Oligoclonal IgG in the cerebrospinal fluid of guinea pigs with experimental allergic encephalomyelitis.
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Animals↗
Biomedical subjects
A Chu
Publications and source records attributed to A Chu.
Two phospholipase pools for prostaglandin synthesis in macrophages.
Macrophages in culture produce prostaglandins in response to a variety of phagocytic and non-phagocytic stimuli. As prostaglandins are not stored in cells, and mammalian cells contain very little free arachidonic acid, synthesis and release of prostaglandins depends on the release of the precursor, arachidonic acid, from cell lipids. Many agents that stimulate cell prostaglandin production act by releasing arachidonic acid, presumably by activating phospholipase A2 (refs 10, 11) or phospholipase C (refs 12, 13), depending on the cell system used. We have shown previously that rabbit alveolar macrophages secrete arachidonic acid as well as prostaglandins in response to phagocytic stimuli. This secretion depends not on particle attachment, but rather on interiorization of the particles. Furthermore, the time course of prostaglandin and arachidonic acid secretion does not parallel that of particle engulfment per se, but of the release of lysosomal enzymes, indicating that the release of arachidonate and prostaglandin is associated with the latter. We now describe experiments which suggest that these are two independent pools of phospholipases in macrophages, one in the lysosomes and one elsewhere.
Animals↗
Evidence for a calcium-sensitive factor which alters the alkaline pH sensitivity of sarcoplasmic reticulum calcium transport.
Oxalase-supported, ATP-dependent Ca2+ uptake by cardiac and skeletal muscle sarcoplasmic reticulum (SR) exhibits a pH profile with the maximal rate of Ca2+ uptake at pH 6.6-6.8 and marked inhibition (90-95%) at pH 7.4-7.6, a point at which Ca2+-dependent ATPase activity is optimal. These observations are noted when the SR is first preincubated in media containing no added Ca2+. This alkaline pH inhibition is not caused by an irreversible perturbation since the Ca2+ uptake rate is fully restored by changing the alkaline pH preincubation medium to pH 6.8. When SR is preincubated with added Ca2+, Ca2+ uptake at alkaline pH (7.4-7.6) is only inhibited by 10-30%. Ca2+ uptake at pH 6.8 is the same regardless of preincubation conditions. A depressed oxalate permeability is not a factor in the observed alkaline pH inhibition of Ca2+ uptake. At alkaline pH, the relationship between the preincubation Ca2+ concentration and the rate of Ca2+ uptake is hyperbolic; the half-maximal free Ca2+ concentration for stabilization of Ca2+ uptake is 8-15 microM with a Vmax equal to the velocity at the optimal pH. The Hill coefficient is 1.0, implying a single class of Ca2+-requiring sites for stabilization at alkaline pH. In contrast to its effect on Ca2+ uptake, the presence of Ca2+ during preincubation does not alter the pH sensitivity of Ca2+-dependent ATPase activity. Thus, the presence of Ca2+ during preincubation may stabilize a state of the CaATPase, conducive to the coupling of net Ca2+ translocation to Ca2+-dependent ATPase activity, which is ordinarily opposed by alkaline pH. The data suggest a single class of Ca2+-requiring sites which favors this coupled state.
Animals↗
Use of Orthoclone monoclonal antibodies in the study of selected dermatologic conditions.
Monoclonal antibodies recognizing human T cell differentiation antigens were used to study lymphocyte populations in three cutaneous diseases. Neoplastic lymphocytes from patients with varying phases of cutaneous T cell lymphoma (mycosis fungoides, Sezary syndrome and related presentations) were reactive with OKT1 and OKT3 (pan T cell reagents) and OKT4 (an antibody defining the functional "helper" T cell subset). The malignant cells lacked membrane antigens reactive with OKT5 and OKT8 (markers of "suppressor" T cells). The presence of an OKT1+, OKT3+, OKT4+, OKT5-, OKT8- phenotype on the neoplastic T lymphocytes of cutaneous T cell lymphoma (CTCL) supports the clinical impression that all phases of CTCL represent a single disease entity. A patient with pemphigus vulgaris, a disease of autoreactive, antiepidermal antibodies was shown to consistently have a marked expansion of the peripheral blood OKT4 reactive T lymphocyte population. These findings suggest that autoantibodies in pemphigus vulgaris may occur in the context of a profound OKT4/OKT5 immunoregulatory imbalance. Peripheral blood lymphocytes from patients ith extensive psoriasis vulgaris had a normal profile of reactivity with the OKT antibodies. In addition, OKT6 (marker of intrathymic T cells) has been shown to react with Ia+ dendritic cells in the epidermis suggesting that this antibody may recognize Langerhans' cells.
