Pituitary adenylate cyclase activating polypeptide (PACAP) with 27 residues

The conformation of pituitary adenylate cyclase activating polypeptide with 27 residues (PACAP27) has been determined by two-dimensional NMR and CD spectroscopies and distance geometry in 25% methanol. Residues 9-20 and 22-25 have well-defined conformations but other residues do not show ordered conformations. The conformation of residues 9-20 is composed of three distinct regions of β turn-like conformation (residues 9-12), α helix (residues 12-14) and the looser helical conformation (residues 15-20), while residues 22-24 form α helix. PACAP27 has a 2 helices separated by a disordered region similar to a VIP analog reported by Fry et al. but is distinct from the VIP analog in the position of the first helix, which is shifted by 2 residues toward the C-terminus, and in the form of the second helix [Fry, D.C., Madison, V.S., Bolin, D.R., Greeley, D.N., Toome, V. and Wegrzynski, B.B. (1989) Biochemistry 28 , 2399-2409].     

Clinicopathological factors predicting recurrence of N0M0 renal cell carcinoma: A case series analysis of one facility

BACKGROUND: Although many factors have been reported as predictors of the recurrence of renal cell carcinoma (RCC), none of the factors are consistent among different studies. In the study presented here, the potential clinicopathological predictors of the recurrence of N0M0 RCC were examined. METHODS: A total of 201 patients who underwent nephrectomy for N0M0 RCC were examined to determine the pathological tumor stage (pT stage), pathological tumor grade of malignancy (tumor grade), symptoms, and tumor size. RESULTS: RCC recurred in 29 patients (14.4%), 50% of whom developed new tumors within 24 months after nephrectomy. The disease-free 3- and 10-year survival rates declined as the pT stage and tumor grade increased: these rates were, respectively, 98.6% and 86.5% for pT1a; 93.7% and 87.9% for pT1b; 100% and 100% for pT2; 78.6% and 58.0% for pT3a; and 88.9% and 16.7% for pT3b. Significant differences in the recurrence rate were noted between pT3 and pT1 or pT2, as well as between grade 3 disease and grade 1 or grade 2 tumors. Multivariate analysis showed that a combination of the pT stage, grade, and presence of symptoms was useful for predicting the recurrence of RCC. CONCLUSION: The present study showed that patients undergoing nephrectomy for N0M0 RCC should be followed-up carefully for 2 years postoperatively with special attention to high pT stage, high grade, and the development of symptoms.     

Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer healing

Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H₂ blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 ± 1.3), peaked during the healing stage (15.4 ± 2.8) and returned to the same level at the scarring stage (10.9 ± 2.0) as normal controls (10.3 ± 1.7). However, the index was not elevated in intractable ulcers (10.3 ± 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.     

Intracavitary administration of OK-432 with subcutaneous priming for malignant ascites in a case of advanced renal cell carcinoma

The intracavitary injection of OK-432 (a streptococcal preparation) with subcutaneous priming has been shown to be an effective immunotherapy for patients with malignant effusion. We applied this treatment in a case of advanced renal cell carcinoma with massive ascites. The patient received 0.2 Klinishe Einheit (KE) OK-432 in the subcutaneous injection twice (day 1 and day 7) followed by 10KE OK-432 intra-abdominal administration (day 9). The treatment was performed safely without major side-effects except for transient pyrexia. A significant reduction of ascites was noted 1 month after the treatment without subsequent re-accumulation. Intracavitary injection of OK-432 with subcutaneous priming seems to be a simple, safe and effective treatment for ascites in advanced renal cell carcinoma.     

Impact of body mass index and visceral adiposity on outcomes in colorectal cancer

Aim: Obesity and visceral obesity are closely related to the development of colorectal cancer, as well as other metabolic complications. We investigated the prognostic significance of body mass index (BMI) and visceral obesity in 273 patients with resectable colorectal cancer. Methods: Visceral fat area (VFA) and subcutaneous fat area were measured on digital images of patients’ computed tomograms obtained before surgery. The patients were divided into two groups according to the cut‐off levels of VFA proposed by Oka et al. Men with a VFA of ≥130 cm² and women with a VFA of ≥90 cm² were classified as obese (VFA‐obese) and the others were classified as non‐obese (VFA‐non‐obese). The patients were also divided into an overweight group and a normal range group, according to their preoperative BMI. Results: There was no significant difference in cumulative recurrence‐free survival (RFS) or overall survival (OS) between the VFA‐obese group and the VFA‐non‐obese group. In the subgroup of patients with Dukes’ C disease (n = 100) there was no statistically significant difference in RFS and OS between the VFA‐obese group and the VFA‐non‐obese group. The results were similar when the patients were classified according to their BMI. Conclusion: Neither obesity nor increased visceral adiposity has any influence on outcomes in patients with resectable colorectal cancer.     

Carbocisteine can scavenge reactive oxygen species in vitro

Background and objective:   Reactive oxygen species (ROS) play an important role in the pathogenesis of various respiratory diseases. Carbocisteine, a mucoregulatory drug, is used in the treatment of several disease states but little information is available about its scavenger effects on ROS. The present study was designed to examine the scavenger effects of carbocisteine on ROS.
Methods:   The oxidation-reduction potential of carbocisteine was measured, and its scavenger effects on hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), hydroxyl radical (OH^•) and peroxynitrite (ONOO^-) were examined in cell-free conditions. The effects of carbocisteine on ROS generated from rat neutrophils, intracellular oxidative stress and release of inflammatory cytokines (IL-8 and IL-6) from IL-1β-induced airway epithelial cells, NCI-H292 cells, were investigated.
Results:   Carbocisteine provided a reducing stage and showed scavenger effects on H₂O₂, HOCl, OH^• and ONOO^- in cell-free conditions. Carbocisteine inhibited ROS generation from rat neutrophils, intracellular oxidative stress and release of IL-8 and IL-6 from NCI-H292 cells. N -acetyl- l -cysteine, a radical scavenger, also inhibited these events related to ROS as well as carbocisteine.
Conclusions:   These results suggest that carbocisteine could exert anti-inflammatory and anti-oxidant effects through directly scavenging ROS in addition to its previously known mucoregulatory effect.     

Development of a Compact, Highly Efficient, Totally Implantable Motor–Driven Assist Pump System

Abstract: We have developed a compact, highly efficient, totally implantable assist pump system, which consists of a motor–driven assist pump and a transcutaneous energy and optical information transmission system. The motor–driven assist pump consists of ad. c. brushless motor and a specially designed miniature ball screw. A magnetic coupling mechanism between the blood pump and an actuator provides active blood filling via mild suction force. The controller consists of a PID follow–up controller using an 8–bit one–chip microcomputer. The volume of the pump is 350 ml, and its controller is 210 ml. Pump outflow of 5. 8 L/min was obtained against a mean afterload of 100 mm Hg. The pump showed a high efficiency rate and good durability. An efficiency rate of 19–21% (pump output/motor input) was obtained during 87 days of continuous pumping. No mechanical trouble occurred for an accumulated period of 6 months.