PubMed Health⌕ Search

Biomedical subjects

A C Johnson

Publications and source records attributed to A C Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Insulin increases transcription of rat gene 33 through cis-acting elements in 5'-flanking DNA.

Gene 33 is a multihormonally-regulated rat gene whose transcription is rapidly and markedly enhanced by insulin in liver and cultured hepatoma cells. To examine the mechanism by which insulin regulates transcription, we have constructed chimeric plasmids in which expression of the bacterial cat gene, encoding chloramphenicol acetyltransferase (CAT), is governed by gene 33 promoter elements and contiguous sequences in DNA flanking the transcription start point (tsp). When transfected into H4IIE hepatoma cells, these constructs gave rise to stably transformed cell lines producing the bacterial CAT enzyme. This expression was increased by insulin treatment in a fashion resembling the effect of this hormone on transcription of the native gene. In vitro transcription assays in nuclear extracts also revealed increased transcription of the chimeric plasmids when the extracts were prepared from insulin-treated rat hepatoma cells. The results demonstrate that induction by insulin is mediated by cis-acting nucleotide sequences located between bp -480 to +27 relative to the tsp.

Animals↗
PubMed1992

Expression and chromosomal localization of the gene for the human transcriptional repressor GCF.

GCF is a human transcriptional regulator that represses transcription of certain genes and is encoded by a 3-kilobase (kb) mRNA (Kageyama, R., and Pastan, I. (1989) Cell 59, 815-825). The expression of GCF was examined in a variety of clonal cell lines. The 3.0-kb GCF mRNA was found to be expressed at the highest level in HUT 102 cells (derived from a T-cell lymphoma). Elevated levels of the GCF mRNA were also noted in KATO III and AGS (gastric carcinomas), FEM-X (melanoma), and U266B1 (myeloma) cell lines. A human fibroblast cell line (WI38) did not express GCF mRNA, and no cross-hybridization to a mouse cell line (NIH 3T3) or monkey cell line (CV-1) could be detected. The GCF cDNA also hybridizes to RNA species of 4.5 and 1.2 kb. The 4.5-kb RNA has the same general expression pattern as the GCF mRNA. Hybridization of cellular RNA with various probes derived from the 3-kb cDNA revealed that the 4.5-kb RNA species only hybridizes to GCF cDNA probes from the extreme 5' end. By using single-stranded RNA probes, hybridization to the three RNA species was detected with the antisense probe for the 5' end (nucleotides 1-561). The single-stranded antisense probe for the region encompassing nucleotides 561-1692 hybridized to the 3.0- and 1.2-kb RNA species. The sense probes for these regions did not hybridize to these RNAs. The GCF gene was localized to a single locus, the chromosome 2 p11.1-11.2 region, by in situ hybridization. Treatment of human KB epidermoid carcinoma cells with phorbol 12-myristate 13-acetate (PMA) lead to a rapid induction of GCF RNA after 1 h and a decline to lower than control levels after 6 h. Epidermal growth factor receptor mRNAs were not increased by PMA until 2 h after treatment and were at their highest level only after GCF mRNAs were decreased. The 4.5- and 1.2-kb RNAs were also induced by PMA with the same kinetics as the GCF mRNA. These results show that the GCF gene is widely expressed in human tissues and cell lines and that the 4.5- and 1.2-kb RNAs have similar expression patterns.

Animals↗
PubMed1992

Auditory degeneration after exposure to toluene in two genotypes of mice.

Two inbred strains of mice, CBA/Ca (with a moderate hearing loss starting late in life) and C57BL/6J (with an early onset of spontaneous auditory degeneration), were exposed to toluene by inhalation (1000 ppm, 12 h/day, 7 days) at either 1 or 6 months of age. Thresholds of auditory brainstem response (ABR) were measured 3-5 days after exposure and assessed repeatedly up to the age of 16 months (C57) or 23 months (CBA). Both strains of mice exposed to toluene at 1 month of age showed a mild loss of sensitivity at a high frequency (31.5 kHz) shortly after exposure. With increasing age, toluene exposure had little effect on the aging process of the auditory system in CBA mice but accelerated age-related hearing loss in C57 mice. The results indicate that toluene exposure can aggravate auditory deterioration only in mice with a strong genetic predisposition to spontaneously precocious age-related hearing loss.

