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J Bean

Publications and source records attributed to J Bean.

At least 19 recordsLinked to original sources
PubMed1999

The spatial organization of apical junctional complex-associated proteins in feline and human corneal endothelium.

PURPOSE: Previous studies suggest that proteins associated with the apical junctional complex (AJC) play essential roles in the development, maintenance and regulation of barrier function in transport epithelium and vascular endothelium. The goal of this study is to identify and determine the spatial organization of several major AJC-associated proteins in normal human and feline corneal endothelium. METHODS: Fresh corneal tissue was obtained from 4 recipient buttons removed during penetrating keratoplasty (two from keratoconus patients, and two from patients with post-traumatic stromal scarring) as well as from 16 cat eyes. En bloc double- and triple-labeling of corneas was performed using phalloidin, and mouse, rat or rabbit antibodies to ZO-1, occludin, pan-cadherin, alpha-catenin, beta-catenin and plakoglobin (gamma-catenin). The 3-D localization of the proteins was then determined in situ using laser confocal microscopy. RESULTS: Similar staining patterns were obtained for the corneal endothelium of normal cat corneas and fresh human buttons. Apically, f-actin was arranged into dense peripheral bands (DPB) in individual cells that were separated from those in adjacent cells. Diffuse phalloidin staining also extended from the DPB into the cytoplasm apically. Although weaker, phalloidin staining also appeared to be associated with the basolateral cell borders. The adherens junction protein, cadherin, formed a thin pericellular band at the apical cell junctions between the DPB. In addition, cadherin staining also appeared to extend along the basolateral cell borders in a convoluted pattern. Staining for alpha-catenin, beta-catenin and plakoglobin each showed a nearly identical organization as cadherin. ZO-1 formed a single apical band that was localized between the DPB; however, no basolateral ZO-1 staining was detected. Interestingly, the distribution of ZO-1 was discontinuous around the cell, with the largest gaps occurring at the Y-junctions between adjacent endothelial cells. Positive staining for occludin was not detected in either human or feline corneal endothelium. CONCLUSIONS: The composition and organization of the AJC of corneal endothelium appears to be different from that of classical transport epithelia; these findings may be related to functional differences between these two cell types.

Adult↗
PubMed1999

Labeling of cycling corneal endothelial cells during healing with a monoclonal antibody to the Ki67 antigen (MIB-1).

PURPOSE: To assess the efficacy of labeling actively cycling corneal endothelial cells by using a monoclonal antibody to the Ki67 antigen (MIB-1) and to determine what changes in f-actin and ZO-1 organization are associated with entry into the cell cycle during wound healing under different culture conditions. METHODS: Three corneal buttons (6 mm diameter) were punched from each cornea of 15 cats. After a mechanical scrape injury (2 mm diameter) was made, buttons were cultured for 24, 48, or 72 h in serum-free media (SFM), SFM plus 10% fetal calf serum, or SFM plus basic fibroblast growth factor (bFGF). Buttons were single and double labeled by using phalloidin, anti-ZO-1, and MIB-1. Counts of Ki67-positive cells were used to determine the number of actively cycling endothelial cells. RESULTS: After culture in SFM, wounds healed by cell spreading with maintenance of normal apical f-actin and ZO-1 organization; Ki67-positive cells were detected near the leading edge in some areas. A significant increase in the number of cycling cells was measured after 48 h of culture in bFGF as compared with SFM (p<0.05); serum increased the number of cycling cells more than both SFM and bFGF (p<0.05). In all cases, positive MIB-1 staining was not observed until 48 h after injury, was limited to cells actively spreading over the wound area, and was diminished after wound closure (72 h). Double labeling demonstrated that endothelial cells exhibited a fibroblastic phenotype in some central areas of cell proliferation after culture in serum or bFGF, but, in general, apical cell border-associated f-actin and ZO-1 organization was partially maintained in most Ki67-positive cells. CONCLUSION: The data suggest that spreading corneal endothelial cells are capable of proliferating and can respond to growth factors, but that dedifferentiation or fibroblastic transformation is not required before entry into the cell cycle. Overall, the MIB-1 antibody appears to be ideally suited to the study of corneal endothelial proliferation during wound healing.

