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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 217 records · Page 12Linked to original sources

Human monoclonal antibodies from patients with rheumatoid arthritis: cross reactions against cellular constituents.

Hybridization of peripheral blood lymphocytes from patients with rheumatoid arthritis has yielded 14 monoclonal antibodies which react with cultured human epithelial cells. Immunofluorescence staining identifies at last five different types of antibody. Solid phase immunosorbent assays show a variety of cross-reaction patterns with nucleic acids, proteoglycan, cardiolipin and plastic, confirming that the various antibodies react with epitopes which are at least slightly different. These conclusions are confirmed by SDS gel electrophoresis and immunoblotting on epithelial cell extracts. Similar antibodies previously found in association with lupus-like disease have been thought to be representative of the high antinuclear antibody response characteristic of lupus. Our data are more consistent with the hypothesis that all or many of these antibodies are part of the normal inflammatory response.

Antibodies, Monoclonal↗

Prostaglandins in colonic anastomotic healing.

In this study we report the effects of flurbiprofen and prostaglandin E2 on anastomotic tensile strength, collagen synthesis, and collagenolytic activity which are in a particularly fine balance in colonic healing. Colonic anastomoses were fashioned in 150 Sprague-Dawley rats which were allocated to receive either 20 mcg prostaglandin E2 in 1 ml saline, 1 ml saline alone (control) intraperitoneally for three days post-operatively, or oral 2.5 mg/kg flurbiprofen daily. Anastomotic bursting pressures, collagen content and collagenolytic activity were measured at three, six, and ten days. It was found that prostaglandin E2-treated animals had significantly weaker anastomoses at three days (102 +/- 6.1 mm Hg; m +/- SEM) compared with the control (126 +/- 7.3; P less than 0.02) or flurbiprofen group (128 +/- 4.6; P less than 0.01) with no differences at six and ten days. Collagen levels were higher in flurbiprofen-treated rats at three days (9.7 +/- 0.2 micrograms hydroxyproline/mg tissue) compared with the control (8.1 +/- 0.4 micrograms/mg; P 0.01) or prostaglandin E2 group (7.2 +/- 0.5 micrograms/mg; P 0.001). These differences were unchanged at six days but were not statistically different at ten days. Collagenolytic activity showed no differences in the three groups during the study. It is concluded that flurbiprofen enhances colonic healing with improved collagen synthesis without affecting collagenolytic activity.

Animals↗

The distribution and characteristics of asbestos fibers in the lungs of Finnish anthophyllite mine-workers.

Measurements of the concentrations and dimensions of uncoated and coated fibers in blocks of tissue taken at the periphery and elsewhere from slices of lungs obtained from two anthophyllite-mine workers are reported. A single block from the lung of a third worker was also analyzed. For the subject examined in most detail, the mean peripheral fiber concentration was greatest in the lower lobe. In the other subject there did not appear to be much variation in fiber concentration with distance from the periphery. The count median lengths of uncoated fibers ranged from about 8 to 12 micron and for coated fibers from 40 to 50 micron. It was apparent that dicing tissue samples, before hypochlorite digestion, led to fracture of the longer uncoated and coated fibers. The results are compared with similar measurements made on the lung of an insulation worker and reported previously.

Aged↗

Retention of 239Pu in the mouse lung and estimation of consequent dose following inhalation of sized 239PuO2.

The retention of 239Pu in the lungs of SAS/4 mice following inhalation exposure to sized 239PuO2 particles is described. When the initial alveolar deposition (IAD) was less than 200 Bq, retention of 239Pu could be described by a two-component exponential expression, about 90% being cleared with a half-time of about 40 days and the remainder with a half-time of about 150 days. Similar amounts of 239Pu were retained up to 3 months with IADs greater than 800 Bq, but clearance was impaired thereafter, the half-time of the second component increasing to about 720 days. The retention of 239Pu was independent of the particle size of the administered 239PuO2. Studies of the retention of 239Pu by individual lobes indicated that there were intrinsic interlobar differences which were enhanced at higher IADs. Lung clearance was also studied by the measurement of 239Pu in feces excreted by groups of mice in the period immediately prior to sacrifice. The estimation of radiation dose to lung is discussed.

Aerosols↗

Hemodilution anesthesia: a valuable aid to major cancer surgery in children.

