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Biomedical subjects

R J Johnson

Publications and source records attributed to R J Johnson.

At least 163 records · Page 9Linked to original sources

Consistency and change in functional status among older adults over time.

Consistency and change between 1984 and the last reinterview (either two, four, or six years later) on 22 individual functional status markers and the five summary scales that they form are examined among the 5,986 members of the Longitudinal Study on Aging who were reinterviewed at least once. At baseline, at least three-fifths of the respondents are without limitations on any individual marker. At the last reinterview, at least 43.4% of the respondents are without such limitations. Among those who had limitations at baseline, at least one-fifth get better. For those without limitations at baseline, one-seventeenth to two-fifths get worse. Difficulties in walking and doing heavy housework were the most common, most likely to develop, and least likely to resolve of any of the ADL or IADL items, and lower body limitations were more common, more likely to develop, and less likely to resolve than upper body limitations. Linear panel analysis of the five summary scales indicates that the top predictors of increased functional limitation are baseline levels of functional limitation, older age, decedent status, and poorer perceived health (in that order). Other less consistent and less robust predictors include the length of the exposure window, being female, having a history of arthritis, lower educational attainment, having fewer nonkin social supports, higher prior physician visit levels, and not living alone.

Activities of Daily Living↗

Use of community-based long-term care services by older adults.

This study uses a previously validated model of disease, disability, functional limitations, and perceived health to predict the use of long-term care (LTC) services in and out of the home. The focus is on (a) the direct effects of the structure of health status on the use of LTC services, (b) how the use of LTC services differs by race and sex, and (c) how the use of LTC services varies by in-home and out-of-home location. The findings indicate that different dimensions of health status affect in-home health services for White men and women, compared to Black women. Basic ADLs are significant predictors among Whites but not among Black females. In addition, sociodemographic and socioeconomic factors are more important influences on the use of out-of-home services than are health status variables. Some of these effects indicate that LTC services are being used by the special groups to which they are targeted (e.g., those living alone). The failure to find other effects (e.g., dependence on social security for income) indicates that the LTC services are not being used more by some targeted groups (e.g., the poor). These findings suggest that simply expanding the supply of LTC services could exacerbate the existing disparities in service use.

Activities of Daily Living↗

Anterior cruciate ligament injury rehabilitation in athletes. Biomechanical considerations.

Postoperative rehabilitation is a major factor in the success of an anterior cruciate ligament (ACL) reconstruction procedure. Clinical investigations of patients after ACL reconstruction have shown that immobilisation of the knee, or restricted motion without muscle contraction, leads to undesired outcomes for the articular, ligamentous, and musculature structures that surround the knee. Early joint motion is beneficial for; reducing pain, capsular contractions, articular cartilage, and for minimising scar formation that limit joint motion. These findings, combined with graft materials that have biomechanical properties similar to the normal ACL, and adequate fixation strength, have led many to recommend aggressive rehabilitation programmes that involve contraction of the dominant quadriceps muscles. Recently, a prospective, randomised study of rehabilitation following ACL reconstruction has presented evidence that a closed kinetic chain exercise programme (foot fixed against a resistance) results in anterior-posterior knee laxity values that are similar to the contralateral normal knee. Also, open kinetic chain exercises (foot not fixed against a resistance) result in increased anterior-posterior knee laxity compared with the normal knee. Criteria must be observed because the relationship between rehabilitation exercises and the healing response of an ACL graft is unknown at present. Biomechanical studies of healing ACL grafts performed in animals have shown that the graft requires a long time to revascularise and heal, and that the biomechanical behaviour of the graft never returns to normal. Functional knee braces provide a protective strain-shielding effect on the ACL when anterior shear loads and internal torques are applied to the knee in the non-weight-bearing condition. However, the strain shielding effect of functional braces decrease as the magnitude of anterior shear and internal torque applied to the knee increase. Future studies should strive to determine the actual loads transmitted across the knee and ACL graft strain during various rehabilitation exercises and relate these to the healing response of the knee and graft.

Anterior Cruciate Ligament Injuries↗

SPARC is expressed by mesangial cells in experimental mesangial proliferative nephritis and inhibits platelet-derived-growth-factor-medicated mesangial cell proliferation in vitro.