Actins↗
PubMed1998

Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.

The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is expressed in glomerular podocytes during a narrow window in kidney development. By immunoprecipitation and protein microsequencing analysis, we have identified a major cellular protein associated with endogenous WT1 to be the inducible chaperone Hsp70. WT1 and Hsp70 are physically associated in embryonic rat kidney cells, in primary Wilms tumor specimens and in cultured cells with inducible expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of the developing kidney, and Hsp70 is recruited to the characteristic subnuclear clusters that contain WT1. The amino-terminal transactivation domain of WT1 is required for binding to Hsp70, and expression of that domain itself is sufficient to induce expression of Hsp70 through the heat shock element (HSE). Substitution of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to restore the functional properties of a WT1 protein with an amino-terminal deletion, an effect that is abrogated by a point mutation in DNAJ that reduces binding to Hsp70. These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation.

Amino Acid Sequence↗
PubMed1998

Area and depth of surfactant-induced corneal injury predicts extent of subsequent ocular responses.

PURPOSE: To correlate area and depth of initial corneal injury induced by surfactants of differing type and irritant properties with corneal responses and outcome in the same animals over time by using in vivo confocal microscopy (CM). METHODS: Six groups of six adult rabbits were treated with anionic, cationic, and nonionic surfactants that caused different levels of ocular irritation. Test materials included slight irritants: 5% sodium lauryl sulfate (SLS), polyoxyethylene glycol monoalkyl ether (POE), and 5% 3-isotridecyloxypropyl-bis(polyoxyethylene) ammonium chloride (ITDOP); mild irritants: 5% 3-decyloxypropyl-bis(polyoxyethylene) amine (DOP) and sodium linear alkylbenzene sulfonate (LAS); and a moderate irritant: a proprietary detergent (DTRGT). Ten microliters surfactant were directly applied to the cornea of one eye of each rabbit. Ten untreated rabbits served as control subjects. Area and depth of initial injury was determined by using in vivo CM to measure epithelial thickness, epithelial cell size, corneal thickness, and depth of stromal injury in four corneal regions at 3 hours and at day 1. Area and depth of corneal responses to injury were evaluated at various times from days 3 through 35 by macroscopic grading and quantitative confocal microscopy through-focusing (CMTF). RESULTS: In vivo CM revealed corneal injury with slight irritants to be restricted to the epithelium, whereas the mild and moderate irritants caused complete epithelial cell loss with increasing anterior stromal damage: DOP < LAS < DTRGT. With the slight ocular irritants there was little or no change in corneal thickness or the CMTF intensity profiles. Three hours after treatment, mild and moderate ocular irritants caused a significant increase in corneal thickness, which peaked at day 1 with DOP (483.3+/-80.1 microm) and LAS (572.3+/-60.0 microm) and day 3 with DTRGT (601.4+/-68.7 microm); returning to normal (similar to control values) by day 7 with DOP and day 35 with LAS and DTRGT. The CMTF intensity profiles also showed significant elevation over that in the anterior stroma, which peaked at day 1 with DOP (14,608+/-4,306 U [U is defined as micrometers X pixel intensity]) and day 3 with LAS and DTRGT (18,471+/-6,581 U and 22,424+/-3,704 U, respectively) and returned toward normal by day 7 with DOP and day 14 with LAS and DTRGT. Elevated CMTF profiles principally reflected the presence of hyperreflective, punctate keratocytes and inflammatory cells at days 1 and 3 and the presence of activated keratocytes at day 7. There was a significant correlation between the elevated CMTF intensity profile and the corresponding macroscopic total score in each eye (r = 0.839; P < 0.001). More important, there was a significant correlation between area and depth of initial stromal injury measured at day 1, regardless of ocular irritant and the stromal response measured by the area under the CMTF intensity profile curve in each cornea (r = 0.87; P < 0.0005). A significant correlation between the area and depth of injury and the area under the corneal thickness curve was also observed in each cornea (r = 0.75; P < 0.0005). CONCLUSIONS: In individual animals, the extent of initial stromal injury correlated with the magnitude of the corneal responses, measured by the change in corneal thickness and the CMTF depth intensity profile. These findings further support the hypothesis that area and depth of injury are the principal factors determining the early responses and eventual repair processes after accidental eye irritation. They also support the proposed use of area and depth of acute injury as a mechanistic correlate to ocular irritation in the development and validation of potential in vitro ocular irritation tests.

