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Biomedical subjects

J Johnston

Publications and source records attributed to J Johnston.

At least 127 records · Page 7Linked to original sources
PubMed1993

Cloning and expression of the cDNA encoding mouse neutrophil gelatinase: demonstration of coordinate secondary granule protein gene expression during terminal neutrophil maturation.

The 92-kD form of human type IV collagenase (gelatinase) is a member of the matrix metalloproteinase family. It is restricted in its expression to the granulocytic lineage of white blood cells. Within neutrophils it resides in secondary granules, which are markers of terminal myeloid differentiation. We have isolated and sequenced the cDNA encoding the murine counterpart to the human 92-kD metalloproteinase from a macrophage cDNA library. The human and murine genes are highly homologous and exist in an identical form in neutrophils and monocyte-macrophages in both species. Two polyadenylation signals are present in the murine 3' untranslated sequence, accounting for equal expression of two messenger RNAs. We have shown that expression of gelatinase mRNA is controlled in a coordinate fashion together with lactoferrin, also a component of neutrophil secondary granules, and that this control occurs at the level of transcription. This is the first definitive demonstration of coordinate transcriptional regulation of secondary granule protein gene expression, a feature of normal myelopoiesis that is deranged in leukemogenesis.

Amino Acid Sequence↗
PubMed1993

Expression of HERV-K proviruses in human leukocytes.

HERV-K is a 50-copy, human endogenous, class 1 retroviral element that contains some polycistrons with gag, pol, and env open reading frames. Although expression of HERV-K proviruses has been shown in cultured human cell lines, expression of these elements has not been shown in human blood leukocytes. Using both reverse transcriptase-polymerase chain reaction and ribonuclease protection techniques, we show HERV-K pol gene expression in human blood leukocytes. Expression in blood leukocytes from 7 normal individuals was from a variety of different HERV-K proviruses, while restricted expression was observed in blood cells of 5 leukemia patients and 3 polycythemia vera patients. Evidence is presented suggesting that the restricted expression in leukemia blood cells is a result of gene regulation, not gene amplification.

Adult↗
PubMed1993

Communication, cognition, and social interaction in the Angelman syndrome.

Persons with Angelman syndrome (AS) have mental retardation, epilepsy, and a characteristic "puppet-like" gait. Behaviorally, they are distinctive because they have no speech and have excessive laughter. A speech and communication evaluation of 7 persons with AS was performed to provide improved understanding of the speech deficit. Assessments included prelanguage and language development, oral motor abilities, and cognitive and social interaction skills. Results indicate that the typical lack of speech may not be due to mental retardation alone. Oral motor dyspraxia, and deficits in social interaction and attention were characteristic of AS and contributed to the lack of speech.

Adult↗
PubMed1993

The relationship between serum cholesterol and serum thyroid hormones in male patients with suspected hypothyroidism.

The relationship between serum cholesterol, thyrotropin, thyroxine and triiodothyronine was investigated in 456 male patients with suspected hypothyroidism. The correlation between serum cholesterol and serum thyroxine (r = 0.0572) and between serum cholesterol and serum triiodothyronine (r = 0.1136) were not significant but the correlation between serum cholesterol and TSH (r = 0.0376) was significant (P < 0.001). The mean serum cholesterol was only significantly increased in the patient groups with a serum TSH greater than 20 mU/L. In 26 patients treated for hypothyroidism with thyroxine replacement there was a significant correlation between the decrease in serum cholesterol and the decrease in serum TSH (r = 0.5334, P < 0.01) but there was poor correlation between the decrease in cholesterol and either the increase in serum triiodothyronine or the increase in serum thyroxine.

Aged↗
PubMed1993

Nitrous oxide: your health not theirs.

At long last the Health and Safety Executive are introducing an occupational exposure standard for nitrous oxide, enflurane, halothane and isoflurane. Fifteen years ago (1977) the National Institute of Occupational Safety and Health in the United States set a threshold limit for nitrous oxide at 25 parts per million (ppm) for an eight hour exposure. On the 1st January 1994 the British standard for nitrous oxide through the Health and Safety Executive will be 100 ppm for an eight hour exposure, four times higher than the American standard.

