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Biomedical subjects

K Brown

Publications and source records attributed to K Brown.

At least 433 records · Page 24Linked to original sources
PubMed1986

v-ras genes from Harvey and BALB murine sarcoma viruses can act as initiators of two-stage mouse skin carcinogenesis.

Activated Harvey murine sarcoma virus ras genes were introduced into epidermal cells in vivo by direct application of retroviruses to mouse skin. Subsequent treatment with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced benign papillomas, some of which progressed to invasive carcinomas. Initiation with virus was irreversible for at least 4 months, since TPA treatment after this latency period produced papillomas within 4 weeks. Analysis of viral integration sites showed that carcinomas are clonal in origin. Both papillomas and carcinomas express virus-specific ras mRNA and the viral form of ras P21 protein. The results show that activated ras genes can replace chemical carcinogens in initiation of mouse skin carcinogenesis. This system presents a novel approach to in vivo analysis of the biological role of oncogenes in epithelial tumorigenesis.

Animals↗
PubMed1986

Complete nucleotide sequence of the Escherichia coli recC gene and of the thyA-recC intergenic region.

The nucleotide sequence of a 6,000 bp region of the E. coli chromosome that includes the 3' end of the coding region for the thyA gene and the entire recC gene has been determined. The proposed coding region for the RecC protein is 3369 nucleotides long, which would encode a polypeptide consisting of 1122 amino acids with a calculated molecular mass of 129 kDa. Mung bean nuclease mapping of a recC specific transcript produced in vivo indicates that transcription of recC is initiated 80 bp upstream of the translational start point. A weak promoter sequence situated 5' to the transcription initiation point has been identified. In the 1953 bp thyA-recC intergenic region there are three open reading frames that would code for polypeptides of molecular mass 30 kDa, 13.5 kDa and 12 kDa, respectively. Although the first and third of these open reading frames are preceded by possible ribosome binding sites, no obvious promoter sequences could be identified. Moreover, transcripts for these reading frames could not be detected.

Amino Acid Sequence↗
PubMed1986

The pharmacokinetics of sodium cromoglycate in man after intravenous and inhalation administration.

The pharmacokinetics of sodium cromoglycate in four healthy volunteers after slow intravenous infusion have been evaluated following measurement of plasma concentrations by radioimmunoassay. The results confirm earlier findings that sodium cromoglycate is rapidly eliminated from the body and that the data can be fitted to a two compartment open model. The pharmacokinetic parameters derived from the intravenous administration were used to evaluate the pharmacokinetics after inhalation administration via the Spinhaler. A model for absorption from the lungs is described which involves absorption at two different rates; this gives a better fit to the observed data than a single absorption rate. A fast absorption rate constant with a mean value of 0.54 min-1 and a slower rate constant with a mean value of 0.0097 min-1 were found. Of a mean total of 2.84 mg absorbed from a 20 mg inhaled dose, 0.68 +/- 0.15 (s.e. mean) mg were absorbed at the fast rate and 2.17 +/- 0.37 mg at the slower rate. These rates probably reflect absorption from different sites within the lungs. The results may have important implications for interpretation of clinical findings.

Absorption↗
PubMed1985

The structure of the human apolipoprotein C-II gene. Electron microscopic analysis of RNA:DNA hybrids, complete nucleotide sequence, and identification of 5' homologous sequences among apolipoprotein genes.

Cloned human apo-C-II cDNA was used as a hybridization probe to identify the human apo-C-II gene in a genomic library constructed in our laboratory. The isolated apo-C-II DNA was studied both by electron microscopy and by direct sequence analysis. Ultrastructural morphological analysis of RNA-DNA hybrids revealed that the apo-C-II gene had complex structures because of regions of inverted complementary sequences in and around the gene forming stem-and-loop structures which interfere with the formation of stable RNA:DNA hybrids. Extensive morphological analysis revealed a minimum of 3 intervening sequences (IVS), and their lengths were measured. Direct sequence analysis of the cloned gene confirmed the presence of 3 IVS. There are 4 Alu type sequences in IVS-I. We sequenced 4340 nucleotides which include 545 nucleotides in the 5' flanking region, the entire gene which spans 3320 nucleotides, and 475 nucleotides in the 3' flanking region which also encompasses an additional Alu sequence. The 5' end of the gene was identified by primer extension and sequencing of the primer extended cDNA. Apo-C-II mRNA structure was deduced from the cDNA sequence, the primer extension experiments, and the genomic sequence. It is 494 nucleotides in length. Its sequence differs from previously published sequences in that there are 7 additional nucleotides before the polyadenylate tail. In the 5' flanking region, nucleotides -234 to -213 encompass a GC-rich region which exhibits high homology (greater than 70%) to the 5' flanking regions of the genes of all the apolipoproteins published to date, namely, apo-A-II (-497 to -471), apo-A-I (approximately -196 to -179), apo-E (-409 to -391), and apo-C-III (approximately -116 to -103). This highly conserved region might represent some evolutionarily conserved sequences from these related genes and/or might represent a region with regulatory function.

