Evidence from twins for acquired cellular immune hyperactivity in type 1 diabetes

Type 1 diabetes has been associated with an increased frequency of activated T cells and T-cell hyperactivity to non-specific and disease-specific stimuli including the islet autoantigen glutamic acid decarboxylase 65 (GAD). To address whether T-cell hyperactivity is genetic or acquired we measured whole blood cytokines in vitro in response to GAD or tetanus in 18 identical twin pairs, nine discordant for type 1 diabetes. In addition, the activity of 2', 5' oligoadenylate synthetase (OAS) in blood mononuclear cells was measured as a marker of viral infection. Interleukin-2 (IL-2) basally and IL-2 and interferon-gamma (IFN-gamma) in response to GAD, were detected more frequently and at higher levels in diabetic compared to non-diabetic twins. IL-10 was not different between groups. OAS activity was increased in diabetic compared to non-diabetic twins and showed a correlation with basal IL-2 and GAD-stimulated IFN-gamma and IL-10. These findings suggest that T-cell hyperactivity in type 1 diabetes is an acquired trait and could reflect persisting virus expression.     

Extended voluntary running inhibits exercise-induced adult hippocampal progenitor proliferation in the spontaneously hypertensive rat

Previous work has shown that voluntary running increases cell proliferation and neurogenesis in the dentate gyrus of the adult hippocampus. Here we report that long-term running for 24 days results in a down-regulation of hippocampal progenitor proliferation to one-half the level of nonrunning controls compared with a fivefold increase in progenitor proliferation seen after 9 days of voluntary running (short-term running). The negative effects seen on proliferation after 24 days of running were prevented by restricting daily running distances (by 30-50%) during 24 days. Long-term running for 24 days increases the response of the hypothalamic-pituitary-adrenal axis, with an increase in adrenal gland weight and increased plasma corticosterone levels, as well as decreased thymus weight, indicating a stress response as a possible mediator of decreased progenitor proliferation. Furthermore, the negative effects seen on the observed stress response after 24 days of running were prevented by restricting daily running distance. Short-term running did not alter these stress parameters compared with nonrunning controls. However, it increased phosphorylated cyclic AMP response element binding protein (pCREB) in the dentate gyrus, an increase that was not seen in nonrunning controls or after 24 days of running. Taken together, these data suggest that voluntary running does not always enhance proliferation and that the decrease in progenitor proliferation seen in long-term running is possibly mediated by mechanisms involving a stress response in the animal. However, a moderate level of long-term running was able to prevent the negative stress-related changes seen in unrestricted long-term running.     

A component of an antigenic rhoptry complex of Plasmodium falciparum is modified after merozoite invasion

Human antibodies affinity purified on an adsorbent prepared from a cDNA clone (Ag44) expressing a portion of a rhoptry antigen were used to characterize the synthesis and fate of the antigen in the asexual blood stages of Plasmodium falcipartum. The rhoptry antigen is synthesized in the mature trophozoite-stage parasites as a 103 kDa polypeptide, is present in the schizonts and merozoites as a 105 kDa polypeptide, is discharged from the rhoptries and found in the newly invaded red cells as a 110 kDa polypeptide. Anti-Ag44 antibodies immunoprecipitate the antigen and two additional polypeptides of 135 and 150 kDa from lysates of infected cells and from culture supernatants. The three polypeptides are associated in a non-covalent complex that persists in the newly invaded red cells. All the components of the high molecular weight rhoptry complex are antigenic and can be precipitated with immune human serum. The 135 kDa polypeptide is identical to a 140 kDa rhoptry antigen previously identified by a monoclonal antibody.     

Creating a mission-based reporting system at an academic health center.

The authors developed a Web-based mission-based reporting (MBR) system for their university's (UC Davis's) health system to report faculty members' activities in research and creative work, clinical service, education, and community/university service. They developed the system over several years (1998-2001) in response to a perceived need to better define faculty members' productivity for faculty development, financial management, and program assessment. The goal was to create a measurement tool that could be used by department chairs to counsel faculty on their performances. The MBR system provides measures of effort for each of the university's four missions. Departments or the school can use the output to better define expenditures and allocations of resources. The system provides both a quantitative metric of times spent on various activities within each mission, and a qualitative metric for the effort expended. The authors report the process of developing the MBR system and making it applicable for both clinical and basic science departments, and the mixed success experienced in its implementation. The system appears to depict the activities of most faculty fairly accurately, and chairs of test departments have been generally enthusiastic. However, resistance to general implementation remains, chiefly due to concerns about reliability, validity, and time required for completing the report. The authors conclude that MBR can be useful but will require some streamlining and the elimination of other redundant reporting instruments. A well-defined purpose is required to motivate its use.     

