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Biomedical subjects

C L Jones

Publications and source records attributed to C L Jones.

At least 73 records · Page 4Linked to original sources
PubMed1993

Collagen studies in newborn rat kidneys with incomplete ureteric obstruction.

Collagen studies in newborn rats with incomplete ureteric obstruction were performed to describe and quantify changes in collagen deposition resulting from urinary tract obstruction at an early developmental age. Incomplete ureteric obstruction was created in three-day-old rats by placing the left ureter in a tunnel formed by the psoas muscle, and sham-operated controls underwent a laparotomy. The rats were sacrificed at 10, 17, 24 or 31 days. Collagen types I, III, IV, and V were localized by indirect immunofluorescence microscopy, the total collagen content of the kidney was quantitated using hydroxyproline analysis, and collagen types I and III were quantitated using cyanogen bromide (CNBr) peptide analysis. Increased immunofluorescent staining for all of the collagens was found in the diffusely widened medullary interstitium of the obstructed kidney, and more focally in the cortical interstitium. Collagen types I, III and V, but not collagen type IV, were also found in bands in the interstitium at the junction of the cortex with the medulla. Increased staining for collagen type IV was found in thickened and tortuous tubular basement membranes (TBM) of the obstructed kidneys. The total collagen content of the obstructed kidney was significantly increased compared to the amounts in both the contralateral kidneys and in the kidneys from sham-operated controls at 24 and 31 days of age (P < 0.01 in each case, Wilcoxon matched pairs rank sum test and Mann Whitney U-test, respectively). The amount of collagen in the kidneys correlated with the degree of hydronephrosis (Spearman correlation test, r = 0.78, P < 0.02). CNBr peptide analysis demonstrated that over 50% of the collagen in the normal neonatal rat kidney was collagen type I and approximately 25% was collagen type III. In the obstructed kidneys most of the collagen was also collagen type I and collagen type III, although the proportion of total collagen comprised by these collagen types was decreased compared with the controls. The amount of collagen type III in the contralateral kidneys was reduced compared to that in the controls. Thus, the neonatal renal response to obstruction resulted in increased amounts of a range of collagens in the interstitium and TBM, and the extent of this response was partially related to the degree of hydronephrosis.

Animals↗
PubMed1993

Parents of children newly diagnosed with cancer: anxiety, coping, and marital distress.

Evaluated anxiety, approach-avoidance coping style, and marital distress in 134 parents of children with cancer shortly after diagnosis. Of the 67 marital pairs studied, approximately 25% of the mothers and 28% of the fathers reported significant marital distress. Regression analyses revealed that marital distress was predicted by a combination of general emotional distress, the discrepancy between the couple's state anxiety levels, and the couple's use of sensitizing coping strategies. Greater differences in anxiety levels between the parents and greater stimulus approach coping activity in the marriage were associated with greater reported marital distress.

Adaptation, Psychological↗
PubMed1993

Recent advances in the management of vesico-ureteric reflux.

Recent studies have demonstrated that both congenital hypoplasia and acquired scarring are involved in the parenchymal lesions associated with reflux nephropathy. Medical therapy can prevent symptomatic infection. While there is no proof that either medical or antireflux surgery prevents acquired scarring, paradoxically there is evidence that surgery adds no benefit to medical therapy, and that the results of medical therapy and surgical therapy are similar in children with isolated severe reflux. The group at most severe risk of renal scarring is infants and the effects of medical and surgical therapy in preventing acquired renal injury in this group have not been sufficiently investigated. On the basis of this information it has been our practice to maintain urine sterility using continuous antibiotic prophylaxis throughout infancy and early childhood. Following the development of reliable urine toilet habit and the ability to collect midstream urine specimens, antibiotics are given according to the frequency of urine infection, and weekly testing of morning urine with nitrite strips at home is used for early detection of infection and prevention of symptomatic infection. Antireflux surgery is mandatory for those children with complicated VUR (such as urinary tract obstruction) and should otherwise be reserved for those having persistent breakthrough infections in infancy and early childhood.

Adolescent↗
PubMed1992

Response of a human megakaryocytic cell line to thrombin: increase in intracellular free calcium and mitogen release.

