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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 415 records · Page 23Linked to original sources

Differences in morphology, growth rate, and protein synthesis between cultured arterial and venous endothelial cells.

Intrinsic differences between aortic and venous endothelial cells were demonstrated by studies of morphology, growth rates, and protein synthesis. Endothelial cells from bovine thoracic aortas (AECs) and inferior vena caval (VECs) were harvested, maintained in cell culture, and characterized. VECs were consistently larger (mean cell diameter 14.3 micron vs 12.7 micron; p less than 0.001) and more pleomorphic than were AECs. Scanning electron microscopy revealed that VECs were thinner than AECs and that VECs had numerous fine, cellular processes that were much less abundant on the AECs. Enzymatic disaggregation of confluent cells resulted in a reduced generation time by the AECs compared with VECs. Moreover, VECs responded to disaggregation by a significantly larger increase in cell size than the AECs. Protein synthesis was quantitated by computer analysis of autoradiograph of two-dimensional gel eletrophoresis and separation of 998 35S-methionine-labeled proteins from cell lysates. Synthesis of 257 proteins was significantly different (p less than 0.05); synthesis of 239 proteins by VECs was either decreased (219) or undetectable (20) compared with those of AECs. In contrast, only 18 proteins were produced in significantly greater quantity by VECs than by AECs. The cytoskeletal proteins actin and alpha- and beta-tubulins were produced in significantly greater quantity by AECs than VECs. These results indicate that cultured endothelial cells of arterial origin are substantially different from those of the venous circulation. These phenotypic differences are maintained in vitro despite eliminating variability in hemodynamic stress and interaction with other cellular elements of the vessel wall.

Animals↗

Alterations in aortic endothelial cell morphology and cytoskeletal protein synthesis during cyclic tensional deformation.

Previous studies have shown that bovine aortic endothelial cells (ECs) in culture respond to repetitive tensional deformation with an increase in deoxyribonucleic acid synthesis and cell proliferation. This study was designed to determine whether cyclic tensional deformation of ECs in vitro induces different morphologic or protein synthetic responses. ECs from passages 6 through 9 were seeded in 35 mm2 well silicone rubber plates at 2 x 10(5) cells/well and allowed to attach for 24 hours. The experimental group was placed in a vacuum-operated stress-providing device that exerted an elongation of 24% at maximum downward deflection of the culture plate bottom and was subjected to repetitive cycles of 10 seconds of 24% maximum elongation and 10 seconds of relaxation for 5 days. The control group was subjected to similar incubation conditions but without stretch. 35S-methionine (500 muCi/well) was added to the plates 24 hours before harvesting, and two-dimensional gels of the harvested lysates (isoelectric focusing with pH 3 to 10 ampholytes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 12.5% gels) were performed and the labeled proteins visualized by autoradiography. The data indicate that there is a differential synthesis of proteins, with synthesis of some proteins decreased or ablated whereas other proteins were increased in response to cyclic mechanical tension. The actin filament organization was evaluated after staining with rhodamine phalloidin, a fluorescent F-actin probe. The ECs subjected to tension had a more polygonal shape and demonstrated pseudopods and actin stress fibers, whereas ECs cultured under static conditions were more rounded and did not express actin stress cables.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Intrathecal administration of 4-hydroperoxycyclophosphamide in rhesus monkeys.

The preactivated cyclophosphamide analogue, 4-HC, does not require activation by hepatic microsomal enzymes to express its cytotoxic activity and therefore, unlike cyclophosphamide, may be useful for the regional therapy of cancer. In the present study, the pharmacokinetics and toxicology of 4-HC were studied following intraventricular administration of 0.4 mg to rhesus monkeys with chronic indwelling Ommaya reservoirs. 4-HC was measured in cerebrospinal fluid (CSF) and plasma with a high-performance liquid chromatography assay utilizing a fluorometric detector following derivatization with m-aminophenol. The mean peak level of 4-HC in ventricular CSF was 100 microM 5 min after administration. The drug was cleared rapidly and the elimination was monoexponential with a mean half-life of 22 min. The mean clearance from CSF (0.33 ml/min) was 10-fold higher than CSF bulk flow. The drug was distributed throughout the subarachnoid space with lumbar levels approaching ventricular levels by 60 min. Neither acute nor chronic neurotoxicity or systemic toxicity was observed during the 6-wk observation period. Concentrations of 4-HC demonstrated to be cytocidal in vitro against human breast cancer, lymphoid leukemia, and rhabdomyosarcoma were readily achieved in CSF following intraventricular administration. This study demonstrates that intraventricular therapy with 4-HC is feasible and suggests that further study of this approach in the clinical setting should be considered.

Animals↗

Infertile or childless by choice? A multipractice survey of women aged 35 and 50.

