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Biomedical subjects

J John

Publications and source records attributed to J John.

At least 55 records · Page 3Linked to original sources
PubMed1998

cis-Active elements of Friend spleen focus-forming virus: from disease induction to disease prevention.

The polycythemic strain of the Friend spleen focus-forming virus (SFFVp) is a replication-defective, acutely transforming retrovirus inducing a bistage erythroleukemia in susceptible mice. The first stage of the disease is an acute polyclonal erythroblastosis induced by the proliferation-promoting effect of gp55. gp55 is expressed from a spliced subgenomic message of SFFVp and stimulates the cellular receptor for erythropoietin. Using a selectable SFFVp that otherwise mimics the specificity of the disease, we demonstrate that the kinetics of the polyclonal expansion depends on the transcriptional strength of the retroviral cis-active elements. By exchanging gp55 for apathogenic genes, we show that SFFVp enhancer and splice signals can be successfully utilized for the development of retroviral vectors mediating very efficient transgene expression in hematopoietic cells. Apathogenic selectable SFFVp-based vectors carrying distinct enhancer alterations are a valuable tool to analyze transcriptional control of leukemia viruses in the absence of oncogenic proteins. Moreover they might have therapeutic potential.

Animals↗
PubMed1998

Appendicitis among African patients at King Edward VIII Hospital, Durban, South Africa: a review.

This retrospective study of 645 black patients, carried out over a five year period, showed that appendicitis is twice as common in males as in females and that it occurs predominantly in young people (median age 20 years). The classical presentation of periumbilical pain (16%) was outnumbered by right iliac fossa pain (36%) and non-specific pain (27%). The majority perforated (43%) and appendiceal inflammation was second commonest (37%). The negative appendicectomy rate was 8.8% and there was a diagnostic error of 14%. Mortality was two per cent mainly from patients complicated by peritonitis. Hospital stay was 7 +/- 7 days, with the longest stay following peritonitis. A diagnosis of appendicitis should always be entertained in an African patient presenting with an acute abdomen and, where the diagnosis is in doubt, a laparotomy should be performed.

Adolescent↗
PubMed1998

Hepatitis A virus: declining seroprevalence in children and adolescents in Southeast Asia.

The prevalence of hepatitis A virus (HAV) in a country largely reflects its standards of hygiene and socioeconomic conditions. Countries which undergo socioeconomic development show major change in HAV prevalence from high to low endemicity, and this is largely reflected in patterns of age-related seroprevalence. This paper presents age-related HAV seroprevalence patterns of SE Asian countries, and highlights how these patterns have changed over recent decades. Singapore, Thailand and Malaysia have experienced a decline in childhood and adolescent HAV seroprevalence, typical of countries which undergo socioeconomic development. By contrast, India has remained a country of high endemicity, with almost universal seroconversion in childhood. The Philippines and Vietnam show age-related seroprevalence patterns typical of high to moderate endemicity, while Indonesia shows significant regional variation in HAV seroprevalence. Populations within countries which exhibit major improvements in endemicity and age related HAV seroprevalence patterns are at risk of HAV epidemics, and a paradoxical increase in incidence tends to occur as seroconversion shifts from children to adults. The residents of these countries, a significant number of whom are at-risk, would benefit from a program of vaccination, as would non-infected individuals visiting high-risk areas.

Adolescent↗
PubMed1998

Frozen shoulder--an algoneurodystrophic process?

The frozen shoulder syndrome and the Sudeck syndrome are clinically in many aspects similar. Radioisotope bone scan shows an increased uptake in the affected areas in both diseases, while standard radiographs show a progressive demineralization. With measurement of bone-mineral density by quantitative digital radiography these local decalcification processes were diagnosed in an early stage of the frozen shoulder syndrome: of 12 patients with primary frozen shoulder 10 had a bone-mineral density decrease of more than 21% in the humeral head of the affected shoulder compared to the unaffected side. In the control groups (n = 32) the difference between affected and unaffected side (left and right humerus of the healthy probands) was in only one case each above 21%. There are several indications in the literature assuming the frozen shoulder to be an algoneurodystrophic process. Our observation supports this hypothesis, and may possibly lead to earlier diagnosis and improved therapeutic management.

Bone Density↗
PubMed1997

[Income, health, and health services utilization in Germany 1992].

