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Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 343 records · Page 19Linked to original sources

Mapping the Ig superantigen-binding site of HIV-1 gp120.

The envelope glycoprotein, gp120, of HIV-1 has recently been identified as a member of the new family of Ig superantigens (Ig-SAg). This classification is based on the selective binding of gp120 to an unusually high proportion of endogenous, nonimmune Ig, and the selective activation of nonimmune B cells by gp120 in vitro. Many, if not all of the nonimmune Ig that bind to gp120 are members of the VH3 Ig gene family. The aim of this study was to determine the epitope on gp120 that was responsible for its Ig-SAg binding activity. To do this, we utilized a panel of 30 peptides derived from gp160 in a competition-binding assay. For five Igs that were tested, as well as for polyclonal serum IgM, two overlapping peptides (each 20 amino acids in length) were identified that were potent inhibitors of gp120 binding. Similarly, the 10 amino acid overlap region of these two peptides had inhibitory activity. Thus, this decamer sequence represented the optimal Ig-SAg epitope or mimotope. The amino acid residue at position 1 of the decamer, and to a lesser extent at position 10, was critical for peptide binding. In addition to this decamer peptide, other peptides that shared modest sequence homology were also selectively inhibitory for specific Ig samples. These findings provide the first definition of an Ig-SAg ligand at the peptide level and will facilitate further structural and biologic characterization of this new class of pathogenic Ags.

Amino Acid Sequence↗

Blindsight in normal observers.

Some patients with lesions in visual cortex lack conscious visual experience but, when tested, exhibit a significant ability, termed 'blindsight', to discriminate visual stimuli. Here we report two different visual displays that induce blindsight in normal observers. Using an objective measure, we show that conscious experience remains defective at presentation times much longer (1 s) than the onset of visual sensitivity (approximately 60 ms). To obtain this effect, we generate a contrast between visual textures and then conceal the contrast by superimposing 'complementary' textures. Complementarity can involve either opposite motion or binocular rivalry and orthogonal orientation. In both cases, observers locate the texture contrast reliably but do not, by either subjective or objective measures, consciously experience it. Taken together with present knowledge of the visual cortical site(s) at which opposite motion and rivalrous orientation interact, this observation bears upon the functional anatomy of conscious visual experience.

Contrast Sensitivity↗

A novel octamer regulatory element in the VH11 leader exon of B-1 cells.

B-1 cells (CD5 B cells) represent an initial fetal wave of B cell lymphopoiesis. B-1 cells have fundamental properties that are unique from conventional B cells, including a restricted Ab repertoire. We investigated the mechanism for the overrepresentation of one such Ig H chain variable-region gene, VH11, by murine B-1 cells. We postulated that a cis-regulatory element contributed to the use of VH11. We observed that the DNA encoding the leader peptide of VH11 was atypically A/T rich and thus was a candidate for nuclear protein binding. By electrophoretic mobility shift analysis, we found that the VH11 leader DNA specifically bound to three protein complexes present in the nucleus of the B-1 cell line AJ9. Of these bands, one was ubiquitous for all cells examined (lymphoid and nonlymphoid); another band was present only in B cells, and the third band was specific for B-1 cells that expressed VH11 or VH12. In addition to its binding properties, the VH11 leader sequence also displayed modest tissue-specific enhancer activity. By DNA footprint analysis, all three protein complexes were found to bind to an octamer motif embedded within the VH11 leader DNA. To identify the octamer-binding proteins, a panel of octamer-specific Abs was used. We found that the ubiquitous band was Oct-1, and the B cell-specific band was Oct-2. The B-1 cell-specific nuclear binding protein was neither Oct-1 nor Oct-2, but may be a novel POU domain protein. We hypothesize that the VH11 leader octamer site may target this gene for preferential rearrangement and/or expression and therefore would be a contributing factor in the increased use of this gene by B-1 cells.

Animals↗

Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis.

OBJECTIVE: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. CONCLUSION: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.

Adult↗

Pathogenesis of spondylarthropathies. Persistent bacterial antigen, autoimmunity, or both?

