The relative ethylumbelliferone dealkylase activity characterizing the effect of different inducers on the hydroxylase system in the liver musomes of female mice

d,l-Camphor was detected as a new inducer of hydroxylase in the liver musomes of female mice. After a 2-day inhalation of d,l-camphor, cyt. P-450 and the ethylumbelliferone dealkylase were increased by 250 per cent and the NADPH-cyt. P-450 reductase by 350 per cent. The product [NADPH-cyt. P-450 reductase activity × cyt. P450 concentration] was shown to be a suitable reference parameter for the ethylumbelliferone dealkylase activity in the liver musomes during the treatment with four different inducers. The relative dealkylase activity Q was much decreased during inhalation of cyclohexane or d,l-camphor.

$\text{Q =}\text{mU ethylumbelliferone dealkylase}\text{mU NADPH-cty. P-450 reductase × nmoles cty. P-450/mg protein}$

Obviously these two inducers preferably enhanced cyt. P-450 species with a low dealkylase activity. The Q-values were reproducible. Q was increased by 100 per cent during induction of a MC-sensitive mouse strain with 3-methylcholanthrene, but it was only moderately decreased by induction with phenobarbital. Corresponding to this, methylcholanthrene is known to selectively induce a cyt. P-448 with high dealkylase activity whereas phenobarbital is known to change the hydroxylase specificity in the liver musomes not very much.     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.     

Income differences in persons seeking outpatient treatment for mental disorders: a comparison of the United States with Ontario and The Netherlands

BACKGROUND: Variations in the relationships among income, use of mental health services, and sector of care are examined by comparing data from 3 countries that differ in the organization and financing of mental health services. METHODS: Data come from the 1990-1992 National Comorbidity Survey (n = 5,384), the 1990-1991 Mental Health Supplement to the Ontario Health Survey (n = 6,321), and the 1996 Netherlands Mental Health Survey and Incidence Study (n = 6031). Analysis of the association between income and use of mental health services was carried out for the population that was between ages 18 and 54 years. Differential use of mental health treatment was examined in 3 sectors: the general medical sector, the specialty sector, and the human services sector. RESULTS: No significant association between income and probability of any mental health treatment was observed for persons with psychiatric disorders in any of the 3 countries. However, there were significant differences among countries in the association between income and sector of mental health care treatment. In the United States, income is positively related to treatment being received in the specialty sector and negatively related to treatment being received in the human services sector. In the Netherlands, patients in the middle-income bracket are less likely to receive specialty care, while those in the high-income bracket are less likely to be seen in the human service sector. Income is unrelated to the sector of care for patients in Ontario. CONCLUSIONS: Future research should examine whether differential access to the specialty sector for low-income people in the United States is associated with worse mental health outcomes.     

Effects of propylene oxide exposure on rat nasal respiratory cell proliferation.

Long-term exposure of rodents to propylene oxide (PO) induced inflammation, respiratory cell hyperplasia, and nasal tumors at concentrations >/= 300 ppm, suggesting a possible role for cytotoxicity and compensatory cell proliferation in PO carcinogenesis. In this study, the effects of PO exposure on histopathology and cell proliferation in nasal and hepatic tissues were studied in male F344 rats exposed by inhalation for 3 or 20 days (0, 5, 25, 50, 300, and 500 ppm). Histopathology revealed an increase in mucous cell hyperplasia in the anterior nasal passages after 20 days of exposure (>/=300 ppm). This was associated with the formation of goblet cell nests. Cell proliferation was measured in the respiratory epithelium (NRE; mucociliary and transitional) lining the anterior nasal passages, the nasopharyngeal meatus (NPM), and the liver using BrdU administered with 3-day osmotic pumps. Significant increases in cell proliferation occurred (>3.6-fold) in the mucociliary epithelium lining the anterior nasal cavity at and above 300 ppm for both exposure periods. In the mucociliary epithelium, the 20-day labeling was commonly associated with nests of goblet cells. Significant increases in cell proliferation (>2.3-fold) were observed in the transitional epithelium at 500 ppm after 3 days of exposure and at 300 and 500 ppm after 20 days of exposure. Significant increases in cell proliferation in the NPM (>2.8-fold) were evident at 500 ppm PO after 3 days and at 300 and 500 ppm PO after 20 days of exposure. No exposure-related changes in cell proliferation were observed in the liver. These studies demonstrate a clear concordance between the site and exposure concentration for tumor induction and those causing significant increases in cell proliferation in the rat nose.     

