Categorization of Hospital Emergency Services—Developing Valid Criteria

In a pilot project sponsored by the California State Emergency Medical Services Authority, validated, verifiable criteria were developed for the vertical categorization of hospital emergency services in 11 different groupings of medical and surgical emergencies. We describe the development of an assessment process and categorization criteria to identify the most appropriate receiving facility for interfacility transfer and, in selected instances, field triage of patients with different levels of severity of illness or injury. We propose that this facility assessment project be used in the critical care planning process for the eventual vertical categorization of hospital emergency services in California and as a template for similar projects in other states.     

Inhibitors of inosinate dehydrogenase

Inosinate dehydrogenase (IMP-dehydrogenase) from Chinese Hamster Ovary cells was found to be inhibited by two types of inhibitors. One type of inhibitor binds competitively at IMP-binding site and other type at NAD-binding site of the enzyme. Some new inhibitors of both classes have been illustrated here and their inhibition constants and type of inhibition determined. NAD-analog of tiazofurin was found to bind with both the sites and this type of inhibitors were found to be non-competitive with IMP and NAD.     

Pressor, tachycardic and feeding responses in conscious rats following i.c.v. administration of dynorphin. Central blockade by opiate and alpha 1-receptor antagonists

Experiments were designed to determine the hemodynamic responses of conscious, unrestrained rats given intracerebroventricular (i.c.v.) injections of dynorphin A-(1-13) and the possible central receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 gb. wt.) received i.c.v. injections (by gravity flow in a total volume of 3 or 5 microliter) of control solutions of sterile saline (SS) or dimethylsulfoxide (DMSO) or 1.5, 3.0 or 6.1 nmol of dynorphin A-(1-13). Blood pressure and heart rate changes were monitored over 2 h after administration; as well, feeding activity was visually assessed and scored over this period. Other groups of conscious rats were pretreated i.c.v. with equimolar doses (3.0-24.4 nmol) of specific receptor antagonists (naloxone HCl, phentolamine HCl, propranolol HCl, yohimbine HCl or prazosin HCl) 10 min before subsequent i.c.v. administration of SS or DMSO/SS or 6.1 nmol of dynorphin A-(1-13). I.c.v. injection of dynorphin A-(1-13) caused a dose-related pressor response, associated temporally with tachycardia. As well, dynorphin evoked feeding activity and some grooming, which occurred when the rats were hypertensive and tachycardic and decreased as heart rate and blood pressure returned to control levels. I.c.v. pretreatment studies indicated that naloxone HCl (12.2 nmol), phentolamine HCl (12.2 nmol) and prazosin HCl (6.1 nmol) blocked the pressor response, tachycardia as well as feeding activity of rats subsequently given dynorphin. The results suggest the pressor and tachycardic effects of conscious rats following i.c.v. dynorphin administration may, in part, be due to behavioral activation (feeding). As well, these data indicate that both opioid as well as alpha 1-adrenergic receptors within the CNS are involved in mediating the pressor, tachycardic and feeding responses of conscious rats given i.c.v. injections of dynorphin A.     

Periodicity of bud bursting in willow (Salix viminalis) as affected by growth regulators

Saunders, P. F. and Barros, R. S. 1987. Periodicity of bud bursting in willow ( Salix viminalis ) as affected by growth regulators.
Lateral vegetative buds of willow ( Salix viminalis L.) were only innately dormant for 3–5 weeks in October; during this time their apices were correlatively inhibited by the bud leaflets. Exogenous gibberellins stimulated the opening of cultured buds when the plants were dormant or entering dormancy. As dormancy was being released, however, cultured buds became more responsive to exogenous cytokinins. Thus the demand for gibberellins and cytokinins for bud opening seemed to be sequential rather than simultaneous. Dormant buds cultured in the presence of abscisic acid remained unopened, but they opened after a chilling treatment. Subsequent growth of such buds as measured by dry matter accumulation, was observed only if a cytokinin was added to the medium.     

Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death

The mechanism of cytotoxic action of 5-fluorodeoxyuridine (FdUrd) in mouse FM3A cells was investigated. We observed the FdUrd-induced imbalance of intracellular deoxyribonucleoside triphosphate (dNTP) pools and subsequent double strand breaks in mature DNA, accompanied by cell death. The imbalance of dNTP pools was maximal at 8 h after 1 microM FdUrd treatment; a depletion of dTTP and dGTP pools and an increase in the dATP pool were observed. The addition of FdUrd in culture medium induced strand breaks in DNA, giving rise to a 90 S peak by alkaline sucrose gradient sedimentation. The loss of cell viability and colony-forming ability occurred at about 10 h. DNA double strand breaks as measured by the neutral elution method were also observed in FdUrd-treated cells about 10 h after the addition. These results lead us to propose that DNA double strand breaks play an important role in the mechanism of FdUrd-mediated cell death. A comparison of the ratio of single and double strand breaks induced by FdUrd to that observed following radiation suggested that FdUrd produced double strand breaks exclusively. Cycloheximide inhibited both the production of DNA double strand breaks and the FdUrd-induced cell death. An activity that can induce DNA double strand breaks was detected in the lysate of FdUrd-treated FM3A cells but not in the untreated cells. This suggests that FdUrd induces the cellular DNA double strand breaking activity. The FdUrd-induced DNA strand breaks and cell death appear to occur in the S phase. Our results indicate that imbalance of the dNTP pools is a trigger for double strand DNA break and cell death.     

Evolutionary relationships amongst archaebacteria. A comparative study of 23 S ribosomal RNAs of a sulphur-dependent extreme thermophile, an extreme halophile and a thermophilic methanogen

The 23 S RNA genes representative of each of the main archaebacterial subkingdoms, Desulfurococcus mobilis an extreme thermophile, Halococcus morrhuae an extreme halophile and Methanobacterium thermoautotrophicum a thermophilic methanogen, were cloned and sequenced. The inferred RNA sequences were aligned with all the available 23 S-like RNAs of other archaebacteria, eubacteria/chloroplasts and the cytoplasm of eukaryotes. Universal secondary structural models containing six major structural domains were refined, and extended, using the sequence comparison approach. Much of the present structure was confirmed but six new helices were added, including one that also exists in the eukaryotic 5.8 S RNA, and extensions were made to several existing helices. The data throw doubt on whether the 5' and 3' ends of the 23 S RNA interact, since no stable helix can form in either the extreme thermophile or the methanogen RNA. A few secondary structural features, specific to the archaebacterial RNAs were identified; two of these were supported by a comparison of the archaebacterial RNA sequences, and experimentally, using chemical and ribonuclease probes. Seven tertiary structural interactions, common to all 23 S-like RNAs, were predicted within unpaired regions of the secondary structural model on the basis of co-variation of nucleotide pairs; two lie in the region of the 23 S RNA corresponding to 5.8 S RNA but they are not conserved in the latter. The flanking sequences of each of the RNAs could base-pair to form long RNA processing stems. They were not conserved in sequence but each exhibited a secondary structural feature that is common to all the archaebacterial stems for both 16 S and 23 S RNAs and constitutes a processing site. Kingdom-specific nucleotides have been identified that are associated with antibiotic binding sites at functional centres in 23 S-like RNAs: in the peptidyl transferase centre (erythromycin-domain V) the archaebacterial RNAs classify with the eukaryotic RNAs; at the elongation factor-dependent GTPase centre (thiostrepton-domain II) they fall with the eubacteria, and at the putative amino acyl tRNA site (alpha-sarcin-domain VI) they resemble eukaryotes. Two of the proposed tertiary interactions offer a structural explanation for how functional coupling of domains II and V occurs at the peptidyl transferase centre. Phylogenetic trees were constructed for the archaebacterial kingdom, and for the other two kingdoms, on the basis of the aligned 23 S-like RNA sequences.(ABSTRACT TRUNCATED AT 400 WORDS)     

Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor.

Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop.     

Structural analysis of the pilE region of Neisseria gonorrhoeae P9

We have determined the nucleotide sequence of an expressed structural pilus gene (pilE) derived from Neisseria gonorrhoeae strain P9-2. Detailed analysis of nucleotide sequences upstream from pilE revealed a silent, truncated pilin gene segment that was linked to families of DNA elements (RS1 and RS3) that have previously been identified at the major silent pilin gene locus (pilS1) and at pilE of the independently isolated N. gonorrhoeae strain MS11ms. A nucleotide sequence downstream from pilE was reminiscent of the recognition sequences of several recombinases, including Tn3 tnpR product (resolvase), suggesting a possible role for site-specific events in the recombinational modulation of pilus expression.