Yasuhiko Kurosu

A role of nitric oxide in Hirschsprung's disease

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the significance of NO in Hirschsprungs disease (HD), enteric nerve responses in colonic tissue obtained from HD patients were investigated. Colonic tissue specimens were obtained from four patients with HD and from 11 patients without constipation who were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine (L-NNA) and L-arginine with the following results: (1) NANC inhibitory nerves were found to act on normal human colon, but had no effect on aganglionic colon; (2) L-NNA concentration dependently inhibited the relaxation in response to EFS in the normal colon, but had no effect on aganglionic colon; and (3) this inhibitory effect was reversed by L-arginine in the normal colon, but had no effect on the aganglionic colon. Nitric oxide mediates the relaxation reaction of NANC inhibitory nerves in the human colon, but the effect of NO was absent in aganglionic colon. The loss of action by NO may be implicated in the impaired motility observed in aganglionic colon.

Electrophysiologic assessments in pudendal and sacral motor nerves after ileal J-pouch-anal anastomosis for patients with ulcerative colitis and adenomatosis coli

PURPOSE: To clarify neurologic function with respect to external anal sphincter and puborectalis muscles after J configuration ileal J-pouch-anal anastomosis for patients with ulcerative colitis and adenomatosis coli, we examined the terminal motor latency in the pudendal and sacral motor nerve (S2-4). METHODS: Latency of the response in the external anal sphincter muscle following digitally directed transrectal pudendal nerve stimulation (PNTML) and in the puborectalis muscle following transcutaneous magnetic stimulation of the cauda equina at the levels S2-4 (SMNLTSS) were measured in 12 patients with ileal J-pouchanal anastomosis; they were divided into a group with continence (7 cases) and a group with soiling (5 cases). Results were compared with data obtained from 12 patients before operation and 15 controls. RESULTS: Conduction delay of PNTML and SMNLTSS in patients with soiling was longest, followed by delay in those without any soiling, then delay in patients before operation, and then controls. In addition, significant differences were also noted between conduction delay of PNTML in controls and those who are incontinent and experience soiling(P< 0.05 andP< 0.01, respectively), and there were significant differences also noted between conduction delay of PNTML in patients before operation and those who are incontinent and experiencing soiling(P< 0.05 andP< 0.01, respectively). Conduction delay of PNTML and SMNLTSS were found in patients before operation rather than in controls. No significant differences were noted between conduction delay of PNTML and SMNLTSS in patients before operation and controls. Significant differences were also noted between conduction delay of PNTML and SMNLTSS in patients who are incontinent and experiencing soiling(P< 0.01, respectively). CONCLUSION: These findings support the hypothesis that soiling after this procedure may be partially caused by damage to pudendal and sacral motor nerves (S2-4).

Relationship between nitric oxide and non-adrenergic non-cholinergic inhibitory nerves in human lower esophageal sphincter

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the the role of NO in the human lower esophageal sphincter (LES), enteric nerve responses in lower esophageal tissue specimens obtained from patients with esophageal cancer (n=7) and patients with gastric cancer (n=6) were investigated. A mechanographic technique was used to evaluate in vitro LES muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including NG-nitro-L-arginine (L-NNA) and L-arginine. Findings were: (1) Cholinergic nerves were those mainly involved in the regulation of enteric nerve responses to EFS in the steady state, and NANC inhibitory nerves acted on the LES; (2) L-NNA concentration-dependently inhibited the relaxation in response to EFS in the LES; and (3) this inhibitory effect in the LES was reversed by L-arginine. These findings suggest that cholinergic and NANC inhibitory nerves play important roles in regulating contraction and relaxation of the human LES, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human LES.

Biological characteristics of neuroblastoma with spontaneous tumor reduction: a case report.

The authors examined the biological characteristics of a neuroblastoma with spontaneous tumor reduction. A 6-month-old boy with a pelvic neuroblastoma underwent surgical extirpation of the tumor 1 month after diagnosis. The size of the tumor reduced spontaneously while he was awaiting operation. The low proliferative activity of the tumor cells and the presence of apoptosis in the tumor tissue were shown by an immunohistochemical method using anti-PCNA antibody and a DNA fragmentation analysis, respectively. These results suggest that the spontaneous tumor reduction seen in this patient may well be caused by the overwhelming apoptosis of tumor cells.