Humans↗
PubMed1993

Opposite response to starvation of Trp/LNAA ratio in lean and obese Zucker rats.

Total blood and plasma free amino acids and plasma urea levels were studied in fed and 24 h fasted Zucker rats. In fed animals there were no differences between obese and lean rats in the overall essential and non essential blood free amino acids. However, starvation reduced blood amino acid levels in the obese animals compared to the lean group, mainly due to changes in the plasma compartment. The reduction of available amino acids from plasma in the obese rats during starvation affected most of the amino acids, including the branched chain amino acids, which showed higher levels in the fed situation than in lean rats. Of particular interest is the opposite response to starvation in lean and obese Zucker rats concerning the plasma ratio of tryptophan (Trp) to the large neutral amino acids (LNAA) which could be implicated in the alteration of food intake and energy expenditure characteristic of obesity.

Amino Acids↗
PubMed1992

A comparative study of intramuscular ketorolac and pethidine in labour pain.

A single dose block randomised double-blind study comparing intramuscular ketorolac, 50 mg of pethidine and 100 mg pethidine was carried out in multiparous women. Pain intensity and sedation effect were recorded at inclusion to the study, half hourly for the first 2 h, then hourly until 6 h after delivery. Maternal and neonatal side effects were noted including the Apgar scores and the baby's requirements for resuscitation. All three treatments are relatively ineffective in relieving labour pain. There was no difference in the analgesic efficacy between the two doses of pethidine but both doses of pethidine were statistically more effective compared with ketorolac. There was no difference in the retrospective assessment of the three groups or when comparison was made with the previous labour. A similar number of patients required further analgesia in each group. In all three groups, no adverse effect occurred in the mother or fetus. Maternal sedation and fetal depression were statistically less in the ketorolac group. Although ketorolac had inferior analgesic effect, its use was not associated with clinically significant sequelae and it showed a superior safety profile compared with either dose of pethidine. The study was not powerful enough to detect a difference between 50 mg and 100 mg of pethidine.

Adolescent↗
PubMed1992

Zidovudine serum, cerebrospinal fluid, and brain concentrations following chronic administration of a new zidovudine formulation via an implantable pump in dogs [corrected].

Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 28-day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (%CV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brain:serum AZT concentration ratios were 0.126 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state greater than 1 microM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy.

Animals↗
PubMed1992

Interferon-induced reversible acute renal failure with nephrotic syndrome.

Although there has been considerable experience with interferons in clinical trials during the past decade, acute renal failure as a side effect of interferon treatments has rarely been reported. We report a case in which acute renal failure with nephrotic syndrome was associated with therapy with two types of interferons. We note incomplete return of renal function upon withdrawal of therapy.

Acute Kidney Injury↗
PubMed1992

Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor.

Transcobalamin I (TCI) is a vitamin B12 binding protein that is found in the secondary granules of mature neutrophils. The expression of the gene for TCI (TCN1) within neutrophils has been shown to be restricted to the later stages of myeloid development and can therefore be used as a marker for granulocyte differentiation. To study transcriptional control regions important in late stage myeloid gene regulation the genomic sequence for TCN1 has been cloned. Clones were isolated from a genomic library constructed in Charon 4A using homologous full-length cDNA probes. Southern blot analysis showed the gene to reside on five EcoRI fragments totaling 14 kb in length. Two overlapping phage clones, containing the entire 14 kb, were isolated and the introns and exons were mapped using Southern blotting and dideoxy sequencing of subclones. The cDNA is represented by nine exons contained within 12 kb of genomic DNA. Comparison of the genomic structure to gastric intrinsic factor (GIF), another vitamin B12 binding protein, revealed a strikingly similar intron/exon structure, with several positionally conserved splice sites. The gene was localized to chromosome 11 using in situ hybridization.

Amino Acid Sequence↗
PubMed1992

Cardiac transplantation in early infancy.

