Characterization of the neuropeptide Y system in the frog Silurana tropicalis (Pipidae): three peptides and six receptor subtypes.

Neuropeptide Y and its related peptides PYY and PP (pancreatic polypeptide) are involved in feeding behavior, regulation of the pituitary and the gastrointestinal tract, and numerous other functions. The peptides act on a family of G-protein coupled receptors with 4-7 members in jawed vertebrates. We describe here the NPY system of the Western clawed frog Silurana (Xenopus) tropicalis. Three peptides, NPY, PYY and PP, were identified together with six receptors, namely subtypes Y1, Y2, Y4, Y5, Y7 and Y8. Thus, this frog has all but one of the ancestral seven gnathostome NPY-family receptors, in contrast to mammals which have lost 2-3 of the receptors. Expression levels of mRNA for the peptide and receptor genes were analyzed in a panel of 19 frog tissues using reverse transcriptase quantitative PCR. The peptide mRNAs had broad distribution with highest expression in skin, blood and small intestine. NPY mRNA was present in the three brain regions investigated, but PYY and PP mRNAs were not detectable in any of these. All receptor mRNAs had similar expression profiles with high expression in skin, blood, muscle and heart. Three of the receptors, Y5, Y7 and Y8, could be functionally expressed in HEK-293 cells and characterized with binding studies using the three frog peptides. PYY had the highest affinity for all three receptors (K(i) 0.042-0.34 nM). Also NPY and PP bound to the Y8 receptor with high affinity (0.14 and 0.50 nM). The low affinity of NPY for the Y5 receptor (100-fold lower than PYY) differs from mammals and chicken. This may suggest a less important role of NPY on Y5 in appetite stimulation in the frog compared with amniotes. In conclusion, our characterization of the NPY system in S. tropicalis with its six receptors demonstrates not only greater complexity than in mammals but also some interesting differences in ligand-receptor preferences.

Bone marrow hyaluronan and reticulin in patients with malignant disorders.

Myelofibrosis is commonly seen in patients with chronic myeloproliferative diseases and sometimes in myelodysplastic syndrome, acute leukaemia and lymphoproliferative diseases. The fibrotic process is evaluated by grading the amount of collagen deposited in the bone marrow interstitium. The established method to evaluate bone marrow fibrosis is staining for reticulin to visualise the collagen fibres. However, the extra cellular matrix does not only contain collagens but also other components, e.g. glycosaminoglycans of which hyaluronan is the most abundant. Hyaluronan is important for structural and cellular functions. Earlier studies have shown that there is a positive correlation between hyaluronan and reticulin staining in healthy volunteers and in patients with de novo acute myeloid leukaemia. In this study bone marrow biopsies from 43 patients with a malignant disease involving the bone marrow were compared with 18 patients with a malignant disease not involving the bone marrow. The intensity of hyaluronan grading was significantly higher in the patients with disease involving the bone marrow compared to the healthy controls but not compared to the patients without disease involving the bone marrow. The staining intensity of reticulin in the bone marrow was significantly higher in the patients with disease involving the bone marrow, compared to those without disease involving the bone marrow and to the controls. In all patients and the controls there was a correlation between hyaluronan and reticulin.

Incidence and risk factors for depression and anxiety disorders: results from a 34-year longitudinal Swedish cohort study.

This study is based on a total cohort (N = 192) of people born in 1902 and 1903 and living in southern Sweden. Subjects were assessed at baseline when 67 years of age and on eight further occasions over 34 years or until death. The participation rate in the nine examinations ranged from 78-100%. Interviews, psychological tests, and medical examinations were used as well as information on medical diagnoses from primary health care records and hospital records. The cumulative probability for the development of clinical depression during the follow-up was 8% and for anxiety 6%. The incidence rate for depression and for anxiety was highest during the period 67-81 years. Persons with poor financial status were more likely to be diagnosed with depression but no significant risk factor for anxiety was found. Only 14% developed depression and anxiety during the follow-up period, females more often than men. The strongest risk factors for the development of depression were perceived economic problems.

Formal support, mental disorders and personal characteristics: a 25-year follow-up study of a total cohort of older people.

The present study was designed to describe the pattern of long-term formal support received by people with mental disorders, and to investigate the relationship between the medical, psychological and social characteristics of the participants and types of formal support. This study is based on a cohort (n = 192) of people born in 1902 and 1903 in a community in Southern Sweden. The research participants were assessed using interviews, psychological tests and medical examinations. Information was collected about the use of primary healthcare and social services. The first assessment took place when the cohort was aged 67 years, and then on eight further occasions until they were 92. The participation rate ranged from 72% to 100%. During the observation period of 25 years, 53% of people with dementia eventually received both home help and institutional care compared to 34% of people with other psychiatric diagnoses and 12% of people with good mental health. The last group had all physical health problems and/or problems with activities of daily living. However, 35% of the dementia group, 46% with other psychiatric diagnoses and 52% of people with good mental health did not receive any formal support. Males and self-employed people were significantly less likely to use formal support. The institutionalised group reported loneliness significantly more often than the other two groups. In a logistic regression analysis, loneliness, low social class, high blood pressure and low problem-solving ability were predictors of formal support use. People with a mental disorder, including dementia, were significantly more likely to use formal support compared to people with good mental health. Social factors were the main factors predicting formal support.

Assessment of liver disease and biochemical and immunological markers in Swedish blood donors with isolated GB virus C/hepatitis G virus viremia.