Adolescent↗
Rapid execution of fan beam image reconstruction algorithms using efficient computational techniques and special-purpose processors.
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Mathematics↗
Pagetoid reticulosis and solitary mycosis fungoides. Distinct clinicopathological entities.
The two cases reported in this paper allow the differentiation of pagetoid reticulosis from solitary lesions of mycosis on the basis of clinical, histological ultrastructural, immunohistochemical and enzyme histochemical studies. The first patient presented with a slowly growing asymptomatic scaly plaque of 30 years duration. Histology of the lesion was typical of pagetoid reticulosis. Immunohistochemical studies showed that the abnormal cells present in the cutaneous infiltrate were not T lymphocytes and ultrastructural studies suggested these were of histocytic origin. The second patient presented with a poikilodermatous lesion present for 14 years with histology of plaque stage mycosis fungoides. Enzyme and immunohistochemistry showed the predominant T cell nature of the cutaneous infiltrate and electron microscopy showed numerous mycosis fungoides cells. In contrast to generalized forms of mycosis fungoides, no peripheral blood monocyte chemotactic defect was found in either case. Both lesions responded to radiotherapy.
Adult↗
Excretion of carcinoma products in irradiated C3H/He mice.
Local low-dose (200 rads) gamma-irradiation to both kidneys impaired the excretion of 3H-labeled tumor products and reduced the survival time of mice carrying carcinomas in the ascites form. Daily i.p. injections of cell-free ascites fluid into tumor-free mice for 3 weeks resulted in the death of 25 of 180 irradiated animals, with no deaths among 180 injected unirradiated controls. The only histologically visible effects of irradiation of the kidneys during ascites tumor growth or during i.p. injections of cell-free ascites fluid was a cloudy swelling of the tubular epithelium in the renal cortex together with excessive protein in the tubular lumens.
Animals↗
The sarcoplasmic reticulum-glycogenolytic complex in mammalian fast twitch skeletal muscle. Proposed in vitro counterpart of the contraction-activated glycogenolytic pool.
Evidence is presented that the sarcoplasmic reticulum (SR)-glycogenolytic complex isolated from fast twitch skeletal muscle is a highly specific, functionally defined compartment for phosphorylase regulation. The addition of ATP alone results in prompt phosphorylase activation which demonstrates calcium dependence similar to the calcium-magnesium ATPase that catalyzes SR calcium transport suggesting that these two calcium-requiring -ystems might interact within the complex. Lowering extravesicular calcium concentration by transport of calcium into the SR lumen resulted in inactivation of phosphorylase a. This effect could be prevented by the addition of the calcium ionophore X537A which inhibits SR calcium sequestration or a calcium EGTA buffer which maintains free calcium. It was mimicked by EGTA addition. Since exogenous phosphorylase b and phosphorylase a were not activated or inactivated, respectively, by the endogenous activating enzymes or phosphatase in the SR-glycogenolytic complex, these regulatory enzymes may be compartmented. In addition, endogenous phosphorylase could be uncoupled from its activating enzymes by amylase treatment. These results suggest that the SR-glycogenolytic complex in fast twitch skeletal muscle is a compartmented system for phosphorylase activation controlled by SR calcium flux, a feature in contrast to the cardiac complex (Entman, M.L., Kaniike, K., Goldstein, M.A., Nelson, T.E., Bornet, E.P., Futch, T.W., and Schwartz, A. (1976) J. Biol. Chem. 251, 3140-3146). We suggest that the complex is the in vitro counterpart of the well documented rapid burst of glycogenolysis which ensures with the onset of contraction.
Adenosine Triphosphate↗
Calcium uptake by two preparations of mitochondria from heart.
