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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 469 records · Page 26Linked to original sources

Automated quantitation of cell density distribution and hyperdense cell fraction in RBC disorders.

An altered state of cell hydration is a hallmark of a number of RBC disorders. The two parameters most often used to characterize the state of cell hydration are (a) the complete cell density distribution profile, and (b) the fraction of cells with densities greater than a defined value. Buoyant density cell fractionation with a variety of polymers has long been the preferred method for obtaining data on cell density distribution. Although this method provides accurate and quantitative information on the state of RBC hydration, its applicability has been limited due to the time-consuming experimental procedure involved in generating the data. A recently developed light-scattering method has been used in the present study to quantitate RBC density distribution. This new method accurately quantitates both the cell density distribution profile and the fraction of dense, dehydrated cells in various RBC disorders. The ability of the automated method to generate this information rapidly makes possible objective testing of different hypotheses concerning the contributions of cell hydration and dehydration to the pathophysiology of various RBC disorders.

Anemia, Sickle Cell↗

A labor of love.

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Acquired Immunodeficiency Syndrome↗

A time for change.

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Chlorhexidine↗

A novel biological effect of atrial natriuretic hormone: inhibition of mesangial cell mitogenesis.

We have investigated the effect of atrial natriuretic hormone on serum-induced mitogenesis in cultured rat mesangial cells. Synthetic peptides, atriopeptin 28 and atriopeptin 24, dose-dependently decreased thymidine incorporation, with a half-maximal effect at approximately 1 nM and a maximal inhibition of approximately 60%. Moreover, atriopeptin 28 significantly decreased the clonal proliferation of mesangial cells. Atriopeptin 28 also decreased resting cytosolic Ca but had no effect on the increase induced by serum, relative to the lower baseline established by atriopeptin 28. Nevertheless, the overall effect of atriopeptin 28 on Ca was to attenuate the serum-induced increase, relative to the original resting level. These results therefore provide evidence for a novel biological effect of atrial natriuretic hormone and suggest that the antimitogenic effect may be mediated by atriopeptin-induced alterations of intracellular Ca dynamics. We speculate that atrial natriuretic hormone may be a modulator of mesangial cell mitogenesis in vivo.

Animals↗

Behavioral stimulation of ovarian growth.

The present study was conducted to test the following hypothesis: male courtship induced egg-laying behavior in the female ring dove is mediated by the female's nest-coo display which feeds back to stimulate her ovarian system through the mechanisms of audio- and proprioceptive feedback. In Experiment I, females were exposed to 24 hr male courtship and then received playback of different nest-coos in the absence of their mates. All playback was effective in inducing the females to perform nest-coo displays, but none as effective as presence of the courting males. A specified level of the female's nest-coo display determined whether there would be changes in follicular diameter. The females which received no playback after 24 hr pairing with the male (control) did not show any change in the follicular diameter. In Experiment II, females were deafened by removal of cochleae and upon recovery paired with males. Half of those deafened females performed nest-coo displays and subsequently laid clutches. The others failed to perform the display and did not lay. We conclude that both proprioceptive feedback and audio-feedback must be involved to yield maximal stimulation of follicular growth by the female's nest-coo display.

Animals↗

Effects of catecholamines on serum lipoproteins of normally fed and cholesterol-fed rabbits.

The effects of catecholamines on the regulation of lipoprotein metabolism have not been defined. We examined the effects of subcutaneously administered slow-release preparations of norepinephrine (2 mg/kg) and isoproterenol (0.2 mg/kg) on the serum lipoproteins of New Zealand White rabbits. Drugs or control suspension were administered daily to three groups of normally fed and three groups of cholesterol-fed rabbits, and lipoprotein analysis was performed at intervals over a 60-hour period. In the normally fed animals, norepinephrine increased the serum levels of triglyceride and phospholipid by factors of 2.4 (P less than .01) and 1.35 (P less than .05), respectively, compared with control animals at 60 hours, but had no effect on serum cholesterol. All components of serum very low density lipoproteins (VLDL: triglyceride, cholesterol, phospholipid, and protein) were significantly (P less than .01) elevated by norepinephrine in the normally fed animals. In the cholesterol-fed animals, norepinephrine at 60 hours significantly increased total serum cholesterol, triglyceride, and phospholipid concentrations by factors of 1.7 (P less than .05), 5.0 (P less than .01), and 1.6 (P less than .05), respectively, compared with controls. The norepinephrine effects in these animals was due to significant elevation of total VLDL and low density lipoproteins (LDL) and all their elemental components. Isoproterenol produced no significant effect on serum lipoprotein levels in the normally fed rabbit, but in cholesterol-fed animals it produced a rise in total serum VLDL and LDL triglyceride concentrations compared with controls at 60 hours. These data demonstrate that catecholamines are involved in the regulation of lipoprotein metabolism.

Animals↗

Thromboxane increases pulmonary vascular resistance and transvascular fluid and protein exchange after pulmonary microembolism.