Mesangial cell proliferation is a characteristic feature of many glomerular diseases and often precedes extracellular matrix expansion and glomerulosclerosis. This study provides the first evidence that SPARC (secreted protein acidic and rich in cysteine) could be an endogenous factor mediating resolution of experimental mesangial proliferative nephritis in the rat. SPARC is a platelet-derived-growth-factor-binding glycoprotein that inhibits proliferation of endothelial cells and fibroblasts. We now show that SPARC is synthesized by mesangial cells in culture and that SPARC mRNA levels are increased by platelet-derived growth factor and basic fibroblast growth factor. Recombinant SPARC or the synthetic SPARC peptide 2.1 inhibited platelet-derived-growth-factor-induced mesangial cell DNA synthesis in vitro. In a model of experimental mesangioproliferative glomerulonephritis, SPARC mRNA was increased 5-fold by day 7 and was identified in the mesangium by in situ hybridization. Similarly, SPARC was increased in glomerular mesangial cells and visceral epithelial cells by day 5 and reached maximal expression levels by day 7. Mesangial cell proliferation increased by 36-fold on day 5 and decreased abruptly on day 7. Maximal expression of SPARC was correlated with the resolution of mesangial cell proliferation. We propose that SPARC functions in part as an endogenous inhibitor of platelet-derived-growth-factor-mediated mesangial cell proliferation in glomerulonephritis and that it could account for the resolution of cellular proliferation in this disease.

Amino Acid Sequence↗

Peripheral blood stem cell transplantation in myeloma using CD34 selected cells.

We have performed nine CD34 selection procedures on peripheral blood stem cells harvested from eight patients with myeloma using the Cellpro avidin-biotin immunoaffinity column (Ceprate). They all received CVAMP chemotherapy to maximum response prior to mobilisation. Six of the patients have been transplanted using these cells, one receiving successive autografts. Median absolute cell numbers processed and retrieved were: 31.1 x 10(9) pre-column, 2.07 x 10(8) in the final product and 30.4 x 10(9) in the column waste. Mean CD34 positivity in the product was 49% (range 18.4-98) with a median CD34+ yield of 31.4% (range 21-37.8). IgH PCR was performed and seven of the eight patients were amplifiable. Of these, two were positive in the pre-column product and both of these were successfully purged with a negative result in the final, post-column product. Patients were transplanted with a median of 2.0 x 10(6) CD34+ cells/kg (range 1.5-9.4) following conditioning with melphalan 200 mg/m2. The mean time to recovery of neutrophils to > 0.5 x 10(9)/l and platelets to > 20 x 10(9)/l was 16 and 17 days, respectively. At a mean follow-up of 9 months, four of the six patients transplanted are alive, three of them in complete remission and one in a clinically stable relapse. One has died of disease relapse and one of progressive neurological problems the aetiology of which was uncertain but there was no sign of progression of their myeloma. We conclude that PBSCT using CD34 selected cells is safe and practical in myeloma following remission induction with CVAMP chemotherapy.

Antigens, CD34↗

The effects of role socialization on the initiation of cocaine use: an event history analysis from adolescence into middle adulthood.

This research examines three relatively unexplored questions about the effects of role socialization on the initiation of cocaine use: (1) What are the effects of adult social roles on the initiation of cocaine use? (2) What are the effects of the life-course timing of entry into adult social roles on the initiation of cocaine use? and (3) What are the effects of life-course timing of the initiation of other drugs -- on the initiation of cocaine use? The data used in these analyses are from a national probability sample of men born between 1944 and 1954, inclusive (N = 1,933). Results indicate that the marital role was the only role which demonstrated a significant effect on the initiation of cocaine use. We find that either early or late entry into the marital role reduces its effect to nonsignificance. The timing of entry in the drug use roles indicates that the later the initiation of drug use the greater the odds of cocaine initiation. Results are discussed in light of the role socialization and developmental perspectives.

Adult↗

Identification of an endotoxin and IFN-inducible cDNA: possible identification of a novel protein family.

