cell mutant tsTM4.

Amino Acid Sequence↗
PubMed1998

Evidence for involvement of the subcoeruleus nucleus and nucleus raphe magnus in urine storage and penile erection in decerebrate rats.

PURPOSE: Micturition and male sexual activity require the lower urinary tract to function. During the sexual act, micturition must be inhibited and urine stored in the bladder. We studied the role of the brainstem in relation to both micturition/urine storage and penile erection in rats. MATERIALS AND METHODS: Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes for stimulation were introduced into the brainstem in decerebrate male rats. Electrical stimulation was used to locate optimally responding sites by monitoring the isovolumetric intravesical pressure and intracavernous pressure. RESULTS: Electrical stimulation of the dorsal nerve of the penis, the subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the caudal pons increased intracavernous pressure, but inhibited rhythmic bladder contractions. Electrical stimulation of Barrington's nucleus (the pontine micturition center in the rat) in the rostral pons induced bladder contraction. Stimulation of the pontine reticular formation did not increase intracavernous pressure. Acute transection of the thoracic spinal cord eliminated rhythmic bladder contractions, but gave rise to sporadic increments of intracavernous pressure. CONCLUSIONS: This electrophysiological study demonstrated that the subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage and penile erection, and that their physiological functions are reciprocally controlled; so that erection leads to inhibition of micturition.

Animals↗
PubMed1998

Developmental and injury induced plasticity in the micturition reflex pathway.

The storage and periodic elimination of urine are dependent upon neural circuits in the brain and spinal cord that co-ordinate the activity of the urinary bladder, the urethra and the striated urethral sphincter. This study utilized anatomical, electrophysiological and pharmacological techniques to examine: (1) the organization of the parasympathetic excitatory reflex mechanisms that control the urinary bladder of the rat and the cat; and (2) the changes in these reflexes during postnatal development and after spinal cord injury. In normal adult cats and rats, the parasympathetic excitatory input to the bladder is dependent upon a spinobulbospinal reflex pathway that is activated by myelinated (Adelta) bladder afferents and that passes through an integrative center (the pontine micturition center, PMC) in the rostral brain stem. Transneuronal tracing studies using pseudorabies virus as well as physiological methods have revealed that the PMC is located in close proximity to the locus coeruleus. Single unit recordings indicate that neurons in the PMC respond to afferent input from the bladder and are excited prior to or during reflex bladder contractions. Glutamic acid is the major excitatory transmitter in the micturition reflex pathway. Glutamatergic transmission which is mediated by AMPA/kainate and NMDA receptors can be modulated by a variety of other transmitters. In neonatal animals, a spinal micturition reflex is activated by somatic afferent fibers from the perigenital region. This reflex is suppressed during postnatal development, but can be unmasked in adult animals following spinal cord injury. Spinal injury also causes the emergence of a spinal bladder-to-bladder reflex which in the cat is activated by capsaicin-sensitive C-fiber bladder afferents. Patch clamp studies in spinal cord slice preparations indicate that developmental and spinal cord injury induced plasticity in sacral parasympathetic reflex pathways is due in part to alterations in glutamatergic excitatory transmission between interneurons and preganglionic neurons. Changes in the electrical properties of bladder afferent pathways may also contribute to the reorganization of bladder reflexes in paraplegic animals.

Animals↗
PubMed1998

A novel immunosuppressant, FTY720, increases the efficiency of a superantigen-induced peripheral T-cell deletion whilst inhibiting negative selection in the thymus.