The Importance of Ventilation in Exercise-Induced Asthma

The degree of post treadmill-running decrease in pulmonary function (Exercise-Induced Asthma) in 11 adult asthmatics was compared with the decrease in pulmonary function followed by resting isocapnic hyperventilation. It was checked that ventilation during the hyperventilation was kept identical to the ventilation during treadmill-running by continuous recording of respiratory frequency, minute ventilation, tidal volume and accumulated ventilation. The temperature of the inspired air was identical in the two situations and the relative humidity was 40% during treadmill-running and 15% during hyperventilation. The average accumulated ventilation during treadmill-running and hyperventilation was 411 1/6 min in both events. The decrease in peak expiratory flow after treadmill-running was 25% and after isocapnic hyperventilation 24%. It is concluded that the ventilation is of more importance for the decrease in pulmonary function after exercise, than the work load.     

Computerized Digital Imaging Techniques Provided by Digital X-ray Radiogrammetry as New Diagnostic Tool in Rheumatoid Arthritis

Purpose Our study evaluates digital x-ray radiogrammetry (DXR) and Radiogrammetry Kit (RK) as a new diagnostic method for the measurement of disease-related osteoporosis including quantification of joint space narrowing dependent on the severity of rheumatoid arthritis (RA). Materials and Methods A total of 172 unselected patients with RA underwent computerized measurements of bone mineral density (BMD) and metacarpal index (MCI) by DXR, as well as a semiautomated measurement of joint space distances at the metacarpal–phalangeal articulation (JSD-MCP 2–5), both were analyzed from plain radiographs of the nondominant hand. Results Correlations between DXR-BMD and DXR-MCI vs. parameters of RK were all significant (0.34 < R < 0.61; p < 0.01). An expected negative association was observed between RK parameters and the different scoring methods (−0.27 < R < −0.59). The maximum relative decrease in BMD vs. MCI as measured by DXR between the highest and lowest RA severity group was −27.7% vs. −27.5% (p < 0.01) for the modified Larsen Score, whereas the minimal value of relative DXR-BMD and DXR-MCI reduction could be documented for the Sharp Erosion Score (−20.8% vs. −26.8%; p < 0.01). The relative reduction of mean JSD-MCP using RK significantly varied from −25.0% (Sharp Erosion Score) to −41.2% (modified Larsen Score). In addition, an excellent reproducibility of DXR and RK could be verified. Conclusion DXR in combination with RK could be a promising, widely available diagnostic tool to supplement the different scoring methods of RA with quantitative data, allowing an earlier and improved diagnosis and more precision in determining disease progression.     

Sleep on the Night Shift: 24-Hour EEG Monitoring of Spontaneous Sleep/Wake Behavior

The present study sought to objectively describe the spontaneous sleep/wakefulness pattern of shift workers during a 24-hour period. Portable Medilog tape-recorders were used for ambulatory EEG monitoring of 25 male papermill workers (25-55 years) during days with night and afternoon work. The results showed that sleep after night work was two hours shorter than after afternoon work. The sleep reduction affected mainly Stage 2 and REM sleep while slow wave sleep was unchanged. In connection with night work 28% of the workers took a nap in the afternoon. These naps contained a large proportion of slow wave sleep and were, apparently, caused by the sleep deficit after the short main sleep period. The EEG recordings also revealed that 20% of the participants had sleep episodes during night work. These naps were as long as the afternoon naps, were experienced as "dozing offs" rather than naps, occurred at the time of the trough of the circadian wakefulness rhythm, and were concomitant with extreme subjective sleepiness and low rated work load. It was concluded that not only the sleep of shift workers was disturbed, but also the wakefulness--to the extent that sleepiness during night work sometimes reached a level where reasonable wakefulness could not be maintained. The latter observation is probably of special importance in work situations demanding a great responsibility for human lives or for great economic values.     

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.