Synaptic organization of the human striatum: a postmortem ultrastructural study

Converging with psycho-social research findings, animal and human laboratory studies indicate that behavioral alternatives are important determinants of drug-taking. To investigate associations between how early adolescents spend their time, i.e. their behavioral repertoire and drug use (use of marijuana, crack/cocaine or inhalants), we analyzed data from an epidemiological sample of 1516 urban middle-school students who had completed private interviews in spring 1993. The interview included a 36-item questionnaire to assess how frequently the youth engaged in different activities; history of drug-taking was assessed separately. Multiple logistic regression was used to estimate associations between drug use and each of seven behavioral domains as well as sex, age and racial-ethnic status. Youths spending a great deal of time working for pay and assuming other adult-like roles were more likely to have initiated drug use (estimated odds ratio, OR = 3.49; p = 0.002). Those who spent much time in religious activities were less likely (OR = 0.2, p <0.001). An exploratory search for interactions disclosed other associations that merit attention in future research. These results corroborate evidence on the potential etiological significance of behavioral repertoire in relation to risk of drug use.     

Vincristine disturbs spontaneous firing of the afferent nerve fibre in ampullary electroreceptor organs

Ampullary electroreceptor organs of the catfish were apically exposed to 0.3 mM vincristine in order to investigate the part played by the microtubular system in stimulus transduction. The main effects were repetitive firing of the afferent fibre, a reduction of the mean spontaneous activity and a reduction of the spike amplitude two to four days after exposure to vincristine. The mean sensitivity was less susceptible to vincristine than the spontaneous activity. Since the shape of the frequency curves remained unchanged and similar effects as described above were also observed after denervation, we conclude that vincristine most likely does not affect electroreceptor cell functioning, but causes degeneration of the afferent fibre.     

Multiplicity of fibronectin-binding alpha V integrin receptors in colorectal cancer

Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer.     

Heat-induced elevation of ceramide in Saccharomyces cerevisiae via de novo synthesis

Sphingolipid-related metabolites have been implicated as potential signaling molecules in many studies with mammalian cells as well as in some studies with yeast. Our previous work showed that sphingolipid-deficient strains of Saccharomyces cerevisiae are unable to resist a heat shock, indicating that sphingolipids are necessary for surviving heat stress. Recent evidence suggests that one role for the sphingolipid intermediate ceramide may be to act as a second messenger to signal accumulation of the thermoprotectant trehalose. We examine here the mechanism for generating the severalfold increase in ceramide observed during heat shock. As judged by compositional analysis and mass spectrometry, the major ceramides produced during heat shock are similar to those found in complex sphingolipids, a mixture of N-hydroxyhexacosanoyl C18 and C20 phytosphingosines. Since the most studied mechanism for ceramide generation in animal cells is via a phospholipase C-type sphingomyelin hydrolysis, we examined S. cerevisiae for an analogous enzyme. Using [3H]phytosphingosine and [3H]inositol-labeled yeast sphingolipids, a novel membrane-associated phospholipase C-type activity that generated ceramide from inositol-P-ceramide, mannosylinositol-P-ceramide, and mannose(inositol-P)2-ceramide was demonstrated. The sphingolipid head groups were concomitantly liberated with the expected stoichiometry. However, other data demonstrate that the ceramide generated during heat shock is not likely to be derived by breakdown of complex sphingolipids. For example, the water-soluble fraction of heat-shocked cells showed no increase in any of the sphingolipid head groups, which is inconsistent with complex sphingolipid hydrolysis. Rather, we find that de novo ceramide synthesis involving ceramide synthase appears to be responsible for heat-induced ceramide elevation. In support of this hypothesis, we find that the potent ceramide synthase inhibitor, australifungin, completely inhibits both the heat-induced increase in incorporation of [3H]sphinganine into ceramide as well as the heat-induced increase in ceramide as measured by mass. Thus, heat-induced ceramide most likely arises by temperature activation of the enzymes that generate ceramide precursors, activation of ceramide synthase itself, or both.     

Assessment of weighting methodology for the National Comorbidity Survey

The authors studied weighting adjustments for the National Comorbidity Survey (1990-1992), a large-scale national epidemiologic investigation of the prevalence, risk factors, and consequences of psychiatric morbidity and comorbidity in the United States. Weighting adjustments for differential selection within households, new construction, unit nonresponse, and poststratification were examined separately and in combination. Specific issues addressed included the magnitude of the bias incurred from ignoring the weights, the added variance from weighting and how well this was predicted by simple formulae, and the performance of methods for trimming the weights. Weights had quite modest effects on point estimates of prevalences but resulted in major increases in variance unless trimmed. The weights after trimming and poststratification appeared to work well. It is suggested that the added variance from weighting be carefully monitored in similar surveys. Alternatives to the use of trimming for controlling variance are worth exploring.     

