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Biomedical subjects

K Sugaya

Publications and source records attributed to K Sugaya.

At least 37 records · Page 2Linked to original sources

In vitro differentiation of multipotent human neural progenitors in serum-free medium.

Stem cells are exciting candidates for therapeutic strategies in neurodegenerative diseases, due to their multipotency and migratory capabilities. We show that stem cell-like embryonic normal human neural progenitors (HNPs) are capable of proliferating in response to mitogenic growth factors and differentiate into diverse CNS cell types in vitro. We present evidence that HNPs differentiate to beta III-tubulin-, glial fibrillary acidic protein- and O4-immuno-positive cells, in both a fetal bovine serum-containing and a non-supplemented, serum-free basal medium. From these findings, we propose that HNPs may differentiate not only in response to exogenous differentiation factor(s) contained in the serum, but also in response to some endogenous factor(s) released from the HNPs, which may regulate the differentiation pathway of these cells.

Antigens, Differentiation↗

Bladder-pumping therapy for the treatment of low-capacity or low-compliance bladders.

The walls of low-capacity or low-compliance bladders are thought to be less elastic than normal. Pumping of the bladder was found to disrupt collagen-fiber bundles in the rat bladder wall, offering the promise of potential clinical application. This result prompted us to use bladder-pumping therapy to soften the bladder wall in patients with low-capacity or low-compliance bladders to restore bladder elasticity. CO(2) gas or air, at a volume below the maximum bladder capacity (</=200 mL), was repeatedly pumped in and out of the bladder through a catheter under caudal anesthesia in 26 patients with low-capacity or low-compliance bladders and without uninhibited bladder contractions, who presented with urinary frequency or incontinence. A respirator was used to control the pumping at 0.5 cycles/s for a duration of 15 minutes. No serious adverse effects were encountered during or after the procedure. Overall subjective improvement was noted 4 weeks after the procedure in 11 of 18 patients with a low capacity bladder (<300 mL) and in five of eight patients with a low-compliance bladder (<20 mL/cm H(2)O). The procedure significantly increased the maximum bladder capacity, single voided volume, and average urinary flow rate after 4 weeks. In the responding patients, subjective improvement lasted from 3 months to over 6 years. Bladder-pumping therapy is an easy and safe procedure and exerts a beneficial effect for a long period, in patients with low-capacity or low-compliance bladders and without uninhibited bladder contractions. Neurourol. Urodynam. 19:19-28, 2000.

Adolescent↗

Pelvic congestion syndrome caused by inferior vena cava reflux.

We present a female patient who had pelvic congestion syndrome caused by inferior vena cava reflux associated with tricuspid regurgitation, but without other symptoms or signs related to her tricuspid regurgitation. Bladder pumping therapy was effective in improving her symptoms.

Female↗

Impact of citrate therapy on the circadian rhythm of urinary magnesium ammonium phosphate saturation in normal individuals.

BACKGROUND: Alkaline citrate has been used widely in the prevention of stone formation. However, the risk of struvite stone during the alkalinizing therapy has not been adequately studied in terms of magnesium ammonium phosphate saturation. METHODS: The circadian rhythm of the urinary saturation of magnesium ammonium phosphate was estimated by using the differential Gibbs' free energy values of magnesium ammonium phosphate before and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g q.i.d. or 3 g t.i.d.) in five healthy male volunteers. RESULTS: The magnesium ammonium phosphate saturation varied during the day, peaking far below the solubility product between 08.00 and 10.30 h and between 13.00 and 18.00 h. The mean peak levels were increased by each treatment regimen in comparison with the control day. The mean increase on day 1 was significant between 10.30 and 23.00 h with the 3 g t.i.d. regimen, but the mean saturation still remained below the solubility product throughout the day. CONCLUSIONS: The urinary magnesium ammonium phosphate saturation appeared hard to exceed the solubility product with a high dose of alkaline citrate.

Adult↗

Putative role of neuronal 5-lipoxygenase in an aging brain.

Aging is associated with increased incidence and/or severity of neurodegenerative pathologies. Oxygen-mediated events are being considered as possible mechanisms responsible for the increasing neuronal vulnerability. Lipoxygenases are enzymes that, as cyclooxygenases (COX), can insert oxygen into the molecule of arachidonic acid and thereby synthesize inflammatory eicosanoids: leukotrienes [due to 5-lipoxygenase (5-LOX) activity] and prostaglandins (via COX activity). It appears that 5-LOX is expressed in central nervous system neurons and may participate in neurodegeneration. 5-LOX-triggered cell death may be initiated by the enzymatic activity of 5-LOX but could also occur via the nonenzymatic actions of the 5-LOX protein; new data point to the possibility that 5-LOX protein exerts actions such as interaction with tyrosine kinase receptors, cytoskeletal proteins, and the nucleus. The expression of neuronal 5-LOX is susceptible to hormonal regulation, presumably due to the presence of hormone-responsive elements in the structure of the 5-LOX gene promoter. The expression of the 5-LOX gene and the activity of the 5-LOX pathway are increased in elderly subjects. One possible mechanism of such 5-LOX up-regulation implies the contribution of aging-associated hormonal changes: relative melatonin deficiency and/or hyperglucocorticoidemia. Thus, the 5-LOX pathway could become a promising target of neuroprotective therapies for the aging brain.