We have discussed partially mutually exclusive, partially overlapping models for the pathogenesis of the spondylarthropathies. Not all possibilities have been presented here; others are discussed elsewhere (77, 78). Furthermore, we have not addressed the issue of B27-negative spondylarthropathy. However, in our opinion, the key to understanding the pathogenesis of the spondylarthropathies lies in the interaction between the class I MHC molecule HLA-B27 and the T cell response. Although a T cell response driven by persisting bacterial antigen is still an attractive hypothesis, it does not explain all the known aspects of spondylarthropathy pathogenesis. The possibility of autoimmunity triggered by bacterial infection needs also to be considered, especially the new idea of HLA-B27-derived peptides presented by class II MHC molecules. The predominant involvement of joints is not easily explained in the case of autoimmunity. Cross-reactivity to joint-specific structures such as type II collagen (79) and/or bacteria inside the joint at the beginning of the immune response, with induction of local autoimmunity, might be involved. Most of the issues raised here could be tested by experiment, and we can expect to learn soon whether any of these models will explain the pathogenesis, or if we have to look further. The PCR technique will facilitate the search for bacteria not only in peripheral joints, but also now in sacroiliac biopsy samples from patients with AS and other spondylarthropathies. A prospective study on ReA in an endemic area should teach us more about predisposing factors (for example for Shigella-induced enteritis, which occurs in many parts of the world outside Europe and the US) (80).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen Presentation↗

Autonomy for nursing home residents: the role of regulations.

The importance of autonomy and choice to nursing home residents' well-being has been well established. This paper examines the complex role of regulation as it affects the autonomy of nursing home residents. Nonstandardized interviews with residents, family members, nursing staff members, and administrators were conducted at three nursing homes in suburban Maryland. These anecdotal interviews identified the most problematic areas where regulations enforce barriers to autonomy and control. These areas include: scheduling of activities of daily living, food portions, physical environment, and documentation. Suggestions for possible improvements are discussed.

Adaptation, Psychological↗

Effect of different protein supplements on motility and plasma membrane integrity of frozen-thawed stallion spermatozoa.

Three experiments were conducted to evaluate the effect of different macromolecule components (egg yolk, skim milk, and BSA) in a widely employed extender for cryopreservation of horse semen. Spermatozoal motility (MOT) and the percentage of spermatozoa with an intact plasma membrane (IPM) were evaluated in frozen-thawed samples. In the first experiment (four Draft Horse stallions, four ejaculates each) a standard freezing extender containing 20% whole egg yolk was modified by replacing extender components (glucose-EDTA solution, 11% lactose solution) with an increasing volume of a skim milk diluent (0, 25, 50, and 75%, v/v). The best results were obtained with an extender containing 75% (v/v) skim milk solution (MOT 24.7%; IPM 46.6%). This extender was further tested in Experiment 2 (three Draft Horse stallions, four ejaculates each) by varying the amount of egg yolk (10 or 20%) and by addition of 5% BSA. Neither the amount of egg yolk nor the addition of BSA significantly influenced postthaw results. Selected extenders from the previous experiments were tested in Experiment 3 (three stallions, four ejaculates each). Again, a mixture of 20% whole egg yolk and a skim milk solution provided the best results (MOT 41.7%; IPM 54.2%). The results of this study indicate that the inclusion of different sources of macromolecules (e.g., egg yolk and skim milk) can improve motility and plasma membrane integrity of frozen-thawed horse spermatozoa.

Animals↗

Stapled ileal pouch-anal anastomosis with resection of the anal transition zone.

We assessed the outcome of stapled ileal J-pouch-anal anastomosis with intersphincteric resection of the anal transition zone in 83 consecutive patients with ulcerative colitis (n = 71) or familial adenomatous polyposis (n = 12). There was no postoperative mortality. Two patients (2.4%) required permanent ileostomy for manifestation of unsuspected Crohn's disease. Major postoperative complications consisted of pelvic sepsis, anastomotic leakage, and pancreatitis with 3.6% each. Both, frequency of bowel movements and degree of continence improved with time. Two years after takedown of the diverting ileostomy 45 patients with ulcerative colitis and 12 with familial adenomatous polyposis were assessed with a frequency of bowel movements of 5.6 +/- 2 and 3.2 +/- 1 per 24 h, respectively (P < 0.05). At this time none of them had major daytime or nighttime incontinence. Minor incontinence was reported by 9% and 14% of the patients with ulcerative colitis during day-time and night-time, respectively. The patients with familial adenomatous polyposis demonstrated better results, without day-time seepage and intermittent nocturnal seepage in only 9%. It is concluded that direct ileal J-pouch-anal anastomosis is a safe procedure with excellent functional results for patients with ulcerative colitis and familial adenomatous polyposis.

