Hiroshi Shiroto

Transport Characteristics of Cephalosporin Antibiotics Across Intestinal Brush-border Membrane in Man, Rat and Rabbit

Abstract— The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush‐border membrane vesicles isolated from man, rat and rabbit was studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush‐border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon). In rabbit jejunal brush‐border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush‐border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used. These results suggest that the transport characteristics of human and rat intestinal brush‐border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of β‐lactam antibiotics.

Transport characteristics of ceftibuten, cefixime and cephalexin across human jejunal brush-border membrane

Abstract— The transport characteristics of orally active cephalosporins, ceftibuten, cefixime and cephalexin have been examined using brush border membrane vesicles isolated from human jejunum. In the initial uptake of ceftibuten, the stimulation and overshoot phenomena were observed in the presence of an inward H+ gradient. Effects of H+ gradient on the uptake of cefixime and cephalexin were low and no overshoot was observed. These transport characteristics, especially uphill transport phenomena, were in agreement with previous results obtained from rat intestinal brush‐border membrane vesicles and suggest that these β‐lactam antibiotics are absorbed by different transport systems, despite their similar molecular structures.

The inhibitory effects of cephalosporin and dipeptide on ceftibuten uptake by human and rat intestinal brush-border membrane vesicles.

Abstract— The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush‐border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H+‐gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration‐dependent with apparent Km and Vmax values of 0·35 min and 2·052 nmol (mg protein)−1 min−1 for human BBMV, and 0·50 mm and 3·056 nmol (mg protein)−1 min−1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver–Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.

Lymphatic endothelium expresses PECAM-1.

The expression of adhesion molecules on the lymphatic endothelium of human small intestine and submandibular lymph node was studied immunohistochemically with the antibodies for selectin family and Ig superfamily members. In both small intestine and submandibular lymph node, lymphatic endothelium did not express intercellular adhesion molecule-1 and endothelial cell-selectin but expressed platelet-endothelial cell adhesion molecule-1 (PECAM-1). Though lymphatic vessels may not have a positive function in leukocyte rolling and adhesion, lymphatic endothelium may interact with leukocytes, with PECAM-1 playing a role.

A randomized controlled study of immunochemotherapy with OK-432 after curative surgery for gastric cancer.

The effect of adjuvant immunochemotherapy including OK-432 (Picibanil) on survival was assessed in patients who underwent curative resection of gastric cancer. Patients enrolled in this randomized controlled study were randomly assigned to group A or group B. Group A patients received 800 mg/d 5′-DFUR (Furtulon) for 2 years from 2 weeks after the operation. Group B patients received OK-432 plus 5′-DFUR by the same regimen as in group A. This study enrolled 288 patients, and 1 patient with malignant lymphoma was excluded. Among the remaining 287 patients, 143 and 144 were allocated to group A and group B, respectively, and their data were included in statistical analysis. The 5-year survival rates for groups A and B were 62.9% and 63.8%, respectively, showing no significant difference (P = 0.7996).

Residual liver recurrence following hepatectomy for metastasis from colorectal cancer.

大腸癌肝転移切除26例の残肝再発に関与する因子につき検討した.性別による差はみられなかったが, 年齢的には61歳以上の高齢者は60歳以下のものより残肝再発率が低かった.直腸癌の方が結腸癌より残肝再発率が高い傾向がみられたが, 肝転移巣の長径, 個数, 分化度では残肝再発率に差はみられなかった.同時性転移と異時性転移でも差はみられず, また, 一期的切除と二期的切除の間にも差はみられなかった.しかし, 術式において, 部分切除例の残肝再発率は4/7 (57.1%) であったのに対し, 広範囲切除例のそれは4/19 (21.1%) と低く, 術式の差が残肝再発率に関与することが示唆された

Evaluation of synchronous hepatic metastasis in relation to the primary site of colorectal cancer. Stream line phenomena and mode of hepatic metastasis.