Aging↗

Influence of temperature on activity of the isolated whole bladder preparation of neonatal and adult rats.

The temperature sensitivity of in vitro whole bladder preparations from neonatal and adult rats with or without chronic partial urethral obstruction was investigated. After the bladder was filled to a volume eliciting isovolumetric contractions, temperature was changed between 19 and 38 degrees C. In all preparations, higher temperatures were associated with higher frequencies of spontaneous intravesical pressure waves (IVPW). In 1- to 2-wk-old neonates, IVPW amplitude increased as the temperature increased; however, in older neonates and normal adults, the opposite occurred. The transition period was at 3 wk of age when bladder volume also markedly increased. At this age as well as in adult rats with outlet obstruction, changing temperature had little influence on the amplitude of IVPW. Thus obstructed outlet bladders and 3-wk-old bladders had similar properties. It is concluded that the properties of bladder muscle are changed during postnatal maturation and that in 3-wk-old rats, when brain control of voiding is emerging, micturition is abnormal, leading to obstructive changes in bladder muscle.

Aging↗

Mammalian cell lines expressing functional RNA polymerase II tagged with the green fluorescent protein.

RNA polymerase II is a multi-subunit enzyme responsible for transcription of most eukaryotic genes. It associates with other complexes to form enormous multifunctional 'holoenzymes' involved in splicing and polyadenylation. We wished to study these different complexes in living cells, so we generated cell lines expressing the largest, catalytic, subunit of the polymerase tagged with the green fluorescent protein. The tagged enzyme complements a deficiency in tsTM4 cells that have a temperature-sensitive mutation in the largest subunit. Some of the tagged subunit is incorporated into engaged transcription complexes like the wild-type protein; it both resists extraction with sarkosyl and is hyperphosphorylated at its C terminus. Remarkably, subunits bearing such a tag can be incorporated into the active enzyme, despite the size and complexity of the polymerizing complex. Therefore, these cells should prove useful in the analysis of the dynamics of transcription in living cells.

Animals↗

New anti-inflammatory treatment strategy in Alzheimer's disease.

Numerous reports have indicated that patients suffering from inflammatory diseases (e.g., arthritis) who take anti-inflammatory medication have a reduced risk of developing Alzheimer's disease (AD). Thus, the first generation of anti-inflammatory cyclooxygenase (COX) inhibitors, such as aspirin and indomethacin, have been tested as potential therapeutics in AD. Because the inhibition of COX-1 is also known to cause tissue damage in the gastrointestinal system from the resultant reduced cytoprotection, selective COX-2 inhibitors are being investigated and tested clinically as potentially better therapeutics for AD patients. However, such drugs may also trigger unwanted effects; for example, the COX-2 inhibitors, which reduce the production of one type of eicosanoids, the prostaglandins, may increase the production of other eicosanoids; i.e., the leukotriene B4 (LTB4), which is one of the most potent endogenous chemotactic/inflammatory factors. LTB4 production is initiated by the enzyme 5-lipoxygenase (5-LOX). The expression of the 5-LOX gene is upregulated during neurodegeneration and with aging. In spite of the fact that 5-LOX and leukotrienes are major players in the inflammation cascade, their role in AD pathobiology/therapy has not been extensively investigated. We propose that the 5-LOX inflammatory cascade may take part in the process of aging-associated neurodegenerative diseases, and we point to the role of 5-LOX in neurodegeneration and discuss its relevance for anti-inflammatory therapy of AD.

Alzheimer Disease↗

Specialized transcription factories within mammalian nuclei.

Recent evidence suggests that active RNA polymerases are concentrated in discrete 'factories' where they work together on many different templates. The evidence that such factories specialize in the transcription of particular groups of genes is reviewed.

Cell Nucleolus↗

Compensatory renal hypertrophy and changes of renal function following nephrectomy.

