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Biomedical subjects

M A Johnson

Publications and source records attributed to M A Johnson.

At least 343 records · Page 19Linked to original sources
PubMed1990

Urinary tract infections in women.

The clinical conditions that cause dysuria in women can usually be differentiated by the history and selected physical and laboratory examinations. Cystitis can be treated with short-course therapy in uncomplicated cases; pretreatment cultures are usually not necessary, since most infections are caused by Escherichia coli. Outpatient treatment of pyelonephritis is appropriate in selected patients. Follow-up culture after treatment of either cystitis or pyelonephritis is indicated to identify those patients requiring longer treatment or urologic evaluation. Recurrent urinary tract infections can be managed with postcoital antibiotics, long-term prophylaxis or patient self-administration of short-course therapy. Bacteriuria and pyelonephritis in pregnancy must be aggressively diagnosed and treated.

Anti-Infective Agents, Urinary↗
PubMed1989

Synthesis in Escherichia coli of the major glycoprotein of human rotavirus: analysis of the antigenic regions.

Various regions of the gene encoding the major neutralization antigen, VP7, of human rotavirus have been expressed in Escherichia coli, as N-terminal fusions to beta-galactosidase under the control of the lac promoter. We have determined that the fusion products of two clones containing regions AB (aa 69-158) and ABC (aa 69-319) were antigenic, reacting with antibodies raised against whole virus. When guinea pigs were immunized with fusion protein purified by monoclonal antibody affinity columns, no neutralizing or virus-binding antibodies were detected, but antibodies binding to denatured VP7 were present.

Antigens, Viral↗
PubMed1989

Regulation of purine deoxynucleoside phosphorylation by deoxycytidine kinase from human leukemic blast cells.

The kinetics and regulation of nucleoside phosphorylation by highly purified human deoxycytidine kinase from leukemic lymphoblasts were studied. The phosphorylation of purine nucleosides by this enzyme showed sensitivity to the endogenous inhibitors dCTP and UDP three times greater than the phosphorylation of dCyd. Examination of nucleotide pools in human T and B lymphoblasts disclosed that the levels of dCTP and UDP in these cells were sufficient to regulate kinase activity. The enhanced sensitivity of the kinase to dCTP and UDP was related to its reduced ability to interact with purine nucleosides. Comparison of the phosphorylation kinetics for pyrimidine and purine dideoxynucleosides used in antiviral therapy showed that the purine nucleosides were at least 50-fold less efficient as enzyme substrates. These results suggest that the phosphorylation of pharmacologically active purine nucleosides by deoxycytidine kinase is regulated by cellular nucleotide pools.

B-Lymphocytes↗
PubMed1989

The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection.

The polymerase chain reaction is an in vitro method for primer directed enzymatic amplification of specific target DNA sequences. The technique was used to detect human papillomavirus types 11 and 16 simultaneously in cellular DNA recovered from cervical smears in 38 women referred for colposcopy to evaluate cytological abnormality and 10 women with no history of cytological abnormality. The polymerase chain reaction was shown to be both specific and sensitive in detecting human papillomavirus DNA such that a single human papillomavirus molecule was detected in 10(5) cells. Of the 38 women with cytological abnormality, all were positive for human papillomavirus on testing with the polymerase chain reaction; 36 were infected with human papillomavirus type 16 and 22 dually infected with human papillomavirus types 11 and 16. Seven of the 10 women with no cytological abnormality were also infected with human papillomavirus type 11 or 16. The use of the polymerase chain reaction will facilitate epidemiological investigation of the aetiological role of human papillomavirus in cervical neoplasia. This preliminary analysis suggests that the prevalence of human papillomavirus infection is greater than previously reported.

Adult↗
PubMed1989

Dystrophin in skeletal muscle. II. Immunoreactivity in patients with Xp21 muscular dystrophy.

