Nitrate therapy may retard glaucomatous optic neuropathy, perhaps through modulation of glutamate receptors

Nitrates have been a major part of the internist's pharmacopoeia for more than 100 years, predominantly for the relief of anginal symptoms. The effects of nitroglycerin on the eye and specifically on intraocular pressure has been investigated with diverse results. However, nitroglycerin may also serve to protect retinal ganglion cells against glutamate mediated toxicity--a form of cell death that may be critical in glaucomatous blindness. Consequently, we therefore sought to evaluate whether nitroglycerin preparations, taken for non-ophthalmic reasons, had an effect on glaucomatous damage.     

Clinical pharmacy services in hospitals educating pharmacy students

In 1995 we conducted a national survey of 1102 acute care hospitals in the United States to determine types of clinical pharmacy services, patient-focused care, and pharmaceutical care used to educate and train pharmacy students, and compared outcomes with surveys in 1989 and 1992. Clinical pharmacy services offered in 50% or more of Pharm.D.-affiliated hospitals (core services) were drug-use evaluation, in-service education, pharmacokinetic consultations, adverse drug reaction management, drug therapy monitoring, protocol management (most common for aminoglycosides, nutrition, antibiotics, heparin, warfarin, theophylline), nutrition team, and drug counseling. Comprehensive pharmaceutical care programs were established in 64%, 42%, and 33% of Pharm.D., B.S., and nonteaching hospitals, respectively. Patient-focused care programs were beginning or established in 77%, 71%, and 60%, respectively. Pharmacists served as care team leaders in 23% of hospitals affiliated with a college of pharmacy. Most common ambulatory care clinics were oncology, anticoagulation, diabetes, geriatrics, refill, and infectious diseases/HIV. For-profit hospitals rarely provided education for pharmacy students. Thus patient-focused and comprehensive pharmaceutical care programs exist according to a hospital's academic program affiliation with Pharm.D. or B.S. degree program.     

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies

The P3 event-related potential (ERP) component was recorded from 7- to 18-year-old children of alcoholics (COAs, n = 50) and age- and sex-matched control children (n = 50) using a visual oddball paradigm, involving nontarget (76%), target (12%), and novel (12%) stimuli. Topographic maps of P3 and associated scalp current density were obtained to supplement a topographic profile analysis. COAs manifested a smaller amplitude P3 to target stimuli over the centroparietal, parietal, and occipital scalp locations than controls. Also, COAs exhibited a smaller amplitude P3 to novel stimuli over the occipital scalp than controls. There were no significant differences between COAs and controls in the P3 scalp topography, indicating that differences in intracranial source strength rather than in source configuration were responsible for the between-group amplitude differences. Also, no significant group differences were observed in the P3 peak latency or in behavioral performance. These results support the notion that the visual P3 may provide a vulnerability marker of alcoholism.     

Treatment of posthemorrhagic hydrocephalus in the preterm infant with a ventricular access device

This study reports mtDNA polymorphisms in both hypervariable segments HV1 and HV2 of the non coding D-loop region from 60 unrelated Koreans. In contrast to two previous Korean data base studies, mtDNA was extracted separately from pulp tissue and root dentin of teeth obtained from dentists. Dentin turned out to be a reliable source of mitochondrial DNA. This can be of practical importance in forensic identification case work after a long post-mortem interval since pulp decomposes rapidly. The extraction method is explained in detail. The mtDNA polymorphisms obtained from 60 teeth of unrelated Koreans were compared with the already existing Korean data base.     

Primary biliary cirrhosis associated with mixed type autoimmune hemolytic anemia and sicca syndrome: a case report and review of literature

A case presenting with an unusual association of primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome is described. The 49-yr-old female primary biliary cirrhosis patient had a confirmed sicca syndrome and presented with jaundice and life-threatening anemia. Laboratory tests revealed positive Coombs' test with coexisting cold and warm autoantibodies. She was successfully treated by blood transfusion with packed red cells lacking any red cell antigens corresponding to serum alloantibodies and pulse methylprednisolone therapy. The patient remained stable under maintenance treatment using oral steroids and ursodeoxycholic acid. This case is probably the first reported showing an association between primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome and was probably induced by heterogenous and complicated autoimmune reactions.     