Animals↗
PubMed1997

High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing.

BACKGROUND: The development of strategies to enhance survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advance in posttransplant patient care. The aim of this clinical trial was to determine the effect of timing and dose of peripheral donor bone marrow cell (DBMC) infusion on graft and patient survival after liver transplantation. METHODS: DBMC, obtained from vertebral bodies, were administered in 101 recipients of liver allografts (OLTX). There were 107 patients for whom DBMC could not be obtained; they received OLTX alone (controls). A total of 5 x 10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2; n=26); or at days 5 and 11 (group 3; n=26). In group 4 (n=40), patients received up to five infusions of 2 x 10(8)/kg DBMC at days 5, 14, 21, 28, and 90 after OLTX. RESULTS: When the results from patients receiving two or more DBMC infusions (groups 2, 3, and 4) are considered, both patient and graft survival were significantly improved compared with the control group (P=0.02 and P=0.01, respectively). In groups 3 and 4, 88.5% and 95% of patients were alive with mean follow-up of 536 and 265 days, respectively, compared with 77.6% of patients in the control group (average follow-up of 452 days) (P=0.02). Graft survival was also significantly improved in groups 3 (88.5%) and 4 (92.5%), compared with the controls (72%) (P=0.007). CONCLUSIONS: The results suggest that dose and timing of DBMC infusions may be important variables affecting allograft survival. A randomized prospective trial is now in progress to compare group 3 DBMC infusion protocol with controls receiving OLTX alone.

Adult↗
PubMed1997

Decreasing disability in chronic back pain through aggressive spine rehabilitation.

This paper discusses specific techniques for rehabilitation of chronic low back pain through aggressive physical therapy with behavioral support. The rationale for approaching the outcome dimensions of impairments in back function and pain-related disability as opposed to chronic pain symptoms is explained. This approach requires that impairments in back function are systematically identified through the quantification of trunk flexibility, straight leg raising, back extensor strength, lifting ability, and endurance. The described treatment approach focuses on eliminating those impairments through aggressive, quota-based exercise and is usually completed within 8 weeks. It requires only a modest amount of space and equipment. Useful behavioral techniques for extinguishing pain behaviors, lessening pain beliefs, and for promoting wellness are described. Results from a treatment program using these techniques demonstrate normal back function and reduced disability for a majority of treated persons. Applying such a program to the VA population is an important challenge.

Back Pain↗
PubMed1996

Insulin sensitivity and blood pressure in a biethnic sample: the Miami Community Health Study.