Early increase of peripheral B cell levels in kidney transplant recipients with CMV infection or reactivation

BACKGROUND: Cytomegalovirus (CMV) infection or reactivation is a frequent complication of renal transplantation. Diagnosis of these conditions relies on the detection of circulating antigen, or of specific IgM and/or IgG, which develop over several weeks. Evocative clinical features may be detected earlier, but lack specificity. Rapid and early changes in the partition of lymphocyte subsets could be an additional indication of pending CMV infection. METHODS: A systematic follow-up of peripheral B lymphocytes identified immunophenotypically by the determination of surface immunoglobulins (sIg), performed in 97 kidney transplant recipients, allowed to identify transient increases apparently predictive of CMV primo-infection or reactivation over the next 3 months. To better define the nature of these B cells, an extended investigation was performed for 14 prospective patients. In addition to surface Ig, membrane CD19, HLA-DR, and CD80 expression were explored. The cytoplasmic presence of mu, kappa, and lambda chains was also examined. B cell function was investigated using the ELISPOT technique, which allows an enumeration of the populations of IgG, IgA, and IgM secreting B cells. RESULTS: Retrospective analysis of the clinical outcome of the cohort of 97 patients evidenced that early transient increases in B cell levels were significantly (P<0.0001) associated with CMV infection. The same trend was noted in the smaller series of patients who benefited from a more extensive investigation of B cells, 10 of whom presented clinical or biological signs of CMV infection. Mature B cells, expressing surface Ig, CD19, DR, and CD80 are those presenting transient increases. No significant variation of preB (cmu+/kappalambda-) or activated (spot-forming) cells was evidenced in these patients. CONCLUSION: Individual examination of each patient's immune reconstitution profile allows to detect transient peaks of mature B cell during the initial immunosuppressive therapy, that appear to be predictive of oncoming CMV infection or reactivation.     

Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells.

Recognition events between hematopoietic progenitor cells (HPC) and bone marrow endothelial cells (BMEC) initiate homing of HPC to the bone marrow. The chemokine SDF-1 is present on BMEC and plays a crucial role in bone marrow engraftment. We studied the role of proteoglycans (PGs) on BMEC in binding and presentation of SDF-1. SDF-1 mRNA was present in three human BMEC cell lines. Competition experiments showed that 125I-SDF-1 alpha binding to the BMEC cell line 4LHBMEC was inhibited by heparins, heparan sulfate (HS) intestinal mucosa, chondroitin and dermatan sulfate (CS/DS), but not by HS bovine kidney. Pretreatment of 4LHBMEC with glycosaminoglycan (GAG)-degrading enzymes or sodium chlorate demonstrated that SDF-1 bound to both HSPGs and CS/DSPGs in a sulfation-dependent manner, as determined with an SDF-1 antibody recognizing the CXCR4-binding site. 4LHBMEC bound four-fold more SDF-1 than HUVEC. Isolated endothelial PGs did not bind SDF-1 in a filter or microplate-binding assay, suggesting the necessity of membrane association. In flow adhesion experiments, endothelial arrest of CXCR4+ KG-1 and not of CXCR4- KG-1a cells increased significantly when SDF-1 was presented on 4LHBMEC. In conclusion, SDF-1 is produced by BMEC and binds to the BMEC cell surface via HS and CS/DS-GAGs, thereby presenting its CXCR4 binding site to HPC contributing to their arrest.     

Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression

A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea, steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled the malabsorption syndrome, was immunosuppression with intravenous high dose methylprednisolone and oral methotrexate maintenance therapy.     

Associations of substance use, abuse, and dependence with subsequent suicidal behavior

General population survey data are used to disaggregate the associations of substance use disorders with suicide attempts in order to evaluate a number of hypotheses about the processes leading to these associations. Data are from the US National Comorbidity Survey (1990-1992). Discrete-time survival analysis is used to study the effects of retrospectively reported temporally prior substance use, abuse, and dependence in predicting first onset of suicidal behavior. Alcohol and drug use predict subsequent suicide attempts after controlling for sociodemographics and comorbid mental disorders. Previous use is not a significant predictor among current nonusers. Abuse and dependence are significant predictors among users for three of the 10 substances considered (alcohol, inhalants, and heroin). The number of substances used is more important than the types of substances used in predicting suicidal behavior. Disaggregation shows that the effects of use are largely on suicidal ideation and nonplanned attempts among ideators. In comparison, the effects of use on suicide plans and planned attempts among ideators are not significant. Clinicians need to be aware that current substance use, even in the absence of abuse or dependence, is a significant risk factor for unplanned suicide attempts among ideators.