The CHRF-288-11 cell line has been previously shown to exhibit properties consistent with a megakaryocytic origin. The response of these cells to thrombin has now been investigated. Thrombin treatment of CHRF-288-11 cells results in both an increase in intracellular free calcium levels and secretion of mitogenic activity and beta-thromboglobulin. Cell viability is not affected. The mitogenic activity released from the cells is due primarily to the presence of basic fibroblast growth factor. Immunohistochemical data indicate a packaging of basic fibroblast growth factor into granular structures. Trypsin and phorbol 12-myristate 13-acetate also initiate release of mitogenic activity from this cell line, whereas under non-stirred conditions collagen and ADP do not. Through measurements of intracellular calcium levels it was determined that thrombin pretreatment of cells ablates a further response to thrombin, but does not block an increase in intracellular calcium levels due to trypsin. This suggests that these two agonists may act through different mechanisms. The thrombin-induced release reaction is inhibited almost completely by the reagents hirudin and dipyridamole, and only partially by indomethacin. These data indicate that the CHRF-288-11 cell line should provide an excellent model system in which to study the packaging of factors into granules which undergo regulated release.

Calcium↗
PubMed1992

Tubulointerstitial nephritis.

Tubulointerstitial nephritis (TIN) describes a range of pathological processes that are at least partly responsible for the progression of renal disease of nearly all aetiologies. TIN is frequently the most important pathological manifestation of progressive glomerulonephritis, obstructive uropathy, reflux nephropathy and cystic diseases, although it may also present as a primary disease process associated with infection, drug use or other immunologically mediated disease. Recent clinical and laboratory research has increased our knowledge of tubulointerstitial structure, physiological function and tubulointerstitial response to injury. This review presents a classification of TIN in which acute and chronic tubulointerstitial diseases are recognized as forming a continuum. Primary TIN and TIN associated with glomerulonephritis, obstructive nephropathy and chronic progressive renal disease are discussed from both clinical and pathogenic aspects. It is argued that chronic TIN is a disease process in which inflammation is accompanied by a destructive tubulopathy and fibrogenesis. In acute TIN there is a cessation and reversal of this process. It is suggested that most forms of TIN have an immunological basis because of the presence of immune cell infiltrates, the occurrence of TIN in several immune diseases and immunological animal models of TIN. However, to date TIN has not been convincingly modified in patients by immune manipulation. Experimental evidence suggesting an important pathogenic role for proteinuria and antigenuria, and the renal tubule cell acting as an antigen-presenting cell is discussed.

Acute Disease↗
PubMed1992

Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.

Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency. In this study, the authors examined some of the cellular and molecular mechanisms regulating the renal accumulation of extracellular matrix (ECM) proteins using rats with puromycin amino-nucleoside (PAN) nephrosis as an acute model system. Puromycin aminonucleoside rats developed reversible nephrotic syndrome accompanied by an interstitial infiltrate of monocytes. The number of interstitial fibroblasts expressing ST4 antigen did not increase. During the first 4 days, steady-state mRNA levels for all genes examined remained at or below control levels. At 1 week, nephrotic syndrome and interstitial inflammation were established, and a period of renal cell proliferation occurred, identified by increased histone mRNA levels and localized by tritiated thymine autoradiography to tubular epithelial cells and occasional interstitial cells. Transforming growth factor-beta (TGF-beta) steady-state mRNA levels were increased eightfold, but returned to control levels by 3 weeks. At week 1, there was a 10- to 20-fold increase in kidney steady-state mRNA levels for genes encoding interstitial matrix proteins collagen I and fibronectin and basement membrane collagen IV. By in situ hybridization, alpha 1(I) procollagen mRNA was localized to interstitial cells. Immunofluorescence microscopy demonstrated focal accumulation of ECM proteins in the tubulointerstitial compartment at 2 and 3 weeks, but by 6 weeks, kidney immunohistology was normal again. Steady-state mRNA levels for the matrix degrading metalloproteinase stromelysin remained at control values, whereas the levels for interstitial collagenase were normal at week 1 and increased twofold to threefold at 2 and 3 weeks. Steady-state mRNA levels for the tissue inhibitor of metalloproteinases (TIMP) increased fivefold at 1 week and returned to baseline values over the next 2 weeks. The results of this study suggest that tubulointerstitial ECM accumulation occurs in rats with acute PAN nephrosis because of the activation of genes encoding several matrix proteins and inhibition of matrix degradation mediated by TIMP. These events are reversed during the phase of recovery from nephrotic syndrome. Increased mRNA levels for TGF-beta, possibly originating from inflammatory interstitial monocytes, are likely to be one of the mediators of the molecular events observed.

Animals↗
PubMed1991

Pulmonary thrombo-embolism in the nephrotic syndrome.