An association between blood pressure and insulin sensitivity among normotensive African-Americans has not been demonstrated consistently in epidemiologic studies. Part of the discrepancy may be due to studying persons with profound obesity-an insulin-resistant state itself. The association between insulin-mediated glucose uptake (i.e., insulin sensitivity) and blood pressure was examined among 25 nondiabetic African-American and 28 white non-Hispanic persons aged 25-44 years who ranged from normal weight to obese, using the hyperinsulinemic euglycemic clamp technique. In bivariate analyses, insulin sensitivity was inversely related to systolic (p < 0.01) and diastolic blood pressure (p = 0.08) among African-American persons and to diastolic blood pressure among white non-Hispanic subjects (p < 0.05). Covariate adjustment for age and sex had only a marginal effect on these results. When the data were pooled and further adjusted for ethnicity, insulin sensitivity remained significantly associated with both systolic and diastolic blood pressure (p < 0.01 for each). To consider the effect of obesity, body mass index (BMI) was divided at the sample median (26.5 kg/m2) and the analyses were repeated within each stratum. Among those whose BMI was below the median value, each increment in insulin sensitivity was associated with a 2-mmHg decrease in systolic blood pressure (p = 0.02). These results suggest that ethnicity was not a strong effect modifier in this sample and indicated that insulin sensitivity was inversely related to blood pressure level in these normotensive African-American and white, non-Hispanic participants.

Adult↗
PubMed1994

Parkinson's disease and brain levels of organochlorine pesticides.

Epidemiological studies have suggested an etiologic relationship between pesticide exposure and Parkinson's disease (PD). Organochlorine pesticides were assayed in postmortem brain samples from 20 PD, 7 Alzheimer's disease (AD), and 14 nonneurological control cases. The three groups were similar in age at death, sex, and demographic variables. Only two of 16 pesticide residues screened were detected. A long-lasting residue of DDT (pp-DDE) was found in the majority of cases of PD and AD, as well as in all the control cases; pp-DDT was significantly more likely to be found in AD controls than the PD cases (Fisher's exact two-tailed, p = 0.04). Dieldrin was detected in 6 of 20 PD brains, 1 of 7 AD, and in none of 14 control samples. Despite the relatively small number of brains assayed, the association between Dieldrin and the diagnosis of PD was highly significant (p = 0.03). Dieldrin, a lipid-soluble, long-lasting mitochondrial poison, should be investigated as a potential etiological agent of Parkinsonism.

Age Factors↗
PubMed1993

Design of a device to exercise hip extensor muscles in children with cerebral palsy.

Children with cerebral palsy (CP) often have weak hip extensor muscles and gait-related difficulties. Current therapeutic techniques do not provide sufficient exercise for this muscle group. In addition to calisthenics, therapists use a traditional tricycle to strengthen leg muscles, yet the mechanics of traditional tricycles are not effective in exercising hip extensor muscles. A new therapeutic tricycle was designed specifically to exercise the hip extensor muscles, and tests compared the traditional tricycle to the new hip extensor tricycle in effectiveness of promoting hip extensor activity in two subjects without CP. The tests demonstrated that the hip extensor tricycle was more effective in promoting hip extensor activity. Tests are underway to investigate the effect of the hip extensor tricycle in improving hip extensor strength and gait in patients with cerebral palsy. This paper describes the design of the hip extensor tricycle and a preliminary investigation of its effectiveness.

Cerebral Palsy↗
PubMed1991

Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Preliminary report.

Colon cells from patients with ulcerative colitis utilize short-chain fatty acids inefficiently and may be exposed to decreased concentrations of these compounds. To test whether irrigation of the inflamed mucosa with short-chain fatty acids is useful, we conducted a six-week preliminary trial in 12 patients with distal colitis. Each patient used twice daily rectal irrigations with 100 ml of a solution containing acetate (80 mM), propionate (30 mM), and butyrate (40 mM). Two patients stopped at three weeks, one because of no improvement and the other because of complete resolution of symptoms. Of the 10 who completed the trial, nine were judged to be at least much improved and showed a change in a mean disease activity index score from 7.9 +/- 0.3 (SE) to 1.8 +/- 0.6 (SE) (P less than or equal to 0.002) and in a mucosal histology score from 7.7 +/- 0.7 (SE) to 2.6 +/- 0.7 (SE) (P less than or equal to 0.002). Thus, ulcerative colitis patients appear to benefit from increased contact with or higher than usual levels of these critical energy substrates.

Acetates↗
PubMed1991

Invasive cutaneous melanoma in elderly patients.

