The host galaxy of a fast radio burst.

In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts. These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations. Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates. Here we report the discovery of a fast radio burst and the identification of a fading radio transient lasting ~6 days after the event, which we use to identify the host galaxy; we measure the galaxy's redshift to be z = 0.492 ± 0.008. The dispersion measure and redshift, in combination, provide a direct measurement of the cosmic density of ionized baryons in the intergalactic medium of ΩIGM = 4.9 ± 1.3 per cent, in agreement with the expectation from the Wilkinson Microwave Anisotropy Probe, and including all of the so-called 'missing baryons'. The ~6-day radio transient is largely consistent with the radio afterglow of a short γ-ray burst, and its existence and timescale do not support progenitor models such as giant pulses from pulsars, and supernovae. This contrasts with the interpretation of another recently discovered fast radio burst, suggesting that there are at least two classes of bursts.

Expression of NOS and VEGF in feline mammary tumours and their correlation with angiogenesis.

In order to define the role of nitric oxide (NO) in feline mammary tumours, the expression of endothelial or inducible nitric oxide synthase (e/iNOS) and vascular endothelial growth factor (VEGF), and their relationship with angiogenesis, was investigated in 23 feline mammary tumours (two hyperplastic, 19 adenocarcinoma, one osteosarcoma and one squamous cell carcinoma) by immunohistochemistry. Tumour angiogenesis was assessed by CD31 immunostaining and was expressed as microvessel density (MVD). In general, iNOS immunoreactivity was localised in tumour cells and occasionally in stromal myofibroblasts, whereas eNOS and VEGF were localised in the cytoplasm of tumour epithelial cells and endothelium. In malignancy, expression of iNOS increased from well- to less-differentiated phenotypes (Grades 1-3) and was significantly higher in G3 and G2 when compared with G1 cases. However, increasing eNOS expression was limited only in hyperplastic lesions and showed no significant changes among the grades. In addition, expression of iNOS was positively correlated with VEGF and MVD in feline mammary tumours and both measures were significantly greater in less differentiated phenotypes (P<0.05). In conclusion, the expression of NOS isoforms in feline mammary tumours depended on tumour grade, and the positive correlations between iNOS and angiogenic markers suggests that iNOS synthesised by tumour cells promotes tumour growth. Thus, iNOS can be used as an important immunohistochemical marker to determine the degree of malignancy and prognosis of feline mammary carcinoma.

Phase II study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

OBJECTIVE: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m(2)/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5-77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7-9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. CONCLUSION: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.

Oligoastrocytoma of the brain in a hooded crane (Grus monacha).

A cerebral tumor was identified at necropsy in a mature female hooded crane (Grus monacha). On gross examination, the cut surface of the tumor revealed a soft gelatinous mass. On histologic examination, the tumor was mainly composed of 2 discrete components that resembled oligodendroglioma and astrocytoma. Both components had anaplastic changes, such as pleomorphism, high proliferative activity, microvascular proliferation, and necrosis. The oligodendrogliomatous component showed a honeycomb appearance formed by the accumulation of variably sized neoplastic cells with perinuclear halos and central nuclei. The astrogliomatous component consisted of remarkably pleomorphic cells, including bizarre giant cells. Immunohistochemistry revealed that the oligodendrogliomatous component cells were partially immunoreactive for vimentin and myelin basic protein, and the astrogliomatous component cells were immunoreactive for vimentin, S-100, and glial fibrillary acidic protein. Based on these findings, the tumor was diagnosed as an oligoastrocytoma.

Needle-shaped deposits on retinal surface in a case of ocular amyloidosis.

PURPOSE: To report a case in which optical coherence tomography (OCT) showed needle-shaped deposits on the retinal surface oriented toward the vitreous cavity and immunohistochemical findings suggested light chain-related amyloidosis. METHODS: A 59-year-old man with no systemic complications had bilateral neovascular glaucoma and vitreous opacities in the right eye. Vitrectomy was conducted on the right eye and the excised vitreous was examined histopathologically. RESULTS: Glass wool-like opacities were observed during vitrectomy. Postoperative fundus examination of the right eye showed retinal hemorrhage and white deposits around blood vessels and on retinal surface. Fluorescein angiography revealed hyperfluorescence of the optic disc, non-perfusion areas, and vascular focal staining. OCT depicted needle-shaped deposits perpendicular to the retinal surface oriented toward the vitreous. Histologic examination of deposits revealed positive reaction for Congo red stain, and immunohistochemical examination demonstrated positive reactivities for anti-lambda and anti-kappa light chains (precursors of amyloid protein), suggesting a diagnosis of light chain-related amyloidosis. CONCLUSIONS: In this case, OCT showed needle-shaped deposits perpendicular to the retinal surface. Special staining with Congo red revealed the deposit to be amyloid deposition. Immunohistochemical staining suggested light chain-related amyloidosis. Vascular obstructive lesions and neovascular glaucoma secondary to retinal vascular damage in amyloidosis warrant particular attention.