Nitric Oxide and Active Oxygen Species in Severe Sepsis and Surgically Stressed Patients

To clarify how the kinetics of nitric oxide (NO) and active oxygen species are correlated with the occurrence of organ dysfunction in sepsis, the levels of monocyte-associated NO2, NO3, and active oxygen species were examined in severely septic patients with multiple organ dysfunction syndrome (group M; n=5), and the results compared with those of postoperative patients who had undergone gastrointestinal surgery (group S; n=5) and healthy volunteers (group C; n=10). The production of NO2 and NO3 by monocytes was significantly higher in group M than in the other two groups, while the production of active oxygen species by monocytes was significantly higher in groups M and S, than in group C. A significant correlation between the production of NO2 and that of active oxygen species by monocytes was noted only in group M. These findings indicate that the simultaneous activation of NO and active oxygen species production by monocytes is a prerequisite for the onset of multiple organ dysfunction in severe sepsis.

Sacral nerve terminal motor latency after ileal J pouch-anal anastomosis for ulcerative colitis

Using a new transcutaneous magnetic stimulation technique, sacral nerve terminal motor latencies (SNTML) were measured after ileal J pouch-anal anastomosis in eight patients with ulcerative colitis, and the results were compared with those obtained from 15 normal subjects. The conduction delay of the SNTML in patients with soiling was significantly longer than that of the continent group as well as that of normal subjects (P<0.01). There were no significant differences in the conduction delay between the continent group and the control subjects. These findings therefore support the hypothesis that such soiling, which is sometimes seen after ileal J pouch-anal anastomosis, is partly due to damage to the sacral nerves.

Indomethacin enhancement of lymphocyte responses to phytohemagglutinin in breast, stomach and colorectal cancer patients

The effect of indomethacin, a prostaglandin synthetase inhibitor, on lymphocyte responses to phytohemagglutinin (PHA) was studied in 111 breast, stomach and colorectal cancer patients. Indomethacin exerted no mitogenic activity and the ethanol in which the indomethacin was dissolved produced no significant effect on the lymphocyte responses to PHA. Compared with the control group (13 healthy subjects and 30 patients with benign disease), indomethacin significantly enhanced the lymphocyte responses to PHA in the cancer patients. The degree of enhancement induced by indomethacin was independent of the primary site of the tumor, but was associated with tumor load. A significant inverse correlation was observed between the degree of enhancement and that of the original lymphocyte responses to PHA. Sequential determinations of the degree of enhancement in selected stomach and colorectal cancer patients revealed that it fell to a low level after curative tumor resection.

Terminal Motor Latency in the Pudendal Nerves After Colectomy with Mucosal Proctectomy and Ileal J Pouch-anal Anastomosis for Ulcerative Colitis

Pudendal nerve terminal motor latencies (PNTML) were measured in eight patients with ulcerative colitis who underwent colectomy with mucosal proctectomy and ileal J pouch-anal anastomosis, using a new digitally directed transrectal stimulation and recording technique, and the results were compared with data obtained from 15 control subjects. The conduction delay of PNTML in the patients with some degree of fecal incontinence was the longest, followed by those without any incontinence, and then the control subjects. These findings support the hypothesis that fecal incontinence after this procedure may be partially caused by damage to the pudendal nerve.

Cell-mediated immune reactions to clinical neuroblastoma

Immunotherapy may be an effective treatment for neuroblastoma. It is of importance to delineate changes in various parameters of tumor immunity over an extended period, before and during the course of treatment, in any given case. In our patients with neuroblastoma, tumor-associated cell-mediated immune-reaction showed a good responsiveness before treatment. However, delayed cutaneous hypersensitivity reactions were shown to be negative in many cases, particularly in those with advanced tumor, and Tγ cells were enormously increased in some cases. During the course of therapy, the tumor-associated cellular immune responsiveness showed a tendency to become negative when the patient was tumor free or was in remission, but showed a tendency to become positive on regrowth, recurrence or metastasis of tumor. The Tγ cells showed much the same fluctuations as did the tumor-associated cellular immune responsiveness.

Unique presentation of heterotopic pancreatic tissue arising from small-bowel mesentery

Heterotopic pancreatic tissue in the small-bowel mesentery is an extremely rare anomaly: no such case has been reported in the English literature. We report a 5-year-old boy in whom the aberrant tissue formed a retroperitoneal cyst. The condition was further complicated by a ventral pancreatic duct defect. The unique clinical manifestations and difficulty in making the diagnosis are discussed.