Apolipoprotein C-II↗
PubMed1985

Depletion of secondary lysosomes in mouse macrophages infected with Leishmania mexicana amazonensis: a cytochemical study.

Leishmania amastigotes lodge and multiply within parasitophorous vacuoles, which can fuse with secondary lysosomes of the host macrophages. This study examines the effect of infection with amastigotes of L. mexicana amazonensis on the secondary lysosomes of mouse macrophage cultures. The cultures were stained for the activities of two lysosomal enzyme markers, acid phosphatase and arylsulfatase, and the light microscopic observations were supplemented by electron microscopy. Nearly all noninfected macrophages contained numerous stained secondary lysosomes. The number of such lysosomes was markedly reduced 24 h postinfection, and the reduction persisted for at least 10 days. Stained secondary lysosomes reappeared after the amastigotes were destroyed by exposure of the cultures to phenazine methosulfate or by placing them at 37.5 degrees C. The depletion of lysosomes shown by cytochemical methods may reflect a high rate of fusion of the lysosomes with the parasitophorous vacuoles, exceeding the rate of formation of new secondary lysosomes. Alternatively, the parasites may inhibit the synthesis of lysosomal hydrolases, or the assembly or formation of primary or secondary lysosomes.

Acid Phosphatase↗
PubMed1985

The reduction of seizure-like behaviors through contingency management.

A 22-year-old mildly retarded male, diagnosed as epileptic and paranoid schizophrenic, was admitted to an inpatient behavior unit for a medication assessment and possible behavioral treatment of uncontrolled seizure-like behavior. Since the patient had rarely been allowed out of his living unit in the past year, treatment consisted of a half-hour walk with a preferred staff member made contingent upon a 24-hr period of time free of any occurrence of seizure-like behaviors. An ABAB reversal design was used to assess experimental control. Data indicated that seizures decreased from a mean of 0.70 per day during the initial baseline phase to 0.36 per day during the final treatment phase. Additionally, the duration of seizures decreased from a mean of 50 min per seizure during the initial baseline phase to 17 min per seizure during the final treatment phase, although the contingency was applied irrespective of duration of seizure-like activity. The patient was discharged to a transitional setting until a community placement could be located.

Adult↗
PubMed1985

Behavioral covariation in the treatment of delusional verbalization with contingency management.

A 23-year-old female with the dual diagnosis of mild mental retardation and emotional disturbance was referred for treatment because of frequent disruptive outbursts. A brief inpatient behavior analysis suggested that delusional verbalization reliably preceded all other aberrant behaviors. Consequently treatment focused mainly on delusional verbalization; the additional aberrant behaviors were observed for behavioral covariation. The treatment package consisted of verbal instructions, modeling of appropriate eating behaviors, contingent verbal reprimand and a 2-min removal of food, and differential reinforcement of other behaviors. The design was a multiple baseline across settings. Results indicate a marked decrease in delusional verbalization in all settings, and, a correlated decrease for disruption, screaming, and out-of-seat behaviors.

Adult↗
PubMed1985

A critique of Hoffman's analysis of schizophrenic speech.

In a recent paper (R. E. Hoffman, L. Kirstein, S. Stopek, & D. V. Cicchetti, 1982, Brain and Language, 15, 207-233), Hoffman et al. outlined a method of analyzing schizophrenic speech. This method is briefly described. When this method was applied to transcripts of psychotic speech in a subsequent study, major flaws in the system became evident. Despite its claims to be a semiobjective method there are still a great deal of intuitive judgments involved and the analyst has to make numerous ad hoc decisions. This applies particularly to the determination of deviance in a transcript.

Humans↗
PubMed1985

Elastic jump in male urethra during voiding: clinical observations in male subjects and experimental studies in dogs.

