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Biomedical subjects

J Brennan

Publications and source records attributed to J Brennan.

At least 109 records · Page 6Linked to original sources

Detection of alpha-1-antitrypsin in hepatocytes in acute and chronic hepatitis.

Twelve of sixteen consecutive needle biopsies of liver with either acute or chronic hepatitis showed positive immunohistochemical staining for alpha-1-antitrypsin (AAT). Only two of the positive biopsies contained numerous, large periodic acid-Schiff positive, diastase resistant (PAS-D) globules in periportal hepatocytes; both patients were Pi MZ but only one had a low serum AAT concentration. The other 15 patients had normal or elevated serum AAT. The accumulation of AAT in hepatocytes, demonstrated by sensitive immunohistochemical staining, may indicate increased synthesis and/or impaired secretion of AAT occurring in association with various types of hepatitis.

Acute Disease↗

Immunohistochemical localization and quantitation of NADPH-cytochrome P-450 reductase in human liver.

An antibody raised in a goat against the human liver NADPH-cytochrome P-450 reductase (EC 1.6.2.4.) enzyme has been used to: 1) immunoquantify the level of this enzyme in human liver microsomes, and 2) study the distribution of the reductase across the human liver acinus. Employing the Western blot procedure, anti-human reductase IgG recognized a single band in human liver microsomes which corresponded in molecular weight to the purified reductase. The content of the NADPH-cytochrome P-450 reductase in six normal human livers varied from 87 to 121 pmol/mg of microsomal protein. NADPH-cytochrome P-450 reductase activity of the same microsomes ranged from 107 to 222 nmol of cytochrome c reduced per min per mg of protein. The correlation between reductase content and activity (r = 0.54) was not statistically significant (p greater than 0.1). The total cytochrome P-450 content (cytochrome P-450 and P-420) of the same microsomes varied from 423 to 1413 pmol/mg of microsomal protein. The average ratio of cytochrome P-450 to NADPH-cytochrome P-450 reductase was 7.1:1 +/- 3.1 (mean +/- SD) in the human liver microsomal preparations studied. The reductase was found to be nonuniformly distributed across the human liver acinus. Although all hepatocytes stained positively for NADPH-cytochrome P-450 reductase, the staining intensity was highest in zone 3 and in some cases also in zone 1 hepatocytes. These results show that human liver contains a gross excess of cytochrome P-450 molecules to NADPH-cytochrome P-450 reductase molecules. Furthermore, the differential distribution of the reductase within the human liver acinus may lead to a better understanding of the mechanism underlining site-specific drug hepatotoxicity.

Cytochrome P-450 Enzyme System↗

A microcomputer system for monitoring ventilation in neonates.

The characteristics of a microcomputer-based system for measuring ventilatory parameters in neonates on mechanical ventilatory assistance are described. The tidal flows of the infant are sensed by a pneumotachometer housed in the wall of a constant pressure plethysmograph. The processed signal from the pneumotachometer is fed to a dedicated analog-to-digital converter and 6502 microcomputer, which, in turn, loads a dual ported RAM buffer with smoothed, digitized, tidal flow data. At the end of each minute the Apple 2+ processes the accumulated data and computes tidal volume, respiratory frequency, minute volume and the difference between inspired and expired volume. Numerical outputs for these variables and a histogram, representing the distribution of tidal volumes for the minute, are printed on a dot matrix printer. This inexpensive system is capable of presenting contemporary, summarized, ventilatory data in a form that is potentially very useful for the clinicians who are managing the care of the infant.

Computers↗

Computed tomography in diffuse lung disease: improving the image.

Diffuse lung disease is often a difficult clinical and radiographic problem to resolve. Standard computed tomography (CT) techniques are often unhelpful. By combining practical physiological criteria with narrow section CT a protocol has been developed which yields more accurate information and is now the standard method of CT investigation of diffuse lung disease in our department.

Bronchiectasis↗

Evaluation of computed tomography and radionuclide scanning in the staging of cutaneous T-cell lymphoma.

Computed tomography (CT) of the abdomen and pelvis was performed on 30 patients with cutaneous T-cell lymphoma (CTCL) as part of their pretreatment staging evaluation. Twenty-two patients also had liver-spleen radionuclide scans. Physical examination revealed limited cutaneous plaque disease in five patients, extensive plaque disease in 11 patients, cutaneous tumors in six patients, and exfoliative erythroderma in eight patients. Generalized palpable adenopathy was detected in 11 patients, localized palpable adenopathy in ten patients, and no adenopathy in nine patients. Peripheral lymph node biopsy specimens showed CTCL in seven patients and dermatopathic lymphadenitis or sinus histiocytosis in 17 patients. Two patients were at disease stage Ia, five were at stage Ib, seven were at stage IIa, two were at stage IIb, seven were at stage III, and seven were at stage IVa. The CT did not reveal intra-abdominal, retroperitoneal, or pelvic adenopathy, or hepatic or splenic abnormalities in any patient. Radionuclide scans demonstrated nonspecific abnormalities in five patients, but did not appear to reflect disease involvement. Computed tomography of the abdomen and liver-spleen radionuclide scans should not be routine staging procedures for CTCL.