The case of a 10.5-year-old boy who had complete right main pulmonary artery thromboembolism complicating steroid-resistant nephrotic syndrome is presented. Despite the massive nature of the lesion clinical symptoms were relatively minor. The thromboembolism was successfully treated with intrapulmonary artery streptokinase. The case highlights the discrepancy that may be found between the clinical and pathological findings in pulmonary thromboembolism in the nephrotic syndrome of childhood.

Child↗
PubMed1991

Pulmonary hemorrhage and necrotizing glomerulonephritis without glomerular immune deposits: report of two cases.

Two children with a syndrome of pulmonary hemorrhage and necrotizing, nonimmune glomerulonephritis are reported. A boy and girl, both of East Indian descent, developed recurrent lung infiltrates from the age of 3 months and 2 years, respectively. Both subsequently presented with pulmonary hemorrhage, fever, arthritis, hematuria, and nephrotic range proteinuria at 1.5 and 6 years of age, respectively. Renal biopsy in each case showed acute, severe, focal and segmental, necrotizing and crescentic glomerulonephritis without immune deposits. Subsequent renal biopsies revealed severe glomerular and tubulointerstitial scarring. No vasculitis or granulomas were seen on renal, skin, or lung biopsies. Antineutrophil cytoplasmic antibodies (ANCA) were not detected in sera taken 1.5 years in the boy and 3.5 years in the girl after the onset of renal disease. The boy was treated with prednisone, azathioprine, and plasmapheresis, but developed progressive renal impairment and commenced dialysis within 4 years. Subsequent to renal transplantation, he developed an immunoblastic lymphoma and died. The girl was treated initially with prednisone and later with cyclophosphamide. After 4 years, she had a normal glomerular filtration rate (GFR). While necrotizing nonimmune glomerulonephritis associated with pulmonary hemorrhage is rare, and cases are characteristically difficult to classify because of many overlapping features, it is possible that these children had a unique illness.

Child↗
PubMed1991

Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis.

A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-beta 1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulo-interstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases--stromelysin or collagenase--and a marked increase for TIMP and TGF-beta 1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation.

Albuminuria↗
PubMed1990

In vitro establishment and characterization of a human megakaryoblastic cell line.

A human megakaryoblastic cell line, designated CHRF-288-11, has been established in vitro through the use of adherent stromal cells in long-term human bone marrow culture. Long-term bone marrow cultures were required for the initial adaptation of the megakaryoblastic cells to culture conditions; however, once adapted, the cells were weaned from the stromal layer until they proliferated in the complete absence of any feeder layers. The seed cells for the establishment of this line were derived from a solid tumor; the cloned cell line derived from this tumor exhibits markers characteristic of megakaryocytes and platelets. Specifically, the cells express platelet peroxidase, platelet factor 4, and platelet Ca+(+)-adenosine triphosphatase (ATPase), glycoprotein IIb-IIIa (CDw41), factor VIII antigen, and the MY7 (CD13) and MY9 (CD33) antigens. The cells do not express the erythroid markers glycophorin A and hemoglobin, the myeloid marker myeloperoxidase, nor markers specific for T and/or B cells. The established cell line produces both basic fibroblast growth factor and transforming growth factor-beta, properties demonstrated previously for the solid tumor. The clonal cell population exhibited a unique, singular karyotype, indicating cellular homogeneity. The cells display a doubling time of approximately 33 hours in either 25% horse or calf serum. Treatment of the cells with 1 X 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) leads to the induction of multi-nucleation and hyperploidy in the cells, with approximately 35% of the cells exhibiting two or more nuclei per cell, and greater than 80% of the cells enlarging in size. The establishment of this unique cell line under defined culture conditions will be beneficial for the future study of megakaryocytic properties expressed by this cell line.

Blotting, Northern↗
PubMed1990

Coagulation abnormalities in chronic peritoneal dialysis.

To determine whether children treated with chronic peritoneal dialysis have a hypercoagulable state, various coagulation and fibrinolytic factor concentrations or activities were measured in 17 children undergoing chronic peritoneal dialysis. The patients had significantly increased activities of factors VII and VIII, and increased concentrations of von Willebrand factor (vWF), fibrinogen, factor XIIIA and factor XIIIS compared to reference values (P less than 0.001 in each case). The activated partial thromboplastin time was prolonged (P less than 0.001) and the thrombin clotting time was decreased (P less than 0.05) in these children. The prothrombin time and activities of factors XII, XI, IX, X, V and II were not significantly different from control values. Protein C concentrations were similar to normal, but antithrombin III concentrations were increased (P less than 0.05). Within the fibrinolytic pathway, decreased concentrations of plasminogen were found (P less than 0.001) and the concentrations of alpha-2-antiplasmin were increased (P less than 0.001). The plasma albumin concentration was below 33 g/l in 13 of the 17 children. The duration of treatment with peritoneal dialysis was directly correlated with vWF concentrations (P less than 0.001) and inversely correlated with factor VII concentrations (P less than 0.01). Of these patients 2 have since had clinical thrombotic episodes. The coagulation abnormalities found may have a role in the occurrence of thrombosis complicating renal transplantation.