Combined saphenous vein with free flap reconstruction in the treatment of carotid stenosis

Revascularization for arterial stenosis in varied anatomic sites exposed to therapeutic radiation has been well described. In most circumstances, symptomatic end organ ischemia has been the indication for surgical intervention. We report the case of a patient who had symptomatic carotid stenosis 40 years after having ipsilateral neck dissection with radiation therapy. We did a saphenous vein graft interposition and free flap reconstruction of the overlying damaged skin.     

Pseudo-outbreak of septicemia due to rapidly growing mycobacteria associated with extrinsic contamination of culture supplement

Between April and December 1994, 23 blood cultures from human immunodeficiency virus-infected patients grew rapidly growing mycobacteria suspected to be Mycobacterium chelonae at a hospital in New Jersey. The isolates were later identified as M. abscessus. Several bacterial species, including M. abscessus, were cultured from an opened multidose supplement vial (BBL Septi-Chek AFB Supplement) that had been used for mycobacterial blood cultures. The M. abscessus isolates from case patients and the supplement vial had identical multilocus enzyme electrophoresis and antimicrobial susceptibility patterns. Finding a contaminated vial of supplement, together with the lack of a distinct syndrome in case patients, was consistent with a pseudo-outbreak.     

Phase I and pharmacological study of CI-980, a novel synthetic antimicrotubule agent

CI-980 (NSC 613862) is one of a novel class of 1,2-dihydropyrido[3, 4-b]pyrazines that inhibits tubulin polymerization, presumably by binding to the colchicine binding site of tubulin. In a Phase I and pharmacological study, 16 patients with advanced solid neoplasms were treated with CI-980 on a continuous 72-h infusion schedule at doses ranging from 3.0-5.4 mg/m2/day every 3 weeks. High rates of central nervous system (CNS) toxicity and neutropenia occurred in both minimally and heavily pretreated patients who were treated with CI-980 doses above 3.75 mg/m2/day, which is the maximum tolerated dose and the recommended dose for additional evaluations. CNS effects, characterized by neurocortical, mood, and cerebellar manifestations, were generally observed toward the end of the infusion and immediately posttreatment and usually resolved within 48 h after the completion of treatment. Toxicity was mild to modest at the 3.75 mg/m2/day dose level. Neither clinical nor pharmacological risk factors that may predispose patients to the development of CNS effects were evident. Although no objective antineoplastic activity was observed in this Phase I study, CI-980 steady-state plasma concentrations achieved at the recommended dose of 3.75 mg/m2/day (mean +/- SE, 5.74 +/- 0.54 nM) approached and exceeded concentrations that have been associated with significant activity in preclinical studies, indicating that additional disease-directed evaluations of CI-980 may be warranted.     

Detection of terminal deoxynucleotidyl transferase (TdT) in nonhematopoietic small round cell tumors of children

In the differential diagnosis of small round cell tumors (SRCTs), terminal deoxynucleotidyl transferase (TdT) is often used as a marker for lymphoblastic lymphomas and leukemias. However, the specificity of TdT using the avidin-biotin-immunoperoxidase (ABC) method is not well documented. To address this issue, we stained paraffin-embedded biopsy specimens of 64 cases of childhood SRCTs using the ABC method with anti-TdT. For any TdT-positive tumors, an additional antibody panel for lymphoid markers was applied. Two patterns of TdT positivity were observed: (1) tumor specific, consisting of strong to moderate nuclear staining, and (2) scattered positive lymphoid cells, usually in a perivascular location and expressing T-cell markers. Analysis showed that 7 of 10 medulloblastomas stained with TdT in a tumor-specific pattern (4 cases moderately to strongly positive in 75-100% of tumor cells, 3 cases weakly to moderately positive in 25-50% of cells). Also, 1 of 19 rhabdomyosarcomas and 1 of 8 Ewing's sarcomas showed moderate to strong tumor-specific TdT staining in 100 and 10% of cells, respectively. Scattered TdT-positive lymphoid cells were observed in 27% of these 64 SRCTs. These findings emphasize that TdT positivity should not be relied upon exclusively for making a diagnosis of lymphoblastic leukemia or lymphoma or ruling out other SRCTs.