Endovascular treatment of ruptured posterior circulation aneurysms using electrolytically detachable coils

The murine interleukin-7 (IL-7) gene was disrupted to examine the role of IL-7 in the lymphoid system. Expansion of lymphoid cells is sharply curtailed in IL-7-deficient mice. This is evident in a dramatic reduction but not elimination of lymphoid cells in the thymus, bone marrow and spleen. The few thymocytes present express CD4 and/or CD8 markers associated with T-cell maturation. Similarly, a limited number of B cells detected in the bone marrow rearrange and express immunoglobulin genes. Small but distinct populations of B and T cells are found in the spleens of IL-7-deficient mice. Thus the signal transmitted by IL-7 plays a central role in the expansion of lymphocytes while it is not absolutely required for their maturation. A transgene that directs expression of IL-7 to lymphoid cells was found to restore the numbers of thymocytes, bone marrow B-cell progenitors and splenic lymphocytes of IL-7-deficient mice to approximately normal levels. This genetic complementation confirms that the lymphoid defect is specifically due to the absence of IL-7 and demonstrates that the expansion of lymphoid cells in an organism is regulated by their exposure to IL-7.     

Effects of marital status on the risk of mortality in poor and non-poor neighborhoods

PURPOSE: The purpose of this paper is to consider whether the mortality risks associated with marital status are conditioned by the socioeconomic quality of neighborhoods. METHODS: The analysis is based on the first National Health and Nutrition Examination Survey 1971-1974 (NHANES I), and the 1987 NHANES I Epidemiologic Followup Survey (NHEFS). Cox proportional hazards regressions were used to assess whether the effect of marital status on the risk of all-cause and cause-specific mortality is altered by local area poverty. Analyses are stratified by age, sex, and urbanicity. RESULTS: The interaction between neighborhood poverty and marital status is suggested for non-elderly men, particularly for cancer mortality and for men in urban areas. Interaction effects are evident among older women residing in urban areas. CONCLUSIONS: The absence of a spouse elevates the risk of mortality but this risk is moderately higher in impoverished neighborhoods, notably in urbanized areas, for non-elderly men and elderly women. Future studies with larger samples of non-married persons where marital status changes are incorporated are needed to improve our understanding of the joint mortality effects of local area poverty and marital status.     

The comorbidity of alcoholism with anxiety and depressive disorders in four geographic communities

The comorbidity of alcoholism with anxiety and depressive disorders was examined in four epidemiologic investigations from diverse geographic sites. Despite variability in lifetime prevalence rates for these disorders, there was strong cross-site consistency in the magnitude and specific patterns of comorbidity. Individuals with alcohol abuse or dependence generally experienced a twofold to threefold increased risk of anxiety and depressive disorders. Phobic conditions typically preceded the onset of alcoholism, but no systematic pattern was observed for panic or depressive disorders. Considerable heterogeneity was also observed concerning the impact of comorbid conditions on symptoms of the index disorder. While the presence of comorbid anxiety or depressive disorders was consistently associated with moderate increases in the symptoms of alcohol abuse or dependence, alcoholism was associated with large increases in the number of depressive symptoms and little or no increase in phobic symptoms. The findings are discussed in terms of the self-medication hypothesis and the etiologic heterogeneity of these forms of comorbidity in the general population.     

Acute fatty liver of pregnancy

Acute fatty liver is a rare but potentially fatal complication of the third trimester of pregnancy. Significant improvements in morbidity and mortality have been reported in the last several years. Despite accumulation of more data about the disease, the exact pathogenesis is unknown. Many women are initially misdiagnosed with other more common causes of liver dysfunction during pregnancy. It is possible that acute fatty liver is an atypical form of preeclampsia because 30% to 40% of women with acute fatty liver also have preeclampsia. Supportive care and expeditious delivery represent the only known treatment. More data are needed about acute fatty liver of pregnancy, but the rare nature of the disease and the likelihood that most cases are not reported in the literature limit the ability systematically to study causation, disease process, and treatment options. Because of the serious condition of most women who develop acute fatty liver of pregnancy, collaboration between critical care and perinatal care providers is essential for optimal maternal-fetal outcomes.     

Yttrium-90-DOTA-peptide-chimeric L6 radioimmunoconjugate: efficacy and toxicity in mice bearing p53 mutant human breast cancer xenografts

