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Biomedical subjects

J Lewis

Publications and source records attributed to J Lewis.

At least 289 records · Page 16Linked to original sources
PubMed1990

A nuclear protein that binds preferentially to methylated DNA in vitro may play a role in the inaccessibility of methylated CpGs in mammalian nuclei.

The effects of DNA methylation on gene expression and chromatin structure suggest the existence of a mechanism in the nucleus capable of distinguishing methylated and non-methylated sequences. We report the finding of a nuclear protein in several vertebrate tissues and cell lines that binds preferentially to methylated DNA in vitro. Its lack of sequence-specific requirements makes it potentially capable of binding to any methylated sequence in mammalian nuclei. An in vivo counterpart of these results is that methylated CpGs are inaccessible to nucleases within nuclei. In contrast, non-methylated CpG sites, located mainly at CpG islands, and restriction sites not containing this dinucleotide, are relatively accessible. The possibility that DNA methylation acts through binding to specific proteins that could alter chromatin structure is discussed.

Animals↗
PubMed1990

Ventilatory failure due to an improperly placed nasogastric tube.

A case is described of a 35-yr-old patient who was transferred to the operating room for the repair of a right ventricular laceration. Prior to transfer a nasogastric tube was placed unknowingly beyond the tracheal tube cuff into the trachea. During the surgery, the patient's head was turned to insert a central venous line at which time the ventilator low pressure alarm sounded and effective ventilation ceased. The problem was corrected by turning off the nasogastric tube suction. It is postulated that the nasogastric tube became unkinked when the head was turned and this led to the evacuation of gas from the lungs and breathing circuit through the nasogastric tube suction. Identification of the problem was complicated by the lack of a temporal relationship between the insertion and connection to suction of the nasogastric tube, and the episode of ventilatory failure.

Adult↗
PubMed1990

Epithelial autonomy in the development of the inner ear of a bird embryo.

The epithelium lining the inner ear contains a large number of differentiated cell types, arranged in precise patterns. Once the otocyst has closed, do the cells differentiate according to mechanisms intrinsic to the epithelium or are they dependent on external influences? In particular, are they governed by signals from the surrounding periotic mesenchyme? And is the closed structure of the inner ear or the otocyst fluid that it contains important for pattern formation and differentiation as it is for adult function? We have examined these questions by two types of grafting experiment. In the first, early (E3, stage 17-18, or E2, stage 13-14) undifferentiated quail otocysts were stripped of their mesenchyme and grafted into the wing buds of chick embryos. Although surrounded by a foreign mesenchyme the otic epithelium differentiated into the standard inner ear cell types. The gross morphology was abnormal, and the sensory hair cells were grouped into a few large patches instead of the usual eight smaller patches; locally, however, the spatial relationships between the differentiated cell types appeared normal. In the second experiment, open fragments of early undifferentiated otocyst (with some adhering mesenchyme) were grafted onto the surface of a limb bud. In this exposed in vivo situation, where the apical surface of the epithelium is bathed by amniotic fluid instead of otocyst fluid, differentiation proceeds normally also. Thus differentiation of inner ear epithelium at these stages does not require any specific influence from otic mesenchyme and proceeds independently of whether the otocyst is open or closed. Such epithelial autonomy creates special opportunities for in vitro analysis.

Animals↗
PubMed1990

Antikindling effects of locus coeruleus stimulation: mediation by ascending noradrenergic projections.

Electrical stimulation of the noradrenergic locus coeruleus (LC) delays the generalization of partial seizures during amygdaloid kindling by increasing the time spent in the earliest stages of seizure development. To determine whether noradrenergic axons projecting to the midbrain and forebrain are involved in this antikindling effect, we examined the effects of lesions of the dorsal noradrenergic bundle, induced by intracerebral infusions of 6-hydroxydopamine (6-OHDA), on kindling and the antikindling action of stimulation of the LC. Stimulation of the LC during amygdaloid kindling increased the number of afterdischarges (ADs) spent in the early stages of partial seizure and decreased the number of ADs spent in later stages of generalized seizure, as has been described previously. LC-stimulated rats also displayed longer durations of AD during early stages of kindling. The antikindling effect of LC stimulation was blocked by lesions of the dorsal bundle, whereas the facilitatory effects of LC stimulation on generalization and on the duration of AD were unaffected by the lesions. These results suggest that the antikindling action of LC stimulation is mediated by the ascending projections of noradrenergic neurons, presumably through enhanced release of noradrenaline. On the other hand, the facilitatory effects of LC stimulation on the development of later stages of seizure and on the duration of AD appear to be independent of the ascending dorsal bundle.