Significant associations of metabolic syndrome and its components with silent lacunar infarction in middle aged subjects.

BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of ischaemic stroke, including silent brain infarction. No study has examined its association with the lacunar subtype. The present cross sectional study examined the relationship between MetS, its components and silent lacunar infarction (SLI) in middle aged subjects. METHODS: We studied 2076 subjects aged 40-59 years with no history of stroke or clinical symptoms, who visited a health care facility for a routine health checkup and underwent brain MRI. MetS was defined according to the National Cholesterol Education Programme Adult Treatment Panel III report. A multiple logistic regression model was used to examine the associations between MetS and SLI while adjusting for age, gender, a past history of ischaemic heart disease and current smoking. RESULTS: MetS was strongly associated with the presence of SLI (adjusted OR 6.52; 95% CI 4.30 to 9.90). Regarding MetS components, elevated blood pressure, impaired fasting glucose, hypertriglyceridaemia and large waist circumference were significantly associated with SLI, independent of an interrelationship between the components, while low high density lipoprotein cholesterol was not significantly associated. CONCLUSIONS: MetS was significantly associated with the prevalence of SLI in middle aged persons. Independent risk factors for SLI not only included elevated blood pressure and impaired fasting glucose, which are well known risk factors, but also hypertriglyceridaemia and large waist circumference.

Validation of the Japanese version of EORTC QLQ-CR38.

PURPOSE: The objective of this study was to test the reliability and validity of the Japanese version of the European Organization for Research and Treatment of Cancer (EORTC) Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38). METHODS: The questionnaire was tested among 109 colorectal cancer patients on several occasions. The timing was prior to treatment with radiotherapy or chemotherapy, during treatment and 3 months following the second assessment. For purpose of test-retest reliability, a subgroup of patients completed the QLQ-CR38 1 week following the third assessment. RESULTS: Multitrait scaling analysis confirmed the hypothesised scale structure of both the function scales and the symptom scales except female sexual problem scale. Cronbach's alpha coefficients for seven of the nine scales exceeded the 0.7 criterion at one or both assessments. The test-retest reliability for all scales except three symptom scales was 0.67 or higher. On the basis of known-groups comparisons, four of 46 comparisons distinguished between patients differing in disease stage, initial and on-treatment performance status and presence or absence of a stoma. Additionally, these scales detected change over time as a function of change in performance status and treatment-induced change. CONCLUSION: These preliminary results suggest that the Japanese EORTC QLQ-CR38 may be a reliable and valid supplementary measure of quality of life in colorectal cancer patients.

Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.

Activation-induced cytidine deaminase expression in follicular lymphoma: association between AID expression and ongoing mutation in FL.

Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. AID has been reported to be specifically expressed in the germinal center (GC). Follicular lymphoma (FL) cells are known to be exposed to GC reaction, as characterized by a high degree of SHM with some heterogeneity in terms of intraclonal microheterogeneity and antigen selection. The heterogeneity of SHM pattern in FL intrigued us to investigate the AID expression. AID expression was investigated in 19 FL materials consisting of 15 cases of FL fresh cells and four cell lines. In all, 10 fresh cells and three cell lines expressed AID, but the others did not. SHM was investigated in 12 fresh cells and four cell lines. The ongoing mutation was significantly different between AID-positive and AID-negative FL fresh cells (unpaired Student's t-test, P=0.047). Ongoing mutation was not seen in any of the cell lines. AID expression was associated with the ongoing mutation in FL fresh cells (two-tailed Pearson's coefficient correlation, r=0.899, P=0.01). The switch off of AID expression may start in the B-lineage differentiation stage counterpart of FL after optimizing SHM, indicated by the cessation of the ongoing mutation in AID-negative FL fresh cells.

Teratoma in a feline unilateral cryptorchid testis.

