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Biomedical subjects

S L Newman

Publications and source records attributed to S L Newman.

At least 55 records · Page 3Linked to original sources
PubMed1986

Diaphragm length and breathing pattern changes during hypoxia and hypercapnia.

In this study diaphragmatic length changes were measured during quiet breathing and during augmentation of breathing with hypoxia and hypercapnia in supine anesthetized dogs. The breathing pattern and the VT-TI relationship during hypoxia were different than those during hypercapnia. The crural diaphragm shortened more than the costal diaphragm with both stimuli, and the amount of shortening in relation to the tidal volume implied that there was considerable distortion of the chest wall during hyperventilation. The velocity of shortening of both parts of the diaphragm at similar levels of ventilation was greater during hypoxia than hypercapnia. The velocities found with hyperventilation suggested that force-velocity considerations did not reduce force generation. Hypoxic stimulation resulted in a reduction in the resting length of both parts of the diaphragm, and was associated with a positive shift in baseline pleural pressure which implied gas trapping. The large tidal diaphragmatic shortening found with augmented breathing and the shorter resting length with hypoxia indicated that length-force properties are important in force generation.

Animals↗
PubMed1986

In vivo length and shortening of canine diaphragm with body postural change.

Using sonomicrometry, we measured the in vivo tidal shortening and velocity of shortening of the costal and crural segments of the diaphragm in the anesthetized dog in the supine, upright, tailup, prone, and lateral decubitus postures. When compared with the supine position, end-expiratory diaphragmatic length varied by less than 11% in all postures, except the upright. During spontaneous breathing, the tidal shortening and the velocity of shortening of the crural segment exceeded that of the costal segment in all postures except the upright and was maximal for both segments in the prone posture. We noted the phasic integrated electromyogram to increase as the end-expiratory length of the diaphragm shortened below and to decrease as the diaphragm lengthened above its optimal length. This study shows that the costal and crural segments have a different quantitative behavior with body posture and both segments show a compensation in neural drive to changes in resting length.

Animals↗
PubMed1986

Caroli's disease: new diagnostic and therapeutic approaches.

Cystic dilatations of the intrahepatic and extrahepatic biliary trees are common congenital anomalies that frequently require surgical intervention. We have presented a case of Caroli's disease in which an accurate diagnosis was made noninvasively preoperatively, using computerized tomography, ultrasonography, and cholescintigraphy.

Bile Duct Diseases↗
PubMed1985

Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3.

Monoclonal antibodies were used to determine the number and molecular form of C3 bound to particulate activators of the complement (C) system by human serum. Sheep erythrocytes (E) coated with IgM (EIgM) and IgG (EIgG) were used to study activation of the classical pathway (CP). Yeast (Y), rabbit erythrocytes (ER), and five species of bacteria (Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae type 3, Streptococcus pyogenes, and Hemophilus influenzae type b) were used to study activation of the alternative pathway (AP). The deposition of C3b onto EIgM and EIgG incubated in C7-deficient human serum was dependent on the serum concentration. At all serum concentrations tested, there was complete conversion of C3b to iC3b. Kinetic analysis of C3b deposition and conversion to iC3b indicated that these events occurred almost simultaneously; the reaction was completed by 15 min. The deposition of C3 onto the AP activators ER and Y was also dependent on serum concentration, and ER, but not Y, required the presence of Mg-EGTA and thus the activation of only the AP. C3b deposition and conversion to iC3b on Y was complete in 15 min, with 82% of bound C3 converted to iC3b. For ER, maximum C3 deposition required 30 min in both the presence and absence of Mg-EGTA. However, after 1 h of incubation, 74% of bound C2 was iC3b in the absence of Mg-EGTA, compared with only 52% in the presence of Mg-EGTA. Thus, even on AP activators, a large portion of C3b may be converted to iC3b, and this conversion is probably controlled by elements on the particle's surface. Studies with the five species of bacteria yielded similar results. Approximately 3-5 X 10(4) molecules of C3 were bound per microorganism, with opsonization being completed in 30 min. Remarkably, only 16-28% of bound C3 was in the form of iC3b, even after 2 h of incubation. The presence or absence of Mg-EGTA, or the addition of purified CR1 to the reaction mixture, did not significantly effect the ratio of C3b to iC3b. Finally, SDS-PAGE and autoradiography of particle-bound 125I-C3 fragments confirmed that there was no conversion of iC3b to C3d,g or C3d. The data obtained about the opsonization of bacteria suggest that the predominant form of C3 that is encountered by inflammatory phagocytes may be C3b.

