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Biomedical subjects

K Miller

Publications and source records attributed to K Miller.

At least 667 records · Page 37Linked to original sources

Metabolic properties of maintained oligodendroglia purified from brain.

Oligodendroglia isolated in bulk from dissected white matter of lamb or calf brain can now be maintained in culture for several days. The cells remain intact and viable during this time. The in vitro incorporation of various radiolabeled precursors into lipids or proteins was examined, and its was found that oligodendroglia synthesize the lipids which are predominant in brain, and especially in myelin. They actively synthesize cholesterol, cerebrosides, sulfatides, and all of the phospholipids, especially phosphatidylcholine. In addition, they produce a variety of radiolabeled proteins, with those of high molecular weight exhibiting the most radioactivity. Thus the cells are metabolically very active in vitro and can be used as a model system to study turnover of lipids in the cell, as well as the synthesis of myelin-specific components.

Animals↗

Ultrastructure of the lung in the rat following exposure to crocidolite asbestos and quartz.

Lung tissue from rats that had inhaled U.I.C.C. crocidolite asbestos or quartz particles showed thickening of the interstitial tissue and the presence of collagen fibres. Aggregates of macrophages in the alveolar spaces were a dominant feature of all the sections examined from asbestos exposed rats. According to the ultrastructural studies described here, all the macrophages were mature cells, indicating that the ingested crocidolite asbestos was non-toxic. Lung sections of rats exposed to quartz particles were significantly different. Single cells were found in the alveolar spaces and many macrophages showed a characteristic pattern of vacuole formation. Other cells contained intracellular membranous lamellated bodies, similar to those found in Type II pneumocytes. Cells containing lamellated bodies were also found in the interstitial tissue. These findings suggest that the two mineral dusts have quite different biological effects on the macrophage and that the development of pulmonary fibrosis may, to some extent, be caused by a different mechanism in each instance.

Animals↗

Retinal surgery complicated by a spontaneously acquired factor VIII inhibitor.

We studied a factor VIII inhibitor spontaneously occurring in an otherwise healthy patient who underwent retinal reattachment. The clotting defect first manifested itself as a delayed hemorrhagic choroidal detachment. His bleeding diathesis was successfully managed by infusion of factor VIII concentrate, prednisone, and cyclophosphamide. Surgical procedures in patients with severe bleeding disorders present a difficult therapeutic problem which can be effectively managed by the close cooperation of the surgeon, hematologist, coagulation laboratory, and blood bank.

Aged↗

Spontaneously acquired factor IX inhibitor in a nonhemophiliac child.

A 2 1/2-year-old, previously healthy child developed progressive swelling of the left leg and a hematoma of the anterior chest wall associated with a falling hemoglobin concentration, as a result of a spontaneously acquired Factor IX inhibitor. Successful management of her condition required a four-volume exchange transfusion and immunosuppressive therapy consisting of cyclophosphamide for four days and prednisone for one month. A brief review of the literature regarding the occurrence and nature of acquired coagulation factor inhibitors and the role of immunosuppressive therapy is also presented.

Blood Coagulation↗

Phosphorylation of proteoglycans in human articular cartilage.

A study of human articular cartilage indicated that componenet proteoglycans can be phosphorylated. Phosphorylation, also found in a specimen of human epiphysial cartilage, occurred when [gamma-32P]-ATP or 32Pi was included in the in vitro incubation medium. Treatment of the phosphorylated proteoglycans with chondroitinase and chondrosulfatases effectively removed the chondroitin sulfate without dephosphorylating the remaining molecule. Since phosphorylation could be effected in a totally chemically defined medium, it appears that the necessary enzyme systems for this reaction are contained entirely within chondrocytes.

Adult↗

The effects of asbestos on macrophages.