Adenomatous Polyposis Coli↗

A community-wide outbreak of hepatitis A: risk factors for infection among homosexual and bisexual men.

PURPOSE: To assess risk factors for hepatitis A infection among homosexual and bisexual men during a community-wide outbreak of hepatitis A in New York City. PATIENTS AND METHODS: Twenty-five homosexual and bisexual men, 20 to 49 years of age with hepatitis A identified from health department surveillance data (cases) were compared with 42 homosexual and bisexual men of similar age distribution who were seronegative for hepatitis A virus and identified from private physician offices (controls). Odds ratio (OR) were determined for acute hepatitis A infection according to demographics, numbers of sexual partners, frequency of specific sexual behaviors, and self-reported human immunodeficiency virus status. RESULTS: Cases had more anonymous sex partners (0 to 1 partner versus > 1 partner) than controls during the 6 weeks before illness onset (OR = 4.4, 95% confidence interval [CI] 1.4 to 14.4). Cases were more likely than controls to have engaged in group sex (OR = 3.8, 95% CI 1.1 to 12.6). Among specific sexual behaviors examined, oral-anal intercourse (oral role) and digital-rectal intercourse (digital role) with anonymous sex partners were more commonly reported by cases than controls (OR = 9.7, 95% CI 1.2 to 78.7 and OR = 2.6, 95% CI 1.0 to 7.4, respectively). Multivariate analysis showed that > 1 anonymous sex partner, group sex, oral-anal intercourse, and digital-rectal intercourse were associated with illness in models controlling for duration of sexual activity. Because these variables were highly correlated, independent risk could not be evaluated in a single model. CONCLUSIONS: Hepatitis A infection among homosexual and bisexual men is associated with oral-anal and digital-rectal intercourse, as well as with increasing numbers of anonymous sex partners and group sex. These findings reinforce the importance of developing educational activities for homosexual and bisexual men that focus on risk reduction for hepatitis A as well as other sexually transmitted disease spread via the fecal-oral route.

Adult↗

In situ hybridization: a new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants.

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Animals↗

[Improvement of temperature and vibration sense in chronic uremia after a single dialysis].

Pathophysiology and pathoanatomy of uremic neuropathy are not yet well understood. A single hemodialysis positively increases nerve conduction velocities of uremic patients, thus demonstrating a functional A alpha-fiber improvement by detoxification. This study tested whether non-invasive Vibrameter and Thermotest studies show a similarly positive effect for A beta-, A delta- and C-fibers and whether the psychophysical techniques might substitute for nerve conduction studies. 20 uremic patients depending on chronic intermittent hemodialysis were examined shortly before and after a hemodialysis. Using a scaled 128 Hz tuning fork, a Vibrameter and a "Marstock"-Thermotest, vibratory and warm and cold thresholds were assessed at both internal malleoli according to the method of limits. In addition, thermal thresholds were determined at the volar aspect of the non-shunted wrist. In nine patients the Vibrameter showed elevated thresholds before and after dialysis as did six patients with the tuning fork. Warm or cold thresholds were abnormal in four patients before treatment and in eight patients after dialysis. This was due to some patients reporting elevated thresholds after dialysis although they had had normal thresholds before the treatment. Still, the overall sum of abnormal thermal or vibratory thresholds at the different tested body sites had decreased after treatment. Moreover, mean values of thermal and vibratory thresholds of the 20 patients improved with dialysis (p < 0.05). Tuning fork results were too coarse and failed to show a dialysis effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Vibrameter testing facilitates the diagnosis of uremic and alcoholic polyneuropathy.

