Flash photolysis of hemoglobin.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R J Morris.
Explore the source record for details and available documents.
The Root effect hemoglobin from Thunnus thynnus, the Atlantic bluefin tuna, remains in the T state at acid pH even when liganded. There are two components in the binding of CO to the T state with rates of 0.01 and 1.0 X 10(6) M-1 S-1 at 20 degrees C, 0.1 M KPi, pH 6.0, and two components in binding to the R state with rates of 1.7 and 8.5 X 10(6) M-1 S-1 as measured by partial flash photolysis at 20 degrees C, 0.05 M Tris-HCl, pH 8.0. A single rate of NO binding of 1.8 X 10(7) M-1 S-1 is found at both pH 6 and pH 8. The rate of binding of NO to dimethyldeuterohemedisulfonate is much higher still at 5 X 10(8) M-1 S-1. The observed rate of NO binding to the protein is not affected by chain differences or by the R to T transition. It may measure the rate of diffusion of ligand to the vicinity of the heme site. The T state components have different NO dissociation velocity constants of 0.004 and 0.07 S-1. The apparent quantum yields for the T state components are approximately 0.035 and 0.0008; the high affinity component has the lower yield. A two-step scheme is used to explain the results. The presence of chain differences and allosteric states is reflected in the intrinsic binding rates of both NO and CO to the heme group.
Explore the source record for details and available documents.
The level of the Thy-1 cell surface antigen on a number of established rat and mouse nerve cell lines can be stimulated by N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (Bt2cAMP), in some cases up to the antigen level found in whole brain. On rat cell line BN1010-3, stimulation is also produced by phosphodiesterase inhibitors, adenosine 3':5'-cycle monophosphoric acid (cAMP) and its 8-bromo derivative, and L-isoproterenol. Hence, antigen elevation appears to occur via cAMP-related metabolism. It is not a consequence of morphological changes brought about by cAMP elevation in these cells, and is apparently independent of the inhibition of cell division by the nucleotide. Elevations of intracellular cAMP levels for at least one hour are needed to produce Thy-1 stimulation, after which an enhanced level of Thy-1 is observable after about 12 h. Continuous stimulation is required to maintain elevated antigen levels, for upon removal of the stimulating agent, the level of Thy-1 returns to the original unstimulated value within 48 h. Potent stimulation of the antigen level is also obtained with butyrate at 1--2 mM, which appears to be acting by a cAMP independent mechanism.
The spectra have been measured of the transient species and the final level of absorption observed in nanosecond laser photolysis of aqueous carbon monoxy- and oxyhaemoglobin. These show that the transient absorption change can be interpreted as being due to an ultrafast ligand recombination following the photolysis. The spectra do not support the earlier interpretation (Alpert, B., Banerjee, R. and Lindqvist, L. (1974) Proc. Natl. Acad. Sci. U.S. 71, 558--562) that this was due to a tertiary structural change of the protein.
The Thy-1 antigen is a cell surface glycoprotein found on a number of tissues of the rat and mouse, including neurons. The amount of this antigen has been measured on several rat and mouse clonal cell lines of nervous tissue origin. Three of the rat cell lines (clones PC12, BN1010-3, BN1010-1) were found to contain substantial amounts of the antigen, having as many as 1.6 million Thy-1 antigenic sites per cell. This amount was independent of the cell density or growth rate. Most, if not all, of the antigen is accessible to antibody binding on the external surface of the cells, and is synthesized by the cells.
Ketazolam (both in once-daily and three-times-daily dosing), diazepam, and placebo were compared for effectiveness in relieving anxious symptomatology in a clinical trial conducted with a total of 222 anxious, non-psychotic outpatients. Results indicated that improvement occurred early in treatment, that ketazolam was equally effective in both once-daily and three-times-daily dosing, and that ketazolam was similar in effect to diazepam. Ketazolam (both once-daily and three-times-daily) and diazepam were significantly (P < 0.05) better than placebo in alleviating symptoms of anxiety, as measured by the Hamilton Anxiety Scale, the Covi Anxiety Scale, and a physician-rated measure of global improvement.
The cell surface differentiation antigen, Thy-1, has been demonstrated by immunofluorescence to be associated with some collagen-based connective tissue. In the rat, the basement membrane of kidney collecting tubules of certain blood vessels, reticulin of the lamina propria, loose connective tissue in the dermis, and collagen fibres within certain nerve cell tumours, bear the antigen. Other, apparently similar, connective tissue (especially that of muscle and liver) lacked Thy-1. In the mouse, only the connective tissue of the skin was found to bear the antigen. The possible origin of this extracellular Thy-1, and its implications for the function of the molecule, are discussed.
Explore the source record for details and available documents.
The cell surface differentiation antigen, Thy-1, was demonstrated by immunofluorescence to be associated with collagen-based connective tissue (mainly basement membrane) around some blood vessels in rat lymphoid organs. This association is highly selective: only certain types of blood vessel within a given lymphoid organ were found to be Thy-1+; and different lymphoid organs (thymus, bone marrow, lymph node and spleen) had characteristic differences in the types of blood vessel that bear Thy-1. In lymph node and spleen the vessels that were Thy-1+ were those involved in lymphocyte recirculation and homing (post-capillary venules and arterioles of white pulp); the possibility that Thy-1 may function in mediating selective adhesion of small lymphocytes to extracellular substrates during recirculation is discussed.