We studied the changes in the serum creatinine level and the volume of the remaining kidney following nephrectomy using contrast-enhanced compounded tomogram (CT) scans. Twenty-five patients undergoing nephrectomy for renal cell carcinoma without obvious disease in the remaining kidney were carefully followed for a period of at least two years at our hospital. Twelve patients received follow-up CT scans each year after nephrectomy. The ellipsoid volume of the kidney was calculated by measuring the 3-dimensional size on CT scans. The mean relative volume (%) of the remaining kidney increased up to year 3 postoperatively, and the final mean relative volume at varying periods from years 2 to 7 was 120%. Kidneys that were smaller prior to nephrectomy showed a tendency to have a larger final relative volume after nephrectomy, although there was no significant correlation between the kidney volume prior to nephrectomy and at final measurement. The mean serum creatinine level was significantly increased at one year after nephrectomy, but it decreased significantly over time. Therefore, both compensatory renal hypertrophy and improved renal function seemed to be established within several years after nephrectomy. However, the improvement of serum creatinine was delayed compared with the increase of kidney volume. That is, renal plasma flow might be increased early by compensatory renal hypertrophy, followed within a few years by an increase in glomerular filtration and a decrease of serum creatinine.

Adult↗

Urinary oxalate, glycolate, glyoxylate, and citrate after acute intravenous administration of glyoxylate in rats.

BACKGROUND AND PURPOSE: Urinary oxalate plays an important role in the formation of calcium oxalate renal stones, and approximately 50% to 60% of urinary oxalate is derived from the endogenous metabolism of glyoxylate. Therefore, we measured urinary oxalate, glycolate, glyoxylate, and citrate concentrations after acute intravenous administration of various doses of glyoxylate in rats to study oxalate metabolism. MATERIALS AND METHODS: Male Wistar rats weighing approximately 200 g were divided into six groups of eight animals each. Anesthetized rats received glyoxylate (0, 1, 2, 5, 10, and 20 mg) intravenously. Urine specimens were collected before and every hour after each dose for 4 hours, and the concentrations of oxalate, glycolate, glyoxylate, and citrate were measured by capillary electrophoresis. RESULTS: Hourly oxalate excretion in the urine peaked at 1 hour after glyoxylate administration, and the peak concentration increased in a dose-dependent manner. Approximately 15% to 30% (mol/mol) of the dose was converted to oxalate within 4 hours and 2% to 4.6% was converted to glycolate. Urinary glyoxylate was not detectable before glyoxylate administration, but large doses resulted in a significant amount of glyoxylate (0.7%-2.3%) appearing in the urine, and the level peaked at 1 hour after administration. Urinary glycolate also peaked at 1 hour after administration of glyoxylate. The urinary citrate concentration generally decreased by 3% to 33% after each dose of glyoxylate, except that it increased slightly after the 20-mg dose. CONCLUSION: Administration of glyoxylate increased urinary oxalate and glycolate excretion in rats, supporting the importance of the glycolate-glyoxylate-oxalate pathway.

Animals↗

Effects of glutamate receptor antagonists on lower urinary tract function in conscious unanesthetized rats.

OBJECTIVES: To study the effects of the intrathecal administered glutamate receptor antagonists on the bladder and urethral activities during isovolumetric bladder contraction in conscious normal and chronic spinal rats. METHODS: Twenty-eight female Wistar rats with and without previous spinal cord transection were used. Before and after intrathecal administration of glutamate receptor antagonist, urodynamic parameters under isovolmetric condition of the bladder were analyzed. RESULTS: In normal rats, MK-801 (noncompetitive N-methyl-D-aspartate [NMDA] receptor antagonist) and LY 293558 (competitive AMPA receptor antagonist) produced a decrease in bladder contraction pressure and urethral activity with dose dependent manner. In chronic spinal rats, detrusor-sphincter dyssynergia (DSD) was developed before drug administration. MK-801 and LY 293558 partially inhibited bladder contraction pressure, and markedly depressed urethral contraction concomitant with bladder contraction. LY 293558 produced urethral relaxation concomitant with bladder contraction. CONCLUSIONS: In both normal rats and chronic spinal rats, two subtypes of glutamate receptors (NMDA and AMPA receptors) in the spinal cord were involved in the control of bladder and urethral activities. The AMPA receptor in the spinal cord seems to take an important role in the development of DSD.

Animals↗

Poorly differentiated sarcoma of the prostate causing obstructive acute renal failure: a case report.

A 12-year-old boy presented to the Naha Municipal Hospital complaining of back pain. After intravenous pyelography, computed tomography, magnetic resonance imaging, ultrasonography and biopsy, he was suspected to have sarcoma of the prostate and was referred to the University of the Ryukyus Hospital. Acute renal failure of the post renal type was evident, accompanied by minimal hydronephrosis. Emergency hemodialysis and right ureterostomy were performed, as was a transurethral prostate biopsy. The specimen showed a poorly differentiated sarcoma not otherwise classifiable. After recovery from surgery, chemotherapy was attempted over 2 months, but the patient died of tumor 250 days after admission.

Acute Kidney Injury↗

Effect of injury to the dorsal funiculus of the thoracic spinal cord on micturition in decerebrate and freely-moving cats.