The novel radioimmunoconjugate, 90Y-DOTA-peptide-chimeric L6 (ChL6), was designed to reduce radiation to critical normal tissues with an exceptionally stable 90Y chelate moiety and a biodegradable linker. Human breast cancer tumors (HBT 3477) in mice were treated with 90Y-DOTA-peptide-ChL6 to examine the effects of increasing dose on the therapeutic efficacy and toxicity of this new agent. METHODS: Groups of athymic mice bearing HBT 3477 xenografts received 4.1- to 14.1-MBq doses of 90Y-DOTA-peptide-ChL6 intravenously. The lethal dose (LD)(50/30), general well-being (weight loss), hematotoxicity and therapeutic efficacy were studied. RESULTS: The LD(50/30) was 12.8 MBq, which corresponded to doses of 17.9 and 50.9 Gy to the total body and tumor (200 mm3), respectively. Deaths were associated with hematotoxicity; no deaths occurred at doses of 9.6 MBq or less. At sublethal doses, the rate of tumor response (cures +/- complete responses + partial responses) increased with increasing dose: 4.1 MBq, 27%; 5.9 MBq, 41%; 8.5 MBq, 69%; and 9.6 MBq, 79% (maximum tolerated dose, MTD). In mice receiving doses of 4.1-9.6 MBq, 6 of 74 (8%) of tumors were cured. Increasing the 90Y dose led to smaller tumor size at nadir and longer tumor regrowth delay but no increase in cure. Although the HBT 3477 p53 gene was found to be mutant resulting in p53 protein not binding DNA breaks, tumors at MTD demonstrated evidence of apoptosis. CONCLUSION: In the human breast cancer athymic mouse model, 90Y-DOTA-peptide-ChL6 had a high therapeutic index and LD(50/30) leading to a 79% response rate at the MTD. The evidence of apoptosis as a mechanism for this tumor response in p53 mutant breast cancer warrants further studies because these observations are relevant to the treatment of lethal breast cancer.     

Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models

OBJECTIVE: To evaluate the safety profile of endometrial ablation performed with a thermal balloon as defined by serosal temperature elevation and depth of injury. DESIGN: Observational study with histopathologic correlation conducted in ex vivo and in vivo phases. SETTING: Academic medical center. PATIENT(S): Twenty patients undergoing total abdominal hysterectomy. INTERVENTION(S): Endometrial ablation with a thermal balloon. MAIN OUTCOME MEASURE(S): Serosal temperature elevation and histologic depth of injury. RESULT(S): Ex vivo phase results revealed serosal temperatures remained within a safe physiologic range (<45 degrees C). Greatest depth of myometrial injury in the premenopausal uteri was 5.8 mm over the anterior lower uterine segment. In postmenopausal uterus. the greatest depth of myometrial injury was 3.8 mm in the anterior midline. In vivo phase results revealed mean (+/- SD) peak serosal temperatures of 36.1 +/- 1.6 degrees C. As with the ex vivo phase. histologic examination revealed deep endometrial and superficial myometrial damage to all areas. The greatest depth of myometrial injury occurred in the midfundus at 3.4 mm. CONCLUSION(S): No patients experienced complications or adverse events secondary to treatment. Results showed that transuterine thermal injury is a highly unlikely scenario. In both phases of this study, histologic examination revealed that temperatures exposed to the endometrial layer were sufficient to cause tissue damage.     

Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of rat-1 fibroblasts and promotes differentiation of K562 cells

The bcr-abl chimeric oncoprotein exhibits deregulated protein tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph)-positive human leukemias, such as chronic myelogenous leukemia (CML). Recently we have shown that the levels of the protein tyrosine phosphatase PTP1B are enhanced in p210 bcr-abl-expressing cell lines. Furthermore, PTP1B recognizes p210 bcr-abl as a substrate, disrupts the formation of a p210 bcr-abl/Grb2 complex, and inhibits signaling events initiated by this oncoprotein PTK. In this report, we have examined whether PTP1B effects transformation induced by p210 bcr-abl. We demonstrate that expression of either wild-type PTP1B or the substrate-trapping mutant form of the enzyme (PTP1B-D181A) in p210 bcr-abl-transformed Rat-1 fibroblasts diminished the ability of these cells to form colonies in soft agar, to grow in reduced serum, and to form tumors in nude mice. In contrast, TCPTP, the closest relative of PTP1B, did not effect p210 bcr-abl-induced transformation. Furthermore, neither PTP1B nor TCPTP inhibited transformation induced by v-Abl. In addition, overexpression of PTP1B or treatment with CGP57148, a small molecule inhibitor of p210 bcr-abl, induced erythroid differentiation of K562 cells, a CML cell line derived from a patient in blast crisis. These data suggest that PTP1B is a selective, endogenous inhibitor of p210 bcr-abl and is likely to be important in the pathogenesis of CML.     

Renal styphlodoriasis in a boa constrictor

Renal styphlodoriasis was diagnosed in a 2 1/2-year-old male boa constrictor (Constrictor constrictor). The snake had been anorexic for 6 months prior to its death. Necropsy revealed numerous hard, white foci of mineralization in the kidneys. Histologic examination revealed distorted renal tubules containing cross sections of trematodes or mineralized debris, tubular epithelial hyperplasia, and chronic interstitial nephritis. Several adult trematodes were recovered and identified as Styphlodora horrida.     

Functional and DNA sequence divergence of the CYP71 gene family in higher plants

During ripening of avocado (Persea americana), the CYP71A1 mRNA and protein accumulate to relatively high levels. Although the CYP71A1 gene was the first plant P450 to be cloned and sequenced, the functional role of this P450 remains obscure. Substrate studies have shown that CYP71A1 will metabolize various monoterpenes (nerol and geraniol), although these have not been detected in ripening fruit. Using DNA from a conserved domain of the CYP71A1 gene, we have explored the scope of the CYP71 (or related) gene family in avocado using low stringency DNA hybridization. This analysis suggests that there are approximately 10-12 genes in the CYP71 family. An alternative approach using PCR gave essentially identical results.