A 14- x 12- x 6-cm (approximately 600 g) cryptorchid testis was surgically removed with the omentum from the posterior portion of the abdominal cavity of a 2-year-old male American Shorthair cat. At the time of a previous orchiectomy, a unilateral testis had been discovered in the scrotum. The cut surface of the cryptorchid testis consisted of solid areas with many cysts containing fluid and spongy soft areas. Histologically, the cryptorchid testis was composed of neuroectodermal components and diffuse immature glial tissues, cystic, tubular, and papillary epithelial tissues, and immature cartilaginous tissues. A metastatic mass in the omentum had histologic structures similar to those of the cryptorchid testis. The present case was diagnosed as teratoma in a feline unilateral cryptorchid testis.

Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice.

We previously reported that gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring plant phenol, can induce apoptosis in four kinds of human lung cancer cell lines in vitro. The present study further investigated the in vivo anti-tumor effects of orally administered gallic acid. Gallic acid reduced cell viability of LL-2 mouse lung cancer cells in vitro dose dependently, with a 50% inhibitory concentration (IC50) value of around 200 microM. C57Black mice were transplanted with LL-2 cells, and administered gallic acid (1 mg/ml in drinking water, ad libitum) and/or cisplatin (4 mg/kg i.p. injection, once a week). The average weight of the transplanted tumors, obtained at 29 days after transplantation, in the mice of control, gallic acid-treated cisplatin-treated and cisplatin plus gallic acid-treated groups was 4.02, 3.65, 3.19 and 1.72 g, respectively. The average tumor weight of the mice treated with cisplatin combined with gallic acid was significantly smaller than that of the control group (p<0.05). The amount of apoptotic cells in the tumor tissues of mice treated with gallic acid and/or cisplatin was significantly higher than those of the control mice. Combination of gallic acid and cisplatin increased the tumor cell apoptosis compared with the treatment with cisplatin alone. The present findings suggest that the combination of gallic acid with an anti-cancer drug, including cisplatin, may be an effective protocol for lung cancer therapy.

2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure-activity relationships of effects on hepatic glucose production induced via agonism of the A(2B) adenosine receptor.

A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The m-primary benzamide derivative 15f was the most potent compound (IC(50)=0.017 microM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity. The IC(50) values in rat hepatocyte glucose assay correlated well with the IC(50) values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2)=0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor.

Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient Fischer rats.

Glucagon-like peptide-1 (GLP-1) is an incretin, which induces glucose-dependent insulin secretion. GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. We investigated whether DPPIV-deficient F344/DuCrj rats show improved glucose tolerance when compared with DPPIV-positive F344/Jcl rats. Oral glucose tolerance test indicated improved glucose tolerance in F344/DuCrj rats, but blood glucose levels of the two strains were almost the same 120 min after the glucose bolus. Valine-pyrrolidide, a DPPIV inhibitor, had no effect on the glucose tolerance of F344/DuCrj rats, but improved that of F344/Jcl rats. Enhanced insulin secretion and high plasma active GLP-1 levels were detected in an intraduodenal glucose tolerance test. Glucose tolerance is improved in DPPIV-deficient F344/DuCrj rats via enhanced insulin release mediated by high active GLP-1 levels. Our results suggest that DPPIV inhibition is a rational strategy to treat diabetic patients by improving glucose tolerance with low risk of hypoglycemia.

Relationship between thallium-201 myocardial SPECT and findings of endomyocardial biopsy specimens in dilated cardiomyopathy.

The purpose of this study was to clarify which myocardial histological findings associated with dilated cardiomyopathy (DCM) are reflected in quantitative 201Tl myocardial SPECT. We obtained studied SPECT images from 21 patients with DCM 10 minutes and 2 hours after they received an injection of 111 MBq 201Tl at rest. We calculated the percent coefficient of variation of myocardial 201Tl counts [%CV(TI)], the washout rate (WR), standard deviation of WR [SD(WR)], extent score (ES) and severity score (SS). We used image analysis to measure % fibrosis, % myocytes, the ratio of fibrous tissue to myocyte tissue (F/My), myocyte size and standard deviation of myocyte size [SD(My)] in left ventricular endomyocardial biopsy specimens. The %CV(Tl) was correlated with % fibrosis and F/My. The ES and SS also correlated with F/My. The correlation between SD(WR) and SD(My) was significant. The present findings suggest that %CV(Tl), ES and SS of rest 201Tl SPECT reflect myocardial fibrosis and that the standard deviation of washout reflects the distribution of myocyte size.

Smoking and mental health: cross-sectional and cohort studies in an occupational setting in Japan.