Bladder sensation is transmitted both via the spinothalamic tract in the lateral funiculus and the dorsal system in the dorsal funiculus. We transected the dorsal funiculus in 10 female cats to clarify the functional roles of these two ascending pathways. The dorsal funiculus was transected at T10 in 5 decerebrate and 5 freely-moving cats, and micturition parameters were compared before and after transection. Transection of the dorsal funiculus did not affect any of the parameters of reflex micturition in the 5 decerebrate cats. Within 1 week after transection, 4 of the 5 freely-moving cats used the normal micturition posture, but the remaining one performed micturition in a prone position as if she had lost micturition sensation. All 5 cats urinated with a normal micturition posture by 2 weeks after transection. The mean single voided volume was decreased transiently up to 1 week, but returned to normal by 2 weeks after transection. None of the 5 cats had any residual urine before and after transection. Both the ascending and descending limbs of the micturition reflex pass through the lateral funiculus. Bladder sensation is transmitted both via the spinothalamic tract coursing in the lateral funiculus and the dorsal system in the dorsal funiculus. The dorsal system may play a major role in the transmission of bladder sensation to the cerebral cortex, but may not be essential.

Animals↗

Expression of superoxide dismutase messenger RNA in adult rat brain cholinergic neurons.

Superoxide dismutase (SOD) protects cells exposed to an excess of the free radical nitric oxide, by preventing the formation of peroxynitrite. Certain central cholinergic neurons express constitutive nitric oxide synthase (nNOS), and presumably they are at risk from peroxynitrite intoxication. Immunocytochemistry for choline acetyltransferase (ChAT) was combined with in situ hybridization histochemistry (ISHH) to examine whether brain cholinergic populations differ with respect to their expression of the messenger RNA molecules (mRNAs) for the manganese-dependent (Mn-SOD) and copper/zinc-dependent superoxide dismutases (Cu /Zn-SOD). The cholinergic neurons located in the reticular formation of the upper brainstem (the laterodorsal tegmental nucleus [LDTN] and the pedunculopontine nucleus [PPN]) were found to express relatively high levels of Mn-SOD mRNA, whereas cholinergic neurons located in the basal forebrain (substantia innominata [SI], diagonal band [DB], medial septum [MS], and the nucleus basalis magnocellularis [nBM]), and the striatal cholinergic interneurons expressed low to intermediate levels of Mn-SOD mRNA. The rank order of median Mn-SOD mRNA density per cholinergic cell was LDTN > PPN > SI > striatum = nBM = DB > MS. This is similar to the rank order of nNOS mRNA densities in the cholinergic cells in these regions (R = 0.9, p < 0.02). The rank order of Cu/Zn-SOD mRNA levels in cholinergic populations (DB > LDTN = PPN =MS > SI = nBM = striatum) was not correlated with nNOS mRNA (R = 0.29, P > 0.05). Thus, for cholinergic neurons, Mn-SOD may be important for protection from NO-related oxidative stress.

Animals↗

[Fornix of vagina suspension for cystocele].

OBJECTIVE: Bladder neck hypermobility causes cystocele in middle to old elderly women. We developed an easy and useful surgical technique for cystocele. METHODS: Thirteen patients with cystocele (grade 2-4) were operated by fornix of the vagina suspension. Patients were placed on lithotomy position under general or spinal anesthesia. Lower midline or lower abdominal transverse incision was made to open the peritoneum and denuded vesicouterine pouch. Several nylon sutures were placed on the lateral side of exposed fornix of the vagina. These sutures were suspended to anterior layer of the rectus sheath. Fornix of the vagina was fixed to the rectus muscle, so the prolapsed bladder wall was pulled up in normal position. RESULTS: Operating time ranged from 15-110 minutes (average 73 minutes). Ten patients of thirteen were successful up to 2-43 months postoperatively. Cystocele recurred in three patients of thirteen. Two patients was re-operated by the same method, but one of them recurred. Two of three recurrent patients had grade 4 cystocele. CONCLUSION: Fornix of the vagina suspension for cystocele seems useful and promising because of easy procedure without serious morbidity, especially in elderly high-risk patients.

Aged↗

[Hypogonadotropic hypogonadism treated with HCG monotherapy: report of 3 cases].

We report 3 cases of hypogonadotropic hypogonadism and the effects of human chorionic gonadotropin (HCG) monotherapy on plasma testosterone levels, which were related to clinical results. The patients were males 29, 21 and 14 years old. Each received 5,000 units of HCG subcutaneously or intramuscularly twice or three times a week for 16 to 40 months. Genital effects, including an increase in testicular volume were seen in all patients after 2 or 3 months. The increase in plasma testosterone level after HCG therapy was significantly correlated with the genital effects similarly to other treatments. Moreover, spermatozoa appeared in one case.

Adolescent↗