Cause of increased right and left atrial pressures in patients with obstructed airflow disease.
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Aged↗
Biomedical subjects
J Butler
Publications and source records attributed to J Butler.
Bioactivity and immunoactivity of growth hormone during dynamic testing of patients with acromegaly.
We have used the Nb2 cell proliferation bioassay for lactogenic hormones to investigate the biological activity of hGH in sera of patients with acromegaly. The specificity of the assay has been improved by the use of monoclonal antibodies to block the activity of individual lactogenic hormones. Disease activity in patients was assessed by scoring signs and symptoms, and by measuring IGF-I concentrations in some patients. Patients with a wide spectrum of disease activity were studied using a TRH test. hGH concentrations were measured by bioassay, RIA and immunoradiometric assay (IRMA) at 0, 20 and 60 min after injection of TRH. There was a high degree of correlation between log10 of all hGH concentrations measured by bioassay and RIA (r = 0.995, P less than 0.0001), between bioassay and IRMA (r = 0.990, P less than 0.0001), and between RIA and IRMA (r = 0.995, P less than 0.0001). In contrast to previous reports, we found no evidence for changes in the bioactivity of hGH secreted after pituitary stimulation.
Acromegaly↗
On the specificity of allopurinol and oxypurinol as inhibitors of xanthine oxidase. A pulse radiolysis determination of rate constants for reaction of allopurinol and oxypurinol with hydroxyl radicals.
Allopurinol has been employed as a "specific" inhibitor of xanthine oxidase in studies of hypoxic/reoxygenation injury. Pulse radiolysis was used to establish rate constants for the reactions of allopurinol and its major metabolite oxypurinol with hydroxyl radicals: values were (1.45 +/- 0.24) x 10(9) M-1 s-1 for allopurinol and (4.95 +/- 0.84) x 10(9) M-1 s-1 for oxypurinol. These rate constants show that, in view of the amounts of allopurinol that have been used in animal studies, hydroxyl radical scavenging by this molecule could contribute to its biological actions, especially if animals are pre-treated with allopurinol, so allowing oxypurinol to form. The ability of allopurinol to protect tissues not containing xanthine oxidase against reoxygenation injury may be related to radical scavenging by allopurinol and oxypurinol.
Allopurinol↗
A comparison of the free radical properties of several anthracycline anti-tumour drugs and some of their analogues.
NADPH consumption and esr spectroscopy have been used to study the rate of formation and signal intensity of free radicals produced by various anthracycline anti-tumour drugs in rat liver microsomal extract. The drugs investigated were Adriamycin, 4'Deoxyadriamycin, Daunorubicin, 4 Demethoxydaunorubicin and Carminomycin. Pulse radiolysis was also used to determine the case of reduction of each of the analogues to its semiquinone radical and some kinetic properties of the radicals produced. It is believed that the occurrence of reactions other than dismutation could be responsible for the shortened lifetimes of the semiquinone radicals observed in biological systems.
Animals↗
Air conditioning and exercise-induced asthma.
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Air Conditioning↗
Fine-needle aspiration cytology in the diagnosis of primary breast cancer.
To evaluate the role of fine-needle aspiration (FNA) cytology in the diagnosis of primary breast cancer, we reviewed our experience over a recent 5-year period at Harbor-UCLA Medical Center. A total of 590 aspirates with subsequent follow-up were documented. One hundred thirty-three primary cancers were histologically proved. Of the 133 cancers, 91 (68%) were diagnosed as malignant by aspiration cytologic examination; another 22 (17%) were reported as suspicious. Of the cancers, 8 (6%) had a benign cytologic diagnosis and 12 (9%) had unsatisfactory smears. No cytologic tests positive for malignancy were found to be benign on histologic examination. With an absolute sensitivity of 75% and a specificity of 100%, we conclude that FNA cytologic examination is highly accurate in the diagnosis of breast cancer. With no false-positive studies, the finding of a clearly malignant cytologic condition obviates the need for biopsy before mastectomy.
Adult↗
Measurements of the Sigma 0c- Lambda c+ and Sigma c++- Lambda c+ mass differences.
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Journal Article↗
High-energy diffraction dissociation of KL0 into exclusive final states.
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Journal Article↗
The scavenging of oxidants by sulphasalazine and its metabolites. A possible contribution to their anti-inflammatory effects?
Sulphasalazine (Salazopyrin) and its metabolites sulphapyridine and 5-aminosalicylate are powerful scavengers of the hydroxyl radical, determined by pulse radiolysis and confirmed by assays based on deoxyribose degradation by hydroxyl radicals. 5-Aminosalicylate can also protect alpha 1-antiprotease against attack by the myeloperoxidase-derived oxidant hypochlorous acid. The ability to scavenge oxidants produced at sites of inflammation may contribute to the anti-inflammatory action of sulphasalazine and its metabolites.
