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Biomedical subjects

R A Murphy

Publications and source records attributed to R A Murphy.

At least 163 records · Page 9Linked to original sources

In vivo and in vitro effects of thymosin and adenosine deaminase on adenosine-deaminase-deficient lymphocytes.

Two siblings with adenosine deaminase deficiency were studied before and during "enzyme replacement" therapy (partial exchange transfusions with normal red cells containing the missing enzyme). The younger sib showed improvement of immunologic function during red-cell therapy alone, whereas in the older sib this improvement occurred only when the transfusions were supplemented by thymosin injections. Their clinical courses correlated with in vitro findings: lymphocytes from the younger sib differentiated to T-cell-rosette-forming cells upon addition of adenosine deaminase alone; lymphocytes from the older sibling required supplemental thymosin to form these cells. Thymic factors appear to influence the response to transfusion therapy in some patients deficient in adenosine deaminase, and supplementation of red-cell transfusion with thymic factors may be required.

Adenosine Deaminase↗

Possible nonspecific immunopotentiation by 2,4-dinitrochlorobenzene sensitization in patients with Hodgkin's disease.

Various immunological parameters were evaluated in untreated Hodgkin's patients before and after sensitization with dinitrochlorobenzene (DNCB). The ratio (r) of these parameters after/before DNCB sensitization for patients and second/first samples in the controls were calculated. There were significantly more patients in the r greater than 1.1 group for PHA and Con A responses and for peripheral blood T cell percentages. These data suggest that DNCB sensitization may have a nonspecific immunopotentiation effect.

Antibody Formation↗

Cellular thin filament protein contents and force generation in porcine arteries and veins.

We estimated the cellular myosin, actin, and tropomyosin contents of vascular smooth muscle from (1) seven major arteries, (2) seven large veins, and (3) the first through third order branches of the uterine vasculature to determine whether variations in the contractile apparatus contribute to the functional diversity of vascular smooth muscle. We obtained the estimates by quantitative densitometry of stained polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. No differences in cellular myosin content were found (18.7 +/- 1.0 mg/g cell wet weight in arteries vs. 17.2 +/- 0.7 in veins). However, the actin and tropomyosin contents were higher in arteries (49.7 +/- 2.9 and 13.1 +/- 0.8 mg/g cell, respectively) than in veins (25.5 +/- 1.4 and 7.0 +/- 0.3 mg/g cell). These differences persisted in the smaller uterine vessels. The higher contents of thin filament proteins in arteries, compared with veins and several other smooth muscle tissues previously studied, may underlie the high force generating capacity of arterial smooth muscle.

Actins↗

Epidermal growth factor in the submandibular gland and serum of mice with muscular dystrophy: chemical properties in dilute gland extracts.

Epidermal growth factor (EGF) has been measured in extracts of submandibular glands from mice with hereditary muscular dystrophy. RIA results show that adult male and female dystrophic mice have significantly less submandibular gland EGF than do unafflicted controls. Despite the differences in gland content of the protein, serum levels of EGF are similar in both dystrophic and control animals. Furthermore, submandibular gland concentrations of amylase are normal in the dystrophic mice, indicating that not all proteins synthesized by the glands are affected. Gel filtration studied reveal that the elution properties of EGF in extracts of glands from dystrophic and control animals are indistinguishable. Unexpectedly, the chromatographic profiles indicate that most of the EGF in gland extracts elutes as a low molecular weight protein when the molecule is studied at low, biologically active concentrations; only a small portion of the protein is associated with a high molecular weight complex. Under the same experimental conditions, submandibular gland nerve growth factor maintains its association with other components in a high molecular weight form.

Amylases↗

Changes in rat aortic actomyosin content with maturation.

It has been reported by several investigators that the maximum active force generating ability (i.e., force/tissue cross-sectional area) of the aorta increases as the animal matures and then declines later in life. The purpose of this work was to determine if changes in the actomyosin content of the aorta occur during maturation which could contribute to the observed changes in force generating ability. The actin and myosin contents of rat thoracic aorta obtained from animals 3, 5, 7, 16 and 43 weeks of age were determined by quantitative gel electrophoresis, and were normalized with respect to tissue mass and protein and DNA contents. The results indicate that the amount of actomyosin (i.e., actin + myosin heavy chains) per tissue mass, protein and DNA increases rapidly during the first 5 weeks after birth and then remains constant. These observations suggest that the increasing actin and myosin heavy chain content of aorta observed early in life could explain in part the increasing force generating ability reported during this period, but that a loss of contractile material is not responsible for the reduction in force generating ability seen later in life.

Actomyosin↗

Secretagogue-mediated discharge of nerve growth factor from granular tubules of male mouse submandibular glands: an immunocytochemical study.

Submandibular glands of male mice were stained for nerve growth factor by light microscopic immunocytochemistry. Nerve growth factor (NGF) was present in the granules of granular tubule cells, with the immunoreactive material often concentrated at the periphery of granules. Administration of the alpha-adrenergic agent, phenylephrine, to animals resulted in a marked depletion of NGF-containing granules from granular tubules. Some release also occurred following administration of the beta-adrenergic agent, isoproterenol. Cholinergic stimulation (pilocarpine) did not result in appreciable loss of immunoreactive granules from these cells. In vitro results were not as clear cut, immunocytochemically, as those obtained with intact animals. It is concluded that discharge of NGF from male mouse submandibular glands is mediated predominantly by alpha-adrenergic activation, and that this phenomenon is readily demonstrated in the intact animal.

