Search PubMed⌕ Search

Biomedical subjects

J E Robertson

Publications and source records attributed to J E Robertson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Immunolocalization of integrins in the human retina.

PURPOSE: Integrins are cell surface proteins that participate in interactions between cells and with extracellular matrix. Binding of integrins to their ligands influences cell activities including proliferation, migration, and differentiation. Expression of integrin subunits from three different subfamilies were examined in human retina. METHODS: Integrins were detected in frozen sections of two human retinas with an avidin-biotin-complex immunohistochemical technique, using nine different monoclonal antibodies specific for alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 2, and beta 3. One retina was from a patient who had conjunctival squamous cell carcinoma, and the other was from uninvolved regions of an eye with a choroidal melanoma. RESULTS: All integrins tested were detectable in consistent patterns in two retinas. All except alpha 2 and alpha 4 were stained vibrantly in retinal and choroidal vessels. All alpha subunit staining of vessels showed overlap or close proximity to beta 1 staining. In addition to vessels, beta 1 was also present in the internal limiting membrane; alpha 2, alpha 3, alpha 4, alpha 5, and beta 2 were all found throughout much of the neural retina, albeit with distinctive staining patterns. Other than in association with vessels, alpha 6 and alpha v were not detected in neural retina, and beta 3 was only weakly detected in the nerve fiber layer; alpha 4 and beta 2 were expressed in the retinal pigment epithelium; beta 1 and beta 2 were strongly expressed in drusen present in one of the eyes. CONCLUSION: Nine integrin subunits have been found to have unique distributions in adult human retina. An understanding of the distribution in normal retina can serve as a useful contrast to patterns of staining associated with retinal diseases.

Antibodies, Monoclonal↗
PubMed1994

Immunolocalization of integrins in proliferative retinal membranes.

PURPOSE: Integrins are cell surface adhesion molecules that serve as receptors for extracellular matrix components or for other cells. Integrins help regulate processes such as cell proliferation, migration, and differentiation. These processes are thought to have fundamental roles in the pathogenesis of proliferative retinal membranes in diseases such as proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Therefore, the authors sought to determine the expression pattern of integrins in human proliferative membranes. METHODS: Tissue was obtained from two patients with PVR, two with PDR, and one subretinal neovascular membrane from a patient with presumed ocular histoplasmosis. Integrins were detected with an avidin-biotin-complex immunohistochemical technique using nine different monoclonal antibodies specific for alpha subunits 2, 3, 4, 5, 6, and V, and beta subunits 1, 2, and 3. RESULTS: All integrin subunits studied were detectable to varying degrees in proliferative membranes. beta 1 and alpha 6 were especially prominent at the edges of most PVR and PDR membranes. Pigmented cells expressed up to nine different integrin subunits, in contrast to normal RPE cells, which immunostained for only alpha 4 and beta 2. Proliferative diabetic retinopathy vessels expressed all nine integrin subunits examined, including alpha 4, which was poorly expressed in vessels of nondiabetic retinas. CONCLUSIONS: Integrin subunits are readily detectable in pathologic membranes. Both PVR and PDR are associated with altered integrin expression in vascular endothelium and pigmented cells. The distribution of integrins at the edge of a membrane suggests a role in the growth or contraction of the membrane, presumably by participating in the interaction between cells and substances such as vitreous collagen. Therefore, integrin antagonists may hold promise for the treatment of proliferative retinopathies.

Adult↗
PubMed1994

Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases.

PURPOSE: Platelet-derived growth factor (PDGF) and its receptors could contribute to the development of proliferative retinal membranes, because PDGF is angiogenic and is both mitogenic and chemotactic for retinal pigment epithelial (RPE) and glial cells, components of membranes. The authors sought to determine whether PDGF ligands and their receptors were present in proliferative retinal membranes. METHODS: To localize PDGF ligands and receptors, the authors examined normal postmortem control retinas, intact eyes with proliferative vitreoretinopathy (PVR) or proliferative diabetic retinopathy (PDR), and membranes removed by vitrectomy from patients with PVR, epimacular proliferation, PDR, or PVR with PDR of previous onset. Sections were stained with antibodies specific for each PDGF ligand and receptor, using an avidin-biotin-complex immunohistochemical technique. To correlate PDGF receptor beta (PDGFR beta) and ligand immunostaining, sections were doubled labelled with antibodies specific for either PDGF-A or PDGF-B. RESULTS: Ligands. In the normal retina and choroid, staining for the A-chain was limited to vascular cells. Only the nerve fiber layer and vessels were positive for the B-chain. In diseased tissue, PDGF-A immunoreactivity was detected as intense staining ( ) of all but one of the proliferative retinal membranes; some RPE cells were positive for PDGF-A, especially in the eye with PDR. PDGF-B was also present in many proliferative retinal membranes but not in RPE cells. Receptors. In the normal retina and choroid, both PDGFR alpha and PDGFR beta were detected only in vessels. In proliferative retinal membranes, both receptors were detected in vessels. Long strands of RPE-like cells at the edges of PVR membranes were strongly positive for PDGFR beta but negative or +/-, respectively, for PDGFR alpha. Double-label assays showed that PDGFR beta was often colocalized with each PDGF ligand, especially in pigmented cells. CONCLUSIONS: PDGF ligands and receptors are widespread in proliferative retinal membranes of different origin. Because PDGFR beta and PDGF-B were colocalized in many of the same cells, the potential for autocrine and paracrine stimulation of cell migration and growth exists. These results are consistent with a role for PDGF ligands and receptors in the pathogenesis of different proliferative retinopathies.