Aminosalicylic Acids↗
The effect of the anthrapyrazole antitumour agent CI941 on rat liver microsome and cytochrome P-450 reductase mediated free radical processes. Inhibition of doxorubicin activation in vitro.
The anthrapyrazole CI941 is one of a new series of DNA complexing drugs which displays high level broad spectrum antitumour activity in mice. In view of the proposed role of drug free radical formation, superoxide generation and lipid peroxidation in anthracycline and anthraquinone induced toxicities, the redox biochemistry of CI941 has been investigated. Studies have been performed in vitro using rat liver microsomes and purified cytochrome P-450 reductase. In addition, the ability of CI941 to undergo chemical reduction has been examined. Pulse radiolysis of CI941 demonstrated that the drug can undergo chemical reduction with a one electron reduction potential of E1(7) = -538 +/- 10 mV. However, electron spin resonance (ESR) spectroscopy studies using either NADPH fortified microsomes or cytochrome P-450 reductase, failed to detect a drug free radical signal. Unlike doxorubicin, CI941 (150 microM) inhibited basal rate microsomal NADPH consumption by 45%. Furthermore, CI941 (50-200 microM) antagonised doxorubicin stimulated (1.8-fold) NADPH oxidation by over 50%. CI941 also antagonised the formation of a doxorubicin free radical ESR signal in a concentration dependent manner. CI941 induced minimal superoxide generation in the presence of either microsomes or cytochrome P-450 reductase and inhibited doxorubicin induced (50 microM) superoxide formation by up to 80% (50-200 microM CI941). Importantly, CI941 inhibits both basal rate and doxorubicin (100 microM) stimulated lipid peroxidation (52% inhibition at 5 microM CI941). These data suggest that CI941 is unlikely to induce free radical mediated tissue damage in vivo. On the contrary, CI941 may have a protective role if used in combination with doxorubicin.
Animals↗
Production of the charmed strange baryon Xi c+ by neutrons.
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Journal Article↗
The reduction of anti-tumour diaziridinyl benzoquinones.
The properties of the semiquinone radicals produced for 2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone (AZQ) and 2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone (BZQ), have been investigated. AZQ semiquinone radicals can be produced from the reduction of AZQ by superoxide radicals, whereas BZQ semiquinone radicals are unstable in the presence of oxygen. The one-electron reduction potentials of the couples Q/Q-. at pH 7.0 were determined as -70 +/- 10 mV for AZQ and -376 +/- 15 mV for BZQ. The difference in these potentials is explained. As a consequence of ESR studies on the enzymatically produced radicals, we have considered the factors which determine the detection of ESR signals for reduced quinones produced in a biological system.
Antineoplastic Agents↗
Monoclonal antibody staining and impact of surgical technique on the identification and quantitation of steroid receptors in human breast cancer.
In this prospective study of 31 patients, paired receptor levels from biopsy and mastectomy specimens were found to be significantly correlated on biochemical assay. Despite this fact, 6 of 20 tumors that were estrogen receptor-positive on biopsy, had a negative assay from the mastectomy specimen, indicating the need for a fresh tumor specimen. Immunocytochemical staining with monoclonal antibody H222 Spy, an antibody specific for the estrogen receptor, was evaluated in 34 biopsy and mastectomy specimens. With a sensitivity of 85 percent and specificity of 93 percent, this technique compares favorably with the standard biochemical assay.
Adult↗
Syndrome of periodic fever, pharyngitis, and aphthous stomatitis.
A syndrome of periodic fever that resembles human cyclic neutropenia in its clinical presentation has been identified in 12 children observed at two major referral centers. Attacks characterized by abrupt onset of fever, malaise, chills, aphthous stomatitis, pharyngitis, headache, and tender cervical adenopathy occur at 4- to 6-week intervals over periods of years. These episodes of illness resolve spontaneously in 4 to 5 days. Mild leukocytosis and elevation of the erythrocyte sedimentation rate during attacks are the only laboratory abnormalities. Affected children grow normally, are not unusually susceptible to infection, and exhibit no long-term sequelae. Attacks may be aborted by short courses of prednisone but do not respond to nonsteroidal anti-inflammatory agents. This syndrome is sporadic and appears to be much more common than cyclic neutropenia.
Blood Sedimentation↗
Group C Niemann-Pick disease: faulty regulation of low-density lipoprotein uptake and cholesterol storage in cultured fibroblasts.
