Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits

N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function.     

Myasthenia in a patient with sarcoidosis and schizophrenia

A 44-year-old male patient was hospitalised with paranoid schizophrenia in 1985. Depot neuroleptic treatment was started which successfully prevented further psychotic relapses for the next ten years. His myasthenia gravis started with bulbar signs in 1997 and the symptoms soon became generalized. The diagnosis of myasthenia gravis was confirmed by electromyography, by positive anticholinesterase test and by the detection of anti-acetylcholine receptor antibodies in the serum. Mediastinal CT examination showed enlarged hilar lymph nodes on the left but no thymic pathology was observed. Mediastinoscopy was performed and biopsies were obtained from the affected nodes. Histology revealed sarcoidosis. The patient suffered respiratory crisis following the thoracic intervention (in September 1998). Combined oral corticosteroid (64 mg methylprednisolone/e.o.d.) and azathioprine (150 mg/day) treatment regimen was initiated and complete remission took place in both the myasthenic symptoms and the sarcoidosis. The follow-up CT scans showed no mediastinal pathology (January 2000). During steroid treatment a transient psychotic relapse occurred which was successfully managed by supplemental haloperidol medication added to his regular depot neuroleptics. The patient currently takes 150 mg/day azathioprine and receives 40 mg/month flupentixol depot i.m. His physical and mental status are stable and he has been completely symptom free in the last 24 months. The association of myasthenia gravis and sarcoidosis is very rare. To our best knowledge no case has been reported of a patient suffering from myasthenia gravis, sarcoidosis, and schizophrenia at the same time.     

Leptospirosis in children

Leptospirosis has a broad spectrum of clinical manifestations varying, from inapparent influenza like illness to fulminant fatal disease with hepato-renal dysfunction and hemorrhagic phenomena. Our cases had fever, puffiness, respiratory distress and bleeding diathesis as leading manifestations. Leptospirosis was suspected in view of epidemic situation prevailing in the city. We report four cases here, three of which survived and one died.     

Chlamydophila (Chlamydia) pneumoniae induces histidine decarboxylase production in the mouse lung

Chlamydophila (Chlamydia) pneumoniae (C. pneumoniae) is the third most common cause of community-acquired pneumonia and is probably involved in the development of certain chronic inflammatory diseases, including atherosclerosis and adult-onset asthma. Histamine, synthesized by histidine decarboxylase (HDC) from L-histidine, plays an essential role in allergic and inflammatory processes and in cell differentiation. The effect of C. pneumoniae infection on the expression of HDC has not been examined. In the present study, normal Balb/c mice and HDC knockouts, and control mice with a CD1 background were infected intranasally with C. pneumoniae. On days 1, 3, 7, 16 and 31 after infection, the normal Balb/c mice were sacrificed and divided into three groups. In the homogenized lungs of the first group, C. pneumoniae titres were determined and demonstrated peak levels on day 7. HDC production was revealed by a Western blot assay throughout the observation period of 1-16 days, and cytokine concentrations were determined by ELISA. The interleukin-3 (IL-3) and interleukin-6 (IL-6) levels were highest on day 1 and on days 1-3, respectively; the interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels reached the maximum on day 7, but the quantity of IL-4 was still three times higher than that in the control group 16 days after infection. The lungs of the mice in the second group were processed for the in situ demonstration of HDC activity, while the lungs in the third group were stained for C. pneumoniae antigen. The HDC activity was increased predominantly in the bronchial epithelial cells, while C. pneumoniae antigens were expressed especially in the interstitial macrophages. The HDC knockout mice exhibited a higher survival rate after C. pneumoniae infection than did the control mice. These results point to a strong association between local histamine production and other inflammatory mediators and are novel in demonstrating the role of histamine in the pathomechanism of C. pneumoniae infections.     

Ureaplasma urealyticum in the development of postpartum endometritis

OBJECTIVE: Investigation of the clinical significance of Ureaplasma urealyticum and its biovars in the development of postpartum endometritis. STUDY DESIGN: Cervical swabs were cultured for U. urealyticum in women presenting endometritis. The positive U. urealyticum cultures (>10(5) cfu/ml) (study group) were compared with those from women without endometritis (control group). Anti-Ureaplasma antibodies were measured and U. urealyticum biovars were determined by polymerase chain reaction. RESULTS: There was no difference between the prevalence of U. urealyticum in the cervical swabs of both groups, however, the number of cfu per culture, showed a significant difference between study and control groups. Out of the culture positive endometritis patients 39% (26/67) had >10(5) cfu/ml compared to 17% of control patients (5/30) P=0.03. No significant disparity between both the groups was found in the prevalence of the parvo biovar (77% versus 71.5%, respectively). The difference in anti-Ureaplasma antibodies reached no statistical significance (30% versus 18% in study and control groups, respectively). CONCLUSIONS: The significant difference in U. urealyticum culture cfu between both groups suggests that U. urealyticum may play a role in the etiology of this infection. This involvement is dependent not only on the presence or absence of U. urealyticum in the culture, but on its colonization rate in the cervix (>10(5) cfu/ml).     