Eleven general practitioners examined the medical records of all women on their lists born in 1950 (617 patients) and 1935 (533 patients) to determine the prevalence of childlessness and specialist consultations about infertility. Eighty eight (14.3%) of the women born in 1950 and 41 (7.7%) of those born in 1935 were childless. Sixty eight women born in 1950 (11.0%) and 17 born in 1935 (3.2%) were considered childless by choice. Involuntary childlessness was found in 20 (3.3%) of the women born in 1950 and 24 (4.5%) born in 1935. Forty two (6.8%) of the women born in 1950 had consulted a specialist about infertility as compared with 19 (3.6%) born in 1935. This study found a significant increase in voluntary childlessness among the younger women; there was no evidence of a change in the prevalence of involuntary childlessness despite the increasing demand for specialist referral, which appeared to be made by women who were parous or destined to become so.

Adult↗

A case of factitious disorder presenting as plumbism.

The case of a young man who presented with lead poisoning is reported. This did not resolve with prolonged treatment and he had several unusual and unexplained bacteraemias. Probable sources of self-administered lead and bacteria were demonstrated and psychiatric assessment showed that the patient had a personality disorder which was consistent with a diagnosis of factitious disorder. Psychiatric management led to the termination of the self-inflicted illnesses and enabled the patient to cope with his personal and social problems.

Adult↗

Culture of abdominal aortic aneurysm contents. An additional series.

We evaluated the microbiologic nature of aneurysm contents. Aerobic and anaerobic cultures were taken from non-blood fluid, laminar thrombus, or ulcerated plaque within aortic aneurysms operated on during an eight-year period. Positive bacterial cultures were obtained from 22 (10.4%) of 211 aneurysms. Staphylococcus epidermidis was the most common organism recovered (12/22, 54%). Bacterial colonization of the arterial wall has a possible role in the pathophysiology of prosthetic graft sepsis. These data are valuable not only in choosing appropriate prophylactic antibiotics for aneurysm repair, but also in experimental efforts to develop an infection-resistant vascular graft by directing the antimicrobial characteristics of agents selected for binding to various prosthetic flow surfaces.

Aorta, Abdominal↗

Magnetic resonance imaging in isolated noncompressive spinal cord syndromes.

The frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan in chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory-supported, definite multiple sclerosis as was the case in 28 patients in this series.

Adolescent↗

Cell responses to biomaterials. I: Adhesion and growth of vascular endothelial cells on poly(hydroxyethyl methacrylate) following surface modification by hydrolytic etching.

Hydrogels of poly(hydroxyethyl methacrylate) (polyHEMA) homopolymer do not normally support the attachment and growth of mammalian cells. By altering the surface it has been possible to dramatically change this cell-substratum interaction so that vascular endothelial cells can attach and completely populate a polyHEMA surface. While this can be achieved by copolymerisation of polyHEMA with methacrylic acid or diethylaminoethyl methacrylate, it is most conveniently achieved by brief treatment of polyHEMA hydrogel with concentrated sulphuric acid. The resultant creation of surface-COOH groups, revealed by electron spectroscopy for chemical analysis, is consistent with the hydrolytic formation of methacrylic acid on the surface layer. Surface--COOH groups created by treatment with chloric or hydrofluoric acids were not effective. Following sulfuric acid treatment, cell adhesion and growth on polyHEMA hydrogel were better than on Teflon and approached those attained on glow-discharge-treated polystyrene. The capacity of acid-treated polyHEMA to adsorb albumin or fibronectin was of the order of 100-fold or 10-fold lower respectively than either polystyrene, Teflon, or segmented polyurethane. Hydrolytic "etching" in this way is proposed as an efficient means of expanding the use of polyHEMA hydrogel as a biomaterial without modifying the overall physicochemical properties of the bulk of the material.

Acrylates↗

STIR sequences in NMR imaging of the optic nerve.

Orbital fat surrounding the optic nerve causes considerable difficulties in NMR imaging due to its high image intensity and the chemical shift artefact. We have investigated the ability of inversion recovery sequences with short inversion times (STIR sequences) to suppress fat signals in imaging the optic nerve. We have also compared the contrast attainable with STIR sequences with that obtainable from other sequences. Measurements were made on 4 normal controls and 5 patients with multiple sclerosis (MS) to obtain typical values of relaxation times and proton densities for orbital fat, cerebral white matter and MS lesions. The fat T1 measurements were used to predict an appropriate inversion time for the STIR sequence and estimate how much residual fat signal might be expected as a result of natural variations in fat T1. STIR sequences can be used to suppress the signal from orbital fat with little residual signal. Measurements from white matter and MS lesions were used to predict the contrast between normal and pathological tissues that is attainable with STIR sequences. STIR contrast compares favourably with that obtainable from other sequences.

Humans↗

Coordinating center follow-up in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.