The response of macrophages to agents such as lipopolysaccharide (LPS) and interferon (IFN) includes the transcriptional activation of numerous genes. We have used the method of differential screening of a RAW 264.7 macrophage cell line cDNA library to isolate and characterize LPS-induced messages. One such message, LRG-47, is induced by LPS, IFN-gamma, and IFN-alpha/beta, but not by a panel of other cytokines or pharmacological activating agents. LRG-47 is homologous to two other IFN-gamma-induced genes, IRG-47 and Mg21. The LRG-47 sequence is approximately 33% identical and 52% similar to both these putative protein products. All three putative proteins, particularly Mg21, bear homology to a T cell product, Tgtp, induced by T cell receptor cross-linking. The three macrophage-derived proteins share areas of homology with GTP-binding proteins, are approximately 415 amino acids in length, and have similar kinetics of induction by IFN-gamma. This suggests that these genes may be members of a new family of IFN-inducible proteins.

Amino Acid Sequence↗

Hepatitis C--associated glomerular disease in liver transplant recipients.

Hepatitis C virus (HCV) infection may be associated with extrahepatic illness including renal disease. We investigated the clinical and virological characteristics of three patients who developed a mesangial proliferative and sclerosing glomerulopathy alone or in association with membranoproliferative glomerulonephritis after liver transplantation for end-stage liver disease secondary to HCV infection. Using polymerase chain reaction technology and the IgM RIBA assay, viral load, genotype and IgM antibody response to HCV in the setting of glomerulonephritis was evaluated. Within 1 year of transplantation, the patients showed decreased renal function, proteinuria and recurrent hepatitis C liver disease. Likewise, HCV viral load increased following transplantation, whereas the viral genotypes remained unchanged. Although the first patient presented with classic type II cryoglobulinemia in association with glomerulonephritis, the second patient developed an IgM directed specifically against the hepatitis C core antigen. The third patient developed a low-titered IgM directed against the hepatitis C core antigen with rheumatoid factor activity but without cryoglobulinemia. All of the patients show IgM in glomerular capillary walls by biopsy. One patient has shown a clinical response to interferon (IFN) alfa-2b therapy without evidence of hepatic allograft rejection. The second and third patients have not responded to IFN or developed hepatic rejection. This study suggests that HCV-associated glomerulonephritis may complicate liver transplantation in conjunction with the production of increased amounts of IgM of variable specificity. The posttransplant setting may provide a unique situation in which to investigate the specific requirements for the onset of renal disease.

Adult↗

Glomerulonephritis in renal allografts associated with hepatitis C infection: a possible relationship with transplant glomerulopathy in two cases.

Chronic infection with hepatitis C virus (HCV) has been identified as a cause of type I membranoproliferative glomerulonephritis (MPGN). HCV infection is common in patients with end-stage renal disease and may persist in renal allograft recipients. MPGN in the allograft may therefore be a manifestation of persistent HCV infection. We report two cases of glomerulopathy with features of both MPGN and transplant glomerulopathy in renal transplant patients chronically infected with HCV. We discuss the course of interferon alfa therapy in both patients as well as a possible relationship of HCV infection with transplant glomerulopathy.

Chronic Disease↗

Membranoproliferative glomerulonephritis associated with hepatitis C virus infection responsive to interferon-alpha.

A 42-year-old man with hepatitis C virus infection, cryoglobulinemia, hypocomplementemia, and nephrotic syndrome is reported. The kidney biopsy showed membranoproliferative glomerulonephritis. The patient was treated with interferon-alpha for 2 months. After the treatment, serum hepatitis C virus RNA became negative and nephrotic syndrome remitted. Repeat biopsy of the kidney revealed an improvement in renal histology. This case confirms an association between hepatitis C virus infection and membranoproliferative glomerulonephritis and the usefulness of interferon-alpha for treatment.

Adult↗

Cellular events in the evolution of experimental diabetic nephropathy.