The exact role of the alveolar macrophage in the pathogenesis of asbestosis is not known. Most studies of the effect of asbestos on macrophages have been concerned with the in vitro biochemical or cytotoxic properties of the dust and have made use of peritoneal macrophages. In general, chrysotile had a toxic effect on the macrophages, whereas amphibole varieties did not. Most forms of absetos, however, are actively fibrogenic in man and animals, and there is no clear correlation between in vitro cytotoxicity of various forms of asbestos and their fibrogenicity. Recent experiments in which animals are exposed to asbestos in vivo provide evidence of alteration of macrophage activity, as demonstrated by changes in surface morphology and IgG receptor sites, as well as released of various secretory products. Deposition of complement components found on the surface of alveolar marcophages from animals exposed to asbestos could be a manifestation of a humoral immune response directed against an altered cell. The capacity of macrophages to participate in inflammation, tissue repair, and immunity suggests an immunopathogenic concept for the development of asbestosis.

Animals↗

The in vivo effects of quartz on rat thoracic lymph nodes.

The histological changes in the regional thoracic lymph nodes of rats exposed to silica dust by inhalation are recorded. A dual response is noted involving both inflammatory and immune mechanisms, resulting in a fibroblastic connective tissue reaction and a plasma-cell-macrophage interaction. It is proposed that the progressive silicotic lesions obstruct the lymphatic channels in the lymph nodes, thus interfering with the lymph drainage from the lung and aggravating the silicotic process in the lung itself.

Animals↗

Breakdown products of C3 and factor B in hemolytic-uremic syndrome.

Serum concentrations of Clq, C4, C3, and Factor B but not properdin were significantly decreased in patients with HUS compared to values in normal control subjects (p value less than 0.01). Sera from 13 HUS patients obtained early after the onset of the disease showed breakdown products of Factor B (Ba, Bb) by immunoelectrophoresis; 12 of these sera showed C3 breakdown products (C3c, C3d). Sera from seven patients studied 1 month to 3 years later no longer demonstrated any breakdown products of Factor B or C3. These data suggest that the complemented system is activate in HUS. The concept that immunological mechanisms play a major role in this disease is additionally supported by the occurrence of IgM, C3, and fibrin in glomeruli and renal vessels.

Adolescent↗

Immune adherence reactivity of rat alveolar macrophages following inhalation of crocidolite asbestos.

The immune adherence phenomenon was used to demonstrate the in vivo deposition of complement on membranes of alveolar macrophages from rats chronically exposed to crocidolite asbestos dust. Pre-treatment of macrophage cualtures with anti-C3 antiserum greatly diminished the level of immune adherence reactivity. Alveolar macrophages exposed to crocidolite asbestos in vitro did not exhibit significant levels of immune adherence reactivity. These results may reflect an in-vivo antigen-antibody-complement interaction on the surface of a alveolar macrophages from animals which have inhaled asbestos dust.

Animals↗

Immunopathology of renal extracellular membranes in diabetes mellitus. Specificity of tubular basement-membrane immunofluorescence.

This study documents the presence of marked immunofluorescence for IgG and albumin in renal extracellular membranes, especially tubular basement membranes (TBM), of patients with severe diabetic nephropathy. A comprehensive immunofluorescent analysis was carried out on kidney tissue from 83 patients--Group I: 24 living normal renal allograft donors and two infants less than one week of age. Group II: 24 patients with severe nephropathy who had juvenile onset of diabetes 16 to 30 years previously and who ranged in age from 20 to 47 years. Group III: 33 patients with severe kidney disease of varied etiologies with an age range of five to 63 years. The sections were assayed for a variety of proteins (immunoglobulins, complement components, and tissue antigens). Kidney sections of all patients with severe diabetic nephropathy were readily distinguished from kidneys of other patients and normals by the intense linear staining of the extracellular membranes, especially the tubular basement membrane for IgG and and albumin. Dual-labeled studies using FITC anti-basement membrane (BM) and tetramethyl rhodamine (TMR) antialbumin demonstrated localization of the albumin predominantly to the outer but also the inner TBM while the BM antisera reacted more intensely with the inner membrane. There is no evidence that an immunologic process is responsible for these findings. These immunofluorescent findings are specific for severe diabetic nephropathy and may reflect structural changes in the renal extracellular membranes that permit entrapment of serum proteins, possibly due to changes in permeability.