Animals↗

Estimates of cellular mechanics in an arterial smooth muscle.

Estimates of force generation or shortening obtained from smooth muscle tissues are valid for individual cells only if each cell is contracting homogeneously and if cells anatomically arranged in series are mechanically coupled. These two assumptions were tested and shown to be valid for the pig carotid media under certain conditions. Homogeneity of cellular responses in carotid strips was estimated from the motion of markers on the tissue during K+ -induced isometric contractions. When tissues were stretched to L0 (the optimum length for force generation), there was little marker movement on stimulation. However, considerable marker movement was observed on stimulation at shorter muscle lengths, reflecting localized shortening or stretching. The mechanical coupling of the very small cells in the media was determined by measuring the dependence of cell length on tissue length. Tissues were fixed with glutaraldehyde during isometric contractions at various tissue lengths (0.4--1.1 x L0). The fixed tissues were macerated with acid and the lengths of the dispersed cells were measured. Cell lengths were broadly distributed at all muscle lengths. However, the direct proportionality between mean cell length and muscle length (as a fraction of L0) indicated that cells which are anatomically in series are coupled force-transmitting structures. We conclude that valid estimates of cellular mechanical function in this preparation can be obtained from tissue measurements at lengths greater than about 0.9L0.

Animals↗

Differences in cellular contractile protein contents among porcine smooth muscles: evidence for variation in the contractile system.

Cellular myosin, actin, and tropomyosin contents and ratios were determined for arterial (carotid, aorta, and coronary), intestinal (circular and longitudinal), esophageal, uterine, and tracheal smooth muscles inthe pig. Tissue protein contents were estimated by densitometry of polyacrylamide gels after electrophoresis of sodium dodecyl sulfate-treated tissue homogenates. Cellular contractile protein contents were estimated by correction for extracellular spaces. Cellular myosin contents were similar in each tissue (average +/- 1 SEM = 19.6 +/- 0.8 mg/g cell wet wt). However, the cellular contents of the thin filament proteins, actin and tropomyosin, were significantly higher in the arteries than in the nonarterial tissues. The calculated weight ratios of actin: myosin averaged 2.6 +/- 0.2 in the three arterial tissues and 1.5 +/- 0.1 in the nonarterial tissues, which may be compared with 0.36 in vertebrate striated muscles. The actin:tropomyosin weight ratios for all tissues were 3.7 +/- 0.1, a value comparable to the skeletal muscle ratio. The physiological implications of variations in the cellular thin filament protein contents are unknown, but these variations probably contribute to the observed differences in contractile function among various smooth muscles.

Actins↗

Estimate of cellular force generation in an arterial smooth muscle with a high actin: myosin ratio.

An in vitro preparation from the media of the pig carotid artery develops somewhat higher force/cell cross-sectional area with one-fifth the myosin content of skeletal muscle cells. The following results suggest that this performance reflects cellular properties rather than the arrangement of cells within the tissue: (1) force development at the peak of the length-force curve is independent of the length of the tissue segment in a strip of constant cross-section, and (2) average cell length is directly proportional to tissue length. We conclude that the contractile system of arterial smooth muscle cells is specialized for force generation and that the mechanical properties of the pig carotid media preparation provide valid estimates of cellular function.

Actins↗

Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: effects of sulfasalazine in vivo and in vitro.

Comparative analysis of the systemic immunity revealed similarities between ulcerative colitis and idiopathic proctitis. In the active stage of both diseases, circulating complement receptor positive cells were increased whereas T-cell percentages and lymphocyte functions were decreased. In severe forms of ulcerative colitis and idiopathic proctitis circulating EAC-phagocytosing esterase positive cells, indicative of activated monocytes, were demonstrated. Successful treatment with salicylazosulfapyridine (SASP) reversed these immunological changes. Incubation of SASP and its metabolites with leucocytes from patients and control subjects, in concentrations similar to those demonstrated in sera from patients treated with SASP, did not alter the immunological changes.

Adult↗

Cholecystokinin cholecystography in the diagnosis of acalculous extrahepatic biliary tract disorders.

Cholecystokinin cholecystography represents a study designed to identify patients with acalculous extrahepatic biliary tract disorders. In this study, a positive cholecystokinin cholecystogram (CCK-GB) was defined as both reproduction of the patient's biliary tract-type pain plus one or more of various roentgen abnormalities. Using these criteria, 20 patients had a positive CCK-GB. After failure of medical management, 19 of these patients came to surgery. Seventeen of 18 available for follow-up were cured of their biliary tract pain by surgery. Follow-up of this group of patients has ranged from one month to 60 months. In view of our findings plus those in other reported series, we conclude that CCK-GB provides a reliable study for the diagnosis of acalculous extrahepatic biliary tract disorders.

Adolescent↗

Dissociation of the 7S-nerve growth factor complex in solution.

Sedimentation and gel-filtration studies of mouse submandibular gland 7S-nerve growth factor (NGF) reveal that this complex dissociates to yield its components at concentrations much higher than those required to exhibit biological activity. Results further indicate that the alpha and gamma protein c omponents of the 7S-NGF complex probably play no role in its biological activity when tested in vitro. The dissociation behavior of 7S-NGF is quite different from the properties of very dilute solutions of the NGF secreted by mouse L cells and of that present in fresh, unpurified submandibular gland homogenates, since both of these proteins display high molecular weights at concentrations where 7s-NGF is fully dissociated. Thus, it could be that 7S-NGF is not the form in which NGF exists in the mouse submandibular gland.

Animals↗