Rapid Rh D genotyping by polymerase chain reaction-based amplification of DNA

Rh (rhesus) D is the dominant antigen of the Rh blood group system. Recent advances in characterization of the nucleotide sequence of the cDNA(s) encoding the Rh D polypeptide allow the determination of the Rh D genotype at the DNA level. This can be of help in cases in which red blood cells are not available for phenotyping, eg, when in concerns a fetus. We have tested three independent DNA typing methods based on the polymerase chain reaction (PCR) for their suitability to determine the Rh D genotype. DNA derived from peripheral blood mononuclear cells from 234 Rh-phenotyped healthy donors (178 Rh D positive and 56 Rh D negative) was used in the PCR. The Rh D genotypes, as determined with a method based on the allele-specific amplification of the 3' noncoding region of the Rh D gene described by Bennett et al (N Engl J Med 329:607, 1993), were not concordant with the serologically established phenotypes in all cases. We have encountered 5 discrepant results, ie, 3 false-positive and 2 false-negative (a father and child). Rh D genotyping with the second method was performed by PCR amplification of exon 7 of the D gene with allele-specific primers. In all donors phenotyped as D positive tested so far (n = 178), the results of molecular genotyping with this method were concordant with the serologic results, whereas a false-positive result was obtained in one of the D-negative donors (also false-positive in the first method). Complete agreement was found between genotypes determined in the third method, based on a 600-bp deletion in intron 4 of the Rh D gene described by Arce et al (Blood 82:651, 1993), and serologically determined phenotypes. The Rh blood group system is complex, and unknown polymorphisms at the DNA level are expected to exist. Therefore, although genotypes determined by the method of Arce et al were in agreement with serotypes, it cannot yet be regarded as the golden standard. More experience with this or other methods is still needed.     

细胞角蛋白20检测在大肠癌微转移中的临床意义

近年来随着微转移在肿瘤研究领域中的广泛开展,人们开始研究大肠癌微转移,以期获得更准确,更早期的转移信息,为临床分期及预后判断、辅助治疗提供更多的依据．随着分子生物学、分子免疫学的迅速发展．使大肠癌的淋巴结、血液、骨髓及各脏器等用常规组织学难以诊断的癌细胞微转移灶的检测成为可能．细胞角蛋白20(cytokeratin-20,CK20)是新近发现的一种多肽,局限在胃肠上皮细胞,具有严格的组织特异性,几乎所有大肠癌都明显表达,优于其他标志物,尤其实用于检测大肠癌微转移．通过检测大肠癌患者淋巴结、血液、骨髓中CK20 mRNA的表达来诊断微转移,对指导临床大肠癌的分期、判断预后复发、指导治疗显示出较高的临床应用价值．微转移是一项独立的预后指标．其价值优于 Dukes分期和肿瘤分级．现综述细胞角蛋白20 检测在大肠癌微转移中的临床应用及意义研究进展．     

Marrow transplantation from hepatitis C virus seropositive donors: transmission rate and clinical course

Bone marrow transplant recipients are at risk for acquiring hepatitis C infection from the donated marrow. Twelve patients who were hepatitis C virus (HCV) RNA-negative pretransplant received marrow from anti-HCV seropositive donors. HCV RNA was present in the sera of seven of these donors. After transplant, serial serum specimens were obtained from all marrow recipients for determination of HCV RNA and aminotransferase levels. All seven recipients of marrow from HCV RNA-positive donors were HCV RNA-positive after marrow infusion; none cleared virus from the serum. All five recipients of marrow from anti-HCV seropositive, HCV RNA-negative donors remained free of HCV RNA in serum up to day 100. Abnormal serum aminotransferases were common in both HCV RNA- negative and HCV RNA-positive marrow recipients. One HCV-infected recipient developed marked elevation in aminotransferases after immunosuppressive drugs were stopped. We conclude that the presence of HCV RNA in the serum of marrow donors is an accurate predictor of HCV infection in marrow recipients. The acute infection was subclinical in all patients. The long-term risk of chronic hepatitis C virus infection in these patients remains to be determined.     

Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis

BACKGROUND & AIMS: Murine autoimmune gastritis, induced by day-3 thymectomy, is characterized by cellular infiltrates and circulating autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. The aim of this study was to analyze the cellular infiltrates and cytokines in autoimmune gastritis. METHODS: Stomachs and blood samples from day-3 thymectomized BALB/c mice were obtained from 2 to 12 weeks after thymectomy for analysis. RESULTS: At 4 weeks, the gastritic infiltrates were composed of macrophages and CD4+ T cells, accompanied by major histocompatibility complex class II expression on gastric epithelial cells. Mucosal B cells, scant at 4 weeks, were abundant at 8 weeks, coincident with the peaking of autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. CD8+ T cells increased marginally during the 12 weeks. Mononuclear cells from diseased stomachs transferred gastritis to nu/nu recipients. At 4 weeks, interleukins 2, 3, 5, 6, and 10; interferon gamma; tumor necrosis factor alpha; and granulocyte-macrophage colony-stimulating factor were detected in gastritic mucosa, but interleukin 4 was not. CONCLUSIONS: The early lesion of autoimmune gastritis is composed of macrophages and CD4+ T cells with major histocompatibility complex class II expression in gastric epithelial cells. Autoantibody production is a late event. Our results are consistent with a lesion mediated by CD4+ T cells producing a mix of Th1- and Th2-type cytokines. (Gastroenterology 1996 Jun;110(6):1791-802)     