Congenital heart disease (CHD) encompasses a full spectrum of severity, ranging from physiologically insignificant (those lesions ameliorated over time without surgical or medical intervention) to those lesions that result in certain death in early infancy. Recent attempts at heart and heart-lung transplantation and surgical palliation have provided options for families of infants at the deadly end of this spectrum. The purpose of this article is to outline the process of one form of intervention--heart replacement during early infancy. The main concerns following transplantation are rejection and infection, but survival rates after transplantation show a good 5-year prognosis in this young age group.

Critical Care↗
PubMed1992

The effect of an educational intervention on the use of peri-operative antimicrobial agents.

The objective of this study was to evaluate the effect of an educational intervention on the prescribing behaviour of doctors who order antimicrobial therapy for patients undergoing abdominal surgery. Two confidential criterion audits were separated by the intervention which involved completion of a 10-item questionnaire followed by a fully referenced answer sheet. The results showed a significant improvement in the prescribing habits of the junior surgical staff after the educational intervention. The overall error rate decreased from 50% to 20% (P = 0.003).

Abdomen↗
PubMed1991

Altered blood amino acid distribution in genetically obese mice.

The present study was undertaken to determine whether the alteration in amino acid distribution between the plasma and cellular compartment of the blood, previously described in dietary-obese rats, also occurs in genetically obese mice. The blood concentration of individual amino acids and its distribution between plasma and cells of lean and genetically obese mice (ob/ob) have been measured. The results demonstrated that genetically obese mice showed a decrease (55%, P = 0.0489) of free amino acids in the blood cells. Most amino acids were affected and among the most noteworthy characteristics was the observation that the reduction in concentration was more pronounced for the total concentration of the essential amino acids which was reduced by 76% (P = 0.0112) compared to cells of lean mice. These results suggest that an altered amino acid distribution between plasma and blood cells is a consequence of both diet-induced and genetic obesities.

Amino Acids↗
PubMed1991

Effects of endurance training on baroreflex sensitivity and blood pressure in borderline hypertension.

Physical training offers a potential nonpharmacological strategy for control of mild and borderline hypertension, but its effect on blood pressure is controversial. We investigated the effects of endurance training on waking and sleeping blood pressure and on baroreflex sensitivity in 16 borderline hypertensive patients. First, 8 patients were assessed before and after a 6-month endurance training programme. Then, when it was clear that blood pressures were lower after training, a further 8 patients were studied not only at the end of the training programme but also after 4 months' abstention from exercise (detraining). Measurements were taken of baroreflex sensitivity (response to iv phenylephrine), blood pressure, R-R interval, and blood pressure and R-R variability. Ambulatory blood pressures were measured in 13 patients (7 trained, 6 detrained) and sleep blood pressures in 6 patients (3 trained, 3 detrained). Increased fitness was associated with a decline in resting arterial blood pressure of 9.7 (SE 2.0) mm Hg systolic and 6.8 (1.2) mm Hg diastolic, and with a decline in ambulatory blood pressure of 4.8 (1.4) mm Hg and 7.5 (2.1) mm Hg, respectively; both p less than 0.05. Baroreflex sensitivity was 14.0 (1.8) ms/mm Hg in the unfit and 17.5 (2.0) ms/mm Hg in the fit; p less than 0.05. Sleep blood pressures were not lower in the fit despite longer sleep R-R intervals. These findings indicate that, in some subjects with borderline or mild hypertension, a physical training programme is sufficient to bring the blood pressure within normal limits.

Adult↗
PubMed1991

Phase II study of 2'-deoxycoformycin in patients with renal cell carcinoma. A National Cancer Institute of Canada Clinical Trials Group study.

The National Cancer Institute of Canada Clinical Trials Group undertook a phase II study of 2'-deoxycoformycin in patients with metastatic renal cell carcinoma. When 2'-deoxycoformycin 4 mg/m2 was administered intravenously weekly for three weeks then every two weeks no significant antitumor activity was noted in 19 evaluable patients. Toxic effects experienced were as expected, consisting primarily of nausea/vomiting, anorexia, and lethargy. It is concluded that 2'-deoxycoformycin at this dose and schedule has no clinical activity in the treatment of metastatic renal cell carcinoma.

Adult↗