Adolescent↗

Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus.

Kidneys of patients with severe diabetic nephropathy demonstrate marked linear immunofluorescent staining of extracellular membranes, including the tubular and glomerular basement membranes (TBM and GBM) and Bowman's capsule. Immunofluorescent studies were carried out on kidney tissue obtained from 12 diabetic and 17 nondiabetic patients from two to 12 years following renal transplantation. The frequency and intensity of SgG and albumin staining of these membranes were significantly greater in the diabetic than in the nondiabetic patients (P less than 0.0005). TBM, GBM, and Bowman's capsule staining did not occur in any of the seven kidneys studies at the time of their transplantation into diabetic recipients. Thus, the abnormalities leading to the deposition or trapping of proteins in renal extracellular membranes occur early after the placement of normal kidneys into the abnormal metabolic environment of the diabetic transplant recipient. The present study supports the concept that basement membrane alterations in diabetes are a consequence of the biochemical perturbations of diabetes rather than a separately inherited genetically linked disorder.

Albumins↗

Immunopathology of the end-stage kidney. Immunoglobulin and complement component deposition in nonimmune disease.

Seventy nephrectomy specimens from patients with end-stage renal disease, four renal biopsies from patients with focal sclerosing glomerulonephropathy (FSGN) and normal renal function, and 17 control biopsies from normal renal allograft donors (Group I) were studied by immunofluorescence with respect to deposition of immunoglobulins and classic and alternative complement (C) pathway components. The end-stage kidneys were divided into three groups according to etiology: 16 patients with immune-mediated glomerulonephritis (Group II), 22 patients with congenital and/or familial renal disease (Group III), and 32 patients with systemic or primary renal disease in which an immune-mediated injury could not be established (Group IV). The pattern of immunoprotein deposition in glomeruli in Groups II, III, and IV, and in biopsies of patients with FSGN was similar: peripheral lobular, globular and/or granular, focal and segmental; it was limited to dying glomeruli or abnormal glomerular segments. A statistically significant correlation existed between the percent of properdin-containing glomeruli and the percent of glomeruli undergoing hyalinization in Groups II, III and IV (II, r=0.67; III, r=0.92; IV, r=0.78). No deposition was observed in normal or completely fibrotic glomeruli. In vitro heterologous complement fixation was demonstrated in 17/19 end-stage kidneys in a similar distribution. Early classic C components, C1q and C4, were detected in a somewhat higher frequency in Group II (14/16) than Group III (11/22) and Group IV (20/32) (Group II vs. III, P=.02 and II vs. IV, P=.07). C3 and properdin were detected in 77 to 100% of all 3 groups; in 18 patients, C3 and properdin were present without detectable C1q and C4. Immunoglobulins, primarily IgM, and components of the classic and alternative C pathways are regularly present in hyalinizing glomeruli irrespective of the etiology of the renal failure. These observations suggest that an immune process is operative in glomerular obsolescence regardless of the underlying etiology of the renal disease.

Adolescent↗

Evaluation of alternate coupling reagents to replace alpha-naphthyl amine for the detection of nitrate reduction.

Four naphthyl compounds, N,N,dimethyl-1-naphthylamine, N-1-naphthyl-ethylene-diamine dihydrochloride, 8-amino-1-naphthol-5-sulphonic acid, and 1-dimethylamino naphthalene-5-sulphonic acid, were evaluated as replacements for alpha-naphthyl amine in the bacteriological nitrate reduction test. These compounds were observed for their ability to detect standardized nitrite concentrations and nitrate reduction in eight bacterial cultures. The results indicated both N,N,dimethyl-1-naphthylamine and N-1-naphthyl-ethylene-diamine dihydrochloride, at concentrations of 0.035 M, were satisfactory alternatives. The working concentration of the latter might be reduced, as indicated by the results of sensitivity tests.

Bacteriological Techniques↗