OBJECTIVE: To investigate signs of liver disease, and biochemical and immunological markers in blood donors with isolated GBV-C/HGV viremia. METHODS: Eighteen donors with isolated GBV-C/HGV viremia were followed up 3-5 years after initial identification. Testing for GBV-C/HGV RNA, GBV-C/HGV-E2 antibodies and a range of biochemical and immunological tests was performed. Thirteen donors consented to liver biopsy. RESULTS: Twelve donors remained GBV-C/HGV viremic at follow-up. Five donors had developed E2 antibodies. Liver biopsies revealed mild portal inflammatory lesions in 6/11 individuals with persistent viremia, and steatosis in 10/13 biopsied donors. CONCLUSION: Steatosis and mild portal inflammatory lesions were found in liver biopsies from several blood donors with isolated GBV-C/HGV viremia.

Intestinal permeability in patients with acute myeloid leukemia.

Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

Hepatitis C virus and GB virus C/hepatitis G virus viremia in Swedish blood donors with different alanine aminotransferase levels.

BACKGROUND: Hepatitis C virus (HCV) is a known blood-borne hepatotropic virus for which antibody screening of blood donors is universally practiced. The newly identified GB virus C (GBV-C) and its strain variant hepatitis G virus (HGV) are of unknown pathogenic significance, and screening of blood donors for this agent has not yet been implemented. Polymerase chain reaction (PCR) is the most sensitive method for detecting HCV viremia and is the only method presently available for the diagnosis of GBV-C/HGV infection. STUDY DESIGN AND METHODS: RNA extracts of sera from 577 anti-HCV-negative blood donors (393 with elevated alanine aminotransferase [ALT] levels, 184 with normal ALT levels) were tested with nested PCR for HCV and GBV-C/HGV directed at the 5'-noncoding regions of the two viruses. RESULTS: One donor with elevated ALT was HCV PCR positive. This donor was anti-HCV negative when recruited to the study but subsequently developed anti-HCV. Of the 19 donors with GBV-C/HGV viremia in the series as a whole, 16 belonged to the group with elevated ALT levels and 3 to the group with normal ALT levels; the group difference in prevalence was nonsignificant (4.1% [16/393] vs. 1.6% [3/184; p = 0.20]). Phylogenetic analysis showed 16 of the GBV-C/HGV isolates to be classifiable as subtype 2a and three as subtype 2b. At follow-up 3 to 5 years later, 11 of 18 donors were still viremic. CONCLUSION: There was no significant difference in GBV-C/HGV viremia in the group with elevated ALT levels and the group with normal ALT levels. The frequency and subtype distribution in the present series were similar to those in other Western countries.

Ventilatory response to CO2 in patients with snoring, obstructive hypopnoea and obstructive apnoea.

Obstructive sleep apnoea (OSA) is caused by an obstruction of the upper airway. Sufficient sensitivity to CO2 in the respiratory centre is known to be a critical factor for adequate tone in the upper airway muscles. The hypothesis of this study is, therefore, that the ventilatory response to CO2 is reduced in patients with OSA. Twenty-six patients who suffered from snoring, 19 snoring patients with obstructive hypopnoea (OH) and 33 snoring patients with obstructive apnoea (OA), were studied. The control group consisted of 25 subjects from a random sample with no history of snoring or daytime sleepiness. Tests of the hyperoxic and hypoxic ventilatory response to CO2 were performed, as well as static and dynamic spirometry. Subjects in the OA group displayed a higher hyperoxic (VE/FetCO2hy = 12.6 l min-1/%) and hypoxic (VE/FetCO2ho = 15.7 l min-1/%) ventilatory response to CO2 than patients with obstructive hypopnoea (VE/FetCO2hy = 8.6 l min-1/%; VE/FetCO2ho = 15.2 l min-1/%), snorers (VE/FetCO2hy = 8.4 l min-1/%; VE/FetCO2ho = 12.7 l min-1/%) and non-snorers (VE/FetCO2hy = 7.6 l min-1/%; VE/FetCOho = 9.6 l min-1/%). Multiple regression analysis reveals that neck circumference, apnoea index, oxygen desaturation index, PCO2 and sex (male gender) are correlated with VE/FetCO2hy (R2 = 0.43). Multiple regression analysis also reveals that ERV (expiratory reserve volume) and sex (male gender) are correlated with VE/FetCO2ho (R2 = 0.21). Arguing against the hypothesis, patients with OSA displayed an increased hyperoxic and hypoxic ventilatory response to CO2. Nocturnal apnoea frequency and the obesity factor in OSA may have contributed to these results.

Quantification of formation and remineralization of artificial enamel lesions with a new portable fluorescence device.

Quantitative laser fluorescence has been reported as a useful method for the non-destructive in vitro and in vivo diagnosis of early enamel caries. A portable system for intraoral use has been developed with a new light source and filter system replacing the laser light to facilitate clinical application. This new device was validated with microradiographic and chemical analyses for assessment of mineral changes in enamel during lesion formation and remineralization in vitro and compared with the laser light equipment. A significant correlation was found between fluorescence changes and mineral loss: r = 0.79 (laser system) and r = 0.84 (portable lamp system). The correlation between the two fluorescence methods was r = 0.93. The portable fluorescence device seemed to be a promising new tool for reproducible and sensitive assessment of the severity of incipient enamel lesions.

Health and social networks as predictors of survival in old age.

A random sample of non-institionalised Swedish elderly (n = 1,062; aged 67 +) were interviewed in 1954. All of them are now deceased; their interview data have been completed with dates of death and causes of death. A measure of survival capacity has been used, based on the endured total mortality risk from examination until death, according to life tables from Statistics Sweden. Survival analyses were performed by gender on the whole sample and on a number of sub-samples defined by age, health-status, social class, and marital status at examination. Physical health status and activity patterns had the overall most significant effects on subsequent longevity. Among the youngest elderly mental health was, however, even more important as a predictor of survival than was physical health. The impact of most other factors like social networks, mobility, and religiosity was of less magnitude, but their importance varied among sub-samples. Most of the variation in survival, however, remains unexplained.