Adolescent↗
PubMed1994

Cytokine mRNA levels in rat ocular tissues after systemic endotoxin treatment.

PURPOSE: An intertwined cascading network of cytokines is believed to direct the development of endotoxin-induced uveitis (EIU). This study investigated mRNA levels of interleukin (IL) 1 alpha, IL-1 beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, transforming growth factor (TGF)-beta 1, and the helper T lymphocyte marker, CD4, during the course of EIU in rats. METHODS: Reverse transcription followed by polymerase chain reaction amplification was used to determine relative mRNA levels in four ocular tissues (iris/ciliary body, cornea, lens, and neuroretina) at 0, 1, 3, 6, 24, and 48 hours after subcutaneous injection of 200 micrograms of Escherichia coli endotoxin. RESULTS: Four general patterns of mRNA expression were observed: (1) constitutively expressed and unaffected by endotoxin; (2) constitutively expressed but further induced by endotoxin, reaching peak levels at 3 hours postinjection; (3) initially undetectable or marginally detectable and induced by endotoxin, with peak levels occurring 3 hours postinjection; and (4) never present at appreciable levels. The most dramatic responses were seen in the mRNA levels of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma in iris/ciliary body. Lesser mRNA level responses were found for IL-1 beta and IL-6 in cornea and for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, and IFN-gamma in neuroretina. Little or no changes in mRNA levels were observed for CD4 or TGF-beta 1 in any tissue or for any mRNA examined in lens. CONCLUSIONS: These data show that subcutaneous endotoxin induces cytokine mRNA expression differentially in ocular tissues. These data support the hypothesis that induction of cytokine expression in iris/ciliary body plays a major role in the development of EIU.

Animals↗
PubMed1993

The value of pathologic factors in predicting cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer-specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate. METHODS: Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer-specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival. CONCLUSIONS: If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials.

Adult↗
PubMed1993

Is prostate specific antigen of clinical importance in evaluating outcome after radical prostatectomy.

Current bias would conclude that elevation of serum prostate specific antigen (PSA) after radical prostatectomy infers failure of the procedure. Since April 1987 preoperative and postoperative serum PSA levels have been obtained on 226 patients who underwent radical perineal prostatectomy for presumed organ confined prostate cancer (stage T1-2N0M0). Clinical failure as defined by elevation of serum acid phosphatase, biopsy proved local recurrence or evidence of malignant disease on bone scan has occurred in 3.9% of the patients with organ confined, 7.0% with specimen confined and 13.2% with margin positive disease. However, when a PSA elevation of greater than 0.5 ng./ml. was used as an indicator of failure the failure rate became 9.8% for the organ confined group, 39.4% for the specimen confined group and 66.0% for margin positive group. Of the patients who failed clinically the interval from initial elevation of postoperative PSA to clinical detection of failure ranged from 2 to 28 months (median 16). Among the patients with an elevated postoperative PSA level but who have not clinically failed followup ranged from 4 to 46 months (median 23). A total of 11 patients had no evidence of failure at greater than 36 months despite the elevated postoperative serum PSA level. These PSA elevations in patients who undergo supposed curative therapy are distressing. However, at this time the majority of these patients have not failed. In the clinically cured patient biochemical evidence of failure may not be sufficient to change the treatment course.

Adult↗
PubMed1993

Recognition of posterior scleritis and its treatment with indomethacin.