Data from the 1992 wave of the Socioeconomic Panel were used to analyse the relation between incomes, need for and utilisation of health care in East- and West Germany employing methods coming from the economic measurement of income distributions. "Self assessed health" and "restricted activities of daily living" were employed as need indicators. Utilisation was measured by the number of "visits to physicians" and "days in hospital". Data was available for 6435 individuals (west) and 3928 individuals (east). Income was defined as equivalent net household income with an equivalence scale derived from the german social assistance program. Compared to the concentration of income all variables in the scope of this study were only marginally concentrated (i.e. equally distributed). A slight concentration of need amongst the lower income was overcompensated by utilisation. Thus a very small impact of the German health care system favouring lower income individuals was measured. The study shows methodological problems when combining data from regions with strongly different income levels instead of analysing them separately. A combined analysis tends to underestimate concentration.

Activities of Daily Living↗
PubMed1997

Pulmonary clearance of 99mTc-DTPA in experimental surfactant dysfunction treated with surfactant instillation.

BACKGROUND: Breakdown of the alveolo-capillary barrier is a characteristic feature of respiratory distress syndrome. Restoration of alveolo-capillary barrier function may be an important aspect of surfactant replacement therapy. We examined the effect of surfactant instillation on alveolo-capillary barrier function in an experimental model of surfactant dysfunction by measuring pulmonary clearance of 99mTc-DTPA. METHODS: Nineteen rabbits were tracheotomized and mechanically ventilated. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Detergent was given to 13 rabbits; seven rabbits were then treated with instillation of natural surfactant, whereas six rabbits received saline. Six rabbits were used as untreated controls. An aerosol of 99mTc-DTPA was administered to all animals and the pulmonary clearance was measured with a gamma camera. RESULTS: 99mTc-DTPA cleared from the lungs with a half-life of 71 +/- 22 min in the control animals, 21.4 +/- 7.4 min in the surfactant-treated animals and 5.8 +/- 1.5 min in the saline-treated animals. The difference in half-life between groups was highly significant (P < 0.001). There was no change in arterial oxygenation or compliance in controls or in animals treated with saline. In animals treated with surfactant, a small transient reduction in arterial oxygen tension and a more long-standing reduction in compliance were observed. CONCLUSION: Surfactant treatment thus significantly attenuated the effect of detergent treatment but did not restore alveolo-capillary transfer of 99mTc-DTPA to normal.

Animals↗
PubMed1997

Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion.

Reexpansion of collapsed lung creates intrapulmonary shear forces. In an earlier study we showed that application of a negative end-expiratory airway pressure (NEEP) to normal rabbit lungs in vivo produced tidal collapse and reexpansion with transient changes in compliance and gas exchange but no histologic damage. In the present study we examined NEEP in a model of surfactant perturbation produced by an inhaled aerosol of 2% and 5% dioctyl sodium sulfosuccinate (DOSS). DOSS increased alveolocapillary permeability without affecting compliance or oxygenation. Repeated collapse and reexpansion (RECOREX), caused by NEEP for 3 h was compared with ventilation with positive-end expiratory pressure (PEEP). Groups ventilated with PEEP maintained normal lung mechanics and morphology even if pretreated with DOSS. NEEP disturbed lung mechanics and gas exchange with persistent dose-related histologic damage in animals pretreated with DOSS. Lungs subjected to NEEP without DOSS had normal morphology. We conclude that perturbation of the surfactant system makes lungs vulnerable to injury by RECOREX. The combination of DOSS and NEEP might lead to leakage of plasma proteins into alveoli, causing inactivation of surfactants and increased shear forces with resulting lung damage. Similar mechanisms may accelerate lung damage in the respiratory distress syndrome.

Animals↗
PubMed1997

Additive nature of distension and surfactant perturbation on alveolocapillary permeability.