A physical phenomenon known as elastic jump occurs downstream of an elastic constriction applied to a collapsible tube. This flow anomaly is analogous to the hydraulic jump that occurs in surface flows. Some investigators have predicted that an elastic jump could occur in the male urethra (during voiding) in the cavernous segment between constrictions at the membranous and meatal regions. To identify and understand this flow anomaly, and to obtain clinical correlations in human male subjects we have attempted several radiological and urodynamic studies in normal and abnormal subjects. The studies were retrograde urethrography, voiding cystourethrography, static pressure recordings during voiding and uroflowmetry. Retrograde urethrography was believed to delineate accurately the anatomy of the bulbous urethra. Voiding cystourethrography showed the geometry of the functional bulb. Our observations in 43 male subjects suggest that the site and degree of elastic jump depend on the severity of bladder neck or prostatic obstruction, magnitude of detrusor pressure (energy) during voiding, degree of distal constriction and position in which the subject voids. The animal studies (23 dogs) confirmed our clinical urodynamic impression.

Adult↗
PubMed1985

Gene expression during terminal differentiation: dexamethasone suppression of inducer-mediated alpha 1- and beta maj-globin gene expression.

Previous studies demonstrated that hexamethylenebisacetamide (HMBA)-mediated murine erythroleukemia cell (MELC) commitment to terminal division could be suppressed by dexamethasone. A rapid (less than 2 hr) increase (step-up) in commitment to terminal cell division was observed if, after 60-70 hr in culture with inducer and steroid, MELC were transferred to medium with HMBA alone. This step-up commitment was not inhibited by actinomycin or cordycepin but was blocked by cycloheximide. In this study, we show that dexamethasone blocks HMBA-mediated activation of alpha 1- and beta maj-globin gene transcription but not the induced chromatin change characterized by appearance of DNase I-hypersensitive regions upstream from the 5' cap sites of the alpha 1- and beta maj-globin genes. A rapid (less than 2 hr) activation (step-up) of alpha 1-globin gene transcription was observed if, after 48-60 hr in culture with HMBA and dexamethasone, MELC were transferred to medium with HMBA alone. Activation of transcription of the beta maj-globin gene requires 12-24 hr of further culture. Cycloheximide inhibits step-up transcription of both globin genes. Thus, dexamethasone blocks HMBA-mediated modulation of transcription of several nonlinked genes whose expression is altered in a coordinated manner during induced MELC terminal differentiation. Further, the steroid blocks at a late step, a step after that which is rate-limiting to HMBA-mediated MELC differentiation.

Acetamides↗
PubMed1985

The nasal absorption of sodium cromoglycate in the albino rat.

The intranasal absorption of sodium cromoglycate has been investigated in the adult male COBS/Wistar rat. Sodium cromoglycate (1 mg kg-1) was instilled into the nasal cavities and for comparison animals were also similarly dosed intravenously or sub-lingually. Serial samples of blood or bile were collected. After intravenous administration, the area under the plasma concentration curve (AUC0-infinity) was 32 micrograms min ml-1 corresponding to a plasma clearance of 13 ml min-1 and an elimination rate constant of 0.049 min-1. Plasma concentrations of radioactivity after intranasal administration rose to a mean peak of 0.3 micrograms ml-1 approximately 20 min after dosing and fell to 0.03 micrograms min ml-1 at 3 h. The AUC0-3 was 19 micrograms min ml-1 corresponding to an absorption of 60% over 3 h. The absorption rate constant (ka) was 0.059 min-1. The total amount of sodium cromoglycate excreted in bile after intravenous administration was 56%. The amount of compound excreted in the bile was 30% after intranasal administration corresponding to an absorption of 53%. Plasma and bile data therefore show good agreement. Total excretion in the bile over 3 h after sub-lingual administration was 3%, demonstrating that this route made no significant contribution to the intranasal results. The absorption of sodium cromoglycate is independent of variations in the technique including changes in the orientation of the rat or blocking of the nasopalatine. The techniques used minimized other competing nasal clearance processes such as mucociliary clearance.

Absorption↗
PubMed1985

Drugs as research tools in psychology: cholinergic drugs and aggression.

A review of studies using cholinergic drugs as tools to investigate the neural mechanisms mediating affective and predatory aggressive behaviour reveals that the same two cholinergic systems are involved with both sorts of behaviour. There is a brain muscarinic system initiating aggression and a nicotinic system which inhibits aggressive behaviour. This evidence suggests that there could be two possible forms of cholinergic therapy for aggression, cholinolytics and nicotinic agonists. These possibilities are discussed.

Aggression↗