The relationship between coffee consumption and serum cholesterol under consideration of smoking history

To provide insight into the stream of Medicare payments over time, a sixteen-year longitudinal study examines three age cohorts of beneficiaries, looking separately at beneficiaries who died during the study period and those who survived. The common wisdom that a small minority of the population accounts for a large majority of health care expenditures is tempered when health care use is examined over an extended period of time. By putting high average costs in the final years of life in the context of a cohort's total lifetime experience, the study shows a leveling of spending over time, resulting in a lower concentration of health care resources on a small fraction of the population.     

Genetic manipulation of antibiotic-producing Streptomyces

The genetic manipulation of Streptomyces species has been facilitated by the development of versatile cloning vectors, robust gene transfer systems and transposable elements. These molecular genetic tools have been used to construct antibiotic-producing strains with improved properties and recombinants for the production of hybrid glycopeptide and macrolide antibiotics, novel anthelminthic agents and novel cytotoxic anthracyclines.     

Real-time patch-cram detection of intracellular cGMP reveals long-term suppression of responses to NO and muscarinic agonists

Cyclic GMP (cGMP) is a crucial intracellular messenger in neuronal, muscle, and endocrine cells. The intracellular concentration of cGMP is regulated by various neurotransmitters, including acetylcholine (ACh) and nitric oxide (NO). While much is known about the biochemical steps leading to cGMP synthesis, little is known about cGMP kinetics in intact cells. Here, we use "patch-cramming," in which an excised, inside-out membrane patch containing cyclic nucleotide-gated ion channels is used as a biosensor, to obtain the first real-time measurements of cGMP in intact cells. Patch-cramming experiments on neuroblastoma cells show that both muscarinic agonists and NO rapidly elevate cGMP. NO elicits cGMP responses repeatedly without decrement, whereas responses to muscarinic agonists exhibit a profound and prolonged desensitization. Remarkably, muscarinic agonists also cause long-term (>30 min) suppression (LTS) of cGMP responses elicited by NO. Biochemical measurements reveal that rat sympathetic neurons also exhibit LTS of cGMP, suggesting that LTS is a widespread mechanism that may contribute to synaptic plasticity.     

Age incidence of meningococcal infection England and Wales, 1984-1991

Gene transfer with vectors derived from murine retroviruses is restricted to cells which are proliferating and synthesizing DNA at the time of infection. This suggests that retroviral-mediated gene transfer might permit targeting of gene integration into malignant cells in organs composed mainly of quiescent nonproliferating cells, such as in the brain. Accordingly, selective introduction of genes encoding for susceptibility to otherwise nontoxic drugs ("suicide" genes) into proliferating brain tumors may be used to treat this cancer. We investigated the efficacy and dynamics of in vivo transduction of growing brain tumors with the herpes simplex-thymidine kinase gene followed by administration of the antiviral drug ganciclovir. Ganciclovir is phosphorylated by thymidine kinase to toxic triphosphates that interfere with DNA synthesis, resulting in the preferential death of the transduced tumor cells. Rats inoculated with 4 x 10(4) 9L gliosarcoma cells into the frontal lobe were treated 7 days later with an intratumoral stereotaxic injection of murine fibroblasts (NIH 3T3 cells) that were producing a retroviral vector containing the herpes simplex-thymidine kinase gene. Controls received vector producer and nonproducer NIH 3T3 cell lines containing the Escherichia coli lacZ (beta-galactosidase) gene as well as nonproducer NIH 3T3 cells containing the thymidine kinase gene. The animals were rested for 7 days to allow time for in situ transduction of the proliferating tumor cells with the herpes-thymidine kinase retroviral vector. The animals were then treated with ganciclovir, 15 mg/kg i.p. twice a day for 14 days. Gliomas receiving an injection of 3-5 x 10(6) thymidine kinase producer cells regressed completely in 23 of 30 rats given ganciclovir therapy, while 25 of 26 control rats developed large tumors. Intratumoral injection of a lower concentration of thymidine kinase vector producer cells (1.8 x 10(6)) resulted in a lower frequency of tumor regression (5 of 13 rats). To estimate the efficiency of in vivo gene transfer, 9L brain tumors were given injections of 5 x 10(6) beta-galactosidase vector producer cells. 5-Bromo-4-chloro-3-indolyl-beta-D-galactopyranaside staining revealed maximal staining of beta-galactosidase within the tumor 7-14 days after injection of the vector producer cells. In vivo transduction rates in harvested tumors ranged from 10 to 70%. There was no evidence of transduction of the surrounding normal neural tissue. Occasional blood vessel endothelial cells within or adjacent to the tumor were observed to be 5-bromo-4- chloro-3-indolyl-beta-D-galactopyranaside positive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Activation of the mouse heart adenosine 5',5"'-P1-P4-tetraphosphate receptor