BACKGROUND: The relationship between smoking and mental health remains unclear. METHODS: We carried out a cross-sectional study and a cohort study on the possible association of smoking and mental health in 782 workers. Using a questionnaire including the 30-item General Health Questionnaire (GHQ-30) and items related to the smoking state, the association between smoking and mental health was evaluated separately in males and females. The subjects were classified into smokers and nonsmokers, and changes in the GHQ score during a 2-year follow-up period were evaluated. To control potential confounding factors, multiple regression analyses were performed. RESULTS: The cross-sectional study showed no difference in the GHQ score between smokers and nonsmokers among males but a significantly higher GHQ score for smokers than nonsmokers among females. This difference among females was confirmed to be significant by multiple regression analysis. The 2-year cohort study showed a decrease in the GHQ score in each group and no reduction in the difference in the GHQ score between smokers and nonsmokers among females. CONCLUSIONS: No difference was observed in mental health between smokers and nonsmokers in males. However, in females, smokers showed poorer mental health than nonsmokers, and this difference remained unchanged even after 2 years.

2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor.

Novel adenosine antagonists, 2-alkynyl-8-aryl-9-methyladenine derivatives, were synthesized as candidate hypoglycemic agents. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. In general, aromatic moieties at the 8-position and alkynyl groups at the 2-position had significantly increased activity compared to unsubstituted compounds. The preferred substituents at the 8-position of adenine were the 2-furyl and 3-fluorophenyl groups. In modifying the alkynyl side chain, change of the ring size, cleavage of the ring, and removal of the hydroxyl group were well tolerated. The order of the stimulatory effects of adenosine agonists on rat hepatocytes was NECA > CPA > CGS21680, which is consistent with involvement of the A(2B) receptor. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, one of the compounds potent in hepatocytes, 15o (IC(50) = 0.42 microM), antagonized NECA-induced stimulation of cyclic AMP production (IC(50) = 0.063 microM). This inhibitory effect was much more potent than those of FK453, KF17837, and L249313 which have been reported to be respectively A(1), A(2A), and A(3) selective antagonists. These findings agree very well with the result that, compared to 15o, these selective antagonists for each receptor subtype showed only marginal effects in rat hepatocytes. These results suggest that adenosine agonist-induced glucose production in rat hepatocytes is mediated through the A(2B) receptor. Furthermore, 15o showed hypoglycemic activity in an animal model of noninsulin-dependent diabetes mellitus, the KK-A(y) mice. It is possible that inhibition of hepatic glucose production via the A(2B) receptor could be at least one of the mechanisms by which 15o exerts its in vivo effects. Further elaboration of this group of compounds may afford novel antidiabetic agents.

Polychlorinated dibenzo-p-dioxin and dibenzofuran concentrations in the serum samples of workers at continuously burning municipal waste incinerators in Japan.

OBJECTIVES: To find whether concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in serum increased in workers at municipal incinerators that burn continuously. METHODS: 30 Workers employed at three municipal waste incineration plants (incinerator workers) and 30 control workers were studied. The incinerator workers had worn dust masks or airline masks during the periodic repair work inside the incinerators. Previous job, dietary habit, smoking habit, distance from residence to the incineration plant, and body weight and height were obtained from a questionnaire survey. Concentrations of PCDDs/PCDFs were measured in the serum of the workers and the dust deposited in the plants. The influence of various factors on serum concentrations of PCDDs/PCDFs was examined by multiple regression analysis. RESULTS: Dust analysis showed the greatest amount of octachlorodibenzo-p-dioxin (OCDD), followed by 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), 1,2,3,4,6,7,8-heptachlorodibenzofuran (HpCDF), and octachlorodibenzofuran (OCDF). The toxicity equivalents (TEQs) of PCDDs and PCDFs in the deposited dust were 4.8, 1.0, and 6.4 ng TEQs/g, respectively, for plants A, B, and C. The mean serum TEQs of PCDDs and PCDFs in the incinerator workers and control workers were 19.2 and 22.9 pg TEQs/g lipid, respectively, for area A, 28.8 and 24.5 pg TEQs/g lipid for area B, and 23.4 and 23.6 pg TEQs/g lipid for area C. No significant differences were found between the incinerator workers and the controls for TEQs of PCDDs and PCDFs separately, and TEQs of PCDDs and PCDFs together. However, the serum 1,2,3,4,6,7,8-HpCDF concentration was significantly higher in the incinerator workers than in the controls for all the three areas. When the exposure index to 1,2,3,4,6,7,8-HpCDF is defined as the product of the concentration of 1,2,3,4,6,7,8-HpCDF in the deposited dust and duration of employment, the concentration of 1,2,3,4,6,7,8-HpCDF in serum increased as the exposure index increased. Multivariate analysis suggested that the serum concentration of HpCDF increased with duration of employment at the incineration plants and OCDF increased with employment of > or = 21 years. The other significant variables (p < 0.01 or p < 0.001) were area for hexachlorodibenzo-p-dioxin (HxCDD) and tetrachlorodibenzofuran (TCDF), Brinkman index for HpCDD, and body mass index (BMI) for tetrachlorodibenzo-p-dioxin (TCDD), HpCDD, and TEQs of PCDDs. CONCLUSION: The serum TEQs of PCDDs and PCDFs was not significantly higher among the incinerator workers, but the serum concentration of 1,2,3,4,6,7,8-HpCDF was. This suggests that the incinerator workers had inhaled dust containing PCDDs and PCDFs while working in plants equipped with incinerators that burn continuously.