Since 1974, 25 children had 27 major cancer operations with the aid of hemodilution anesthesia. This includes operations for Wilms' tumors, liver tumors, adrenal tumors, pancreatic tumors, ovarian tumors, and resection of metastatic thoracoabdominal tumors. With the use of this method, operative blood loss has been greatly reduced and operative technique improved. At the beginning of surgery, whole blood is removed from the patient and replaced with three times the volume of a balanced electrolyte solution to maintain intravascular volume. After the time of significant blood loss has ceased, the patient's own blood is returned and diuresis stimulated with furosimide to remove the infused electrolyte solution. Hypothermia, allowing the temperature to drift down to just below 32 degrees C, helps protect vital organs against hypoxia and arterial hypotension to a mean of 50 torr systolic pressure is well tolerated and further reduces blood loss. Adequate tissue oxygenation can be maintained safely during hemodilution to a hematocrit value of 14 percent. Use of bank blood transfusion was necessary in only 6 of 25 patients. It was given when the calculated postoperative hematocrit value would be less than 30 percent. The diluted blood lost during surgery has a low red blood cell volume per milliliter and each milliliter lost depletes the total red blood cell volume by a lesser amount. Also, the ease and speed of surgery may be facilitated by the nearly bloodless operative field. Provided respiratory support is maintained, these children showed only minor clinical effects from this large fluid infusion. The majority of patients who are Jehovah's Witnesses accept this technique with the modification that we keep the blood moving and in direct contact with the patient's vascular system. Carefully planned and meticulously applied short-term hemodilution anesthesia provides a safe method for minimizing operative blood loss and reduces the difficulty of major cancer surgery in children.

Anesthesia↗

Distribution and characteristics of amphibole asbestos fibres, measured with the light microscope, in the left lung of an insulation worker.

Concentrations of uncoated and coated amphibole fibres were measured postmortem in samples taken from the periphery of both upper and lower lobes of the left lung of an insulation worker. Similar measurements were made on a more limited range of samples from elsewhere in the lung and on a hilar lymph node. The mean concentration of uncoated fibres in the upper lobe was twice that in the lower. Significant differences were observed in the mean concentration of uncoated fibres in different regions of the periphery, the diaphragmatic region having the lowest value. Variations in the concentrations of both uncoated and coated fibres in the costal region of the lower lobe may have been related to the effect of rib structures on ventilation. Concentrations of fibrous and non-fibrous dust were well correlated in the peripheral samples. The length distributions of uncoated and coated fibres were also measured and differences detected in fibres from the various regions of the lung. This work emphasises the care required in sampling lung tissue in order to obtain representative material for the determination of fibre concentration.

Asbestos↗

Evidence for a dose-dependent inflammatory response to quartz in the rat lung and its significance in early changes in collagen metabolism.

The response of the rat lung to a range of doses of quartz at 50 and 100 days after its administration by intratracheal instillation has been assessed by bronchopulmonary lavage. The effects on the number of polymorphonuclear leukocytes (PMN), lymphocytes and macrophages are described. In addition the concentrations of soluble protein and hydroxyproline and the activities of lactate dehydrogenase, PZ peptidase and collagenase in lavage fluid supernatants were measured and an assessment of the hydroxyproline content of recovered cells was made. Finally PZ peptidase and collagenase were assayed in PMN-enriched cell fractions and in samples obtained from short-term culture of recovered macrophages. There was a dose-dependent increase in the recovery of all three cell types, and in the amounts of lactate dehydrogenase, protein and hydroxyproline in lavage fluids, which showed no signs of resolution over the 100-day period studied. Measurements of PZ peptidase and collagenase suggested that the PMN, not the macrophages, are the major source of these degradative enzymes. The relevance of these findings with regard to the importance of PMN in quartz-induced fibrosis is discussed.

Animals↗

The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts.

The acute response of the rat lung to a range of fibrous materials has been investigated by bronchopulmonary lavage, at dose levels of 0.5 and 1.0 mg, 1 and 7 days after their administration by intratracheal instillation. The materials chosen for study included UICC chrysotile A, amosite, crocidolite and anthophyllite, and samples of S. African "long" amosite and glass fiber. In addition, the subacute response to 1, 2 and 3 mg of chrysotile and amosite has been studied at 50 and 100 days after instillation. In the acute phase at 1 day after instillation, the response to chrysotile was greater than that to any of the other materials, but by 7 days there was no gradation in the response to different dusts. In the subacute phase, cell recoveries were low, and it was not possible to assess the long-term cytotoxic or fibrogenic effects of amosite and chrysotile by analyses of lung washes, even though biochemical and histological methods indicated gross changes in lung pathology.

Animals↗

Dose-dependent effects in the subacute response of the rat lung to quartz. I. The cellular response and the activity of lactate dehydrogenase in the airways.