Incubation of mutant Niemann-Pick C fibroblasts with low-density lipoprotein (LDL) resulted in excessive internalization of lipoprotein and extensive cellular over-accumulation of unesterified cholesterol. The uptake of LDL by the mutant cells appeared to occur through the classic LDL receptor pathway and internalized lipoprotein was processed in lysosomes. Lipoprotein uptake into mutant cells was associated with delays in the initiation of established cellular cholesterol homeostatic responses. Subcellular fractionation of mutant Niemann-Pick C fibroblasts accumulating LDL-cholesterol showed excess unesterified sterol to be localized in the light lysosome-light membrane region of a Percoll gradient, and revealed that cholesterol storage was associated with a specific alteration in the normal profiles of lysosomal marker enzymes.
Cells, Cultured↗
Remission of hypoparathyroidism during lactation: evidence for a physiological role for prolactin in the regulation of vitamin D metabolism.
We studied a young woman with surgical hypoparathyroidism who, on her usual maintenance dose of calcitriol, developed hypercalcaemia 9 d postpartum when lactation was established. Serum values of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) values were very high (127 pg/ml). The patient remained without exogenous calcitriol treatment for 40 d, during which time serum 1,25(OH)2D3 levels remained within the normal range and serum calcium fell with a half-time of 27 d. The requirements for calcitriol increased to antepartum levels when lactation had ceased. There was a close negative correlation between requirements for calcitriol and serum PRL values. After weaning, an episode of hypercalcaemia was induced by increasing the dose of calcitriol. On stopping calcitriol the serum 1,25(OH)2D3 fell to low values (4 pg/ml) within 2 d and serum calcium fell with a half-time of 3 d, necessitating the early reintroduction of calcitriol. We conclude that in hypoparathyroidism exogenous vitamin D requirements fall during lactation because of enhanced endogenous production of 1,25(OH)2D3. The lactation-associated increase in circulating 1,25(OH)2D3 concentrations thus results from a parathyroid hormone-independent mechanism, possibly by an effect of PRL on the 1 alpha-hydroxylase.
Adult↗
Temperature alters bronchial blood flow response to pulmonary arterial obstruction.
Lobar bronchial blood flow has been reported to increase and decrease acutely after pulmonary arterial obstruction (PAO). Because bronchial blood flow (Qbr) to the trachea and bronchi is influenced by inspired air temperature, we investigated whether temperature differences could explain these disparate results. In 10 open-chested dogs the left lower lobe (LLL) was isolated and perfused in situ with autologous blood at a controlled temperature with an independent vascular circuit. The abdomen and the chest of the dog were enclosed in a Plexiglas box in which air was fully humidified and temperature could be regulated. Qbr, determined by the reference flow technique using 16 micron microspheres, was measured before and 30 min after onset of PAO with the air in the box being either at 27 or 39 degrees C and with warmed LLL blood (37 degrees C) in the latter condition. Anastomotic bronchial blood flow [Qbr(s-p), determined as overflow from the closed LLL vascular circuit and measured in ml X min-1 X 100 g dry lung wt-1 X 100 Torr mean systemic pressure-1] was measured continuously at both temperatures. Both before and after PAO, Qbr and Qbr(s-p) were closely correlated: Qbr (ml/min) = 1.12 + 0.978Qbr(s-p); R = 0.912. This was true regardless of the presence or the absence of pulmonary flow, showing that the distribution of bronchial blood flow between the anastomotic and the nonanastomotic portion does not change acutely during PAO. When the air in the box was 27 degrees C, Qbr(s-p) was 19.5 +/- 5.2 (SE) and increased to 38.6 +/- 8.1 with PAO (P less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Acute increases in anastomotic bronchial systemic to pulmonary blood flow due to generalized lung injury.
Since pulmonary blood flow to regions involved in adult respiratory disease syndrome (ARDS) is reduced by hypoxic vasoconstriction, compression by cuffs of edema, and local thromboses, we postulated that the bronchial circulation must enlarge to provide for the inflammatory response. We measured anastomotic bronchial systemic to pulmonary blood flow [QBr(s-p)] serially in a lung lobe in 31 open-chest dogs following a generalized lobar injury simulating ARDS. The pulmonary circulation of the weighed left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in anesthetized dogs. QBr(s-p) was measured from the amount of blood which overflowed from this closed vascular circuit corrected by any changes in the lobe weight. The LLL was ventilated with 5% CO2 in air. The systemic blood pressure (volume infusion), gases, and acid-base status (right lung ventilation) were kept constant. We injured the LLL via the airway by instilling either 0.1 N HCl or a mixture of glucose and glucose oxidase or via the pulmonary vessels by injecting either alpha-naphthylthiourea or oleic acid into the LLL pulmonary artery. In both types of injury, there was a prompt rise in QBr(s-p) (mean rise = 247% compared with control), which was sustained for the 2 h of observation. The cause of this increase in flow was studied. Control instillation of normal saline into the airways or into the pulmonary vessels did not change QBr(s-p) nor did a similar increase in lobar fluid (weight) due to hydrostatic edema. Neither cardiac output nor systemic blood pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