Posterior scleritis is a rare disease, the clinical signs of which may vary. There is no consensus on the appropriate method of treatment for this disease. Some have advocated treatment with nonsteroidal antiinflammatory drugs, whereas others have reported variable success with potentially more toxic therapy. Patients with posterior scleritis constitute approximately 1% of the uveitis clinic population at the Casey Eye Institute in Portland, Oregon. The cases of 6 patients with posterior scleritis, the diagnosis of which was elusive, are reported. Posterior scleritis was generally confirmed by ultrasound examination. Each of the patients responded to treatment with indomethacin, which was usually the sole method of nontopical therapy. Thus, recognition of this relatively rare disease had marked implications for treatment.

Adult↗
PubMed1993

Retinal pigment epithelial cells produce interleukin-1 beta and granulocyte-macrophage colony-stimulating factor in response to interleukin-1 alpha.

The retinal pigment epithelium (RPE) is clinically involved in diverse ocular inflammatory diseases. Because perturbed RPE cells produce a variety of inflammatory substances, RPE cells may play an integral part in these diseases. Interleukin-1 (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are pleiotropic cytokines with the ability to trigger numerous inflammatory responses. This report shows that cultured human RPE cells synthesize interleukin-1 beta (IL-1 beta) and GM-CSF in response to the potentially inflammatory cytokine, IL-1 alpha, but not to E. coli endotoxin. Control RPE cells made little or no mRNA or protein for either IL-1 beta or GM-CSF. Upon stimulation of the cells by IL-1 alpha, both IL-1 beta and GM-CSF mRNAs were readily apparent by 3 hours, persisted for over 24 hours, and were translated into immunologically detectable proteins. GM-CSF protein was secreted into the culture medium, whereas IL-1 beta protein remained cell associated. The IL-1 alpha-induced mRNA and protein production were inhibited by dexamethasone. These observations provide additional evidence that RPE cells are capable of playing a pivotal role during ocular inflammation.

Blotting, Northern↗
PubMed1992

Complications of radical cystectomy and urinary diversion: a retrospective review of 675 cases in 2 decades.

A retrospective review was performed on all 675 patients who underwent radical cystectomy and urinary diversion during 2 decades. Of the patients 197 were treated from 1969 to 1979 (group 1) and 478 were treated from 1980 until 1990 (group 2). The mean age of patients in group 1 was 56.7 years versus 64.2 years in group 2 (p < 0.001). The overall operative mortality rate in both groups was 2.5%. A total of 215 patients (31.9%) experienced postoperative complications (within 30 days of surgery). The morbidity rate was nearly identical between the 2 groups (32.0% for group 1 versus 31.8% for group 2, p = 0.962). Of note, however, there was a decreased incidence of wound infections and wound dehiscence among the patients in group 2 compared to group 1. Long-term complications occurred in 198 of the 675 patients (29.3%). At followup group 1 had a 35.5% incidence of long-term complications versus 26.8% in group 2 (p = 0.022). Most notably there was significant improvement in the incidence of ureteroenteric anastomotic strictures when comparing groups 1 (11.2%) and 2 (5.2%) (p = 0.006).

Cystectomy↗
PubMed1992

Radical prostatectomy: the pros and cons of the perineal versus retropubic approach.

Radical prostatectomy is frequently recommended for the treatment of localized adenocarcinoma of the prostate. The use of the perineal versus the retropubic approach is mostly dependent upon the experience of the individual surgeon. This study was performed to evaluate the short-term differences between the 2 operations. Between 1988 and 1989, 173 patients were identified with organ confined prostate cancer (stage A or B) who were treated with radical prostatectomy. Of this total population 122 patients underwent radical perineal prostatectomy (group 1) and 51 patients underwent radical retropubic prostatectomy (group 2). The median estimated blood loss for group 1 was 565 cc and for group 2 it was 2,000 cc (p less than 0.001). Group 1 received a median of 0 units of blood during hospitalization, while group 2 received a median of 3 units of blood (p less than 0.001). The total operative time was slightly shorter for group 1 but the anesthesia time was similar for both patient populations. There was no difference in the incidence of positive surgical margins, and in in-hospital and long-term complication rates between the 2 groups. In light of these significant findings it is our belief that the radical perineal prostatectomy is an excellent approach for the treatment of adenocarcinoma of the prostate.

Adult↗
PubMed1991

Uveitis precipitated by nonpenetrating ocular trauma.