Administration, Inhalation↗
PubMed1992

The role of the prosthodontist regarding aspirative dysphagia.

Certain swallowing disorders characteristically may follow head and neck surgeries and neurologic disorders. Aspiration is one of the possible symptoms of dysphagia. Since aspiration can be life-threatening, prosthodontists should help to identify patients who aspirate. This article describes the normal swallowing physiology, the pathophysiology of swallowing disorders, and the prosthetic role in the treatment of patients experiencing head and neck surgical operations and neurologic disorders that may cause aspiration.

Deglutition↗
PubMed1992

Involvement of residues 296-299 in the enzymatic activity of tissue-type plasminogen activator.

The tetra-alanine substitution variant KHRR 296-299 AAAA of tissue-type plasminogen activator (t-PA) was previously shown to have enhanced fibrin specificity and enhanced activity in the presence of fibrin compared with the wild-type form of the molecule. The structural requirements for these alterations in enzymatic activity were investigated by constructing several amino acid substitution variants at each of the positions from 296 to 299 and evaluating their activities under a variety of conditions. Effects on plasminogen activator activity were common among the point mutants at positions 296-299; nearly all had a phenotype similar to the KHRR 296-299 AAAA variant. The greatest effects on enzymatic function were found with multiple substitution variants, but some single charge reversals and proline substitutions had substantial effects. The enhanced fibrin specificity of KHRR 296-299 AAAA t-PA results in less fibrinogenolysis than seen with wild-type t-PA. Approximately four times greater concentration of KHRR 296-299 AAAA compared with wild-type t-PA was required to consume 50% of the fibrinogen in human plasma.

Alanine↗
PubMed1992

Auditory sensitivity in rats exposed to toluene and/or acetyl salicylic acid.

The present study investigates whether exposure to acetyl salicylic acid (ASA) affects the permanent auditory loss, caused by simultaneous exposure to toluene. Rats were exposed to toluene by inhalation (1,000 ppm), or to ASA by gavage (100 mg kg-1), or to both toluene and ASA, during 10 days. Toluene exposure caused a loss of auditory sensitivity recorded as auditory brainstem response, and no loss was found after exposure to ASA alone. The group exposed to both ASA and toluene had a more severe sensitivity loss (p < 0.05) at all frequencies compared with all other groups immediately after (2-5 days) exposure and also 4 months later. The results indicate that ASA permanently potentiates toluene induced loss of auditory sensitivity.

Acoustic Stimulation↗
PubMed1992

Esophagogastric ring: why and when we see it, and what it implies: a radiologic-pathologic correlation.

Schatzki first reported a ring-like structure at the esophagogastric mucosal junction in 1953. There is still no uniform agreement as to its exact location, etiology, or clinical importance. We found an esophagogastric ring in 15% to 18% of 22,368 patients having routine upper gastrointestinal examinations. It was present only in patients with cephalad displacement of the esophagogastric junction and only in those who had sharply and circumferentially marginated transition of esophagogastric mucosal junction. It is postulated that the esophagus shortens on vagal stimulation by contracture of the longitudinal esophageal muscle, which causes a mucosal infolding at the esophagogastric junction. In a small group of these patients, fibrosis apparently develops in this region and results in a fixed organic circumferential diaphragm, which may cause obstructive symptoms. These concepts affect therapeutic alternatives.

Barium Sulfate↗
PubMed1991

Vestibular-oculomotor, opto-oculomotor and visual function in the rat after long-term inhalation exposure to toluene.

Pigmented rats were exposed to toluene (1000 ppm, 21 h/day) for 6 or 11 weeks. The function of the vestibulo- and opto-oculomotor systems was tested one month after the end of the exposure by recording of nystagmus, induced by vestibular or optokinetic stimuli. The eye movements were recorded by a magnetic search coil technique. The optokinetic gain in the exposed animals was reduced compared to a control group. There was also a slight reduction in gain during sinusoidal oscillatory vestibular stimulation. No effect of the toluene exposure on the gain or duration of nystagmus during acceleratory or deceleratory rotatory stimulation was demonstrated, nor was there any change in the duration of the optokinetic after-nystagmus. The function of the visual system was tested 2 to 5 days after exposure by recording the electroretinogram and the visual evoked response. The conduction velocity in peripheral nerve was also measured. No effect of the toluene exposure on these variables was seen. The results indicate that long-term inhalation of toluene causes a long-lasting, possibly permanent, lesion within the vestibulo-cerebellum. They gave no evidence that such exposure affects peripheral vestibular or visual function.