Animals↗
PubMed1985

Phagocytosis by receptors for C3b (CR1), iC3b (CR3), and IgG (Fc) on human peritoneal macrophages.

Human peritoneal macrophages (HPM) obtained via laparoscopy were examined for the presence and functional capacity of complement and Fc receptors. Between 5 and 20 ml of peritoneal fluid containing 1-2 X 10(6) macrophages/ml was available for each study. Macrophages made up 80-95% of the cells in the fluid. Fc and C3 receptors on HPM were characterized by rosette formation with, and phagocytosis of, IgG- and C3-coated sheep erythrocytes (E). ElgG were bound by 82% and ingested by 63% of HPM, with 4-15 E ingested/HPM. The HPM formed rosettes with EC3b (56%) and EC3bi (71%) but not EC3d,g or EC3d. Antibodies to complement receptors type 1 (CR1) and type 3 (CR3) inhibited rosette formation with EC3b and EC3bi, respectively, indicating that HPM possessed separate and distinct receptors for the C3b and iC3b ligands. In 60% of the samples studied, HPM demonstrated the ability to ingest both EC3b and EC3bi, as well as ElgG. Because of the heterogeneous nature of the cells obtained in peritoneal fluid, due to their progressive change from monocytelike cells into mature macrophages, HPM were separated by 1 g velocity sedimentation into fractions of increasing maturity. They were then examined for phagocytosis via Fc and complement receptors. Fc receptor mediated phagocytosis occurred throughout the monocyte-to-macrophage maturation sequence, while the ability of HPM to ingest via CR1 and CR3 was maturation dependent, with ingestion via CR3 occurring before CR1, in a manner analogous to in vitro differentiation of monocyte-derived macrophages.

Erythrocytes↗
PubMed1985

Platelet-monoamine oxidase activity in Reye's syndrome.

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Adolescent↗
PubMed1985

Lingular lung biopsy: is it representative?

Some investigators feel that the lingula should be avoided as a site of open lung biopsy because of the assumed prevalence of nonspecific changes. We sought to judge the validity of the lingular biopsy by examining specimens of the lingula and left lower and right upper lobes from 50 consecutive unselected autopsies. Sections were stained with hematoxylin-eosin and Masson's trichrome and were examined for the extent of fibrosis, pulmonary vascular changes, and acute and chronic inflammation. Using both a morphometric and a semiquantitative grading system (r = 0.80), we noted that both fibrosis and pulmonary vasculopathy were more evident in the lingula than in either of the 2 other lung segments (p less than 0.05 ANOVA, Newman-Keul test). There was no difference between the lingula and other segments for either acute or chronic inflammation (p greater than 0.10), and there was no difference in any of the morphologic parameters between the right upper and left lower lobes (p greater than 0.10). We conclude that the lingula shows nonspecific changes and thus may not be a valid biopsy site.

Biopsy↗
PubMed1985

Respiratory muscle dysfunction after herpes zoster.

We report an unusual neurologic complication of herpes zoster. After thoracic herpes zoster, our patient complained of severe shortness of breath as a result of myoclonus of the abdominal muscles as documented by electromyography. The myoclonus resulted in repetitive interruption of expiratory air flow, resulting in shortness of breath and a staccato speech. This case demonstrates the need to evaluate the function of all the respiratory muscles in a patient complaining of dyspnea.