Adolescent↗
PubMed1990

Polymeric IgA and immune complex concentrations in IgA-related renal disease.

Polymeric IgA (PIgA) and immune complex concentrations in IgA-related renal disease were measured in cross sectional and longitudinal studies to establish the relationship between these parameters and both mucosal infection and renal dysfunction. These studies were performed in 50 patients with IgA nephropathy (IgAN), 17 patients with Henoch Schönlein purpura nephritis (HSPN), 11 control patients with IgA negative, diffuse mesangial proliferative glomerulonephritis (DMPGN) and 50 healthy controls. Total PIgA (PIgAT) and PIgA subclass concentrations were measured using a secretory component binding enzyme immunoassay and isotype specific immune complex concentrations were measured using conglutinin (K) binding immunoassays. In cross sectional studies patients with IgAN were found to have increased concentrations of PIgAT, PIgA1, K-IgA1 and K-IgA2 compared to controls. In the longitudinal studies controls and patients had significant increases in PIgAT and PIgA1 concentrations during infection. However, in patients with IgAN, the increases were greater, persisted for longer, and PIgA2 concentrations were also increased. K-IgA1 and K-IgA2 concentrations increased significantly during episodes of infection in IgAN patients in contrast to controls. Patients with HSPN had results similar to those of IgAN patients. No significant correlation was found between PIgA or K-IgA concentrations, and either serum creatinine concentrations or the degree of hematuria. The results indicate that patients with IgA-related renal disease have abnormal regulation of PIgA and immune complexed IgA, and that these abnormalities are exaggerated during mucosal infection.

Adolescent↗
PubMed1990

Quantitative assessment of covariation between neuropsychological function and location of naturally occurring lesions in humans.

Studies of localization of brain function in humans depend on analysis of covariation between the location of naturally occurring lesions and measures of neuropsychological ability. Such an analysis presents two problems: how to represent numerically the infinite variety of lesion locations, sizes, and shapes; and how to assess covariation between the location measure and performance. We present a mathematical model of lesion location and its relationship with performance. To demonstrate its utility, the model is applied to a sample of 53 patients with naturally occurring brain lesions who were administered a standard battery of neuropsychological tests. Importance functions derived for the neuropsychological measures generally conform to expectations. Sensory and motor abilities were localized correctly within the contralateral hemispheres, and language functions were localized in the left frontal region. Lesion location accounts for substantially more variation in performance than does lesion volume, with location accounting for more than 50% for some left-hemisphere functions.

Brain↗
PubMed1990

Control of gingivitis and calculus by a dentifrice containing a zinc salt and triclosan.

The effect of unsupervised brushing with a dentifrice containing two antiplaque agents, 0.5% zinc citrate and 0.2% triclosan, on gingival health, plaque, supragingival calculus, and the oral flora was compared to brushing with a non-active control dentifrice. Volunteers were given oral hygiene instruction and their teeth were professionally cleaned. They then used a placebo dentifrice for a pre-experimental phase of 1 month, before being stratified into two groups on the basis of their initial plaque, gingival bleeding, and calculus levels, sex, and age. Over the following 6 months, one group used the control while the other used the test dentifrice. Plaque levels, gingival bleeding, and calculus were assessed at baseline and at 3 and 6 months. Supragingival plaque was sampled for microbiological analysis at the initial examination, at 3 and 6 months (conclusion of study period) and 3 months after the study. Representative oral bacteria and the development of bacterial resistance to triclosan were monitored. Results showed that plaque was reduced and gingival health significantly improved during the 1-month pre-experimental period. During the experimental period, this improvement was not maintained by the control group as gingival bleeding and calculus increased. In contrast, gingival bleeding and calculus levels of the test group were maintained significantly below those of the placebo group. Plaque levels were lower in the test group after 3 and 6 months, but the groups were not significantly (P = 0.05) different. No shifts in oral flora or development of bacterial resistance to triclosan were detected.

Adolescent↗