Administration, Inhalation↗
PubMed1990

The effect of ursodiol on the efficacy and safety of extracorporeal shock-wave lithotripsy of gallstones. The Dornier National Biliary Lithotripsy Study.

BACKGROUND: In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments. We designed our study to determine the value of administering this agent. METHODS: At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy. RESULTS: The stones were fragmented in 97 percent of all patients, and the fragments were less than or equal to 5 mm in diameter in 46.8 percent. On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P less than 0.0001) had gallbladders that were free of stones after six months. Among those with completely radiolucent solitary stones less than 20 mm in diameter, 35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo (P less than 0.001) were free of stones after six months. Biliary pain, usually mild, occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months (P less than 0.01). There were few adverse events. Only diarrhea occurred with a significantly different frequency in the two groups: 32.6 percent were affected in the ursodiol group, as compared with 24.7 percent in the placebo group (P less than 0.04). Severe biliary pain occurred in 1.5 percent of all patients, acute cholecystitis in 1.0 percent, and acute pancreatitis in 1.5 percent; endoscopic sphincterotomy was performed in 0.5 percent, and cholecystectomy in 2.5 percent. CONCLUSIONS: Extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones, and equally safe. Treatment was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones.

Blood Pressure↗
PubMed1989

Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene.

Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.

Animals↗
PubMed1988

Epidermal growth factor receptor gene promoter. Deletion analysis and identification of nuclear protein binding sites.

To determine the location of sites that may be important for the function of the promoter of the epidermal growth factor (EGF) receptor gene and to characterize the factors that bind to these sites, the promoter region was analyzed by deletion analysis, exonuclease III protection and gel retardation assays with crude and fractionated nuclear extracts and DNase I footprinting using purified Sp1. Transfection of chimeric chloramphenicol acetyltransferase plasmids containing various deletions of the EGF receptor gene promoter into CV-1 cells indicated that the region between -178 and -16 (initiator ATG is +1) is sufficient for promoter activity. Exonuclease III protection assays revealed the presence of eight specific nuclear protein binding sites in the region between -481 and -16. Gel retardation assays confirmed that multiple protein binding sites exist in this region (-481 to -16) and quantitatively agree with exonuclease III protection. DNase I footprinting using purified Sp1 showed that this transcription factor can bind to four sites (-457 to -440, -365 to -286, -214 to -200, and -110 to -84) in the EGF receptor gene promoter and therefore may play a role in its regulation.

Animals↗
PubMed1988

Expression of epidermal growth factor receptor proto-oncogene mRNA in regenerating rat liver.

The expression of EGF receptor mRNAs in regenerating rat liver was measured using two nonoverlapping cDNA probes for the human gene from a highly conserved region. These probes (pE7 and pE62) both hybridized to RNA species of 10 and 6 kb. The 10 and 6 kb RNA species were shown to decrease in the first 12 hours after partial hepatectomy. However, significant increases above control levels were noted at 24h and 72h. The level of alpha-actin mRNA increased as has been previously reported. These results suggest that a transcriptional and/or a posttranscriptional regulatory mechanism exists in regenerating rat liver with respect to EGF receptor gene expression.

Actins↗
PubMed1988

Gene-specific acquisition of hormonal responsiveness in rat liver during development.