The aim of this study was to determine whether the effects of alveolar distention and surfactant dysfunction on alveolocapillary barrier function are different and additive. Pulmonary clearance of aerosolized technetium-99m-labelled human serum albumin (99mTc-HSA) was used to characterize barrier function after perturbing the surfactant system with the detergent dioctyl sodium sulphosuccinate either singly or in combination with large tidal volume ventilation (LTVV). Clearance was measured for 3 h (Experimental ventilation) in four groups (n = 6 each) of rabbits: 1) Controls; 2) Detergent; 3) LTVV; and 4) Detergent + LTVV. Restoration of clearance (Recovery) was studied for 3 h under conventional ventilation. The half-life of clearance (t 1/2) decreased during LTVV (305 min) compared to 1,055 min in Controls. Detergent induced a biexponential clearance with slow (t 1/2S) and fast (t 1/2F) half-lives of 670 and 15.4 min, respectively. The fast fraction (fF) was 0.20. Clearance in the Detergent + LTVV group was also biexponential. The t 1/2F and fF were similar to the Detergent group. The t 1/2S was similar to the LTVV group. The fF in this group increased to 0.36 during Recovery (p < 0.01 versus Detergent group and p < 0.05 versus Experimental ventilation). The diverse kinetics of clearance during large tidal volume ventilation and surfactant dysfunction suggest the presence of different mechanisms affecting the barrier. The mechanisms have additive characteristics, which superimpose to produce lung injury.

Aerosols↗
PubMed1997

Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs.

The reason why some infants with respiratory distress syndrome fail to respond to surfactant, or respond only transiently, is incompletely understood. We hypothesized that resuscitation with large breaths at birth might damage the lungs and blunt the effect of surfactant. Five pairs of lamb siblings were delivered by cesarean section at 127-128 d of gestation. One lamb in each pair was randomly selected to receive six manual inflations of 35-40 mL/kg ("bagging") before the start of mechanical ventilation, a volume roughly corresponding to the inspiratory capacity of lamb lungs after prophylactic surfactant supplementation. Both siblings were given rescue porcine surfactant, 200 mg/kg, at 30 min of age. Blood gases and deflation pressure-volume (P-V) curves of the respiratory system were recorded until the lambs were killed at 4 h. The P-V curves became steeper after surfactant in the control group, but no such effect was seen in those subjected to bagging. At 4 h, inspiratory capacity and maximal deflation compliance were almost three times higher (p < 0.01) in the controls than in the bagged lambs. The latter were also more difficult to ventilate and tended to have less well expanded alveoli and more widespread lung injury in histologic sections. We conclude that a few inflations with volumes that are probably harmless in other circumstances might, when forced into the surfactant-deficient lung immediately at birth, compromise the effect of subsequent surfactant rescue treatment. Our findings challenge current neonatal resuscitation practice of rapidly establishing a normal lung volume by vigorous manual ventilation.

Animals↗
PubMed1996

A glass fiber/diethylaminoethyl double filter binding assay that measures apoptotic internucleosomal DNA fragmentation.

A filter binding assay that measures internucleosomal DNA fragmentation associated with apoptosis is described. The assay is based on a novel principle that consists of using simultaneously two kinds of glass fiber filters to harvest [3H]thymidine-prelabeled cells following their incubation with inducers of apoptosis. One filter, which is neutral, traps intact chromatin and high-molecular-weight DNA. The other filter, which is positively charged with DEAE active groups, traps low-molecular-weight DNA fragments. DNA fragmentation is quantified by measuring the radioactivity retained by each of the filters. The assay was evaluated with the histiocytic lymphoma cell line U937 and the topoisomerase inhibitors camptothecin, etoposide, and doxorubicin. These agents caused a dose-dependent decrease of radioactivity in the neutral filter and a parallel increase of radioactivity in the DEAE filter. Irradiation-induced single strand breaks and topoisomerase-mediated primary DNA damage were not detected by this method. Consistent with the detection of internucleosomal DNA fragmentation, the effects measured by this assay were prevented by the endonuclease inhibitor zinc acetate and by the metabolic inhibitor sodium azide. Results obtained using this assay were validated by observation of DNA ladders on agarose gels and by morphologic examination of apoptotic features. Evaluation of the assay in a mock screen demonstrated that the introduction of the DEAE filter increases the assay sensitivity and eliminates false positives. Thus, this assay may be used in high-throughput screening approaches to discover novel modulators of apoptosis.

Antineoplastic Agents↗
PubMed1996

Male sexual behaviour not abolished after medial preoptic lesion in adult rats.

N-methyl-D-aspartic acid (NMDA) was injected into the medial preoptic area (mPOA) of 10 rats to destroy the neurones in this region. Male sexual behaviour was scored before, and on days 2, 6, 10, 17, 24 and 31 after the administration of NMDA. The neurones in the injection site were destroyed in all the rats, but male sexual behaviour was only transiently reduced in the animals with lesions largely restricted to the mPOA. These findings are in contrast to the earlier reports of permanent suppression of sexual behaviour after electrolytic lesion, with damage to the neurones and fibres of passage. The present study shows that the mating behaviour could be expressed even after the destruction of the neurones in the mPOA.