Afferent Pathways↗
PubMed1990

Sociodemographic and health factors in the well-being of homeless men in Sydney, Australia.

Throughout the world, homelessness is generally increasing. This paper examines some of the historical precedents and, in an Australian sample, some of the factors leading to ill-health in this group. All studies have shown the ill-effects on health of being homeless and in this group drinking alcohol and length of time on skidrow appear to be the major factors. It is also suggested that the homeless are generally from comparatively disadvantaged backgrounds before becoming homeless, and more likely to be migrants. They were also less likely to have ever married and more likely to have been in jail or psychiatric institutions.

Alcoholism↗
PubMed1990

Serum levels of methadone in maintenance clients who persist in illicit drug use.

This study examined pharmacological factors contributing to persisting drug abuse by methadone maintenance clients. Three groups of clients, drawn from one treatment programme, were studied: persistent heroin users, persistent benzodiazepine users, and control subjects who were not using illicit drugs in addition to methadone. Persistent abusers mostly had high trough serum methadone levels, and their ongoing drug use appears to reflect a preference for a different drug effect rather than inadequate methadone dose. Several clients did have the expectation that methadone should prevent them from using other drugs; such expectations may diminish the effectiveness of treatment.

Anti-Anxiety Agents↗
PubMed1990

Surfactant treatments alter endogenous surfactant metabolism in rabbit lungs.

The effect of exogenous surfactant on endogenous surfactant metabolism was evaluated using a single-lobe treatment strategy to compare effects of treated with untreated lung within the same rabbit. Natural rabbit surfactant, Survanta, or 0.45% NaCl was injected into the left main stem bronchus by use of a Swan-Ganz catheter. Radio-labeled palmitic acid was then given by intravascular injection at two times after surfactant treatment, and the ratios of label incorporation and secretion in the left lower lobe to label incorporation and secretion in the right lung were compared. The treatment procedure resulted in a reasonably uniform surfactant distribution and did not disrupt lobar pulmonary blood flow. Natural rabbit surfactant increased incorporation of palmitate into saturated phosphatidylcholine (Sat PC) approximately 2-fold (P less than 0.01), and secretion of labeled Sat PC increased approximately 2.5-fold in the surfactant-treated left lower lobe relative to the right lung (P less than 0.01). Although Survanta did not alter incorporation, it did increase secretion but not to the same extent as rabbit surfactant (P less than 0.01). Alteration of endogenous surfactant Sat PC metabolism in vivo by surfactant treatments was different from that which would have been predicted by previous in vitro studies.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1990

Axial anterior chamber depth after trabeculectomy.

Trabeculectomy was performed on 14 consecutive phakic eyes, and measurements of axial anterior chamber depth were taken preoperatively and on postoperative days 1, 2, 3, 6 and 14. The mean maximal change in anterior chamber depth occurred on the 1st postoperative day, while the anterior chamber reached its shallowest state on the 2nd postoperative day. No significant change in mean anterior chamber depth occurred on successive visits from postoperative day 1 through 14. The anterior chamber approached the preoperative level by postoperative day 14. Because reformation of anterior chamber after trabeculectomy takes about 2 weeks, close observation is essential when marked shallowing occurs early.

Adolescent↗
PubMed1990

Retinoic acid modulation of the early development of the inner ear is associated with the control of c-fos expression.

The effects of retinoic acid (RA) on the early development of the inner ear were studied in vitro using isolated chick embryo vesicles. Low concentrations of RA (1-50 nM) inhibited vesicular growth in stage 18 otic vesicles that were made quiescent and then reactivated by either serum or bombesin. Growth inhibition was concentration-dependent and was paralleled by a reduction in the rate of DNA synthesis as measured by [3H]thymidine incorporation. Half-inhibition occurred between 1 and 10 nM RA, and the full effect at 20 nM. Retinoic acid, in the presence of serum, induced the precocious differentiation of (1) secretory epithelium, the tegmentum vasculosum and endolymphatic sac and (2) early sensory and supporting epithelia. These structures were positioned in their corresponding normal presumptive areas. The overall direction of growth was reversed by RA and the ratio of the internal to the external vesicular surface area increased with RA concentration. The expression of the nuclear proto-oncogene c-fos in the developing otic vesicle was transient and stage-dependent. High levels of c-fos mRNA were positively correlated with cell proliferation. Incubation of growth-arrested otic vesicles with bombesin plus insulin at concentrations that induced cell proliferation produced a strong induction of c-fos. This mitogen-induced expression was suppressed by 25 nM RA. The results suggest (1) a role for retinoic acid in controlling the early development of the inner ear and (2) that this control is effected through the regulation of the proto-oncogene c-fos.

