High risk for unbalanced segregation of some reciprocal translocations: A large pedigree containing distal 4q trisomy from t(4;7)(q28;p22)

We report on a familial t(4;7)(q28;p22) with 2:2 adjacent‐1 unbalanced segregation producing duplication of 4q28→qter in multiple offspring. Within the large four‐generation pedigree, a carrier had a reproductive outcome that was approximately equal for 1) the balanced translocation, 2) normal chromosomes, and 3) viable 4q trisomy or pregnancy loss. The three individuals with chromosomal confirmation of trisomy 4q28→qter (comprising approximately 1.8% of the haploid autosomal length) had similar mental and developmental retardation, hypotonia, restricted speech, seizures, and facial anomalies but no cardiac, renal, or skeletal anomalies. It is suggested that these latter severe malformations, associated with the classic 4q2 to 3 group of anomalies, were from an imbalance outside 4q28→qter and were not necessarily related to the relatively large size of the trisomic segment. Multiple different chromosomes are reported to be rearranged with 4q in the production of distal 4q trisomy. The incidence of 4q rearrangement remains unexplained, but once it is present in a family, viability of a large trisomy in 4q seems to explain the number of affected individuals reported. © 2001 Wiley‐Liss, Inc.     

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.     

Caries Prevalence and Severity for 12-Year-Old Children in Latvia

ObjectivesTo study caries prevalence/severity in 12-year-old children in Latvia and potential risk indicators.MethodsA cross-sectional oral-health national survey of 12-year-old children was conducted in 2016. A nationally representative stratified-cluster probabilistic sample of 2,138 pupils in 92 schools was selected. Children were examined by seven calibrated examiners (kappa inter-examiner, intra-examiner scores of 0.71–0.77, 0.81–0.97, respectively) at school. Enamel-non-cavitated decay (D₁), enamel cavitation (D₃), dentine cavitation (D₅), missing (M) or filled (F) status at the tooth (T)/surface (S) levels were evaluated, and decayed, missing, and filled (DMF) index scores for severity, along with the Significant Caries Index (SiC), were calculated. An associated caries factor questionnaire was completed by participants.ResultsThe prevalence of caries was 98.5% for D₁MFT, 79.7% for D₃MFT, and 71.9% for D₅MFT. The means (standard deviations) for severity were 9.2 (5.3) for D₁MFT, 3.3 (3.0) for D₃MFT, and 2.4 (2.4) for D₅MFT, and 5.6 (2.1) for the SiC. Indicators associated with a lower risk of caries (D5MFT) were irregular dental visits (prevalence odds ratio POR = 0.45, 95% confidence interval (CI): 0.36, 0.56) and irregular use of mouthwashes (POR = 0.73, 95% CI: 0.60, 0.89).ConclusionsWe found a high caries prevalence and severity in 12 year-old children in Latvia. Although the WHO target for 2010 (D₅MFT ≤ 3) is met, the values for caries prevalence (D₅MFT > 0 = 71.9%) and severity (D₅MFT = 2.5) in 12-year-old Latvian children are higher than the European averages (D₅MFT > 0 = 52%, D₅MFT = 1.1).     

Failure of estrogen to protect the substantia nigra pars compacta of female rats from lesion induced by 6-hydroxydopamine

The immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and in the ventral tegmental area (VTA) after intranigral infusion of 6-hydroxydopamine (6-OHDA, 6 microg/side) was analyzed in ovariectomized adult female Wistar rats. Estrogen replacement for 52 days (400-microg 17-beta-estradiol capsules) did not prevent the loss of TH-immunoreactive cells induced by 6-OHDA in the SNpc. This result indicates that the neuroprotective effect of dopaminergic mesencephalic cells is not observed with long-term estrogen replacement.     

Experimental Encephalitozoon cuniculi infection in dexamethasone-immunosuppressed mice

OBJECTIVE: Microsporidian Encephalitozoon cuniculi has been recognized as an opportunistic pathogen in immunosuppressed individuals, such as AIDS patients. The objective of the study was to develop pharmacologically immunosuppressed animals as a model of the natural occurring E. cuniculi infection. METHODS: Distinct groups of adult Balb-C mice were immunosuppressed with different doses of dexamethasone (Dx, 3 or 5 mg/kg/day, intraperitoneal route - IP) and inoculated with E. cuniculi spores by IP route intraperitoneally. Control groups (inoculated animals but non-immunosuppressed and non- inoculated animals but immunosuppressed) were also used. The spores of E. cuniculi were previously cultivated in MDCK cells. The animals were sacrificed and necropsied at 7, 14, 21, 28 and 35 days post-inoculation. Tissue fragments were collected and processed for light microscopy studies, using Gram-chromotrope and hematoxylin-eosin staining techniques. RESULTS: In all immunosuppressed and inoculated inoculated immunosuppressed mice,specially in those that received 5 mg/kg/day of dexamethasone, the most prominent necropsy findings were hepatomegaly and splenomegaly. The experimental inoculation resulted in a disseminated non-lethal infection, characterized by granulomatous lesions in several organs (liver, lungs, kidneys, gut and brain) but notably in the hepatic tissue. Spores of E. cuniculi were only seen in few animals treated with 5 mg/kg/day of Dx at 35 days post-infection. CONCLUSIONS: Microsporidiosis in Dx-immunosuppressed mice provides a useful model for studies of the microsporidial infection, resembling that one naturally occurring in immunodeficient individuals with AIDS.     