A novel immunosuppressant, FTY720, was generated by chemical modification of ISP-I, an immunosuppressive compound purified from culture filtrates of Isaria sinclairii. FTY720 directly induces apoptotic cell death in lymphocytes, which is believed to be the mechanism by which this drug exerts its immunosuppressive effect. We examined the effect of FTY720 treatment on antigen-induced apoptotic cell death in peripheral T cells and thymocytes. A superantigen, staphylococcus enterotoxin B (SEB), induces T-cell antigen receptor (TCR) Vbeta-specific apoptotic cell death in mature T cells in vivo. In this well-documented experimental system, FTY720 administration significantly enhanced the efficiency of superantigen-induced T-cell deletion. We also determined that apoptotic cell death with DNA fragmentation induced in T-hybridoma cells after stimulation in vitro with anti-TCR antibodies was enhanced in the presence of non-cytolytic doses of FTY720. In sharp contrast, negative selection of T cells in the thymus, another example of antigen-induced apoptosis, was found to be inhibited by FTY720 treatment. A rescue effect was observed on clonal deletion in the H-Y-specific TCRalpha beta transgenic male thymus. In a chicken egg albumin (OVA)-specific TCRalphabeta transgenic system, OVA-induced apoptotic cell death of CD4+CD8+ thymocytes was also inhibited by FTY720 injection. Thus, FTY720 increased the susceptibility of mature T cells to TCR-mediated apoptosis but decreased that of immature thymocytes. The results in this report suggest that the potent immunosuppressive effect of FTY720 is, in part, a result of the augmentation of effects on antigen-induced apoptosis in mature T cells, and that two distinct apoptotic cell death pathways are operating in mature and immature T cells.

Animals↗
PubMed1998

New medicinal treatment for severe gingivostomatitis.

We formulated de novo a poraprezinc-sodium alginate suspension (P-AG) as a specific treatment for severe gingivostomatitis and administered it to 15 patients who had developed such inflammation while on chemotherapy. Very high utility of P-AG was demonstrated and the response was classified as excellent in 10 patients and good in 5 patients. The mechanism of the beneficial effect of P-AG in treatment of severe gingivostomatitis accompanied by hemorrhagic erosion and ulcers is considered to involve the mucosal protective effect, free radical scavenging activity and tissue repair promoting action of poraprezinc together with the hemostatic action of sodium alginate.

Adult↗
PubMed1998

[Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis].

BACKGROUND: Radiation therapy has widely been used for cancers in the pelvis. Radiation cystitis, one of the late complications, presents often as hemorrhagic cystitis, which is refractory to the conventional therapy and may threaten the patient's life. We used hyperbaric oxygen therapy on patients with radiation cystitis to test its potential benifit. METHODS: Ten patients aged from 46 to 81 years with a mean of 62 years underwent one or more courses of hyperbaric oxygen therapy according to their symptoms, consisting of 20 sessions (3 to 5 sessions a week) at the Department of Hyperbaric Medicine, the University of the Ryukyus Hospital in the 9-year period from 1985 to 1994. They included 8 patients having a history of cervical cancer, one with external genital cancer and one with vaginal cancer. During the 75 min hyperbaric oxygen therapy patients received 100% oxygen at 2 absolute atmosphere pressure in the Multiplace Hyperbaric Chamber. RESULTS: Hematuria subsided and subjective symptoms including urinary frequency improved in seven patients. Cystoscopic findings including mucosal edema, redness, and capillary dilation were partially improved. The procedure subjectively and objectively palliated the 10 patients in a favorable manner. CONCLUSIONS: To date we have not armed any active procedure to control radiation-induced refractory hemorrhagic cystitis in terms of efficacy, invasiveness, and adverse effects. Therefore, in consideration of our clinical results, hyperbaric oxygen therapy appears to be useful for radiation cystitis.

Aged↗
PubMed1997

Induction of manganese superoxide dismutase in BV-2 microglial cells.

The regulation of the manganese-dependent superoxide dismutase (Mn-SOD) was studied in immortalized microglial cells (line BV-2). BV-2 cells, activated with lipopolysaccharide (LPS), exhibited an increase in Mn-SOD-like immunoreactivity, that was associated with an accumulation of nitrite in the culture medium and an increase in immunoreactivity for the inducible type of nitric oxide synthase (i-NOS). The i-NOS inhibitor L-N6-(1-iminoethyl)-lysine (NIL, 600 microM) suppressed the nitrite accumulation and the increase in Mn-SOD-like immunoreactivity in activated cells without significant effect on the level of i-NOS-like immunoreactivity. The NO donor sodium nitroprusside dose-dependently increased Mn-SOD-like immunoreactivity in NIL-pretreated BV-2 cells. These results indicate that the induction of Mn-SOD in activated BV-2 cells is mediated in part by NO, or its metabolites.

