secretion was determined (60 minutes) and rats given saline or LPS (0.05-20 mg/kg IP), a model used to mimic organ dysfunction.One hour later, rats were given pentagastrin (PG; lOp.g/kgIV) or saline and acid output collected for another two hours.The lowest dose of LPS shown to inhibit acid secretion and not cause gastric injury was also used to assess its effects on H/K-ATPase expression.Data were analyzed using ANOVA (n -5/group).Results: As shown in the figure below, LPS dose dependently inhibited basal and PG stimulated acid secretion.LPS (0.5 mg/kg) increased expression of catalytic a subunit H/K-ATPase mRNA (Northern blot / densitometry) in the absence of PG (1.94 vs. 0.89; p = 0.05) compared to saline.In the presence of PG, LPS did not have this effect (0.80 vs. 0.81; p = ns).Western blot analysis did not show any difference in a subunit immunoraactivity (not shown}.However, confocal microscopy demonstrated that PG increased staining for H/K-ATPase subunits in the parietal cell secretory membranes when compared to controls whereas in all LPS treated rats, H/K-ATPase subunits were localized to the tubulovesicular elements without insertion into the membrane.Conclusion: These data suggest that gastric colonization during sepsis is due to inhibition of acid secretion by LPS inhibiting internalization of the H/K-ATPase subunits into the secretory membrane rather than by down regulation of transcriptional or translational events.

Background: Previous work in this laboratory has shown that acid challenge of the rat gastric mucosa is signalled to the brainstern via capsaicinresistant vagal afferents.This study examined whether tachykinins and glutamate participate in the transmission between vagal afferents and neurons in the brainstem as monitored by the expression of c-fos messenger ribonucleic acid (mRNA) in the nucleus of the solitary tract (NTS) and area postrema (AP).Methods: Forty-five min after intragastric administration of hydrochloric acid (HCI, 0.5 M, 10 mlIkg) to conscious rats, the brainstem was removed, cryosectioned and processed for in situ hybridization autoradiography with a c-fos oligo-desoxyribonucleic acid probe.Drugs were given subcutaneously 15 min before the gastric acid challenge.Results: Exposure of the gastric mucosa to HCI (0.5 M). but not saline (0.15 or 0.5 M), caused many neurons in the NTS and some neurons in the AP to express c-fos m RNA.The NMDA-type glutamate receptor channel blocker MK-801 (2 mg/kg), the NK[ tachykinin receptor antagonist GR-205, 171 (3 mg/kg) and the NK 2 receptor antagonist SR-I44, 190 (0.1 mg/kg) failed to significantly inhibit the gastric acid-evoked transcription of c-fos mRNA in the NTS.While the double combinations of MK-801 plus 171,[190][191][192][193][194][195][196][197][198][199][200][201][202][203][204][205] 190 were also without effect, the triple combination of MK-801, 190 attenuated the gastric acid-evoked transcription of c-fos mRNA in the NTS by 48 % (P < 0.01).In the AP, MK-801 alone significantly enhanced the gastric acid-induced expression of c-fos mRNA, an effect that was abolished by coadministration of the tachykinin antagonists 190 which per se had no effect.Conclusions: Our data show that glutamate acting via NMDA receptors and tachykinins acting via NK] and NK 2 receptors cooperate in the transmission between vagal afferents and medullary neurons following a gastric mucosal acid insult.These findings may have a bearing on the neuropharmacology of dyspepsia.

症例は69歳女性で,下腹部痛・血便を主訴に来院した.注腸造影大腸内視鏡にて2型進行S状結腸癌と診断し,S状結腸切除術を施行した.病理学的には,ss,n1(+)の中分化腺癌であった.他院での2回の注腸造影写真をretrospectiveに検討すると,23カ月前に,ほぼ同一の部位に長径0.6cmのIsp型隆起性病変を認め,また8カ月前には,同部位に長径3.1cmの隆起性病変を認めていた.tumor doubling time(DT)は全経過で76.4日と極めて短期間であり,また前半で64.4日,後半で117.9日とむしろ後半で延長していた.分子生物学的検査では,p53蛋白の異常蓄積を認め,Ki-67が強陽性であり,急速な発育との関連が示唆された.今後は,遡及的検討例において,DTと分子生物学的検査との相関についてさらに集計・検討が必要と考えられた.

Conclusions: In patients with UC, clusters contractions were significantly more frequent (*=p<.01)than in controls, during fasting and especially after the meal.This non-specific pattern could be related either to the coexistence of IBS and IBD, or be expression of functional abnormalities of smooth muscles and nerves induced by the chronic inflammation.

1980年から1991年の間に切除された全周性大腸癌は107例であり, このうちA群 (イレウスを伴った症例 : 16例), B群 (軽度の閉塞症状を伴った症例 : 37例), C群 (閉塞症状をまったく有しなかった症例 : 54例) に分類し, A群の臨床病理学的特徴および予後に関して他の2群と比較検討した. 年齢, 性別, 肉眼型, リンパ節転移度, 脈管侵襲および組織学的進行度では3群間に有意差は認められなかった. 腫瘍径ではA群はC群に比べ縦径は有意に短く (P<0.05), 横径も短い傾向を認めた. A群の腫瘍占拠部位は, 左側結腸に多く, 直腸に少なかった. 根治度A切除大腸癌症例, 根治度A結腸癌症例および根治度Aでかつリンパ節転移を認めない大腸癌症例の5年生存率でもA群は他の2群と有意差を認あず, イレウスの長期予後に対する影響は少ないと考えられた. イレウスをともなった大腸癌においても積極的な切除と郭清が必要と考えられた.