[Analyses of work-relatedness of health problems among truck drivers by questionnaire survey].

In order to estimate occupational risk factors for health problems among truck drivers, a questionnaire survey of working conditions, job content in truck transportation, subjective symptoms and present illnesses was carried out among 541 truck transportation workers in 1997. The valid response rate was 85.7%, and 134 local truck drivers, 199 long-distance truck drivers and 71 clerical workers were analyzed. First, to examine occupational risk factors and health problems among the three groups, the authors analyzed working conditions, job content in truck transportation, subjective symptoms and present illnesses. Second, to estimate the work-relatedness of health problems among local truck drivers and long-distance truck drivers, logistic regression analyses were conducted, and odds ratios and 95% confidence intervals were computed. The prevalence rates of working factors affecting health problems of truck drivers were significantly higher than those of clerical workers in the items on irregular shift work, working environment, working posture, handling heavy materials, job stress due to overloading and long working time and limited time off. The prevalence rates for subjective symptoms (ringing in the ears, neck pain and low back pain) and present illnesses (hypertension, ulcers in the digestive tract, back injuries, whiplash injuries and hemorrhoids) among truck drivers were significantly higher than those of clerical workers. In logistic regression analyses, many work-related items except age, BMI and smoking habit showed significantly higher odds ratios for subjective symptoms and present illnesses of truck drivers. Odds ratios for hypertension, heart diseases and related subjective symptoms among local truck drivers were significantly increased by job career, twisting posture, vibration and driving stress. Odds ratios for gastro-duodenal diseases and related subjective symptoms were significantly increased by narrow working space, sleeping in the truck, driving distance, squatting posture and driving stress. Odds ratios for ringing in the ears among local truck drivers were significantly increased by job career, long working time, narrow working space, sleeping in the truck and driving stress. Odds ratios for musculo-skeletal diseases and related subjective symptoms were significantly increased by overwork, vibration, narrow working space, sitting posture and shortage of recess. Odds ratios for fatigue symptoms were significantly increased by the shortage of recess, vibration and driving stress. In order to cope with the health problems of truck drivers, it is recommended that working conditions and work loads for among truck drivers as described above be improved.

Multiple prolactin-releasing activity in the bovine hypothalamic extract.

The prolactin (PRL)-releasing activity (PRA) in the bovine hypothalamic extract (BHE) was compared to that of known substances with PRA and further characterized by gel filtration and reversed-phase high performance liquid chromatography (RP-HPLC). Crude BHE produced marked dose-dependent stimulation of PRL secretion from the cultured rat adenohypophysial cells. Among the synthetic substances examined, vasoactive intestinal peptide (VIP), thyrotropin-releasing hormone (TRH) and beta-endorphin (END) showed significant PRA. However, the flatter dose-response slope for TRH compared with BHE or the small amounts of VIP and END in BHE suggested that these peptides could not account for the major active elements of BHE. Oxytocin and interleukin-1beta were also tested, but they exhibited no PRA in our assay system. Gel filtration of BHE on the Sephadex G-100 column yielded two peaks of PRA distinct from TRH, VIP and END. One eluted in the void and the other in more retarded fractions. The latter fractions were pooled and subjected to the two-step RP-HPLC. The PRA was separated into three peaks designated peaks I, II and III in the first RP-HPLC experiment. Furthermore, the second RP-HPLCs with finer resolution revealed that peak II as well as peak III consisted of three peaks, while peak I eluted as a single peak. Most of these seven PRA peaks exhibited different RP-HPLC profiles from those of the newly characterized PRL-releasing peptides. These findings again provide confirmatory evidence that BHE contained unique factors different from the above known substances.