Animals↗
PubMed1990

Traumatic haemarthrosis causing femoral head subluxation.

We report seven children in whom traumatic haemarthrosis of the hip had produced lateral subluxation of the femoral head, which is different from the apparent displacement seen in Perthes' disease. In all seven cases, aspiration of the haemarthrosis allowed reduction of the femoral head, and follow-up for a mean of 14 months revealed no evidence of avascular necrosis of the proximal femoral epiphysis. Traumatic haemarthrosis of the hip in children appears to be a clinical entity which can produce femoral head subluxation. Aspiration and traction is the treatment of choice and can cure the condition.

Child, Preschool↗
PubMed1990

Fibrin formation inhibits the in vitro cytotoxic activity of human natural and lymphokine-activated killer cells.

The biological significance of the interaction of the haemostatic factors with tumour cells remains unclear. It has been hypothesized that fibrin deposition around tumour cells could help those cells to escape destruction by cytotoxic effector cells. To obtain direct evidence in support of this possibility, the effect of fibrin formation on in vitro cytotoxicity of human natural killer (NK) or lymphokine-activated killer (LAK) cells was investigated by comparing their cytotoxic activity with various human tumour cell lines in the presence of human serum or plasma. The data demonstrate that pre-incubation of human tumour cells with plasma, but not serum, substantially diminished or completely abrogated the cytotoxic effects of these killer cells. This was shown to be due to fibrin formation. The degree of coagulation and the number of radioactive tumour cells trapped in the clot correlated with the extent of inhibition of NK or LAK cytotoxicity. Abrogation of LAK activity was also observed when the effector cells were pre-exposed to plasma or when effector and target cells were simultaneously mixed with plasma and trapped in a fibrin clot. Similar results were obtained when, instead of whole plasma, the cytotoxic effect of LAK and NK cells was studied in the presence of fibrinogen and thrombin. When heparin was added, fibrin formation was prevented and no inhibition of LAK/NK cell cytotoxicity was observed. In studies of the mechanisms of inhibition of LAK cell activity by fibrin, target - effector cell conjugate formation was found to be blocked. When plasma was added post-binding (15-30 min after mixing effector and target cells) although coagulation occurred, no effect on cytotoxicity was observed, supporting the conclusion that fibrin interfered with binding rather than the lytic phase of cytotoxic cell activity. Thus, the present data demonstrate that fibrin deposition around tumour and/or effector cells can protect tumour cells from immune destruction and diminish the efficiency of the cytotoxic LAK/NK cells.

Blood Coagulation↗
PubMed1989

Metabolism of intratracheally administered unsaturated phosphatidylcholines in adult rabbits.

Twenty-five adult rabbits were each injected intratracheally with a solution containing 1-palmitoyl-2-[3H]palmitoyl phosphatidylcholine (DPPC) and 1-palmitoyl-2-[14C]oleoyl-PC that had been associated with with 32P-labeled natural rabbit surfactant. The animals were killed in groups of 5 at 1, 4, 8, 15 and 24 h after isotope injection. Isotope recovery and PC specific activities were measured in alveolar washes, lung homogenates, lamellar bodies and microsomes. The percent clearance per h of PC was very similar for the three labels and were; 3.56, 3.44 and 3.00%, respectively, for the 3H-, 14C- and 32P-labeled PC in the total lung (alveolar wash plus lung homogenate) and 3.84, 3.79 and 3.70%, respectively, for alveolar wash alone. The intracellular pathways of the three labels were assessed by comparing the specific activities in the lamellar bodies over 24 h as well as comparing the ratios of lamellar body to microsome specific activities over this period. These ratios were very similar for the monoenoic and saturated PC labels over time, indicating comparable recycling. In a separate experiment, three other unsaturated species; 1,2-[14C]dioleoyl-PC, 1-palmitoyl-2-[14C]linoleoyl-PC, and 1-palmitoyl-2-[14C]arachidonyl-PC were compared to 1-palmitoyl-2-[14C]oleoyl-PC. Recovery in the alveolar wash and total lung were similar at 16 h for all four labeled phospholipids. The intracellular pathways were also similar, except for the arachidonyl compound. More relative to the lamellar bodies as compared to the other. Thus, the catabolic pathways were similar for the saturated and unsaturated PC species initially present in the airspaces. The only metabolic difference between the compounds appears to be in the intracellular handling of the arachidonic species.

1,2-Dipalmitoylphosphatidylcholine↗