In the preceding paper a sensitive Western blotting analysis system based on the use of a monoclonal antibody to dystrophin was described. Here we report the immunoreactivity on blots and on unfixed frozen sections of muscle from patients with Duchenne (DMD) and Becker (BMD) muscular dystrophy. Muscle from 3 BMD patients showed variation both in the band pattern observed on blots and in the immunocytochemical labelling of dystrophin on frozen sections. In contrast to previous reports, we were able to detect some minor dystrophin bands on blots from 6 of 9 DMD biopsy samples. Tissue sections from 8 of the 9 contained isolated fibres with dystrophin-positive labelling. We conclude that the majority of DMD patients have muscle fibres which can synthesize dystrophin in a limited manner.

Adolescent↗
PubMed1989

Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat.

Renal distribution of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, an 18% reduction (p less than .025). Second study: Male Sprague-Dawley rats were made prostaglandin deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin deficient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p less than .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.

Animals↗
PubMed1989

Diminished foveal sensitivity may predict the development of advanced age-related macular degeneration.

Visual function testing was performed on one eye with drusen from each of 18 elderly patients in 1984. Eleven patients had advanced age-related macular degeneration (AMD) in the fellow eye, and seven had only bilateral drusen. These patients were all followed prospectively (median, 45 months), at which time one eye had a new vessel membrane, three eyes had pigment epithelial detachments, and one eye had geographic atrophy. Only two of these five eyes had AMD-related visual loss in the fellow eye in 1984. The degree of loss of foveal dark-adapted sensitivity in 1984 predicted which patients developed advanced AMD with 100% sensitivity and 92% specificity. The presence of high-risk drusen characteristics in 1984 predicted the development of advanced AMD with 100% sensitivity but only 55% specificity. For this small group of patients, foveal dark-adapted sensitivity loss was an excellent predictor of the subsequent development of advanced AMD in eyes with drusen. A prospective study of a large group of patients with drusen is being undertaken to validate this finding.

Aged↗
PubMed1989

A glomerular defect in prehypertensive Dahl S rats, which limits their capacity to increase GFR.

There is a great need to discover traits that predict future human hypertension. Our previous studies found abnormal glomerular filtration rates (GFRs) in isolated kidneys of Dahl S rats. Such GFR alterations were sought in intact, low NaCl, prehypertensive Dahl S rats. Such Dahl S rats are genetically susceptible to NaCl hypertension but are normotensive on low NaCl. On .3% low NaCl, BP of 12 Dahl S rats averaged 138 mm Hg v 131 in 12 Dahl R rats (NS). Glomerular filtration rates under inactin anesthesia were measured during two 20-minute periods before a 20-minute amino acid infusion and also during three 20-minute periods after the amino acid infusion. Before the amino acid infusion, GFRs averaged 3.3 mL/min in S rats v 3.25 in R rats (NS). After the amino acid infusion, R rats showed a progressive rise in GFR: 4.7, 5.1 and 5.4 in three successive 20-minute periods. In these same three periods after amino acids, the S rats had GFRs of 3.8, 3.8, and 3.8. Thus R rats had an 81% increase of GFR after amino acids, whereas S rats increased only 18%, a 78% lower increase, P less than .001. The R rats had the normal rise of GFR in response to an amino acid load. Prehypertensive S rats had virtually no increase in GFR after the amino acid infusion. Even though both S & R rats had BPs well within the normal range, the ability to increase GFR after amino acid infusion was markedly impaired in prehypertensive S rats. This defect could possibly be used to predict future hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1989

Atherosclerotic cholesterol ester deposition is markedly reduced with a high-potassium diet.