Animals↗
PubMed1996

Magnetic resonance imaging of NMDA-induced lesion of the medial preoptic area and changes in sleep, temperature and sex behaviour.

Destruction of the medial preoptic area (mPOA) neurons of rat brain, induced by intracerebral injection of N-methyl D-aspartic acid (NMDA), has been studied by employing the non-invasive Magnetic Resonance Imaging (MRI) technique. Changes in the MRI images are compared and correlated with the functional changes after the mPOA lesion. The progress of the lesion at the injected site has been monitored (using MRI) from 15 min to 1 month after the stereotaxic microinfusion of NMDA (5 micrograms in 0.2 microliter). This study shows that the localised hyperintense (bright) area starts appearing at the mPOA from 3 h after NMDA injection, and the brightness increases progressively for about 2 days. The size and brightness of hyperintense area decrease thereafter. It has not been possible to locate the lesion site after 3 days, using MRI, except in one rat where a vacuole-like area was seen at the NMDA injected site on postmortem histological examination. The reduction in sleep after the mPOA lesion does not show any correlation with the changes in MRI, as it persists throughout the 3 weeks of recording. On the other hand, the initial drastic reduction in male sex behaviour and the increase in body temperature correlated to some extent with the increased brightness in MRI at the site of lesion. The size and location of the hyperintense area, observed during the first 2 days, match with the lesioned area which was histologically identified after 1 month of NMDA administration. Control administration of normal saline into the mPOA did not produce any alteration in the brightness of the MRI image and practically no loss of neurons at the injected site. Though some functional changes have correlation with the alteration in MRI, this cannot be used to interpret the changes in all the physiological parameters. This study also demonstrates that the disappearance of the brightness in MRI should not be taken to indicate a positive prognosis. Though the lesion could not be seen in MRI within 2 hours, its detection after 3-4 h (but within 3 days) after NMDA lesion would give very valuable information for long term studies.

Animals↗
PubMed1996

Magnetic resonance imaging of temporal changes of neurotoxic lesion in the rat.

Destruction of striatal neurons in the rat brain, induced by intracerebral injection of N-methyl D-aspartic acid (NMDA), has been visualized noninvasively by magnetic resonance imaging (MRI). The changes in images were monitored from 12 h to one month after the stereotaxic microinfusion of NMDA (10 micrograms in 0.4 microliter) into the striatum, using a T2-weighted rapid acquisition by relaxation enhancement (RARE) sequence. A localised hyperintense (bright) area was visible after 12 h at the site of the injection, and it persisted for the next three days. The size of the hyperintense area decreased thereafter and, after one week, the increased brightness was restricted to the lateral ventricle. Post-mortem histological examination, done after one month, showed a dilated lateral ventricle. The size and location of the lesioned area, identified in histological sections, corresponded to the hyperintense area observed during these initial days after NMDA lesion. The present study demonstrates that noninvasive MRI techniques, using a typical RARE sequence, offer a powerful tool for the early detection of neurotoxic lesion of the brain area, although some caution is required in its use for estimating the size of the lesioned area three days after its formation. The present findings indicate that, in long-term studies, alterations of the neighbouring structures, such as enlargement of the ventricular system, may confound the MRI evaluation of neurotoxic lesions in vivo.

Animals↗
PubMed1996

Respiratory mechanics in rabbits ventilated with different tidal volumes.

Respiratory mechanics was studied in 11 rabbits at tidal volumes (VT) of 6.7, 10, and 20 ml/kg. Flow interruptions were performed during the full respiratory cycle. The viscoelastic pressure (Pve) was measured as the dynamic elastic pressure (Pel(dyn)) after flow cessation minus the static elastic pressure (Pel(st)). Static elastic and viscoelastic parameters were determined with numerical technique. Static hysteresis was minimal even at large VT. The Pel(st)-V curve was linear at small VT and in 6 animals at moderate VT. In 5 animals at moderate VT and in all animals at large VT, a linear segment with constant compliance was followed by a segment with decreasing compliance. The Pve-V curve could be described with a linear model only at small VT. A non-linear model was needed at increased VT. Compliance increased with VT. Both static and viscoelastic behaviours were linear up to larger volume ranges at large VT compared to moderate VT.