過去16年間に当科で手術を施行した75歳以上の高齢者大腸癌は60例で,50歳以上70歳未満の対照者群319例,39歳以下の若年者群18例の内,主に単発癌を比較の対象とし臨床的特徴と遠隔成績を検討した.高齢者群は,(1)占拠部位では右側結腸に有意に多かった.(2)壁深達度は,漿膜内にとどまる症例が多く比較的浅い傾向.(3)リンパ節転移陽性率は低い傾向.(4)手術直接死亡例はないが他病死例が多く,他病死を除いたら5年生存率は対照者群と比べて差はなかった.高齢者大腸癌は,壁深達度は浅く,リンパ節転移率も低い傾向にあり,D2もしくはD3の適切なリンパ節郭清にて根治度AまたはBの切除が可能であり,高齢といえども患者の状態の許す限り積極的に対照者群と同様の郭清を伴った根治切除術を心がけるべきである.高齢者では術前より全身状態の悪い症例が多く,合併疾患の術前後の管理を充分に行えば対照者群と同等の成績が期待できる.

Local resection of the lower rectum was performed for the treatment of malignant polypoid lesions in 22 patients. The clinical outcomes of the procedure are summarized as follows; 1. For IIa + IIc type malignant polyp, transanal wedge resection of the entire rectal wall or a transsacral tube resection of the rectum should be performed; as a minimal preventive measure against local recurrence. 2. Early invasive carcinoma (sm) has a metastatic potential on distant organs. 3. In the case of polypoid carcinoma invading the muscle layer (pm), local resection was conducted only in the patients with distant metastasis or with serious complications and in aged patients. 4. When postoperative histological examination reveals a mistake in operative strategy, the patient should be reoperated immediately.

To clarify the physiological role of the mechanism that adrenergic nerve inhibits Ach release from intramural cholinergic nerve endings, the influence of Midaglizole, alpha 2-adrenergic receptor antagonist, to postprandial gastrointestinal motilities in conscious dogs was investigated. Postprandial motilities of gastric antrum, duodenum, ileum, and colon were significantly enhanced by Midaglizole (3.0-5.0 mg/kg body weight, i.v.). These excitatory responses were abolished by atropine (0.05-0.1 mg/kg body weight, i.v.). On the other hand, in most cases (29 cases out of 32), when Midaglizole was administered during quiesent phase of IMC, no change occurred in gastrointestinal motility. However, after subliminal dose of pentagastrin or cisapride, which stimulated Ach release from intramural cholinergic neuron without development of motility, was administered, Midaglizole induced phasic, postprandial motility-like contraction in gastrointestinal tract. Even in the fasted state, when Midaglizole was administered intragastrically, irregular contractions with high amplitude occurred in every regions from gastric antrum to colon. And these excitatory responses were abolished by atropine. Similar reaction was observed also in truncal vagotomized dogs. These results suggest that it is the physiological mechanism that adrenergic nerve presynaptically inhibits Ach release from intramural cholinergic neuron, which is the main mechanism of development of postprandial motility, acting on alpha 2-adrenergic receptor, and has tonic control of postprandial motility.

The action of cisapride on physiological and disturbed gastrointestinal motor function was investigated in conscious and anesthetized dogs and the mechanism of action involved. Regardless of the presence or absence of vagal innervation, administration of cisapride (0.2 mg approximately 1.0 mg/kg body weight, i.v.) during the quiescent period of interdigestive migrating contractions (IMC), induced non-migrating IMC-like motility in the entire gastrointestinal tract from gastric body to distal colon. Administration of cisapride in the digestive state resulted in the excitatory response of increased amplitude of digestive peristalsis and strong IMC-like motility was not observed. All of these excitatory responses in gastrointestinal motility disappeared by the administration of atropine (0.5 mg approximately 0.1 mg/kg body weight, i.v.). Furthermore, the excitatory response in gastrointestinal motility induced by cisapride in anesthetized dogs disappeared by the administration of TTX (10 micrograms/kg of body weight, i.v.). These results suggest that the excitatory action of cisapride on the gastrointestinal motility is based on its mechanism in which cisapride acts on the cholinergic neurones in the gastrointestinal wall to stimulate ACh release, resulting in the increase in gastrointestinal motility. Cisapride caused powerful IMC-like motility in the ileum of animal with pseudo-obstruction-like motor disturbance which had been seen after preparation of Thiry loop (ileum). This motility migrated from the proximal ileum to the Thiry loop and then to the distal ileum. Trimebutine maleate also demonstrated this effect, but metoclopramide and domperidone were ineffective. Administration of cisapride at the doses (0.2 mg approximately 1.0 mg/kg body weight, i.v.) causing stimulated motor response in the gastrointestinal tract did not induce significant secretion of gastric acid, pancreatic juice and bile.