Intrarenal oxygen tension measured by a modified Clark electrode at normal and low blood pressure and after injection of x-ray contrast media

 The oxygen tension (pO₂) in the rat kidney was studied using a Clark microelectrode with a guard cathode behind the sensing cathode. The mean (± SEM) outer tip diameter of the electrodes used was 5.5 ± 1.9 μm. The zero-pO₂ current amounted to 12.5 ± 0.9 pA at 37°C; at air saturation it was 252 ± 22.9 pA. Rats with a systolic blood pressure (BP) above 80 mmHg (where 1 mmHg = 133 Pa) showed an average pO₂ in the cortex of 45 ± 2 mmHg and in the outer medulla of 31 ±1 mmHg. In rats with a BP below 80 mmHg a paradoxically high outer medullary pO₂ of 40 ± 4 mmHg was found, while the pO₂ in the cortex was 27 ± 4 mmHg. Changes in pO₂ were also noted in the renal cortex and outer medulla after intravenous injections of the x-ray contrast medium diatrizoate (370 mg iodine/ml). In rats with normal BP, injection of diatrizoate caused a slight fall in pO₂ in the renal cortex, from 42 ± 4 to 38 ±4 mmHg. In the medulla pO₂ decreased significantly from 34 ± 6 to 20 ±4 mmHg. Ringer’s solution did not induce any changes. Received: 9 September 1996 / Received after revision: 22 May 1997 / Accepted: 23 May 1997     

Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families

BACKGROUND: There is a lack of knowledge on child health as well as family well-being in IVF/ICSI twins. METHODS: These data originated from questionnaires completed by mothers taking part in a national cohort study of twin and singleton births occurring in Denmark in 1997. The overall response rate was 83%. The three cohorts consisted of all IVF/ICSI twin children (n = 472), all IVF/ICSI singletons (n = 634) and all non-IVF/ICSI twin children (n = 1132) born in Denmark in 1997. RESULTS: No major differences in physical health were observed between IVF/ICSI twins and non-IVF/ICSI twins. Compared with IVF/ICSI singletons, more IVF/ICSI twins were admitted to a neonatal intensive care unit (NICU) (P < 0.01) and more had surgical interventions (P = 0.03) and special needs (P = 0.02), moreover they had poorer speech development (P < 0.01). Correspondingly, IVF/ICSI twin mothers rated their infant's general health poorer than IVF/ICSI singleton mothers did. All discrepancies between IVF/ICSI twins and singletons disappeared after stratification for birthweight except for NICU admissions and speech development. Multiple logistic regression analyses showed that both IVF/ICSI and non-IVF/ICSI twin parents experienced more marital stress [odds ratio (OR) 2.9, 95% CI 2.2-3.8] and that twins had more impact on the mother's life (OR 1.7, 95% CI 1.2-2.4) compared with singletons. Nevertheless, the only predictor of low divorce/separation risk was IVF/ICSI treatment. CONCLUSION: Our study indicates that physical health of IVF/ICSI twins is comparable with that of non-IVF/ICSI twins. However, physical health of IVF/ICSI twins is poorer and the implications for the families stronger compared with IVF/ICSI singletons.     

High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients.

BACKGROUND: Human parvovirus B19 (B19) polymerase chain reaction (PCR) is now a routine analysis and serves as a diagnostic marker as well as a complement or alternative to B19 serology. The clinical significance of a positive B19 DNA finding is however dependent on the type of tissue or body fluid analysed and of the immune status of the patient. OBJECTIVES: To analyse the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients. STUDY DESIGN: Parvovirus B19 DNA was analysed in paired bone marrow and serum samples by nested PCR technique. Serum was also analysed for B19-specific IgG and IgM antibodies and the results were compared with clinical and epidemiological data. RESULTS AND CONCLUSIONS: B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group. A high frequency of parvovirus B19 DNA was thus detected in bone marrow samples in rheumatic patients. The clinical data does not support a direct association between B19 PCR positivity and rheumatic disease manifestation. Therefore, the clinical significance of B19 DNA positivity in bone marrow samples from rheumatic patients must be interpreted with caution.     

Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients

Helicobacter pylori chronically colonizes the stomach and duodenum and causes peptic ulcers or gastric adenocarcinoma in 10 to 20% of infected individuals. We hypothesize that the inability of patients to clear H. pylori infections is a consequence of active suppression of the immune response. Here we show that H. pylori-infected individuals have increased frequencies of CD4(+) CD25(high) T cells in both the stomach and duodenal mucosa compared to uninfected controls. These cells have the phenotype of regulatory T cells, as they express FOXP3, a key gene for the development and function of regulatory T cells, as well as high levels of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) protein. In contrast, mucosal CD4(+) CD25(low) and CD4(+) CD25(-) cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4(+) CD25(high) T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4(+) CD25(high) cells are also increased in the stomachs of H. pylori-infected patients with gastric adenocarcinoma, particularly in cancer-affected tissues. These findings suggest that regulatory T cells may suppress mucosal immune responses and thereby contribute to the persistence of H. pylori infections.     

Evidence for the involvement of the posterior parietal cortex in coordination of fingertip forces for grasp stability in manipulation

Grasp stability during object manipulation is achieved by the grip forces applied normal to the grasped surfaces increasing and decreasing in phase with increases and decreases of destabilizing load forces applied tangential to the grasped surfaces. This force coordination requires that the CNS anticipates the grip forces that match the requirements imposed by the self-generated load forces. Here, we use functional MRI (fMRI) to study neural correlates of the grip-load force coordination in a grip-load force task in which six healthy humans attempted to lift an immovable test object held between the tips of the right index finger and thumb. The recorded brain activity was compared with the brain activity obtained in two control tasks in which the same pair of digits generated forces with similar time courses and magnitudes; i.e., a grip force task where the subjects only pinched the object and did not apply load forces, and a load force task, in which the subjects applied vertical forces to the object without generating grip forces. Thus neither the load force task nor the grip force task involved coordinated grip-load forces, but together they involved the same grip force and load force output. We found that the grip-load force task was specifically associated with activation of a section of the right intraparietal cortex, which is the first evidence for involvement of the posterior parietal cortex in the sensorimotor control of coordinated grip and load forces in manipulation. We suggest that this area might represents a node in the network of cortical and subcortical regions that implement anticipatory control of fingertip forces for grasp stability.     

The involvement of CD14 in stimulation of cytokine production by uronic acid polymers

In this study the molecular mechanisms behind the stimulatory activities of the uronic acid polymers poly mannuronic acid (poly M), high M alginate and oxidized cellulose (C60XY) were investigated and compared with lipopolysaccharide (LPS). The cytokine-inducing abilities of the uronic acid polymers and LPS were examined on CD14-positive human monocytes and CD14-negative U373 astrocytoma cells. It was found that LPS induced monocytes and U373 cells to produce tumor necrosis factor (TNF) and interleukin(IL)-6, respectively, by different mechanisms. The poly uronic acids induced monocytes to produce TNF, but with 100-1000 times less potency compared to LPS. On U373 cells, LPS at concentrations ? 32 ng/ml resulted in a dose-related IL-6 production, whereas the poly uronic acids had negligible effects even at 1 mg/ml. The binding data demonstrate that only the CD14-positive monocytes in the peripheral blood mononuclear cells population bound poly M. Furthermore, poly M was found to bind to CD14 in the presence of serum. Antibodies against CD14 also inhibited the TNF-inducing activity of the three uronic acid polymers tested. In conclusion, these results demonstrate that uronic acid polymers induce TNF production through mechanisms which involve CD 14.     

Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

Do children take the same number of steps every day?

The purpose of this study was to examine the day-to-day variability in pedometer-assessed physical activity (steps/day). A total of 1,443 children aged 6-12 years from the United States (195 boys, 254 girls), Sweden (257 boys, 252 girls), and Australia (229 boys, 256 girls) wore a pedometer for 4 consecutive weekdays. Repeated measures analysis of variance was used to examine daily differences in steps/day and the coefficient of variation (CV) was calculated for each individual to describe the day-to-day variability. Overall, mean steps/day were higher among boys (14,698 +/- 3,373 steps/day) than girls (12,086 +/- 2,929 steps/day). Significant differences were found between the 4 monitoring days for the entire sample; however, the absolute mean differences were small (55-958 steps) with an overall effect size of 0.01. This trend was apparent regardless of age, gender, and country. Individual CVs ranged from approximately 2 to 88% and the overall mean CV approximated 22%. An age-related increase in the mean CV was observed between 6- and 12-year-old children. The age x gender x country interaction was not significant (P > 0.05). These findings have implications toward the proper design, analysis, and interpretation of studies regarding physical activity among children. Beyond this aspect, our results lend insight into potential age-related biological mechanisms that may also influence daily levels and patterns of physical activity.