Abdominal Muscles↗
PubMed1985

Lymphokine-induced monocytic differentiation as a possible mechanism for hypercalcemia associated with adult T-cell lymphoma.

Patients with adult T-cell lymphoma frequently have hypercalcemia. Bone biopsies from these patients show increased numbers of osteoclasts. We hypothesized that substances produced by the malignant T-cell caused these phenomena by increasing the formation and/or activity of osteoclasts. To test this hypothesis, we cultured U937 cells in conditioned media from a clonal T-cell line derived from a patient with adult T-cell lymphoma and hypercalcemia. This conditioned media produced maturational changes in the U937 cells as evidenced by decreased proliferation, increased adherence, increased expression of complement receptors, and formation of multinucleated giant cells. These changes were synergistically enhanced by the addition of 1 alpha, 25-dihydroxyvitamin D3 which is known to promote monocyte differentiation. We also tested interleukin 2 and gamma- and alpha-interferon to see if they were responsible for the maturational changes. Although some effects were seen, these lymphokines could not account for all the changes induced by the T-cell conditioned media. These findings support the above hypothesis and suggest that other unidentified factors may promote the differentiation of osteoclast precursors and be involved in the pathogenesis of the hypercalcemia.

Calcitriol↗
PubMed1985

Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1.

Three children from two unrelated families had a history of recurrent bacterial infections, and their neutrophils were shown to have deficient phagocytic and respiratory responses and possible deficiencies in chemotaxis or adherence. Their neutrophils were strikingly deficient in the ability to ingest or give a respiratory burst in response to unopsonized bakers' yeast or zymosan (Z). Tests for neutrophil and monocyte CR1 (C3b/iC3b receptor) and CR3 (iC3b receptor) demonstrated rosettes with both EC3b and EC3bi. However, EC3bi were bound only to CR1, and not to CR3, because EC3bi rosettes were inhibited completely by anti-CR1. Neutrophils, monocytes, and natural killer (NK) cells also did not fluorescence stain with monoclonal antibodies specific for the alpha-chain of CR3 (anti-Mac-1, anti-Mol, OKM1, and MN-41). Quantitation of C receptors with 125I monoclonal anti-CR1 and anti-CR3 indicated that neutrophils from each patient expressed normal amounts of CR1 per cell but less than 10% of the normal amount of CR3. Examination of neutrophils by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that a normal glycoprotein of approximately 165,000 daltons was missing. Immunoblotting of these gels indicated that the missing band was the alpha-chain of CR3. Subsequent analysis of all three patients' cells also demonstrated a deficiency of LFA-1 alpha-chain and the common beta-chain that is shared by the CR3/LFA-1/p150,95 membrane antigen family. The deficiency of LFA-1 probably explained the absent NK cell function, as normal NK cell activity is inhibited by anti-LFA-1 but not by anti-CR3. The reduced phagocytic and respiratory responses to Z were probably due to CR3 deficiency, because treatment of normal neutrophils with anti-CR3, but not anti-FLA-1, inhibits responses to Z by 80% to 90%. Ingestion of Staphylococcus epidermidis by normal neutrophils was shown to be partially inhibited by monoclonal antibodies to the alpha-chain of either CR3 or LFA-1, and monoclonal antibody to the common beta-chain inhibited ingestion by 75%. Thus, both CR3 and LFA-1 may have previously unrecognized functions as phagocyte receptors for bacteria. The absence of this type of nonimmune recognition of bacteria by these children's neutrophils may be one of the reasons for their increased susceptibility to bacterial infections.

Antigens, Surface↗
PubMed1984

The distribution of the CR3 receptor on human cells and tissue as revealed by a monoclonal antibody.

