Rationale for extent of lymph node dissection for right colon cancer

PURPOSE: The extent of lymph node dissection optimal for the prognosis of right colon cancer is investigated. METHODS: Between 1946 and 1991, 275 patients had curative operation for right colon cancer. A retrospective analysis of rate and degree of lymph node metastasis was performed in each of the 275 patients, and survival rate was estimated in 197 patients who could be followed over a period of three years or more. RESULTS: In most of the curative operative cases of right colon cancer, metastasis to epicolic and paracolic nodes was restricted up to 10 cm proximal or distal to the tumor margin, and metastasis in the central direction was restricted up to main nodes. When cancer metastasized to infrapyloric lymph nodes, dissection of the nodes resulted in a higher rate of long-term prognosis. The five-year cumulative survival rates showed no statistically significant difference between any two of the N0 to N3 lymph node metastasis groups. CONCLUSION: The dissection procedure for right colon cancer involved removal of 10 cm of normal bowel both proximal and distal to the lesion and, in the central direction, dissection of regional lymph nodes along the main trunk artery up to main nodes,i.e., nodes situated anterior to the surgical trunk, which was confirmed to have a therapeutically satisfactory benefit. Infrapyloric lymph nodes must be dissected when metastasis to the nodes is suspected. In cases of cecal or ascending colon cancer in which the middle colic artery is no longer the main trunk artery, a right hemicolectomy with resection of only the right branch of the middle colic artery will usually suffice.     

A new model rat with acute bronchiolitis and its application to research on the toxicology of inhaled particulate matter

The aim of the present study was to establish a useful animal model that simulates humans sensitive to inhaled particulate matter (PM). We have developed a new rat model of acute bronchiolitis (Br) by exposing animals to NiCl2 (Ni) aerosols for five days. Three days following the Ni exposure, the animals developed signs of tachypnea, mucous hypersecretion, and bronchiolar inflammation which seemed to progress quickly during the fourth to fifth day. They recovered from lesions after four weeks in clean air. To assess the sensitivity of the Br rats to inhaled particles, two kinds of PM of respirable size were tested with doses similar to or a little higher to the recommended threshold limit values (TLVs) for the working environment in Japan. Titanium dioxide (TiO2 = Ti) was chosen as an inert and insoluble particles and vanadium pentoxide (V2O5 = V), as a representative soluble and toxic airborne material. The Br rats exposed to either Ti or V were compared the pathological changes in the lungs and the clearance of particles to those in normal control or Br rats kept in clean air. The following significant differences were observed in Br rats: 1. delayed recovery from pre-existing lesions or exacerbated inflammation, 2. reductions in deposition and clearance rate of inhaled particles with the progress of lesions. The present results suggest that Br rats are more susceptible to inhaled particles than control rats. Therefore, concentrations of particulate matter lower than the TLVs for Japan, which have no harmful effects on normal lungs, may not always be safe in the case of pre-existing lung inflammation.     

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial. Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women’s coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.     

Bone Metastases from Soft Tissue Sarcomas

The incidence, distribution, time of appearance, and radiologic findings of bone metastases from soft tissue sarcomas, exclusive of lymphomas, were evaluated in 320 patients with soft tissue sarcomas. Thirty patients (9.4%) had evidence of 58 bone metastases. Five of 30 patients presented with metastases, and 25 of 30 patients developed metastases up to 66 months after presentation with a mean time interval of 21.3 months. The incidence of skeletal metastases differed among histologic subtypes of sarcomas; alveolar soft part sarcoma (5 of 8), dedifferentiated liposarcoma (2 of 4), angiosarcoma (2 of 4), and rhabdomyosarcoma (5 of 16) tended to show a higher incidence of bone metastases. The sarcomas metastasized to the regional bones close to the primary tumor in 16 (53%) of 30 patients and to the axial bones in 18 (60%). On conventional radiographs, the osseous metastases demonstrated predominantly osteolytic changes, and evidence of pathological fracture was observed in 31% of 58 metastases.     

An event-related potential study in schizophrenia using Japanese sentences

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.     

Release of cytochrome c from mitochondria to cytosol in gerbil hippocampal CA1 neurons after transient forebrain ischemia

We examined cytosolic cytochrome c in gerbil hippocampal CA1 and CA3 regions after induction of 5-min ischemia by immunoblotting. In the CA1 region, cytochrome c was detected in the cytosolic fraction from 1 to 6 h after ischemia by Western blotting, while it was not detected in the CA3 region. Following intraventricular administration of cyclosporin A (CsA), detectable cytosolic cytochrome c was dramatically decreased, and about 80% of CA1 neurons survived after ischemia. The present studies demonstrate that cytochrome c is translocated from mitochondria to the cytosol in the early stage of delayed neuronal cell death, and suggest the involvement of the mitochondrial permeability transition.     