In several models of progressive glomerular disease, mesangial cell proliferation, phenotypic change and increased growth factor expression precede up-regulation of genes for extracellular matrix components (ECM) and mesangial expansion. To examine these events in diabetic nephropathy (DN) we conducted sequential studies of glomeruli in rats with streptozotocin induced DN. We found prominent mesangial cell proliferation at three days (4.34 +/- 2.24 PCNA + cells/glom vs. 1.6 +/- 0.74 in controls, P < 0.001) associated with increased alpha-actin expression. PDGF B-chain mRNA was slightly increased at day one, and PDGF B-chain immunostaining was slightly increased at days one and six. Staining for bFGF was significantly increased at three days (2.2 +/- 0.6 vs. 1.2 +/- 0.1 in controls, P < 0.01). There was also an early increase in platelets in glomeruli of diabetic animals, and platelet depletion significantly inhibited the early phase of proliferation. In addition to mesangial cell proliferation, a prominent glomerular macrophage infiltration began at day three and peaked at day 30 (3.94 +/- 1.47 vs. 2.08 +/- 1.13 in controls, P < 0.01). TGF-beta mRNA increased at days 14 and 30. Insulin treatment prevented mesangial cell proliferation, actin expression, and macrophage infiltration, and normalized TGF-beta expression at 14 and 30 days. These multiple cellular events preceded any detectable increases in glomerular gene expression or deposition of collagen I, IV or laminin.

Animals↗

Platelet-derived growth factor A-chain expression in developing and mature human kidneys and in Wilms' tumor.

Regulated expression of PDGF A-chain may be important in kidney development. We employed two polyclonal antisera to detect expression of PDGF A-chain in fetal and normal adult kidneys by immunohistochemistry. Specificity of the antisera was demonstrated by Western blots of fetal and adult kidneys, demonstrating monospecific bands at 10 to 15 kD, and by absorption studies with PDGF-A peptide. PDGF A-chain is uniformly expressed by visceral glomerular epithelial cells and the epithelial cells of the distal nephron, including collecting ducts and contiguous urothelium lining the renal pelvis, in both fetal and adult kidneys. Fetal kidneys also demonstrate expression of PDGF A-chain at the earliest stages of vesicle formation from the metanephric blastema; this expression is then only intermittently detectable in developing glomeruli until differentiation of visceral epithelial cells occurs. Fetal and mature arterial smooth muscle cells, and some express PDGF A-chain. In situ hybridization with a riboprobe made from PDGF A-chain cDNA showed close correlation of mRNA expression with protein immunohistochemistry. PDGF A-chain expression was also identified in epithelial elements of 5/6 Wilms' tumors studied. These are the first studies to localize PDGF A-chain expression in human kidney and suggest sites of activity for PDGF A-chain in development, neoplasia, and in the renal arterial sclerosis of aging.

Aging↗

Cyclosporine A induced arteriolopathy in a rat model of chronic cyclosporine nephropathy.

Chronic cyclosporine (CsA) nephrotoxicity is a major complication of heart, bone marrow, and renal transplantation, and is characterized in humans by striped interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of hilar arterioles. This last feature is highly specific for cyclosporine injury and has been difficult to reproduce in normotensive animal models. Salt-depletion has been shown to sensitize rodents to the effects of CsA and accelerate the disease process. We conducted sequential studies in chronically salt depleted, pair fed rats treated with CsA (15 mg/kg, s.c.) or an equivalent dose of olive oil vehicle, and found a histologic lesion associated with CsA that consisted of striped cortical interstitial fibrosis, tubular dilatation and atrophy, and hyalinization of many afferent arterioles. The arteriolopathy was first detected at day 10 with progressive hyalinization of arterioles continuing until termination of the study at day 35. The arteriolopathy consisted initially of eosinophilic granular transformation of smooth muscle cells comprising afferent hilar glomerular arterioles, and progressed to foci of smooth muscle cell vacuolization and accumulation of discrete hyaline deposits in vessel walls. Electron microscopy demonstrated marked accumulation of typical renin granules throughout the smooth muscle cell cytoplasm, corresponding to the eosinophilic granular transformation revealed histologically. Immunocytochemistry confirmed the up-regulated production of renin in these vessels. This study documents a rodent model for CsA arteriolopathy and CsA-associated interstitial fibrosis that strikingly reproduces the most characteristic nephropathic effects of cyclosporine found in human patients treated with this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