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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 199 records · Page 11Linked to original sources

Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone.

Previous studies of episodic hormone secretion of the hypothalamic-pituitary-gonadal axis in normal men have produced conflicting results due to examinations of small cohorts of subjects or to limited sampling techniques. We evaluated gonadotropin and testosterone (T) secretory patterns in 20 normal men by sampling blood at 10-min intervals for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). T concentrations were also analyzed at 20-min intervals in 10 subjects. A previously unappreciated spectrum of gonadotropin and T secretory patterns was observed in normal men. Both mean LH concentrations and mean LH pulse amplitudes varied fourfold between individuals. LH interpulse intervals varied from 30 to 480 min (mean 119 +/- 32). Results also suggested a relative refractory period at the level of the hypothalamus or pituitary. In three subjects, a striking nighttime accentuation of LH pulsations was noted. Through use of Fourier analysis, a diurnal variation in LH was observed in the population (P less than 0.02). Mean FSH levels showed marked variation between individual subjects, with discrete pulses rarely observed. No diurnal variation in FSH secretion was noted. Serum T concentrations determined at 6-h intervals ranged from 105 to 1,316 ng/dl between subjects. When T was measured at 20-min intervals, marked intermittent declines in the T concentrations to levels well below the normal range were observed in 3 of 10 subjects. T secretion was found to lag behind LH secretion by approximately 40 min (P less than 0.02).

Adult↗

Cause of the raised wedge pressure on exercise in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) markedly increase their pulmonary artery wedge pressure on mild exercise even though they have no overt left heart disease and no increase in the esophageal pressure (as a reflection of mean intrathoracic pressure). We wondered if lung distension due to gas trapping during the hyperpnea of exercise might cause the wedge pressure to rise by increasing juxtacardiac pressures above esophageal pressures. If this were so, then (1) tachypnea alone, without exercise, should cause the FRC and intracardiac pressures to increase in patients with COPD, (2) there should be an increase in FRC associated with the rise in wedge pressure on exercise, and (3) these changes should not occur in patients without COPD. We studied 39 patients with COPD (Ppa = 21 +/- 6 mm Hg [mean +/- SD], FEV1 [% predicted] = 39 +/- 16) and 13 control patients with similar pulmonary artery pressures but no airflow obstruction (Ppa = 22 +/- 20 mm Hg, FEV1 [% predicted] = 110 +/- 24). In those with COPD, light exercise raised the FRC by 0.5 +/- 0.5 L. Tachypnea alone, at the rate present during exercise, raised the FRC by 0.6 +/- 0.4 L and there was a 10% increase in left lower lobe area on lateral chest X-ray. Wedge, right atrial, and pulmonary artery pressures rose together during tachypnea with and without exercise. By contrast, in the control patients without COPD, the right atrial pressure change on exercise did not reflect that of the left atrium in extent or direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Serum free thyroxine and free tri-iodothyronine in normal children.

Serum free thyroxine (fT4) and free tri-iodothyronine (fT3) were measured in 138 normal school children, adolescents and their younger siblings, whose ages ranged from 3 months to 18 years. Mean fT4 concentration (16.8 pmol/L) was similar to the adult mean concentration of 17 pmol/L and all the values were within the adult reference range. At all ages the fT3 range was considerably higher than the adult reference range and the overall mean fT3 concentration (8.3 pmol/L) was at the upper limit of normal in adults. In subjects aged 13-18 years the mean fT4 concentration was higher and the mean fT3 concentration lower than in children aged 0-12 years. The reasons for these differences are not known, but the data obtained provide a useful guide to the interpretation of serum free thyroid hormone measurements in children.

Adolescent↗

Biological activity of serum prolactin in patients with primary hypothyroidism.

Prolactin bioactivity was measured in sera from 22 patients with primary hypothyroidism and 13 euthyroid control subjects and compared with estimates of immunoactivity given by radioimmunoassay. The Nb2 rat lymphoma cell assay was modified to improve specificity for prolactin and used to measure bioactivity. Results of serum prolactin levels obtained using the bioassay were closely correlated with radioimmunoassay results in both hypothyroid patients and control subjects. Mean bioactivity/immunoactivity ratios in patients were not significantly different from those in control subjects. Mean prolactin concentration measured by both assays was significantly higher in patients than control subjects. Serum prolactin in patients with primary hypothyroidism appears to have essentially normal bioactivity as measured in the Nb2 assay, in contrast with a report of major differences between activity in radioreceptor assay and RIA in hypothyroid patients.

Animals↗

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↗

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↗

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↗

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↗