The mouse monoclonal antibody MN-41 has been characterized as an anti-human iC3b receptor (CR3) antibody on the basis of its ability to inhibit the binding of EC3bi indicator cells to monocytes and polymorphonuclear cells while having no effect on their Fc and C3b receptors. Use of this monoclonal antibody in indirect immunofluorescence studies with dual fluorochrome labels established the widespread distribution of CR3 in man--detected on 97% of circulating monocytes, 90% of granulocytes, 17% of T lymphocytes, and 28% of B lymphocytes while erythrocytes and platelets were negative. Isolated peritoneal macrophages were 90% positive while pulmonary macrophages were 83% positive. Monocytes in culture for 8 days were universally positive. Within tissues, CR3 reactive cells displayed unique topographical localization within the spleen, tonsil, and lymph nodes whereas numerically fewer positive cells were scattered within hepatic sinusoids, papillary dermis, medullary regions of the thymus, and submucosa of the small intestine. CR3 was not detected on Raji cells, glomerular epithelial cells, or placental stromal cells. Immunoprecipitation and electrophoretic separation of two glycoprotein bands of 150,000 and 95,000 Da suggest possible structural homology of CR3 in man and mouse (Mac-1 antigen).

Animals↗
PubMed1984

Small bowel obstruction in chronic granulomatous disease.

Intestinal obstruction, enteritis, and colitis have been reported in patients with previously documented chronic granulomatous disease (CGD). We describe here an 11-year-old boy whose initial presentation was compatible with inflammatory bowel disease. A mild but persistent dermatitis was his only other manifestation of CGD.

Child↗
PubMed1984

Phagocytosis by human monocyte-derived macrophages. Independent function of receptors for C3b (CR1) and iC3b (CR3).

Human monocytes and monocyte-derived macrophages were examined for their ability to bind and ingest C3-coated sheep erythrocytes (E). Greater than 90% of monocytes and macrophages formed rosettes with EC3b and EC3bi prepared with 15,000-20,000 molecules of C3 per E. Binding of EC3b to the monocyte or macrophage surface was inhibited by rabbit anti-C3b receptor (CR1), but was not inhibited by two different monoclonal anti-C3bi receptor (CR3) antibodies. EC3bi rosette formation was inhibited by monoclonal anti-CR3, but not by anti-CR1. Monocytes and macrophages did not form rosettes with similarly prepared EC3d,g or EC3d. Macrophages cultured for 7 days, but not freshly isolated monocytes, phagocytosed both EC3b and EC3bi. This ability was a consequence of macrophage maturation, as no external stimuli were present during in vitro culture. Experiments directed to determine if EC3b was converted to EC3bi before ingestion suggested that macrophage CR1 and CR3 mediated phagocytosis independently. No evidence was obtained that during the phagocytosis assay, macrophage factor I converted EC3b to EC3bi. The number of E bound or ingested by monocytes and macrophages was dependent on the number of molecules of C3b or iC3b bound per E. Monocytes and macrophages did not require the presence of either Ca++ or Mg++ for rosette formation with EC3b, whereas both divalent cations were required for optimum rosette formation with EC3bi. The presence of divalent cations was required for macrophage phagocytosis of EC3b and EC3bi. For ingestion of EC3b, Mg++ alone was sufficient, and the addition of Ca++ did not increase the number of EC3b ingested. For ingestion of EC3bi, both Ca++ and Mg++ were required for optimal phagocytosis, and their effect was concentration dependent and additive.

Calcium↗
PubMed1984

Resolution of pulmonary inflammation.

Mononuclear phagocytes are suggested to play a major orchestrating role in the resolution of inflammatory processes in the lung. Particular emphasis is placed on their participation in the progression from a lesion with neutrophils as the dominant infiltrating cell to one that contains macrophages, on the macrophage's role in removing neutrophils and cell debris, and on their promotion of repair mechanisms. It is suggested that monocytes must mature into macrophages before they are capable of active participation in the resolution of inflammation.

Animals↗