Cellular and humoral autoimmune responses against human eye muscle membrane antigen in Graves' disease

75 patients with Graves' disease (54 with ophthalmopathy) were investigated using the tests of leucocyte adherence inhibition and immune adsorption with 125I-labelled Staphylococcus Protein A, against human eye muscle "crude" membrane antigen. The results of positive leucocyte adherence inhibition (10 out of 26 vs. 1 out of 28, P less than 0.05) and anti-human eye muscle membrane antibody index (mean +/- S.D.) (1.89 +/- 1.20 vs. 0.84 +/- 0.38, P less than 0.001) showed a correlation with the patients with clinically active eye disease and the HLA-B8 antigen in Graves' ophthalmopathy (P less than 0.01). Positive leucocyte adherence inhibition was observed in 9 out of 21 cases of Graves' disease without ophthalmopathy, but its prognostic relevance has to be confirmed in the development of ophthalmopathy.     

Polymorphic metabolizing genes and susceptibility to atherosclerosis among cigarette smokers

Atherosclerosis (AR) is the leading cause of morbidity and mortality in the US and cigarette smoking is a major contributing factor to the disease. Like cigarette smoking in lung cancer, genetic susceptibility may be an important factor in determining who is more likely to develop AR. However, the current emphasis has been on susceptibility based on altered cardiovascular homeostasis. In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR. We found that the GSTT1 null allele and the fast allele of mEH(*) (exon 4) are associated with risk for AR. Furthermore, the combined genotypes GSTM1 null/ CYP2E1(*)5B, GSTM1 null/mEH YY, and GSTT1 null/mEH YY are significantly associated with susceptibility to AR (OR = 15.42, 95% CI = 1.33-77.93, P = 0.021; OR = 3.48, 95% CI = 1.63-8.04, P = 0.0008; OR = 3.4; 95% CI = 0.99-17.38, P = 0.05; respectively). We have also conducted cytogenetic analysis to elucidate if induction of chromosome aberrations (CAs) is a biomarker of AR susceptibility. We found that among cigarette smokers (AR patients and smoker controls), individuals having the GSTM1 null allele had a significantly higher frequency of CAs compared to those with the normal allele (P < 0.05). This association was not found among nonsmokers. In addition, individuals who had inherited the CYP2E1(*)5B allele exhibited a significantly higher CA frequency (8.0 +/- 0.82) compared to those with the CYP2E1 wild-type genotype (4.31 +/- 0.35). Since the analysis of genetic susceptibility factors is still in its infancy, our study may stimulate additional investigations to understand the roles of genetic susceptibility and cigarette smoking in AR.     

Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens

Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell-mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen-loss variants. However, no direct evidence has been provided in non-viral-induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (> or =3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p=0.0080), or compared with their first primary melanoma (p=0.0013). Regression was consistent with an 'immunization effect' seen in murine tumour transplantation studies, where inoculation with > or =3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART-1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p=0.0041) and in the last versus first tumour in multiple primary patients was found (p=0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 loss (median 0%, mean 11) compared with matched metastases from patients with non-regressing primary melanoma (median 51%, mean 50) (p=0.0013). MART-1 antigen-loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART-1-specific cytotoxic T lymphocytes (CTLs) (p=0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance.     

Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure.