In the VA Cooperative Study of Coronary Artery Bypass Surgery, follow-up by the participating investigators was completed in 1984 and annual centralized follow-up by the coordinating center for an additional 5 years was initiated in 1985. Follow-up was restricted to key outcomes that could be reliably obtained in most patients-survival, severity of angina, myocardial infarction and bypass surgery. Ninety-five percent of patients consented to annual follow-up by telephone or mail. At the first annual follow-up, 95% of all survivors were contacted; 95% were also contacted at the second follow-up. In the initial follow-up, survival status was known in all patients and severity of angina was recorded in 93% of survivors; all bypass operations and all but one infarct identified were documented by a discharge summary. Our results indicate that coordinating center follow-up was effective in a long-term study of a chronic disease and depended on the willingness of patients to participate, the experience of the interviewers, and the ability of the coordinating center to contact patients and retrieve outcome data. This report describes the methods used for the centralized follow-up of the surviving patients and summarizes the initial follow-up results. The limitations and advantages of this approach are also discussed.

Clinical Trials as Topic↗

Bipolar affective disorder in adolescence: a 10-year study.

A descriptive study of bipolar affective disorder in adolescent patients, conducted over a 10-year period, is presented. The diagnosis of 30 subjects referred to an adolescent treatment facility of a major teaching hospital was reviewed using DSM-III criteria, and antecedent symptomatology and signs were documented. Common diagnostic features included schizophreniform phenomenology, motoric and vegetative changes, suicidal and inappropriate sexual behaviour and a stormy first year of illness. A positive family history was frequently noted, as was the relevance of various forms of loss as a precipitant of the first episode. Timely recognition and multidisciplinary management, including the use of lithium, are discussed. It appears that the prognosis of bipolar affective disorder in adolescence is better than was previously believed, probably as a result of earlier diagnosis and more frequent recognition.

Adolescent↗

The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. A quantitative study.

The form and distribution of MRI abnormalities in 114 patients with clinically definite multiple sclerosis (MS) have been compared with observations on 53 apparently healthy individuals, 129 patients with isolated focal neurological lesions with which MS often presents (51 patients with optic neuritis, 44 with isolated brainstem lesions and 34 with isolated spinal cord syndromes) and 105 patients with disorders which may be confused clinically or radiologically with MS. The latter comprised 55 patients with cerebral vascular disease (including 7 cases of dementia with diffuse white matter disease), 24 with degenerative ataxic disorders, 8 with cerebellar tonsillar ectopia, 7 with sarcoidosis and 11 with a variety of other disorders. Periventricular abnormalities were found in all but 2 patients with MS and discrete white matter lesions in all but 12. Characteristically the periventricular changes in MS were irregular in outline. Periventricular abnormalities which were often milder and of smooth outline were seen in 37/55 patients with cerebral vascular disease, 9/24 with cerebellar degeneration, 5/7 with sarcoidosis and in 2/3 apparently healthy individuals over the age of 60. The appearances in the 7 cases of dementia resembled those with advanced MS. Cerebellar and/or brainstem atrophy characteristic of the cerebellar degenerations, in the absence of white matter abnormalities, was helpful in making the distinction from MS. Congenital anomalies and tumours in the region of the brainstem and foramen magnum were readily shown. More than half the patients with symptoms attributable to isolated focal neurological lesions had additional lesions at presentation. MS cannot be diagnosed in these cases at presentation, but repeat scans after 5 to 20 months in 25 patients with optic neuritis and 10 with clinically isolated brainstem lesions have shown new lesions in 7 (20%). The patients with new lesions fulfil the criteria for clinically probable MS (Poser et al., 1983). Measurements of T1 and T2 in vivo permitted the distinction of acute from chronic brainstem lesions. There were quantitative differences in T1 and T2 between the normal appearing white matter in MS and normal brain. Studies of postmortem brains provided convincing evidence that the MRI abnormalities in MS correspond with plaques. Evidence is adduced to support the view that an important source of the abnormal NMR signals in acute lesions is oedema, and in chronic lesions is gliosis; demyelination per se is unlikely to make an important contribution.

Adolescent↗

Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema.

Magnetic resonance imaging (MRI) has been used quantitatively to define the characteristics of two different models of experimental cerebral oedema in cats: vasogenic oedema produced by cortical freezing and cytotoxic oedema induced by triethyl tin. The MRI results have been correlated with the ultrastructural changes. The images accurately delineated the anatomical extent of the oedema in the two lesions, but did not otherwise discriminate between them. The patterns of measured increase in T1' and T2' were, however, characteristic for each type of oedema, and reflected the protein content. The magnetisation decay characteristics of both normal and oedematous white matter were monoexponential for T1 but biexponential for T2 decay. The relative sizes of the two component exponentials of the latter corresponded with the physical sizes of the major tissue water compartments. Quantitative MRI data can provide reliable information about the physico-chemical environment of tissue water in normal and oedematous cerebral tissue, and are useful for distinguishing between acute and chronic lesions in multiple sclerosis.

Animals↗