Humans↗

Randomized trial of high-dose cytarabine versus amsacrine in acute myelogenous leukemia in relapse: a Leukemia Intergroup Study.

Patients with acute myelogenous leukemia in relapse who were ineligible for further anthracycline therapy either because they were judged to be anthracycline resistant or had received the maximum doses were randomized to receive high-dose cytarabine (3 g/m2 every 12 hours for 6 days) or amsacrine (75 mg/m2 daily for 7 days). The response rates in both groups were similar: three of 25 patients given high-dose cytarabine and three of 23 given amsacrine obtained complete remissions.

Adolescent↗

Changes in the characteristics of the bone marrow during therapy for acute non-lymphocytic leukemia: relationship to response to remission induction therapy.

The bone marrows of patients with acute non-lymphocytic leukemia being treated with 'high dose' cytosine arabinoside remission induction therapy were sampled prior to the initiation of chemotherapy, after 6 days of therapy and again 7 days after the conclusion of therapy. These studies demonstrated that the marrows of patients who would enter remission (CR patients) contained less leukemic cells prior to therapy than patients who would fail to enter remission because of persistent leukemia (resistant disease, or RD patients). A comparison of the day 6 and 7-day post-therapy marrows with the pretherapy marrow demonstrated that while the % reduction in leukemic cells was greater for CR patients than for RD patients, the absolute reduction in leukemic cell mass was the same for both groups. While there was no relationship between the percentage of cells in S phase and the pretherapy leukemic cell mass, the greater the pretherapy leukemic cell mass the greater the likelihood that the leukemic cells would be resistant to the metabolic effects of cytosine arabinoside in vitro.

Aged↗

Does the oral zinc tolerance test measure zinc absorption?

Increases in plasma zinc concentration were compared with radiozinc absorption after oral test doses. Ten healthy, fasting subjects were each given 385 mumol zinc chloride (25 mg Zn) labelled with 0.5 muCi 65ZnCl2 and a non-absorbed marker, 51CrCl3, dissolved in 100 ml of water; another 10 persons were given 354 mumol zinc chloride and 125 g of minced turkey containing 31 mumol zinc also labelled with 65Zn and 51Cr. Measurements were made of plasma zinc concentration at hourly intervals for 5 hours, radiozinc absorption by stool counting of unabsorbed radioactivity 12-36 hours later, and radiozinc retention by whole body counting at 7 days. The mean percentage of radiozinc absorbed and retained in the body from the two test meals was found to be identical (42%). In contrast the increased area under the plasma zinc curve up to 5 hours after the turkey meal, 28 +/- 9 mumol/L (mean +/- SD) was significantly less than that for zinc chloride alone, 47 +/- 15 mumol/L, p less than 0.005. Despite this difference, a good correlation was found between the area under the plasma zinc curve and 65Zn absorption in individual subjects after each meal. The discrepancy between the results of zinc absorption derived from the plasma zinc curve and 65Zn absorption for the liquid and solid test meals was most likely explained by binding of zinc to food and delayed gastric emptying of the solid meal. With a test meal of turkey meat at least this dampened the plasma appearance of zinc but did not affect its overall absorption.

Administration, Oral↗

Temporal orientation in the pre-senium and old age.

Temporal orientation in 235 normal elderly subjects was examined and compared with previous results from a young adult population. Orientation for time in the elderly remains reasonably intact; the major exception to this was inaccurate recall of the date, which was most pronounced among women in the older group studied (71 +).

Aged↗

Inhibition of DNA synthesis by cytosine arabinoside: relation to response of acute non-lymphocytic leukemia to remission induction therapy and to stage of the disease.

The sensitivity of leukemic marrow cell DNA synthesis to cytosine arabinoside (araC) exposure in vitro was studied in specimens obtained from patients with acute non-lymphocytic leukemia. Cells from patients who had been treated with araC in the past were more likely to be resistant to the effect of araC on DNA synthesis than cells obtained from patients who had not been so-treated previously. Resistance to the effects of araC on DNA synthesis was associated with the failure of high-dose araC therapy to induce remissions in relapsed patients, whereas remission induction failure in previously untreated patients was not associated with araC resistance.

Acute Disease↗