1968年から1987年までに経験した同時性肝転移58例を, 原発巣の占居部位別に検討した.肝転移率はS状結腸癌 (27.0%) と盲腸癌 (26.9%) に高く, 肝転移の個数は孤立性が22.4%, 多発性が77.6%であったが, 占居部位による個数には差はなかった.壁深達度別にみた肝転移率では, S状結腸癌と盲腸癌が深達度のすすんだもので直腸癌より高かったが, これらの病悩期間をみると前二者は直腸癌よりむしろ短かった.門脈血流に一定の法則があるとするstream line phenomenaを原発巣と肝転移巣の占居部位の上から検討したが, S状結腸癌は直腸癌より右葉へ転移しやすく, 逆に左葉へは転移しにくく, 盲腸癌は右葉へ転移しやすかった.

Clinical feature and management of early cancer of the large bowel with submucosal invasion.

1971年から1985年までに当科で経験した大腸sm癌15例に検討を加えた. 初発症状は血便が53%と最も多く, 占居部位ではS状結腸以下の下部大腸が73%を占めていた. 肉眼形態はIp, Is型が全体の86%を占めており, 腫瘍の最大径は2cm代のものが33%と最も多かった. 病理組織学的には高分化腺癌9例, 中分化腺癌6例であり, 脈管侵襲はly (+) が2例, v (+) が1例にみられた. 15例中n1 (+) が2例, 異時性肝転移が1例あり, これらのrisk factorは術前にかならずしも予測しえないものもある. したがって, その治療に際しては進行癌に準じた一次リンパ節の郭清をともなう腸管の切除が必要と考える.

Clinical analysis of hepatic surgery for primary liver cancer with glucose intolerance.

は じめ に 原発 性肝癌 は肝 硬変 を 合併す る ことが多 く,耐 糖能 異 常 を有す る症例 を しば しば経 験 し,そ の術 前 ・術後 管 理 が問題 とな る.今 回,耐 糖 能異 常 を有す る原 発性 肝 癌 の術前 ・後術 の血 糖値 変動 お よび術 後合 併症 との 関係 につ いて検討 した. I.方 法お よび対 象 原 発性 肝 癌 手 術 例 を,1970年 日本 糖 尿 病 学 会 勧 告 値1)(表1)に 従 い,50g・O-GTTに お いて,空 腹 時血 糖140mg/dl以 上,ま た は1時 間値160mg/dl,2時 間値 130mg/dl以 上 とと もに満 たす ものを糖 尿 病 域 と し, 空 腹時血 糖100mg/dl以 下,1時 間値140mg/dlお よび 2時 間値100mg/dl以 下 の全 て を満 たす もの を正 常 域 とし,糖 尿病 域 に も正 常域 に も属 さな い ものを境 界域 とし3群 に分 けた. また 各症例 の50g・OGTT時 の ΔIRI/ΔBS2)30分 値, お よび ΣIRI/ΣBS3)180分 値 を求 め て(表1),イ ンス リン応 答能 お よび分泌 量 を検 索 し,術 後 血糖 推移 お よ び術後 合併症 との関係 につ い て検 討 した. 対象症 例 は1975年 か ら1984年 まで の10年 間 に当 科 で 経 験 した原 発 性肝 癌 手術 症 例148例 の うち検索 可 能 で あ った111例 であ る(表2). 検 索症 例111例 中,非 硬変例 は52例 で硬 変合 併例 は59 例 で あ った.耐 糖 能異 常例 で糖 尿病 域 を示す もの は45 例,40.5%で あ り,境 界域 は44例,39.6%に み られ, 表1 耐糖能異常 の判定基準および検検索項 目 1)50gブ ドウ糖 負荷試験(50g・O-GTT)

Clinical application and its appraisal of the laser surgery to advanced carcinoma of the digestive organs

In the advanced carcinoma of the digestive organs, the local recurrence is a major problem in surgery. We have applied a laser irradiation to the area after lymph node dissection in the surgery for the carcinoma of the GI tract and to the raw surface of the liver after hepatic resection. Experimental study demonstrated that the laser surgery have an advantage to prevent the local recurrence. Of 133 patient undergoing the laser surgery, ten patients underwent the laser irradiation and none of these developed the local recurrence so far after 4 years in the longest-term follow up. 47 patients underwent hepatic resection using a laser knife and proved to be a good prognosis. Postoperative prognosis although enough estimation can not be made is preliminarily favolable as a whole.