[Mixed gonadal dysgenesis].
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Biomedical subjects
Publications and source records attributed to Takahiko Mitsui.
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Transplanting neuronal and glial restricted precursors (NRP/GRP) into a midthoracic injury 9 d after contusion improved bladder and motor function, diminished thermal hypersensitivity, and modified lumbosacral circuitry compared with operated controls (OP-controls). Histological analysis showed that NRP/GRP survived, filled the lesion site, differentiated into neurons and glia, and migrated selectively. Volume of spinal cord spared was increased in NRP/GRP recipients, suggesting local protection. Bladder areflexia developed in both operated groups, but NRP/GRP recipients exhibited an accelerated recovery, with decreased micturition pressure and fewer episodes of detrusor hyperreflexia. Because noradrenergic receptors proliferate after spinal injury and descending noradrenergic pathways contribute to regulation of bladder control, we examined the effects of administering an alpha-1A-adrenergic antagonist, Tamsulosin, on urodynamics. This improved all cystometric parameters in both operated groups, and micturition pressure in NRP/GRP rats recovered to normal levels. Both operated groups initially showed increased sensitivity to a thermal stimulus applied to the tail; the NRP/GRP rats showed significant improvement over time. NRP/GRP grafts also produced greater recovery of hindlimb function in several tests, although both groups showed persistent and similar deficits in locomotion on a grid. Because bladder, hindlimb, and tail sensory and motor functions are organized through lumbosacral cord, we examined descending and primary afferent projections at L6-S1. The density of serotonergic, noradrenergic, and corticotrophin releasing factor-positive fibers increased in the NRP/GRP group compared with OP-controls, suggesting some sparing and/or sprouting of these modulatory pathways. Immunocytochemical staining density of dorsal root axons in the dorsal horn increased in the OP-controls but appeared normal in the NRP/GRP group. Synaptophysin immunoreactivity in the lumbosacral dorsal horn was similar among groups, consistent with restoration of synaptic density in both groups of operated animals but by different pathways. We suggest that local protection provided by NRP/GRP resulted in increased sparing/sprouting of descending pathways, which prevented sprouting by dorsal root axons, and that this modification in lumbosacral circuitry contributes to the recovery of function.
We examined whether fibroblasts, genetically modified to express BDNF and NT-3 (Fb-BDNF/NT3) and transplanted into a thoracic spinal injury site, would enhance recovery of bladder function and whether this treatment would be associated with reorganization of lumbosacral spinal circuits implicated in bladder function. Rats received modified-moderate contusion injuries at T8/9, and 9 days later, Fb-BDNF/NT3 or unmodified fibroblasts (OP-controls) were delivered into the cord. Fb-BDNF/NT3 rats recovered from areflexic bladder earlier, showed decreased micturition pressure and fewer episodes of detrusor hyperreflexia, compared to OP-controls. There were also improvements in hindlimb function in the Fb-BDNF/NT3 group although locomotion on a more challenging substrate (grid) and tail withdrawal latency in response to a thermal stimulus showed persisting deficits, little recovery, and no differences between the groups. Immunocytochemistry at L6-S1 revealed changes in density of afferent and descending projections to L6-S1 cord. The density of small dorsal root axons increased in the superficial layers of the dorsal horn in OP-controls but not in Fb-BDNF/NT3, suggesting sprouting of primary afferents following injury that was inhibited by Fb-BDNF/NT-3. In contrast, the trophic factor secreting transplants stimulated sprouting and/or sparing of descending modulatory pathways projecting to the lumbosacral spinal cord. No differences in synaptophysin immunoreactivity were seen in the dorsal horn which suggested that synaptic density was similar but achieved by sprouting of different systems in the two operated groups. Fb-BDNF/NT3 transplanted into injured spinal cord thus improved both bladder and hindlimb function, and this was associated with reorganization of spinal circuitry.
We investigated the topographical localization of c-fos expression in the midbrain periaqueductal gray matter (PAG) to detect nociception-induced neural activity in the PAG. In conscious female Wistar rats, c-fos expression was induced by continuous intravesical infusion of saline or 0.1% acetic acid. Number of c-fos protein (Fos)-positive cells was counted at each coronal section of the PAG as well as Barrington's nucleus. Fos-positive cells were also counted at L1 and L6 of the spinal cord, where most of the hypogastric and pelvic nerve afferent terminals project, respectively. Compared with saline infusion, acetic acid infusion provoked irritative bladder responses characterized by a marked increase in the frequency of bladder contractions, and induced a significant increase in the number of Fos-positive cells in both L1 and L6 of the spinal cord. Following acetic acid infusion, there was a significant increase in the number of Fos-positive cells in all coronal sections of the PAG compared with saline infusion, especially in the caudal part of the PAG. The increase in the number of Fos-positive cells was mainly observed in the ventrolateral and lateral parts of the caudal PAG, and in the dorsal part of the rostral PAG. However, there was no difference in the number of Fos-positive cells in Barrington's nucleus between saline and acetic acid infusion. In conclusion, nociception induced by chemical bladder irritation influences neural activity in the PAG. Implication of topographical difference in Fos expression in the PAG and its relevance to changes in bladder function remain to be elucidated.