Ca/+ transport and respiratory characteristics of two preparations of cardiac mitochondria (Palmer, J.W., Tandler, B. and Hoppel, C.L. (1977) J. Biol. Chem. 252, 8731-8739) isolated using polytron homogenization (subsarcolemmal mitochondria) and limited Nagarse exposure (intermyofibrillar mitochondria) are described. The Nagarse procedure yields mitochondria with 50% higher rates of oxidative phosphorylation than the polytron-prepared mitochondria in both rat and dog. Rat hear intermyofibrillar mitochondria contain 50% more cytochrome aa3 than the polytron preparation, whereas in the dog, cytochrome aa3 content is not significantly different. Cytochrome oxidase activities and cytochrome c, c1 and b contents were comparable in both populations of rat and dog heart mitochondria. The V of succinate-supported Ca2+ accumulation for Nagarse-prepared mitochondria from rat heart was 1.8-fold higher than the polytron-prepared mitochondria. In dog heart, the Nagarse preparation showed a 3.0-fold higher V for Ca2+ uptake compared to the polytron preparation. A lower apparent affinity for Ca2+ was demonstrated in the intermyofibrillar mitochondria for both species (Km is 2-2.5-fold higher). The Hill coefficient was 1 both mitochondrial types. Subsarcolemmal mitochondria from both species were treated with Nagarse to determine the role of this treatment on the observed differences. Nagarse did not alter any kinetic parameter of Ca2+ uptake. The properties of these mitochondria with reference to their presumed intracellular location may pertain to the role of mitochondria as an intracellular Ca2+ buffering mechanism in contractile tissue.
Absorption↗
The dynamic spatial reconstructor: a computed tomography system for high-speed simultaneous scanning of multiple cross sections of the heart.
A new generation whole-body computed tomography system has been developed to provide accurate visualization and measurement of the vital functions of the heart, lungs, and circulation. This dynamic spatial reconstructor system (DSR) provides stop-action (.01-sec), rapidly sequential (60-per-second), synchronous volume (240 simultaneous adjacent 1-mm-thick transaxial sections) reconstructions and display of the full anatomic extents of the internal and external surfaces of the heart throughout successive cardiac cycles, and will permit visualization of the three-dimensional vascular anatomy and circulatory functions in all regions of the body of patients with cardiovascular and other circulatory disabilities.
Animals↗
Ultra high speed transaxial image reconstruction of the heart, lungs, and circulation via numerical approximation methods and optimized processor architecture.
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Blood Circulation↗
Application of optimized parallel processing digital computers and numerical approximation methods to the ultra high-speed three-dimensional reconstruction of the intact thorax.
In order to achieve the computational capability to carry out many thousands of cross-sectional reconstructions, necessary to support a prototype high temporal and spatial resolution cylindrical scanning multiaxial tomographic unit, a series of design, software simulation, and fabrication studies is underway to develop a special-purpose high-speed reconstruction computer. This processor will rely upon integrated circuit arithmetic components of advanced design, and highly parallel architecture to execute X-ray based transaxial reconstruction algorithms at the rate of hundreds of cross sections/sec.
Computers↗
The rep mutation. VI. Purification and properties of the Escherichia coli rep protein, DNA helicase III.
The protein product of the rep gene of Escherichia coli is required for the replication of certain bacteriophage genomes (phi X174, fd, P2) and for the normal replication of E. coli DNA. We have used a specialized transducing phage, lambda p rep+, which complements the defect of rep mutants, to identify the rep protein. The rep protein has been purified from cells infected with lambda p rep+ phage; it has a molecular weight of about 70 000 and appears similar to the protein found in normal cells. Stimulation of phi X174 replicative form DNA synthesis in vitro was observed when highly purified rep protein was supplied to a cell extract derived from phi X-infected E. coli rep cells and supplemented with replicative form DNA. The purified protein has a single-stranded DNA-dependent ATPase activity and is capable of sensitizing duplex DNA to nucleases specific for single-stranded DNA. For this reason we propose the enzyme be called DNA helicase III. We infer that the rep protein uses the energy of hydrolysis of ATP to separate the strands of duplex DNA; the E. coli DNA binding protein need not be present. The rep3 mutant appeared to make a limited amount of active rep protein.