Animals↗
PubMed1996

Improved retroviral vectors for hematopoietic stem cell protection and in vivo selection.

Therapeutic gene transfer into hematopoietic cells is critically dependent on the evolution of methods that allow ex vivo expansion, high-frequency transduction, and selection of gene-modified long-term repopulating cells. Progress in this area needs elaboration of defined culture and transduction conditions for long-term repopulating cells and improvement of gene transfer systems. We have optimized retroviral vector constructions based on murine leukemia viruses (MuLV) to overcome the transcriptional repression encountered with the use of conventional Moloney MuLV (MoMuLV) vectors in early hematopoietic progenitor cells (HPC). Novel retroviral vectors, termed FMEV (for Friend-MCF/MESV hybrid vectors), were cloned that mediate greatly improved gene expression in the myeloerythroid compartment. Transfer of the selectable marker multidrug resistance 1 (mdr1), FMEV, in contrast to conventional MoMuLV-related vectors currently in use for clinical protocols, mediated background-free selectability of transduced human HPC in the presence of myeloablative doses of the cytostatic agent paclitaxel in vitro. Furthermore, FMEV also greatly improved chemo-protection of hematopoietic progenitor cells in a murine model system in vivo. Finally, when a second gene was transferred along with mdr1 in an FMEV-backbone, close to 100% coexpression was observed in multidrug-resistant colonies. These observations have significant consequences for a number of ongoing and planned gene therapy trials, for example, stem cell protection to reduce the myelotoxic side effects of anticancer chemotherapy, correction of inherited disorders involving hematopoietic cells, and antagonism of HIV infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Risk factors associated with vancomycin-resistant Enterococcus faecium infection or colonization in 145 matched case patients and control patients.

Risk factors and mortality associated with vancomycin-resistant Enterococcus faecium (VREF) infection or colonization were examined at a tertiary care hospital by comparing 145 patients who had VREF isolates (cases) to 145 patients with vancomycin-susceptible Enterococcus faecium (VSEF) isolates (controls). The number of deaths per 100 person-days of hospitalization after diagnosis did not differ significantly between VREF patients (1.2) and VSEF patients (0.8). Multivariate analyses found that the duration of hospitalization ( > or = 7 days), intrahospital transfer between floors, use of antimicrobials (i.e., vancomycin and third-generation cephalosporins), and duration of vancomycin use ( > or = 7 days) was independently associated with VREF infection or colonization. This study, which has a large sample size, confirms some earlier observations regarding risks for VREF infection or colonization and identifies factors that may be potentially exploited to develop interventional strategies for the control of this emerging nosocomial problem.

Adolescent↗
PubMed1996

Effect of detergent combined with large tidal volume ventilation on alveolocapillary permeability.

The combined effect of large tidal volume ventilation (LTVV) and detergent-induced surfactant dysfunction on the clearance kinetics of technetium-99m-labelled diethylene triamine pentaacetate was investigated. Four groups of rabbits (n = 6 in each) were studied: (1) controls, (2) detergent, (3) LTVV, and (4) detergent + LTVV. Clearance was measured for 3 h and the kinetics was analysed by fitting mono- and biexponential equations to the clearance curve and was expressed as a half-life (T 1/2). Pulmonary clearance of 99mTc-DTPA was monoexponential in control animals (T 1/2 = 194 min) and in animals ventilated with LTVV (T 1/2 = 43 min, P < 0.01 compared with controls). In contrast, clearance was biexponential after detergent administration with or without LTVV. T 1/2 values of the fast and slow compartments were 5.4 and 80 min, respectively, with the fast fraction comprising 81% of the radioactivity after detergent alone. When detergent was combined with LTVV, clearance was bicompartmental as with detergent alone, with the same size of the fast fraction. However, clearance from each of the slow (P < 0.01) and fast compartments (P < 0.05) increased significantly. Clearance from the slow compartment was thus similar to T 1/2 during LTVV alone. Large tidal volume ventilation induced a faster than normal clearance of a single compartment, whereas detergent induced kinetics that was distinctly bicompartmental. The mechanisms increasing permeability of the alveolocapillary barrier after detergent and during LTVV seem different and may be additive.

Aerosols↗