Peak oxygen uptake, ventilatory threshold and leg extension power in apparently healthy Japanese]

Peak oxygen uptake, ventilatory threshold (VT) and leg extension power were measured in 832 apparently healthy subjects (421 males, 411 females) aged 30-60 decades who performed medical examination at 4 health check up facilities. 1) Peak oxygen uptake was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (ml/kg/min) = 46.6 - 0.36 x AGE, (r = 0.447, p < 0.001) in male and Y (ml/kg/min) = 35.3 - 0.23 x AGE, (r = 0.407, p < 0.001) in female. 2) VT was greater in male than female, and less decreased with age compared to maximal aerobic power. Single regression formula on age were Y (ml/kg/min) = 22.6 - 0.13 x AGE, (r = 0.371, p < 0.001) in male, Y (ml/kg/min) = 20.0 - 0.10 x AGE, (r = 0.301, p < 0.001) in female. 3) Leg extension power was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (W/kg) = 31.9 - 0.27 x AGE, (r = 0.539, p < 0.001) in male and Y (W/kg) = 20.9 - 0.18 x AGE, (r = 0.510, p < 0.001) in female. Subjects in the present study showed height, weight and walk steps per day similar to those in National Nutrition Survey. Comparison of Peak oxygen uptake, ventilatory threshold and leg extensor power to previous studies revealed that these parameters were quite similar to the counterparts in the previous studies with less selection bias. It was suggested that subjects in this study were quite similar to normal Japanese population, and that Peak oxygen uptake, VT and leg extension power in the present study were of value for the evaluation of health related fitness in community and workplace.     

Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs

sigma Receptor antagonists may be effective antipsychotic drugs that do not induce motor side effects caused by ingestion of classical drugs such as haloperidol. We obtained evidence that 1-(2-dipropylaminoethyl)-4-methoxy-6H-dibenzo[b,d]pyran hydrochloride 2a had selective affinity for sigma receptor over dopamine D2 receptor. This compound was designed to eliminate two bonds of apomorphine 1 to produce structural flexibility for the nitrogen atom and to bridge two benzene rings with a -CH2O- bond to maintain the planar structure. In light of the evidence, N, N-dipropyl-2-(4-methoxy-3-benzyloxylphenyl)ethylamine hydrochloride 10b was designed. Since compound 10b had eliminated a biphenyl bond of 6H-dibenzo[b,d]pyran derivative 2a, it might be more released from the rigid structure of apomorphine 1 than compound 2a. The chemical modification of compound 10b led to the discovery that N, N-dipropyl-2- [4-methoxy-3-(2-phenylethoxyl)phenyl]ethylamine hydrochloride 10g (NE- 100), the best compound among arylalkoxyphenylalkylamine derivatives 3, had a high and selective affinity for sigma receptor and had a potent activity in an animal model when the drug was given orally. We report here the design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine derivatives 3.     

Reductive debromination of (alpha-bromoiso-valeryl)urea by intestinal bacteria

The reductive debromination of the hypnotic (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by intestinal bacteria has been studied. The caecal contents of rats, mice, hamsters, guinea-pigs and rabbits had significant debrominating activity toward (alpha-bromoiso-valeryl)urea. The cell-free extract of intestinal bacteria from the caecal contents of rats had debrominating activity in the presence of both flavin mononucleotide (FMN) and NADH (or NADPH) under anaerobic conditions. Seven pure strains of intestinal bacteria were also tested and the highest activity was observed with Clostridium sporogenes. The cell-free extract of Clostridium sporogenes had debrominating activity in the presence of both FMN and NADH (or NADPH), and this activity was inhibited by sodium arsenite and potassium cyanide. The activity of the cell-free extract was also supported by the photochemically reduced form of FMN. The debromination in intestinal bacteria seems to proceed in two steps--reduction of flavins by bacterial flavin reductase(s) in the presence of NADPH or NADH, and then the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by bacterial dehalogenase(s) using the reduced flavins as an electron donor. These results indicate that intestinal bacteria play a role in the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea in animals. The debromination is inhibited by oxygen and dependent on flavins.