Bacterial Proteins↗
Limited surgical excision as the basis of a comprehensive therapy for cancer of the breast.
A comprehensive program of therapy has evolved with collaborating roles for surgery, pathology, radiotherapy, and chemotherapy. Our experience includes 131 patients with breast cancer treated at the Massachusetts General Hospital since 1956 by limited excision of the cancer. The tumors of 10 patients were noninvasive or sluggishly so; the patients received no further therapy. Because of the invasive character of their tumor, 121 patients received heavy postoperative irradiation. In 12 of these 121, the irradiation has been followed by immediate and prolonged chemotherapy. It is too soon to judge the effect of the chemotherapy, but survival rates of those treated by limited excision and primary irradiation compare favorably with those of patients treated by radical mastectomy.
Adult↗
Determining antibiotic levels in the blood.
Methods for the rapid determination of antibiotic blood levels require particular organisms or special conditions or long incubation. A method was developed for the rapid determination of antibiotic blood levels which requires no special equipment and is rapid. Special stains are not required. Utilizing bacteria from standard Kirby-Bauer sensitivity plates, a suspension is prepared and a pour plate made. Organisms which are sensitive to the questioned antibiotic and resistant to other antibiotics the patient is receiving are chosen. Muller-Hinton is the best general agar. Wells are cut, and antibiotic standards, antibiotic controls, and the patient's serum introduced. Within three to four hours, zone sizes can be read and the antibiotic blood level calculated. The materials and technical facility required should not preclude any laboratory from successfully performing the method.
Anti-Bacterial Agents↗
Incidence and causes of failures to control by irradiation the primary lesions in squamous cell carcinomas of the anterior two-thirds of the tongue and floor of mouth.
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Carcinoma, Squamous Cell↗
Myocardial infarction and risk region relationships: evaluation by direct and noninvasive methods.
Optimal quantitation of myocardial infarction requires resolution of the three-dimensional geometry of the ischemic region at a time that progression of tissue necrosis has been completed and can be sharply delineated from noninfarcted myocardium but before significant remodeling of the ventricular chamber. Although this can be achieved at two to three days after coronary occlusion by histologic techniques, a variety of technologies including two-dimensional echo, CTT, SPECT, PET, and NMR have demonstrated potential for providing noninvasive quantitative measurements of the extent of myocardial infarction. Additional studies are needed to clarify the utility of these technologies for resolving the highly variable transmural distribution of infarction that is present in the clinical setting. Assessment of the region at risk for infarction, the ischemic zone, requires quantitative measurements of the degree of ischemia as well as the size of the ischemic region. Although the above technologies may provide quantitative measurements of the dimensions of the ischemic zone, the utility for resolving the highly variable transmural distribution of regional myocardial blood flow using clinically applicable methodologies has not been convincingly established at present. It is possible that cine CT, new generation PET, and NMR technologies may eventually provide noninvasive quantitative measurements of regional myocardial blood flow.
Animals↗
Somatosensory evoked potentials and magnetic resonance imaging in syringomyelia.
Somatosensory evoked potentials (SEPs) to median and posterior tibial stimulation were obtained in 22 patients with syringomyelia. All patients had magnetic resonance imaging (MR) which defined the maximum transverse diameter of the syrinx as well as its longitudinal extension. SEP was abnormal in 16 (72%) patients. Median and posterior tibial SEPs were abnormal in 11 and 15 patients respectively. Both tests were abnormal in 10 patients. Ten patients showed absence of one or more central potentials (P/N13, N20, N22) and 7 patients demonstrated increased conduction times (N9-N20, P/N13-N20, N22-P40). The mean maximum transverse diameter of the syrinx was 7.5 mm in patients with normal SEPs and 16.2 mm in patients with abnormal SEPs. Abnormal SEP was observed in all 5 patients with loss of position sense, in 9 of 13 (69%) with loss of superficial pain and temperature, and 1 of 2 patients with motor deficit only. Central SEP abnormalities were observed in 3 of 5 patients with sensory deficits indistinguishable from a peripheral neuropathy and in 2 patients in the asymptomatic extremity. Three of 4 patients with syringomyelia and Chiari malformation had a normal SEP.
Adolescent↗