We have previously demonstrated that mouse brain membrane fractions have a specific, saturable receptor for diadenylated nucleotides. Binding is specific for two adenosines, and the length of the phosphate bridge is critical, with four phosphates being optimal [Hilderman et al. (1991) J. Biol. Chem. 266, 6915-6918]. In this report, we demonstrate that adenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) binding to its receptor is dependent upon an activation step that requires divalent cations and a serine protease. Monoclonal antibodies (Mabs) are identified that inhibit Ap4A binding to its membrane receptor. These antibodies recognize a 212-kDa membrane protein. However, SDS-PAGE analysis of Ap4A cross-linked to membrane fractions reveals that Ap4A is not attached to the 212-kDa peptide but to a 30-kDa polypeptide. Appearance of the 30-kDa polypeptide is dependent on the activation step, and one of the inhibitory antibodies blocks its appearance. We suggest that the protease-dependent processing step involves cleavage of the 212-kDa component with the appearance of an active 30-kDa receptor.     

Multifrequency tympanometry in chinchillas

Multifrequency tympanometry (MFT), using probe frequencies ranging from 226-2,000 Hz, was performed on normal chinchillas to obtain normative data against which to compare results from animals with middle ear pathology. A series of validating experiments was conducted to determine the effects of anatomical alterations of the middle ear on MFT. These included artificially extending the ear canal, opening the bulla, injecting saline into the middle ear, and disrupting the ossicular chain. The results indicate that MFT characteristics of chinchilla ears are qualitatively similar to those observed in normal humans and patients with middle ear disease, and MFT provides information that is not available from the 226-Hz tympanogram.     

Reductions in self-injury produced by transcutaneous electrical nerve stimulation

Transcutaneous electrical nerve stimulation is used to reduce pain but also may be useful for self-injurious behavior (SIB). In the current investigation, a microcurrent electromedical device, classified as a transcutaneous electrical nerve stimulator (TENS), was applied with a man with Down syndrome who displayed SIB that persisted in the absence of social contingencies. Although clinically significant results were not maintained, a clear difference in the rates of SIB during active and inactive TENS was observed.     

Fine needle aspiration cytology of papillary neoplasms

This article covers the fine needle aspiration biopsy cytomorphology of papillary carcinomas of different organs, differential diagnoses, and clinical correlation. Diagnostic problems and helpful cytologic features are emphasized. The purpose is to have a concise source of information that helps the pathologist to evaluate these neoplasms.     

Deep-level Transient Spectroscopy of GaAs/AlGaAs Multi-Quantum Wells Grown on (100) and (311)B GaAs Substrates

Si-doped GaAs/AlGaAs multi-quantum wells structures grown by molecular beam epitaxy on (100) and (311)B GaAs substrates have been studied by using conventional deep-level transient spectroscopy (DLTS) and high-resolution Laplace DLTS techniques. One dominant electron-emitting level is observed in the quantum wells structure grown on (100) plane whose activation energy varies from 0.47 to 1.3 eV as junction electric field varies from zero field (edge of the depletion region) to 4.7 × 10⁶ V/m. Two defect states with activation energies of 0.24 and 0.80 eV are detected in the structures grown on (311)B plane. The E_c-0.24 eV trap shows that its capture cross-section is strongly temperature dependent, whilst the other two traps show no such dependence. The value of the capture barrier energy of the trap at E_c-0.24 eV is 0.39 eV.