Sodium butyrate enhances fetal globin gene expression in erythroid progenitors of patients with Hb SS and beta thalassemia

Increasing the expression of the gamma globin genes is considered a useful therapeutic approach to the beta globin diseases. Because butyrate and alpha-amino-n-butyric acid (ABA) augment gamma globin expression in normal neonatal and adult erythroid progenitors, we investigated the effects of sodium butyrate and ABA on erythroid progenitors of patients with beta thalassemia and sickle cell anemia who might benefit from such an effect. Both substances increased fetal hemoglobin (Hb F) expression in Bfu-e from 7% to 30% above levels found in control cultures from the same subjects with sickle cell anemia. The fraction of cultured erythroblasts producing Hb F increased more than 20% with sodium butyrate treatment in 70% of cultures. In most cultures, this produced greater than 20% total Hb F and greater than 70% F cells, levels which have been considered beneficial in ameliorating clinical symptoms. Alpha: non-alpha (alpha-non-alpha) imbalance was decreased by 36% in erythroid progenitors of patients with beta thalassemia cultured in the presence of butyrate compared with control cultures from the same subjects. These data suggest that sodium butyrate may have therapeutic potential for increasing gamma globin expression in the beta globin diseases.     

Early and late components of error monitoring in violent offenders with psychopathy

BACKGROUND: One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. METHODS: Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. RESULTS: Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. CONCLUSIONS: Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately.     

Nutritional and socioeconomic factors in motor development of Santal children of the Purulia district, India

Aims

The aim of this study was to characterize the motor development of 5-12 year-old Santal children of the Purulia district of West Bengal, India. The effect of socioeconomic and nutritional status on motor development was also examined.

Study design

841 (427 boys and 414 girls) Santal children were examined in this cross-sectional study. The nutritional status of each child was assessed by height-for-age z-score based on WHO reference data. Socioeconomic status (SES) was measured by the updated Kuppusswami scale. Motor development was measured using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Short Form (BOT-2).

Results

Sex had a significant (p < 0.05) effect on children's score of running speed and agility, upper-limb coordination and strength with higher scores for boys than girls. Children with a height-for-age z-score of − 2 or less were significantly more likely to have a total BOT-2 z-score of − 2 or less compared with children at a healthier height-for-age range (Χ² = 271.136, p < 0.0001). Well-nourished children scored significantly higher (p < 0.05) than undernourished children in total BOT-2 score and in all individual motor subtests. Regression analysis showed that nutritional status, socioeconomic status and height have a significant impact on total BOT-2 score (p < 0.001). Age and sex were found to be influencing factors in motor development.

Conclusion

Santal children's motor proficiency is around the 1st percentile when compared with normative BOT-2 data. This may be, in part, a result of nutritional and economic disparities between children on who the BOT-2 was normed and Santal children, supporting the role of nutrition in motor development. Additionally, Santal children with lower SES and poorer nutritional status have lower motor proficiency compared with Santal children with comparatively higher SES and nutritional status.     

Relationship between sex of parent and child on weight loss and maintenance in a family-based obesity treatment program

OBJECTIVE: To determine if the sex of the participating parent/child pair is a contributing factor in initial weight loss and maintenance within a family-based obesity treatment program. DESIGN: A 2-year family-based obesity treatment program targeting one overweight parent and one overweight child. SUBJECTS: One overweight parent (body mass index (BMI) > or = 25) and child (> or = 85th BMI percentile) from 164 families. MEASUREMENTS: Parameters of body weight, including height, weight, BMI, z-BMI, percent overweight (BOV) at baseline and at 6-, 12- and 24-month follow-up time points. RESULTS: Children within the opposite-sex dyads had greater weight loss (P < 0.01) at 6- and 12-month time points compared with children in the same-sex dyads. Parents within opposite-sex dyads had significantly greater weight loss at 24 months (P < 0.05) compared with those in the same-sex dyads. When individual dyads were examined, the change in child z-BMI after 6 months was greater for the mother-son dyad as compared to the mother-daughter and father-son (P < 0.05). For parent z-BMI, the mother-daughter dyad consistently exhibited the poorest results. At 6- and 12-month time points, parents in the mother-daughter dyad lost significantly less weight than parents in all other dyads (P < 0.05), and at 24 months, parents in the mother-daughter dyad lost less weight than parents in the opposite-sex dyads (P < 0.05). CONCLUSION: These data reveal that child-parent sex interactions can strongly influence the outcome of obesity treatment when both parent and child are the target for weight loss. The reasons that underlie this effect remain to be determined.     

Concurrent chemoradiation for oesophageal cancer: Factors influencing myelotoxicity

Concurrent chemotherapy and radiation (CT/RT) for localized oesophageal cancer can cause life-threatening myelo-suppression. This non-randomized study examines 95 patients from three Australasian centres treated on the Trans-Tasman Radiation Oncology ‘definitivechemoradiation ‘ study. Duration of fluorouracil infusion and patient age were independently predictive of myelotoxicity after the first cycle of CT/RT. Overall rates of grade III and IV neutropaenia were 23% and of thrombocytopaenia 8% following the first cycle of chemotherapy. Five neutropaenic septic episodes followed the first cycle and six the second. All five patients recovered after the first cycle but there were four treatment-related deaths occurring after the second cycle of CT/RT. Recommendations are made concerning initial dosing, dose reductions and delays to minimize adverse patient outcomes from myelosuppression.