In a normal rat on a normal diet, no cholesterol esters are detected in the aorta by gas chromatography. Stroke-prone spontaneously hypertensive rats (SHR) were fed for 3 months a basic diet containing 4% cholesterol, 14% coconut oil and 7% NaCl. One group of 13 rats ingested a normal (0.5%) level of potassium in the diet. Another group of 10 rats ingested a high (2.1%) potassium level. Mean intra-arterial blood pressures averaged 165 mmHg in the normal-potassium group and 161 mmHg in the high-potassium group (NS). Serum cholesterol levels averaged 229 mg/dl in the normal-potassium group and 214 mg/dl in the high-potassium group (NS). Total aortic cholesterol esters per rat involving 16- and 18-carbon chain fatty acids averaged 187 micrograms in normal-potassium rats versus 68 micrograms in high-potassium rats. These were the main esters; other esters were negligible. Thus, the high-potassium diet reduced cholesterol ester deposits by 64% (P less than 0.0003), even though blood pressures and cholesterol levels were quite similar in the two groups. Both high cholesterol and high blood pressure injure endothelial cells and increase the invasion of macrophages and vascular smooth muscle cells into the intima; they also increase endothelial permeability to proteins. With high plasma cholesterol levels, these processes lead to atherosclerosis with cholesterol ester deposition. The high-potassium diet, by protecting endothelial cells, can greatly decrease this cholesterol ester deposition. This effect could be useful for preventing heart attacks and sudden coronary death in human hypertension.

Animals↗
PubMed1989

Molecular biology of rotaviruses. VIII. Quantitative analysis of regulation of gene expression during virus replication.

A sensitive and quantitative solution hybridization assay recently developed in this laboratory has been applied to the study of the regulation of viral gene expression in rotavirus-infected cells. Measurement of the cumulative level of viral plus-strand (mRNA) synthesis at hourly intervals throughout the growth cycle has provided evidence for both quantitative and qualitative regulation of transcription. Qualitative control was found only when cycloheximide was used to block protein synthesis in infected cells, when transcription of four of the viral genes (genes 5, 6, 7, and 9) was independent of protein synthesis. Quantitative regulation was demonstrated by the accumulation of mRNA to much higher levels for some of the viral genes (e.g., genes 2 and 7) relative to others (e.g., genes 4 and 6). In addition to quantitative control at the level of transcription, measurement of the relative molar amounts of the various viral proteins at 6.5 h postinfection showed that their levels did not directly reflect those of their encoding RNAs, indicating the existence of translational control of gene expression in the rotavirus system. Analysis of the levels of minus strand synthesized for each viral gene showed that they were not all accumulated to the same level. The significance of this result in the light of the presumed similarities in replication strategy to that of the mammalian reoviruses is discussed.

Animals↗
PubMed1989

Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis.

In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.

Adult↗
PubMed1989

How is the NaCl signal transmitted in NaCl-induced hypertension?

Is the NaCl signal perceived as a small increase in the concentration of NaCl in extracellular fluid? We used 8 g NaCl/100 g soluble nutrients and fed only a hypertonic (1.4% NaCl) or a hypotonic (0.45% NaCl) drink to Dahl salt-sensitive (DS) rats. After 12 weeks, 11 rats receiving the hypertonic drink had a mean blood pressure of 195 mm Hg versus 195 mm Hg in 12 rats receiving the hypotonic drink. Thus, the high-NaCl signal seems unrelated to a higher NaCl concentration in extracellular fluid, thereby suggesting volume signals. Most volume controls are near the third brain ventricle (3V). As a working hypothesis, high dietary NaCl may swell the tissues surrounding 3V, which is slitlike. Such swelling would partially close the upper part of the slit and cause ependymal cells and nerve fibers on opposite walls to touch, possibly leading to hypertension in susceptible humans or rats. To test this, we stereotaxically blocked the aqueduct with inert silicone to produce hydrocephalus of 3V in DS rats and thus prevent ependymal cells and nerve fibers from touching. After blocking or sham-blocking the aqueduct, either a 6% NaCl diet or a 0.23% NaCl diet was started. Intra-arterial blood pressure was taken after 6 weeks. A group of 28 sham-blocked rats and a group of 29 blocked rats, all fed a 0.23% low NaCl diet, had equal blood pressures averaging 130 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