Sesquiterpene synthases from grand fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of delta-selinene synthase and gamma-humulene synthase

Grand fir (Abies grandis) has been developed as a model system for the study of oleoresin production in response to stem wounding and insect attack. The turpentine fraction of the oleoresin was shown to contain at least 38 sesquiterpenes that represent 12.5% of the turpentine, with the monoterpenes comprising the remainder. Assays of cell-free extracts from grand fir stem with farnesyl diphosphate as substrate indicated that the constitutive sesquiterpene synthases produced the same sesquiterpenes found in the oleoresin and that, in response to wounding, only two new products were synthesized, delta-cadinene and (E)-alpha-bisabolene. A similarity based cloning strategy yielded two new cDNA species from a stem cDNA library that, when expressed in Escherichia coli and the gene products subsequently assayed, yielded a remarkable number of sesquiterpene products. The encoded enzymes have been named delta-selinene synthase and gamma-humulene synthase based on the principal products formed; however, each enzyme synthesizes three major products and produces 34 and 52 total sesquiterpenes, respectively, thereby accounting for many of the sesquiterpenes of the oleoresin. The deduced amino acid sequence of the delta-selinene synthase cDNA open reading frame encodes a protein of 581 residues (at 67.6 kDa), whereas that of the gamma-humulene synthase cDNA encodes a protein of 593 residues (at 67.9 kDa). The two amino acid sequences are 83% similar and 65% identical to each other and range in similarity from 65 to 67% and in identity from 43 to 46% when compared with the known sequences of monoterpene and diterpene synthases from grand fir. Although the two sesquiterpene synthases from this gymnosperm do not very closely resemble terpene synthases from angiosperm species (52-56% similarity and 26-30% identity, there are clustered regions of significant apparent homology between the enzymes of these two plant classes. The multi-step, multi-product reactions catalyzed by the sesquiterpene synthases from grand fir are among the most complex of any terpenoid cyclase thus far described.     

Characterization of and functional antigen presentation by central nervous system mononuclear cells from mice infected with Theiler's murine encephalomyelitis virus

We examined the phenotype and function of cells infiltrating the central nervous system (CNS) of mice persistently infected with Theiler's murine encephalomyelitis virus (TMEV) for evidence that viral antigens are presented to T cells within the CNS. Expression of major histocompatibility complex (MHC) class II in the spinal cords of mice infected with TMEV was found predominantly on macrophages in demyelinating lesions. The distribution of I-As staining overlapped that of the macrophage marker sialoadhesin in frozen sections and coincided with that of another macrophage/microglial cell marker, F4/80, by flow cytometry. In contrast, astrocytes, identified by staining with glial fibrillary acidic protein, rarely expressed detectable MHC class II, although fibrillary gliosis associated with the CNS damage was clearly seen. The costimulatory molecules B7-1 and B7-2 were expressed on the surface of most MHC class II-positive cells in the CNS, at levels exceeding those found in the spleens of the infected mice. Immunohistochemistry revealed that B7-1 and B7-2 colocalized on large F4/80(+) macrophages/microglia in the spinal cord lesions. In contrast, CD4(+) T cells in the lesions expressed mainly B7-2, which was found primarily on blastoid CD4(+) T cells located toward the periphery of the lesions. Most interestingly, plastic-adherent cells freshly isolated from the spinal cords of TMEV-infected mice were able to process and present TMEV and horse myoglobin to antigen-specific T-cell lines. Furthermore, these cells were able to activate a TMEV epitope-specific T-cell line in the absence of added antigen, providing conclusive evidence for the endogenous processing and presentation of virus epitopes within the CNS of persistently infected SJL/J mice.     

Multiple-spell, discrete-time survival analysis of developmental data: object concept in pigtailed macaques

To measure cognitive development in 123 pigtailed macaques, we calculated medians and quartiles for the milestones of classical (Piagetian) object concept development (plain reach, partial-hide, full-hide, and A-not-B) in both 2-dimensional (screen) and 3-dimensional (well) tasks. Using multiple-spell, discrete-time survival analysis, we examined the influence of 4 independent variables (starting age, sex, birth weight, and task) on the probability of completing the milestones on any given test. The significant predictors for completion of the well sequence were birth weight and task. The best predictors for completion of the screen sequence were birth weight, number of test sessions, and interaction between birth weight and task. Birth weight had a greater predictive relationship in the earlier stages. This analysis provided information that cannot be obtained with traditional parametric methods.     

Transposition flaps adn full-thickness skin grafts used as interposition tissue: progressive physiological expansion

Expressing proteins and polypeptides as fusions to ubiquitin offers the advantage of an often dramatic increase in yield, and the ability to produce any desired amino-terminal residue upon ubiquitin cleavage. The recent availability of cloned ubiquitin-cleaving enzymes has enhanced this technique for both bacterial and eukaryotic host systems.