PURPOSE: Neuroplasticity in afferent pathways, including C-fiber bladder afferents, is believed to be one of the major causes of changes in bladder function after partial urethral obstruction. We determined if capsaicin sensitive C-fiber bladder afferents are involved in the development of pre-micturition contractions after partial urethral obstruction in the rat. MATERIALS AND METHODS: Female Wistar rats were preemptively treated with capsaicin (100 mg/kg subcutaneously) or resiniferatoxin (0.3 mg/kg subcutaneously) prior to the creation of obstruction. Before and 6 weeks after obstruction micturition profiles were compared among the 3 groups, including obstructed rats preemptively treated with capsaicin (BO/CAP) or resiniferatoxin (BO/RTX) and untreated obstructed rats (BO/-). In addition, conscious filling cystometry was performed after obstruction. RESULTS: Instillation of capsaicin solutions into the eye or bladder induced significant irritative reactions in BO/- but not in BO/CAP or BO/RTX, indicating that the effect of pretreatment with capsaicin or resiniferatoxin lasted 6 weeks. Voided volume per micturition on micturition profiles was decreased after partial urethral obstruction in all 3 groups. On conscious filling cystometry a significant increase in bladder capacity, voided volume and micturition threshold pressure was noted in BO/CAP but not in BO/RTX compared with BO/-. In contrast, there was no significant change in residual volume, voiding efficiency or micturition pressure among the 3 groups. The prevalence of pre-micturition contractions was 100% in BO/CAP and BO/RTX, and 83% in BO/-. CONCLUSIONS: Capsaicin sensitive C-fiber afferents are not essential to induce pre-micturition contractions but they are involved in functional alterations in bladder afferent pathways after partial urethral obstruction in rats.
PURPOSE: Bladder dysfunction is a serious consequence of spinal cord injury. Cellular transplantation into the injured spinal cord can promote axonal growth and functional recovery. We investigated whether EG6 immortalized neural stem cells transplanted into the injured spinal cord of the rat contribute to a recovery of lower urinary tract function. MATERIALS AND METHODS: The spinal cord of 14 female Wistar rats was injured by compression. In 7 rats 9 days after spinal cord injury BrdU (5-bromo-2'-deoxyuridine) labeled EG6 cells were transplanted into the injured spinal cord. Seven operated (OP) control rats received intraspinal injections of culture medium alone. Voided volume per micturition was assessed in a metabolic cage for 24 hours on days 14 and 28 after transplantation. On day 28 saline was infused via a catheter inserted into the bladder and intravesical pressure was measured in OP control and EG6 transplant rats. RESULTS: EG6 cells identified by BrdU immunocytochemistry survived in the injured spinal cord. Voided volume per micturition significantly increased in EG6 transplant rats by day 28 after transplantation. Micturition pressure significantly decreased in EG6 transplant rats compared with OP controls. Although voided volume did not differ, post-void residual urine was significantly less in EG6 transplant than in OP control rats. Thus, voiding efficiency was significantly greater in EG6 transplant rats compared with OP controls. There was no difference in the incidence of detrusor hyperreflexia. CONCLUSIONS: Transplanted EG6 cells survived in the injured spinal cord and had beneficial effects on the recovery of voiding function after spinal cord injury in the rat.
A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.
PURPOSE: Several kinds of perceptions, including distention and coldness, arise from the bladder. Information on bladder fullness conveyed by mechanoreceptors within the bladder wall contributes to the basic micturition reflex via the bulbospinal reflex pathway, whereas cold stimulation of the bladder is processed differently. To elucidate the human brain mechanisms of voluntary urine storage and bladder cold perception we performed positron emission tomography scanning to examine brain regions activated by bladder distention or cold stimulation. MATERIALS AND METHODS: A total of 17 right-handed healthy male volunteers were catheterized via the urethra for bladder infusion. Subjects were divided into 2 groups for 2 types of positron emission tomography, namely the bladder distention group-11 who were 24 to 41 years old and the intravesical ice water group-6 who were 24 to 38 years old. Data were analyzed by the statistical parametric mapping procedure. RESULTS: Significant brain activation during maximum urine storage (bladder distention) were found in the pons, midbrain periaqueductal gray, anterior insula, putamen, thalamus and anterior cingulate gyrus. On the other hand, intravesical ice water instillation significantly activated several regions in frontal and parietal lobes, amygdala-hippocampus area and crus cerebri ventral border. Distribution of the activated regions after intravesical instillation of ice water overlapped none of those observed after bladder distention. CONCLUSIONS: Our data show that the brainstem as well as more rostral regions are involved in voluntary urine storage and these regions are functionally separated from those associated with bladder cold perception in healthy individuals.
OBJECTIVES: To examine the sex difference in the prevalence and severity of lower urinary tract symptoms in Japanese men and women. METHODS: Of 970 individuals who attended the public lectures by urologists and a famous veterinarian that were organized as a public service of the 88th Annual Meeting of the Japanese Urological Association (June 2000, Sapporo, Japan), 677 (70%) completed the self-administered International Prostate Symptom Score (IPSS) questionnaire. The scores of 653 attendees aged 30 to 79 years (446 men, mean age 67.5 and 207 women, mean age 60.7) were the basis of this study. RESULTS: A significant age-related increase in IPSS and quality-of-life score was observed in both men and women. The ratio of moderate (IPSS 8 to 19) to severe (IPSS 20 or greater) symptoms in the 50s, 60s, and 70s was 52%, 72%, and 80% in men and 27%, 36%, and 55% in women, respectively. Additional analysis in each decade showed that at age 50 years and older the total score and voiding symptom score of IPSS, as well as the quality-of-life score, were significantly greater in men than in women. CONCLUSIONS: The total IPSS and quality-of-life score correlated highly with age in both sexes. At the age of 50 years and older, men had severer voiding symptoms than did women. Although the age-related changes in bladder function predispose both men and women equally to lower urinary tract symptoms, the higher incidence of bladder outlet obstruction in men having a prostate may have a significant influence on the higher voiding symptom score in men.
The role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1) and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c-fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6)) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose dependently reduced the total number of c-fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK(1) receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c-fos expression, significantly inhibited c-fos expression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L(6) level, but only at the dorsal horn of the L(1) level. These results indicate that NK(1) receptor is involved in spinal c-fos expression after lower urinary tract irritation and that NK(1) and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.