Animals↗
PubMed1997

mRNA for the m4 muscarinic receptor subtype is expressed in adult rat brain cholinergic neurons.

A number of pharmacological, anatomical, and immunological studies have previously addressed the subtype identity of the hippocampal muscarinic pre-synaptic autoreceptor. A preponderance of findings indicate that it is of the M2 pharmacological type. Both the m2 and m4 molecular subtypes exhibit M2 pharmacology and there are few drugs that differentiate between these receptors. Pharmacological attempts at defining the hippocampal autoreceptor have yielded conflicting results. The basal forebrain is relatively enriched in m2 muscarinic receptor mRNA and protein, and lesions that denervate the hippocampus of its basal forebrain cholinergic input have shown a decrement in m2, but not m4, receptor protein in the hippocampus. Thus, the anatomical data obtained to date tend to support the view that the m2 subtype is expressed as the hippocampal autoreceptor. We have combined in situ hybridization histochemistry (ISHH) with immunocytochemistry to choline acetyltransferase to examine whether mRNA for the m4 subtype of muscarinic receptor is expressed in central cholinergic neurons. The m4 muscarinic mRNA was found at moderate levels in all subdivisions of the cholinergic basal forebrain, including the medial septum/diagonal band complex (MS/DB). The m4 mRNA was also found in striatal cholinergic interneurons, in the cholinergic reticular core of the upper brainstem, and in brainstem cholinergic motor neurons. Muscarinic m4 receptor mRNA was also found in many non-cholinergic cells in the brain. For example, the hippocampal pyramidal neurons, dentate gyrus granule cells, and entorhinal cortical pyramidal neurons express relatively high levels of m4 mRNA, while in the brainstem the dorsal raphe and pontine reticular nuclei express relatively high levels of this mRNA. The finding of m4 mRNA in the MS/DB cholinergic neurons suggests that this receptor protein might be expressed as an autoreceptor in hippocampal cholinergic terminals.

Animals↗
PubMed1997

Cloning and sequencing for the largest subunit of Chinese hamster RNA polymerase II gene: identification of a mutation related to abnormal induction of sister chromatid exchanges.

In order to analyze the mutation sites related to abnormal induction of sister chromatid exchanges (SCEs) in the RNA polymerase II largest subunit (RpII LS) gene of the Chinese hamster CHO-KI cell mutant, we have completely sequenced the whole region of the RpII LS cDNAs obtained from normal and mutant cells. By comparing both sequences, a mutation that results in an amino acid (aa) change in the RpII LS gene was found. This aa change was Pro (CCC) to Ser (TCC) at position 1006. Multiple alignment for aa sequences of RpII LS from various species revealed that this Pro residue was highly conserved throughout the eukaryotes. Considering the differences in physico-chemical properties between Pro and Ser residues, the Pro-->Ser substitution may alter the RpII LS structure.

Amino Acid Sequence↗
PubMed1997

Immunostimulation protects microglial cells from nitric oxide-mediated apoptosis.

Cellular oxidative stress from excess free radicals can initiate apoptosis in some cell types. Thus, we hypothesize that cells expressing nitric oxide synthase (NOS) will also express anti-oxidative stress mechanisms, in order to prevent self-intoxication by the free radical, nitric oxide (NO). To test this hypothesis, we investigated the vulnerability of microglial cells (BV-2 line) to NO produced by the NO donor sodium nitroprusside. Damage to the cells was measured by an in situ detection method of DNA fragmentation, an indicator of apoptosis. Activation by lipopolysaccharide (LPS) dose-dependently protected BV-2 cells against NO toxicity (up to 67%) while unactivated BV-2 cells were vulnerable to NO. Our results indicate that activation of BV-2 cells induces protection mechanisms against NO toxicity.

Animals↗