Blood-brain barrier breakdown following gliotoxic drug injection in the brainstem of Wistar rats

Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans disruption and supposed blood-brain barrier (BBB) breakdown The aim of this study was to investigate the BBB integrity after the injection of 0.1% EB (group E) or 0.9% saline solution (group C) into cisterna pontis of Wistar rats. Brainstem fragments were collected from 24 hours to 31 days post-injection for ultrastructural study and GFAP immuno-histochemical staining. Some animals received colloidal carbon ink by intravenous route at the same periods. In rats from group C, there was no sign of astrocyte loss and no leakage of ink from blood vessels in the injection site. In group E, astrocyte disappearance began at 48 hours and some areas were still devoid of astrocytic processes 31 days after. Leakage of carbon particles was seen from 48 hours to 7 days in the EB-induced lesions. Tight junctions did not show any detectable ultrastructural change due to the lack of perivascular astrocytes.     

Is immunity in diabetic patients influencing the susceptibility to infections? Immunoglobulins,complement and phagocytic function in children and adolescents with type 1 diabetes mellitus

OBJECTIVE: Previous reports suggest an increased susceptibility of diabetes patients to infections, but little information is available on possible underlying immunologic dysfunctions. The aim of this study was to evaluate humoral factors in pediatric patients with type 1 diabetes mellitus. METHODS: There were 66 diabetic patients (39 males:27 females; 5-17 yr) classified into two groups according to levels of glycohemoglobin (limit 9%): Group C - controlled (n = 33) and Group UC - uncontrolled (n = 33). We evaluated five patients in C and six in UC who reported previous infections. Immunologic analysis included measurement of plasma concentrations of immunoglobulins (Ig), C3, and C4 levels (turbidimetry); functional hemolytic assays for complement evaluation (CPH for classical and APH for alternative pathways), quantification of C4 isotypes C4A and C4B (ELISA), phagocytosis assays, measurement of bactericidal activity against Staphylococcus aureus, as well as tests of fungicidal capacity for Candida albicans. RESULTS: The UC Group had higher mean age, received higher insulin doses, and had higher concentrations of glycohemoglobin than the C Group. No significant differences in duration of the disease or nutritional conditions were detected between the groups. Lower IgA values in C (10/33) and lower IgG levels in UC (23/33) were detected, and there were inverse relationship with HbA1c values. Analysis of CPH, APH, C3, and C4 showed normal levels in both groups and no statistical correlation with the HbA1c. However, 9/33 children of the UC Group had decreased C3 values. C4B levels were below the normal range in 8/20 and correlated with higher HbA1c. Both phagocytic assays for S. aureus and Candida albicans were within normal limits. CONCLUSIONS: Low IgG concentrations and to some degree reduction in C4B levels were related to impaired metabolic control. No strong link between the immunological alterations was found in diabetic patients and the occurrence of infections.     

Evolving features of lung adenocarcinoma in Rio de Janeiro, Brazil

Formerly considered rare, adenocarcinoma has become the commonest form of primary lung cancer in developed countries. Its clinical presentation has changed, with central tumors becoming more frequent. We reviewed all biopsies with a diagnosis of primary lung cancer obtained from October 1988 to April 1997 in a tertiary care hospital in Rio de Janeiro. Medical records from adenocarcinomas were analysed. Adenocarcinoma was the commonest form of lung cancer (168/409, 41%). Central tumors were observed in 43% according to radiological criteria and 47% according to bronchoscopic criteria. The frequency and clinical presentation of adenocarcinoma have evolved lately in Rio de Janeiro.     

Drosophila mediopunctata microsatellites II: cross-species amplification in the tripunctata group and other Drosophila species

Heterologous amplification of 134 recently developed Drosophila mediopunctata microsatellites is here reported. Cross-species amplification was analyzed in 30 species of the Drosophila and Sophophora subgenera, and emphasis was given to the tripunctata group. The overall microsatellite transfer rate was 48%. The highest cross-species amplifications were observed in D. unipunctata (n = 94) and D. roehrae (n = 82). The phylogenetic proximity to D. mediopunctata did not correspond to greater numbers of successfully amplified microsatellites. Of the 134 microsatellite loci, 21 failed to amplify in all species and 18 were detected in all of them. A UPGMA dendrogram, based on Jaccard’s similarities in the tripunctata group, recovered few expected phylogenetic relationships. The data demonstrated that many D. mediopunctata microsatellites are now available as potentially useful markers for genetic investigation and conservation of other Drosophila species.     

Morphological aspects of rabbit masseter muscle after cervical sympathectomy

The objective of this paper was to study the effect of sympathetic innervation on morphological and histochemical aspects of skeletal muscle tissue. Rabbit masseter muscle was studied using histochemical and immunohistochemical methods for periods of up to 18 months post-sympathectomy. The morphological and enzymatic characteristics of control masseter muscles were similar on both the left and right sides. The main features were muscle fibres with a mosaic pattern and a predominance of type IIa fibres, followed by type I. Type IIb fibres showed very low frequency. Sympathectomized animals showed varying degrees of metabolic and morphological alterations, especially 18 months after sympathectomy. The first five groups showed a higher frequency of type I fibres, whilst the oldest group showed a higher frequency of type IIb fibres. In the oldest group, a significant variation in fibre diameter was observed. Many fibres showed small diameter, atrophy, hypertrophy, splitting, and necrosis. Areas with fibrosis were observed. Thus cervical sympathectomy induced morphological alterations in the masseter muscles. These alterations were, in part, similar to both denervation and myopathy. These findings indicate that sympathetic innervation contributes to the maintenance of the morphological and metabolic features of masseter muscle fibres.