Quantitative analysis of DNA levels in maternal plasma in normal and Down syndrome pregnancies

BACKGROUND: We investigated fetal and total DNA levels in maternal plasma in patients bearing fetuses affected with Down syndrome in comparison to controls carrying fetuses with normal karyotype. METHODS: DNA levels in maternal plasma were measured using real-time quantitative PCR using SRY and beta-globin genes as markers. Twenty-one pregnant women with a singleton fetus at a gestational age ranging from 15 to 19 weeks recruited before amniocentesis (carried out for reasons including material serum screening and advanced material age), and 16 pregnant women bearing fetuses affected with Down syndrome between 17 to 22 weeks of gestation were involved in the study. RESULTS: The specificity of the system reaches 100% (no Y signal was detected in 14 women pregnant with female fetuses) and the sensitivity 91.7% (SRY amplification in 22 of 24 examined samples). The median fetal DNA levels in women carrying Down syndrome (n=11) and the controls (n=13) were 23.3 (range 0-58.5) genome-equivalents/ml and 24.5 (range 0-47.5) genome-equivalents/ml of maternal plasma, respectively (P = 0.62). The total median DNA levels in pregnancies with Down syndrome and the controls were 10165 (range 615-65000) genome-equivalents/ml and 7330 (range 1300-36750) genome-equivalents/ml, respectively (P = 0.32). The fetal DNA proportion in maternal plasma was 0%-6 % (mean 0.8%) in women carrying Down syndrome and 0%-2.6 % (mean 0.7 %) in the controls, respectively (P=0.86). CONCLUSIONS: Our study revealed no difference in fetal DNA levels and fetal DNA: maternal DNA ratio between the patients carrying Down syndrome fetuses and the controls.     

Spontaneous regression of neoplasms: new possibilities for immunotherapy

In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, loss or simple inactivation of the function of tumour suppressor genes and the production of certain growth factors. Genes for suppression of the development of the neoplastic cellular immunophenotype, as well as inhibitory growth factors, have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently detected in various neoplasms. Telomerase activation is regarded as essential for cell immortalisation and its inhibition may result in spontaneous regression of neoplasms. This phenomenon of neoplasms occurs when the malignant tissue mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic growth. This definition makes it clear that the term 'spontaneous regression' applies to neoplasms in which the overall malignant disease is not necessarily cured and to cases where the regression may not be complete or permanent. A number of possible mechanisms of spontaneous regression are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualised and adequate antineoplastic immunotherapy (alternative biotherapy) is also discussed.     

Expression of SH2D1A in five classical Hodgkin's disease-derived cell lines

The Src homology 2 domain protein 1A (SH2D1A) is a small, 128-amino acid protein consisting of a single SH2 domain; it is probably involved in signal regulation. It is expressed in activated T and natural killer (NK) cells, but not in B lymphocytes. It was discovered in studies on the rare hereditary condition X-linked lymphoproliferative disease (XLP). Individuals with this condition either lack or carry an altered protein. The serious symptoms (fatal mononucleosis) present almost exclusively at the first encounter with Epstein-Barr virus (EBV). The absence of SH2D1A in B cells, which are the targets of EBV, has to be reconciled with this clinical situation. In an earlier search for B lymphocytes expressing SH2D1A, we detected it in EBV-carrying type I Burkitt's lymphoma (BL) lines. We now show SH2D1A in 5 EBV-negative classical Hodgkin's disease (HD)-derived cell lines. Two lines belong to the T lineage and 3 to the B lineage. One B-HD line, which originated from nodular lymphocyte-predominant Hodgkin's lymphoma and differed in phenotype, was SH2D1A-negative. This finding is in accordance with the previously reported abundant SH2D1A mRNA in Hodgkin and Reed-Sternberg (HRS) cells. We thus found SH2D1A expression in lines of malignant origin assigned to the B lineage. Its presence in HRS cells may lead us closer to an understanding of the pathophysiology of the serious syndrome connected with EBV infection in XLP patients, because HRS-like cells have been detected in the lymphoid tissue of patients with infectious mononucleosis. It is likely therefore that in addition to the demonstrated functional defect of T and NK cells imposed by the SH2D1A mutation, the behavior of certain EBV-infected B lymphocytes is also modified.     

Tularemia on Martha's Vineyard: seroprevalence and occupational risk

We conducted a serosurvey of landscapers to determine if they were at increased risk for exposure to Francisella tularensis and to determine risk factors for infection. In Martha's Vineyard, Massachusetts, landscapers (n=132) were tested for anti-F. tularensis antibody and completed a questionnaire. For comparison, serum samples from three groups of nonlandscaper Martha's Vineyard residents (n=103, 99, and 108) were tested. Twelve landscapers (9.1%) were seropositive, compared with one person total from the comparison groups (prevalence ratio 9.0; 95% confidence interval 1.2 to 68.1; p=0.02). Of landscapers who used a power blower, 15% were seropositive, compared to 2% who did not use a power blower (prevalence ratio 9.2; 95% confidence interval 1.2 to 69.0; p=0.02). Seropositive landscapers worked more hours per week mowing and weed-whacking and mowed more lawns per week than their seronegative counterparts. Health-care workers in tularemia-endemic areas should consider tularemia as a diagnosis for landscapers with a febrile illness.