Cloned cDNAs were used in hybridization analyses to assess hormonal responsiveness of two similarly regulated genes in livers of late-term fetal rats. Transcription of the tyrosine aminotransferase gene and of gene 33 (Lee et al.: J Biol Chem 260:16433-16438, 1985) is enhanced by glucocorticoids and by each of the usually antagonistic hormonal agents, insulin and cAMP, in adult liver, and that of both genes is developmentally activated at or just prior to birth. The mRNA of gene 33 was found to be significantly increased by each of the hormonal regulators in livers of fetuses treated in utero. Expression of the nearly silent aminotransferase gene in fetal liver was appreciably increased by cAMP but was refractory to control by either glucocorticoids or insulin; capacity of this gene to respond to insulin was not realized until several days postpartum. The data indicate specificity in the developmental acquisition of the capacity of individual genes to respond to hormonal regulators.

Animals↗
PubMed1988

Toluene exposure during maturation of intraocular brain tissue transplants: alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine.

The effects of chronic toluene exposure on central neurons were examined using syngeneic grafts into the anterior chamber of the eye. Young adult albino rats with intraocular brain transplants inhaled toluene (1000 ppm) for 9 weeks starting at the time of transplantation, or from Week 8 to 17 after the graft was placed in oculo. Control animals were exposed to room air during the same intervals. Toluene treatment during development did not affect general growth or morphology of any of the brain areas examined. The distribution of neurofilament or glial fibrillary acidic protein immunoreactivity was similar in the experimental group and control group as well. Extracellular recordings of cerebellar Purkinje neurons showed a significantly reduced spontaneous firing rate, of 15-25%, both in intraocular transplants and in cerebellum in situ in toluene exposed animals. Postsynaptic sensitivity of intraocular and in situ Purkinje neurons to norepinephrine (NE) was evaluated. Purkinje neurons in transplants exposed to toluene during development were markedly supersensitive to superfused NE as compared to controls, while neither Purkinje neurons in mature cerebellar grafts nor cerebellum in situ showed any effects of the toluene treatment on NE sensitivity. The tissue content of NE in transplants exposed to toluene during maturation, evaluated with high-performance liquid chromatography coupled with electrochemical detection, was greater than that in the control grafts. Moreover, the content of free (3-methoxy-4-hydroxyphenyl) ethylene glycol (MHPG) was increased in both transplant and host cerebellum after toluene exposure. Taken together, these data indicate that toluene exposure during development of cerebellar grafts in oculo causes changes in postsynaptic noradrenergic sensitivity as well as decreased spontaneous activity of Purkinje neurons. Toluene exposure of adult cerebellum in situ or in oculo appears to decrease the Purkinje neuron discharge rate and increase NE turnover, but has no marked effect on postsynaptic NE sensitivity.

Administration, Inhalation↗
PubMed1988

Systemic mastocytosis and mastocytosis-like syndrome: radiologic features of gastrointestinal manifestations.

Mastocytosis is a disorder of unknown etiology characterized by an abnormal proliferation of tissue mast cells, and/or by degranulation of abnormally behaving mast cells that show no proliferation, but release myriad active metabolites. This results in a wide spectrum of signs and symptoms that fluctuate considerably. The presently available diagnostic tests vary in their specificity and sensitivity. We have evaluated the role of radiologic studies in 78 confirmed cases of systemic mastocytosis and/or mastocytosis-like syndrome, including barium meal and small bowel follow-through (UGI-SBFT).

Adolescent↗
PubMed1988

Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease.

The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promoter outside the confines of the cell. Previously, we reported the isolation of the human EGF receptor gene promoter. The promoter is highly GC rich, contains no TATA or CAAT box, and has multiple transcription start sites. An S1 nuclease-sensitive site has now been found 80 to 110 base pairs (bp) upstream from the major in vivo transcription initiation site. Two sets of direct repeat sequences were found in this area; both conform to the motif TCCTCCTCC. When deletion mutations were made in this region of the promoter by using either Bal 31 exonuclease or S1 nuclease, we found that in vivo activity dropped three- to fivefold, on the basis of transient-transfection analysis. Examination of nuclear protein binding to normal and mutated promoter DNAs by gel retardation analysis and DNase I footprinting revealed that two specific factors bind to the direct repeat region but cannot bind to the S1 nuclease-mutated promoter. One of the specific factors is the transcription factor Sp1. The results suggest that these nuclear trans-acting factors interact with the S1 nuclease-sensitive region of the EGF receptor gene promoter and either directly or indirectly stimulate transcription.

Animals↗