We compared the effects of inhibition of thromboxane synthetase with antagonism of thromboxane A2 (TxA2)/prostaglandin H2 receptors on the changes in pulmonary hemodynamics and pulmonary transvascular fluid and protein exchange following thrombin-induced pulmonary microembolism. Studies were made in chronically instrumented unanesthetized sheep prepared with lung lymph fistulas. Control thrombin challenged sheep (n = 5) were compared to animals pretreated with Dazoxiben (the Dazoxiben-thrombin group, n = 8) or animals pretreated with L-640,035 (the L-640,035-thrombin group, n = 5). In the control-thrombin sheep, plasma TxA2 concentration rose after thrombin and the response was inhibited in the Dazoxiben-thrombin group. The rise in the plasma TxA2 concentration was greater in the L-640,035-thrombin group than in the control-thrombin group. In the control-thrombin group, thrombin produced a sustained increase in the pulmonary transvascular protein clearance (pulmonary lymph flow x lymph/plasma protein concentration ratio) and pulmonary vascular resistance (PVR). In the Dazoxiben-thrombin group, increases in both pulmonary transvascular protein clearance and PVR after thrombin were less than in the control-thrombin group. In the L-640,035-thrombin group, thrombin initially increased pulmonary transvascular protein clearance and PVR to the same levels as the control group; however, both protein clearance and PVR declined with time, in contrast to the sustained responses in the control-thrombin group. These differences may be related to the initially greater increase in plasma TxA2 concentrations after thrombin in the L-640,035-treated animals. The results indicate that TxA2 plays a role in mediating the increases in PVR and contributes to increases in pulmonary transvascular fluid and protein exchange after thrombin-induced pulmonary microembolism.

Animals↗

The activation of C3 and C4 in human serum by immune complexes containing mouse monoclonal antibodies of different isotype and affinity: effects on solubilisation.

Radioimmunoassays for C3a and C4a have been used to measure the activation of complement in human serum by immune complexes containing DNP-BSA and each of 11 mouse anti-DNP monoclonal antibodies of varied isotype and affinity. When preformed complexes were added to serum, those containing IgG2 or IgM were potent activators of C4, whilst IgG1 complexes were less efficient. C3 activation in normal serum was similar for complexes containing IgG1, IgG2a, IgG2b or IgM. IgA complexes did not activate C3 or C4. Solubilisation of complexes was greatest for IgM and IgG2b and least for IgG2a and IgA. In serum containing Mg2+ EGTA C4 activation was abolished and the amount of C3 activation was lower for all IgG and IgM complexes. Antibodies of the same isotype did not necessarily activate complement to the same extent. Unexpectedly, three of the four IgMs activated C3 in EGTA. For IgMs, neither complement activation nor solubilisation correlated with affinity. For IgG1 antibodies, solubilisation was inversely proportional to affinity. C3 or C4 activation did not correlate with affinity.

Animals↗

Genetic amniocentesis at 14 weeks or less.

The recent clinical trials indicate that EA is feasible. The use of ancillary tools, such as ultrasound, requires only a slight modification of the previously established techniques for MA. The amniotic fluid can be obtained and cultured. Combining the reported populations sampled, the procedural and cytogenetic failure rate were 2.0% and 0.3% respectively. The necessary information for prenatal diagnosis in the situations listed previously can be obtained. The one exception to this would be the patient at increased risk for NTD. As noted above, diagnostic levels for AFAFP have been established beginning at 13 weeks gestation. Therefore, amniocentesis before 13 weeks gestation should not be considered an option for these patients. The majority of the findings in these "pilot" studies have been promising, but the issue regarding the safety of EA has not been answered. Harrison et al. theorized that the function of the physiology hydramnios was to "provide a distention growth stimulus to the uterus ... and conversely to share in the maintenance of uterine inhibition." The amniotic fluid is constantly being replaced, having a complete turnover approximately every 3 hours. Does the reduction in volume, for even a short period of time, change the "distensive forces" enough to increase the pregnancy loss rate? Later publications have associated MA with increased rates of congenital orthopedic anomalies and neonatal pulmonary compromise. The true existence of these complications continues to be debated in the literature. Two of the authors have indicated that none of the reported neonates exposed to EA have had such anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniocentesis↗

Epstein-Barr virus gene expression in nasopharyngeal carcinoma.

Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.

Antibodies, Monoclonal↗

Chicken epidermal growth factor (EGF) receptor: cDNA cloning, expression in mouse cells, and differential binding of EGF and transforming growth factor alpha.

The primary structure of the chicken epidermal growth factor (EGF) receptor was deduced from the sequence of a cDNA clone containing the complete coding sequence and shown to be highly homologous to the human EGF receptor. NIH-3T3 cells devoid of endogenous EGF receptor were transfected with the appropriate cDNA constructs and shown to express either chicken or human EGF receptors. Like the human EGF receptor, the chicken EGF receptor is a glycoprotein with an apparent molecular weight of 170,000. Murine EGF bound to the chicken receptor with approximately 100-fold lower affinity than to the human receptor molecule. Surprisingly, human transforming growth factor alpha (TGF-alpha) bound equally well or even better to the chicken EGF receptor than to the human EGF receptor. Moreover, TGF-alpha stimulated DNA synthesis 100-fold better than did EGF in NIH 3T3 cells that expressed the chicken EGF receptor. The differential binding and potency of mammalian EGF and TGF-alpha by the avian EGF receptor contrasts with the similar affinities of the mammalian receptor for the two growth factors.

Amino Acid Sequence↗