The response of the rat lung to a range of doses of quartz at 50 and 100 days after its administration by intratracheal instillation was investigated by bronchopulmonary lavage. The effects on the numbers of polymorphonuclear leucocytes, lymphocytes and macrophages recovered are described. In addition, the size distribution of the recovered macrophages was followed and measurements of total numbers of macrophages in the lung were made using a radioactive tracer technique. Finally, the activity of the cytoplasmic enzyme, lactate dehydrogenase, in lavage fluid supernatants was recorded. There was a dose-dependent increase in the recovery of all three cell types and an increase in the total numbers of macrophages in the lungs which showed no signs of resolution over the 100 day period studied. Increasing levels of lactate dehydrogenase were also dose-dependent and well correlated with the numbers of polymorphs and lymphocytes recovered. The importance of this prolonged inflammatory reaction in relation to the fibrogenic action of quartz is discussed.

Animals↗

Separation of two molecular species of the Sm antigen by affinity chromatography with murine monoclonal and human anti-nuclear autoantibodies.

Nuclear ribonuclear protein (nRNP) and Sm were extracted from a 30-60% ammonium sulphate fraction of rabbit thymus extract by affinity chromatography. Immunoadsorbent columns were prepared from IgG extracted from an anti-nRNP serum, an anti-Sm serum and two monoclonal autoantibodies derived from a MRL/lpr mouse. All four immunoadsorbents isolated both nRNP and Sm antigens indicating that they exist as the 'nRNP/Sm complex' A species of Sm which did not bind to the anti-nRNP column and which was subsequently purified with the anti-Sm column was termed 'free Sm'. The Sm in the complex and free Sm were immunologically identical on immunodiffusion and gave similar polypeptide bands on polyacrylamide gel electrophoresis. However, they differed in that complexed Sm was sensitive to heat and RNAase. These studies provide direct evidence of a physical association between the nRNP and Sm antigens and indicate an additional molecular species of Sm whose resistance to RNAase may be due to different associated RNA species.

Animals↗

Alveolar deposition of sized particles of 239PuO2 in the mouse.

Data on the alveolar deposition of 239PuO2 particles in the mouse are presented. It is shown that alveolar deposition falls with increasing activity median aerodynamic diameter (AMAD) over the range 0.6 to 2.4 microns. In the mouse, any peak in alveolar deposition must occur at an AMAD of less than 1 micron. Information is also provided on the relative lobar concentrations (RLCs) of 239PuO2. The RLC is greatest in the right apical lobe and increases quite sharply with AMAD. The RLCs of the other lobes of the right lung decline with AMAD. The RLC in the left lobe is relatively unaffected by AMAD.

Aerosols↗

Hydralazine, antinuclear antibodies, and the lupus syndrome.

The incidence of patients with positive antinuclear antibody test results rose during three years of treatment with hydralazine. At the end of that period over half of the patients (both rapid and slow acetylators) had titres exceeding 1/20, but the rate of rise was faster in the slow acetylators than in the rapid. There was a significant relation between the cumulative dose of hydralazine and the proportion of patients found to have antinuclear factors. Fewer black patients had positive test results than white. Patients whose antinuclear antibody test results changed fron negative to positive during the study showed this change five to 26 months after beginning treatment. Some patients showed a substantial fall in antinuclear antibody titre even though hydralazine was continued. From these findings patients in whom test results for antinuclear antibody became positive during treatment with hydralazine need not have the drug stopped unless they have clinical features of the lupus syndrome.

Acetylation↗

Improved survival in children with osteosarcoma following resection of pulmonary metastases.

Despite the effectiveness of improved chemotherapy and radiotherapy, surgical resection of all gross metatastic disease from the lung appears to improve the survival of children with osteosarcoma. At Children's Orthopedic Hospital and Medical Center (COHMC), from 1952 through 1980, 55 patients were treated for osteosarcoma. Twenty-eight of these patients (4 with active disease) were surviving in January 1981. Six patients had pulmonary metastases at diagnosis and 28 patients developed pulmonary metastases after diagnosis. From 1964 through 1980, 17 patients had 34 thoracotomies for resection of metastases. Seven of these 17 patients (41%) are surviving and remain free of disease. The disease was often bilateral, and in most patients more than one thoracotomy was required to erradicate recurrent disease. No patient who developed pulmonary metastases from osteosarcoma survived without surgical resection of all gross disease. An aggressive surgical approach to the treatment of osteosarcoma metastatic to the lung in children appears worthwhile.

Adolescent↗