Immunofluorescence and cytolysis studies using antisera against the xeno- and alloantigenic components of the Thy-1 molecule have shown that in adult mouse bone marrow more cells bear the xeno than the alloantigen. Allo+ cells form a subset of a larger, xeno+ population. Xeno+ allo- 'prothymocytes' can be induced to express the alloantigen in vitro; this could result from the unmasking of cryptic antigen, the presence of which is demonstrated, rather than de novo antigen synthesis. Some xeno+ allo- cells are involved in splenic haemopoiesis, either as a subpopulation of precursors, or as accessory helper cells.
One hundred twenty patients from each of 6 family practices were surveyed to determine the prevalence of symptom-based psychiatric illness (emotional distress) in family practice. Assessments of presence or absence of emotional distress and the severity of this distress were made using ratings made by the treating physician and by the patient. Nineteen percent of the surveyed patients were designated by their physicians as having "high distress," and 21% by the patient-completed abbreviated Hopkins Symptom Checklist (HSCL-25). High concordance (86.7%) existed between the "case" assessment by the physician and the patient's own rating of distress. For the majority of "high distress" patients, pharmacotherapy was considered the treatment of choice by physicians.
To ascertain if a genetically determined slow drug acetylation rate is correlated with the development of spontaneous systemic lupus erythematosus (SLE), as it is in drug-induced SLE, acetylation phenotypes of 27 patients with spontaneous SLE were determined after administration of dapsone. Thirty-three percent were slow acetylators, 63% were rapid acetylators, and one was indeterminate, a distribution not significantly different from that expected in control subjects. Among 4 pairs of first-degree relatives, all of whom had spontaneous SLE, 7 of the 8 individuals were rapid acetylators. We conclude that people who are slow acetylators are at no greater risk for developing spontaneous SLE than are rapid acetylators and that the slow acetylation phenotype is not correlated with familial SLE.
Thirty-two biopsies of kidneys and of normal skin were performed simultaneously on patients with systemic lupus erythematosus (SLE) to determine whether the deposition of immune reactants in skin was correlated with the severity of renal injury or with several serologic measures of systemic disease activity. Immunofluorescent deposits at the dermal-epidermal junction (lupus band test) did not correlate with any clinical or histologic measures of glomerulonephritis or with serologic abnormalities. Immune deposits in dermal venules were found in 56% of the skin biopsies and were correlated with hypocomplementemia and higher levels of immune complexes in serum, and possibly with glomerular subendothelial electron dense deposits. Azathioprine therapy was correlated with absence of both sub-epidermal and vascular immune deposits. Immuno-fluorescent findings on serial skin biopsies on 13 patients were highly inconsistent. It is concluded that the lupus band test is clinically useful only as a diagnostic aid but not helpful in assessing renal or serologic activity of lupus, and that dermal vascular deposits of immunoglobulin or complement are more frequent than previoulsy recognized and correlate with measures of circulating immune complexes.
Explore the source record for details and available documents.
Three approaches were used to demonstrate the presence of Thy-1 antigen on the surface of pluripotent hemopoietic stem cells in the rat. In the first, stem cells from fetal liver, neonatal spleen, and adult bone marrow were prevented from forming hemopoietic colonies in the spleens of irradiated recipients spleen (colony-forming unit assay) by incubation with antibodies to Thy-1 antigen. Highly specific rabbit heteroantiserum to purified rat brain Thy-1 antigen and mouse alloantisera to Thy-1.1-positive thymocytes were equally effective. This inhibition was neutralized by purified Thy-1 antigen. In a second series of experiments, Thy-1-positive and Thy-1-negative populations of nucleated bone marrow cells were separated by the FACS. All of the hemopoietic stem cell activity was recovered in the Thy-1-positive population. The stem cells were among the most strongly positive for Thy-1 antigen, being in the upper 25th percentile for relative fluorescence intensity. The relationships of Thy-1 antigen to the rat bone marrow lymphocyte antigen (BMLA) was shown in a third series of experiments. Rabbit anti-BMLA serum, which is raised against a null population of lymphocyte-like bone marrow cells, has been shown to have anti-stem cell activity. Here we demonstrate by double immunofluorescence, cocapping, and differential absorption studies that Thy-1 and BMLA are parts of the same molecule.
Explore the source record for details and available documents.
A patient who has had three distinct recurrences of disseminated histoplasmosis over 22 years is presented. Measurements of cellular and humoral immune response to histoplasmin antigens were compared with previously reported data. Although initially sulfisoxazole therapy led to regression of disease, over the past 13 years she has required three courses of amphotericin B, each time with resolution of signs and symptoms. Despite minimal evidence of a cellular or humoral immune response to this organism, the patient has done well. Although disseminated histoplasmosis is often a fatal disease, this woman has tolerated the infection well.