Graft failure is associated with a high mortality rate. To date, regimens invoked for second transplants have resulted in inconsistent engraftment with high transplant-related mortality (TRM). We here report 16 consecutive patients, aged 4-59 years, who received second HSCT (HSCT-2) at a median of 45 days following primary or secondary failure of an initial unmodified (N = 3) or T cell-depleted (TCD) (N = 13) HSCT (HSCT-1). HSCT-1 was administered after myeloablative total body irradiation (TBI)- or alkylator-based conditioning for acute leukemias (N = 7), MDS (N = 6), CML (N = 2), and Fanconi anemia (N = 1). All patients experienced 1 or more infectious complications between HSCT-1 and HSCT-2, and 10 patients had active infections at the time of HSCT-2. Cytoreduction regimens used for HSCT-2 included fludarabine (Flu) in combination with cyclophosphamide (CTX) (N = 9), or thiotepa (Thio) (N = 5). In addition, 1 patient received Flu alone and 1 patient Thio combined with CTX. Antithymocyte globulin (ATG) (N = 11) or Alemtuzumab (N = 3) was added pretransplant to prevent rejection. For HSCT-2, donors included HLA-matched (N = 3) or mismatched (N = 8) related, or matched (N = 2) or mismatched (N = 3) unrelated donors. The primary graft donor was used in 6 of 16 cases. The grafts administered were unmodified peripheral blood stem cell transplantation (PBSCT) (N = 5) or bone marrow transplantation (BMT) (N = 3), TCD PBSCT (N = 8). All patients achieved engraftment at a median of 12 days and evaluable patients achieved complete donor chimerism. Six patients are alive with a median follow-up of 49 months, including 4/9 conditioned with Flu/CTX. In this series, outcome was statistically superior for younger patients (相似文献   

Association of First-Week Nutrient Intake and Extrauterine Growth Restriction in Moderately Preterm Infants: A Regional Population-Based Study

The purpose of this study was to determine the influence of first-week nutrition intake on neonatal growth in moderate preterm (MP) infants. Data on neonatal morbidity and nutrition intake on day of life 7 (DoL7) were prospectively collected from 735 MP infants (32^0/7–34^6/7 weeks gestational age (GA)). Multivariable regression was used to assess the factors associated with extrauterine growth restriction (EUGR) defined as a decrease of more than 1 standard deviation (SD) in the weight z-score during hospitalization. Mean (SD) gestational age and birth weight were 33.2 (0.8) weeks and 2005 (369) g. The mean change in the weight z-score during hospitalization was −0.64 SD. A total of 138 infants (18.8%) had EUGR. Compared to adequate growth infants, EUGR infants received 15% and 35% lower total energy and protein intake respectively (p < 0.001) at DoL7. At DoL7, each increase of 10 kcal/kg/d and 1 g/kg/d of protein was associated with reduced odds of EUGR with an odds ratio of 0.73 (95% CI, 0.66–0.82; p < 0.001) and 0.54 (0.44–0.67; p < 0.001), respectively. Insufficient energy and protein intakes on DoL7 negatively affected neonatal growth of MP infants. Nutritional support should be optimized from birth onwards to improve neonatal weight growth.     

Spinal intramedullary schwannomas—report of a case and extensive review of the literature

Neurosurgical Review - Intramedullary schwannomas (IMS) represent exceptional rare pathologies. They commonly present as solitary lesions; only five cases of multiple IMS have been described so...     

Women’s Self-Care in the Reproductive Age: An Essential Agenda

Archives of Sexual Behavior -     

Effect of tetrakis-μ-3,5-diisopropylsalicylatodiaquodicopper(II) on the status of reduced glutathione in freshly isolated hepatocytes

Effects of different concentrations of tetrakis--3,5-diisopropylsalicylatodiaquodicopper(II) (Cu(II)₂(3,5-DIPS)₄(H₂O)₂) on the reduced status of glutathione (GSH), the major nonprotein thiol in tissues, were investigated using freshly isolated hepatocytes. Cu(II)₂(3,5-DIPS)₄ below 100 M did not have any significant effects on either the GSH content or viability of the hepatocytes, but at 150–250 M it decreased both parameters after 1 h of incubation. The decrease in cellular GSH was not followed by an increase in the oxidized form of GSH (GSSG) in the cell suspension. The addition of deferoxamine with Cu(II)₂(3,5-DIPS)₄ to the hepatocyte suspension prevented depletion in GSH content and loss of cell viability by Cu(II)₂(3,5-DIPS)₄. Both GSH depletion and loss of cell viability were found to be Cu(II)₂(3,5-DIPS)₄ dose dependent. From these results, it appears that Cu(II)₂(3,5-DIPS)₄ penetrated the cell membrane and acted by decreasing the GSH level by forming a copper-glutathione complex.