Although penetrating trauma is a well-recognized cause of uveitis, the role of nonpenetrating trauma in initiating uveitis is not defined. We analyzed the records of 496 patients seen at the uveitis clinic at our institution. Twenty-four of these 496 patients (4.8%) suspected that the cause of their intraocular inflammation was related to previous nonpenetrating trauma. In contrast, only one of 251 patients (0.4%) attending the general ophthalmology clinic for routine care provided a history of recent trauma or attributed the present ocular complaint to trauma (P less than .02). Patients with posttraumatic uveitis were usually male (19 of 24, 79%), younger (31 +/- 16 years) than the average patient examined in the uveitis clinic, and more likely to have unilateral disease. In ten (42%) of the patients the trauma was work-related. Bilateral inflammation was seen in eight (one third) of the patients and 17 of 28 patients (71%) had a considerable degree of inflammation posterior to the lens. Many patients had an identifiable cause of uveitis such as ankylosing spondylitis, Reiter's syndrome, sarcoidosis, or acute retinal necrosis; but most patients had no known predisposition. The role of nonpenetrating trauma in initiating uveitis has implications for diagnosis and treatment.

Accidents, Occupational↗
PubMed1991

Surgical management and prognosis of renal cell carcinoma invading the vena cava.

A total of 44 patients with renal cell carcinoma and vena caval tumor thrombus underwent surgical resection. Of these patients 27 had primary tumor confined within Gerota's fascia, negative lymph nodes and no distant metastases (stage T3cN0M0). Patients who underwent extraction of a mobile tumor thrombus from the vena cava had a 69% 5-year survival rate (median 9.9 years) but patients with tumor thrombus directly invading the vena cava had a 26% 5-year survival rate (median 1.2 years), which improved to 57% (median 5.3 years) if the involved vena caval side wall was resected successfully. Of these patients 17 had renal cell carcinoma with vena caval thrombus as well as extrafascial extension, regional lymphadenopathy or distant metastases, and the 5-year survival rate was less than 18% in all groups (median survival less than 0.9 years). Prognosis was determined by the pathological stage of the renal cell carcinoma and by the presence or absence of vena caval side wall invasion but not by the level of tumor thrombus extension. Patients with incomplete resection of localized renal cell carcinoma with tumor thrombus do not survive any longer than those with extensive cancer, positive lymph nodes or distant metastases. However, when partial venacavectomy establishes negative surgical margins then survival markedly improves.

Adult↗
PubMed1991

Retinal vasculitis--a primer.

Retinal vasculitis is a diagnosis that is generally suggested by an ophthalmologist. Frequently patients with the disorder are referred to nonophthalmologists for further diagnostic evaluation or treatment. The criteria for defining vasculitis differ greatly between ophthalmologists and other physicians. To facilitate collaboration between ophthalmologists and their colleagues, we have sought to clarify the term "retinal vasculitis" by discussing its subcategories, the potential role of antiphospholipid antibodies, and the etiology of retinal vasculitis. We offer guidelines for evaluating the disorder and treating patients.

Humans↗
PubMed1990

Photographic grading in the retinopathy of prematurity cryotherapy trial.

We report a system for photographic grading of the posterior fundus features of retinopathy of prematurity and correlation of such features with potential future visual function. The severity of temporal vessel traction, retinal fold, macular ectopia, retinal detachment, retrolental mass, blood vessel attenuation, retinal pigment epithelial scarring, and cataract was assessed by review of photographs at the Fundus Photograph Reading Center, Portland, Ore, according to a scheme designed to avoid bias or knowledge of treatment status. Reliability for all features was in the fair to excellent range (kappa greater than .40), except for blood vessel attenuation (kappa = .18), which was not a factor in the final outcome determination. The grading scheme provided the basis for the 3-month conclusions of the multicenter trial of cryotherapy for retinopathy of prematurity. This system will have further application in the 12-month Cryotherapy for Retinopathy of Prematurity Study conclusions and in future long-term correlation with visual acuity as the trial patients mature.

Cataract↗
PubMed1990

Postoperative radiotherapy of the prostate for patients undergoing radical prostatectomy with positive margins, seminal vesicle involvement and/or penetration through the capsule.

A group of 159 patients previously reported as having margins positive for disease after radical prostatectomy with or without adjunctive postoperative radiation was reanalyzed to determine whether the reported benefit did indeed exist. Upon re-examination of the 159 patients 15 were identified who did not receive radical prostatectomy but who were analyzed as if they had received this therapy. An updated review of the total pool of 159 patients with analysis as to failure, death of any cause or death of prostatic cancer demonstrated no benefit of postoperative radiation therapy for margin positive disease. Exclusion of patients who did not receive radical prostatectomy and analysis as described also failed to identify any benefit of postoperative adjunctive radiation therapy.

Adenocarcinoma↗
PubMed1989

Complications of therapy for testicular cancer.

Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.

Antineoplastic Combined Chemotherapy Protocols↗