The diagnostic sensitivity of Vibrameter and tuning fork examination towards uremic and alcoholic neuropathy was tested in 75 patients. In 40 uremic and 35 alcoholic patients, we compared the sensitivity of neurological examination, nerve conduction studies (NCS) and vibration thresholds assessed at the malleoli by means of Vibrameter and scaled tuning fork. Vibrameter results were correlated with NCS. Polyneuropathy was diagnosed in 52 patients, but in 16 patients diagnosis depended upon inclusion of Vibrameter testing in the examination protocol. In uremic patients, Vibrameter (47.5%) showed abnormalities as often as NCS (45%), and more often than clinical (32.5%) or tuning fork examination (2.5%). In alcoholic patients, Vibrameter revealed abnormalities more often (60%) than NCS (34.3%) or tuning fork (14.3%). Correlations between NCS and vibratory thresholds were low (-0.52 < or = Rs < or = -0.35). Vibrameter studies are far more sensitive than tuning fork tests. The technique complements NCS and refines the diagnosis of uremic and alcoholic neuropathies.

Adult↗

Early sacroiliitis in patients with spondyloarthropathy: evaluation with dynamic gadolinium-enhanced MR imaging.

PURPOSE: To investigate the diagnostic value of gadolinium-enhanced magnetic resonance (MR) imaging in the detection of early sacroiliitis. MATERIALS AND METHODS: Of 125 patients with back pain, 72 had inflammatory back pain and had a diagnosis of spondylarthropathy; the other 53 patients had other mostly mechanical causes of back pain and served as the control group. The 72 patients with spondyloarthropathy were further subdivided into two groups according to established radiographic criteria for ankylosing spondylitis. While group 2 patients (n = 36) with a diagnosis of ankylosing spondylitis had definite radiographic changes in the sacroiliac joints, group 1 patients (n = 36) with undifferentiated spondylarthropathy had no such findings. RESULTS: While no contrast enhancement was found in normal sacroiliac joints, significantly different degrees of enhancement (P < .05) related to the patients' degree of pain were clearly detected in both groups of patients with spondyloarthropathy. Contrary to the mostly normal findings with precontrast MR imaging and with radiography, dynamic MR imaging revealed small erosions (< 1 mm) in 47 (72%) of the 65 inflamed joints in group 1 and juxtaarticular osteitis in 53 (82%). CONCLUSION: Contrast-enhanced MR imaging allows detection of sacroiliitis in early stages.

Adolescent↗

Relationship among seminal characteristics, fertility and suitability for semen preservation in draft stallions.

Seminal characteristics, fertility and the response to semen preservation (liquid storage and cryopreservation) were evaluated in 4 Draft stallions (Percheron 2, Breton 2). Seminal characteristics (gel-free volume, sperm concentration, sperm morphology, percentage of motile spermatozoa) were assessed in 5 ejaculates from each of the 4 stallions. The fertility of the stallions was calculated retrospectively as the accumulated pregnancy rate over 3 breeding seasons. Five ejaculates from each of the stallions were subjected to liquid storage at 5 degrees C. The percentage of motile spermatozoa (PMS) was assessed at 0, 24, 48 and 72 hr. Cryopreservation was done with a glucose-EDTA-lactose egg yolk extender and a skim milk-based extender containing clarified egg yolk (4 replicates per stallion). PMS and the percentage of spermatozoa with an intact plasma membrane (IPM) were evaluated before and after freezing. Although semen characteristics and fertility were within a physiological range, significant differences among stallions were found for gel-free volume, percentage of morphologically normal spermatozoa, PMS, and fertility but there was no clear relationship between these parameters. The response to liquid storage of diluted semen samples differed among stallions and best results were obtained in a stallion with the highest initial motility. The freezability of semen from the 4 stallions was poor with both of the freezing protocols (PMS range 13.8%-26.3%; IPM range 19.5%-38.0%). Results of liquid storage and cryopreservation were not correlated in individual stallions and were not related to their fertility. Since predictability for the response to semen preservation is low, the suitability of individual stallions for semen preservation has to be examined carefully.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Pentoxifylline inhibits secretion of O2- and TNF-alpha by alveolar macrophages in patients with sarcoidosis].

Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.

Adult↗