Clinical and pathologic variables were compared between "older" (greater than or equal to 70 years) and "younger" (30 to 39 years) patients with primary invasive cutaneous melanoma. Older patients had more nodular melanomas and acral lentiginous melanomas (58%); superficial spreading melanomas predominated in younger patients (74%). Mean tumor thickness was greater in the older patients (3.95 vs 2.02 mm). Invasive levels 2 and 3 occurred more often in younger patients (41.1% vs 13%); level 5 occurred more often in older patients (30.4% vs 5.3%). Microscopic ulceration occurred more often in older (46.4%) than in younger patients (19.4%). Older patients classified as clinical stage I at presentation or with primary lesions 1.50- to 3.00-mm thick had poorer survival. Younger women survived longer than younger men; this was not true of older patients. The elderly patients with cutaneous melanoma were more likely to have poor prognostic features and thus more likely to die from melanoma than the younger patients.

Adult↗
PubMed1990

5,5-Dimethylthiazolidine-4-carboxylic acid (DTC) as a proline analog with restricted conformation.

Spectroscopic evidence is presented for the lack of intramolecular hydrogen bonding in a simple peptide derivative of 5,5-dimethylthiazolidine-4-carboxylic acid (Dtc). The infrared spectrum of Boc-Pro-Ile-OMe 1 in nonpolar solvents displays two N-H stretching bands at 3419 and 3330 cm-1 in CCl4 and one at 3417 and 3328 cm-1 in CHCl3. The low frequency band at 3328-3330 cm-1 may be assigned to conformations with an intramolecular hydrogen bond between the Ile N-H and Boc C = O. The band at 3417-3419 cm-1 is the normal Ile N-H stretch. In the polar solvent CH3CN only one NH stretching band at 3365 cm-1 is observed. The IR spectrum of Boc-Dtc-Ile-OMe 2, on the other hand, displays one N-H stretching band at 3423 cm-1 in CCl4 and one at 3418 cm-1 in CHCl3. The IR spectrum of 2 does not display the N-H stretching band that would arise from intramolecular hydrogen bonding between the Boc C = O and Ile N-H. The lack of intramolecular hydrogen bonding for Boc-Dtc-Ile-OMe 2 was evident also in the NMR spectra in nonpolar solvents. The 1H-NMR spectrum of the Pro dipeptide 1 in 50% CDCl3/C6D6 at 20 degrees displayed two Ile-NH signals at 6.58 and 7.74 ppm. The latter signal corresponds to the intramolecularly hydrogen bonded Ile-NH in the trans-Boc isomer of 1 (60% of the total population), while the former signal corresponds to the nonhydrogen bonded Ile-NH in the cis-Boc isomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Methods for the reduction of AIDS social anxiety and social stigma.

A cognitive-social model is proposed for the study of AIDS social attitudes. Features of the ambivalent (fear and compassion) public belief system toward PWAs are outlined and ways to increase altruism and reduce fear are specified. Three studies are reported using cognitive-social methods for the reduction of AIDS social anxiety and social stigma. Study 1 found that cognitive inoculation and abbreviated group desensitization equally reduced AIDS social anxiety measured by a verbal scale. One form of brief group desensitization was superior to basic factual, counterphobic inoculation in reducing desire for social restriction of persons with AIDS (PWAs). In Study 2 subject improvisational role playing of PWAs increased positive attitudes toward PWAs and desire for altruistic actions but did not reduce measured fear. Knowledge of AIDS was negatively correlated with AIDS social anxiety and desire for patient restriction. AIDS social anxiety was negatively correlated with altruism and positively correlated with homophobia. In Study 3, three forms of experimenter-guided mastery imagery reduced AIDS social anxiety and increased AIDS altruism. Results of these studies may have relevance to reducing high-risk contagious behavior, as well as to reducing AIDS social stigma and social anxiety. A componential model of AIDS education is described.

Acquired Immunodeficiency Syndrome↗