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Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 127 records · Page 7Linked to original sources

Penile advancement and lengthening in spinal cord injury patients with retracted phallus who have failed penile prosthesis placement alone.

Even in the presence of a penile prosthesis, a subset of spinal cord injury patients remains unable to maintain a condom catheter securely due to inadequate penile shaft length and disappearance of the corpora beneath the pubic fat pad when in the sitting position. We describe 3 patients in whom a successful resolution to this problem has been achieved with rational surgical management, including lysis of the suspensory ligament of the penis, approximation of the infrapubic soft tissues posterior to the corpora so as to advance the corpora anteriorly and buttress against posterior migration (retraction) in the sitting position, maximizing the length and fit of prosthetic rods, and, when indicated, release of infrapubic skin tethering with a modified Z-plasty technique.

Adipose Tissue↗

Anti-idiotypic antisera raised against monoclonal antibody specific for a p24 gag region epitope detects a common interspecies idiotype associated with anti-HIV responses.

One potential strategy for the control of human immunodeficiency virus (HIV) infection is immune network manipulation using anti-idiotypic antibodies: this study was undertaken to demonstrate experimentally the potential of such an approach which, in a more highly evolved form, could be used for the treatment of the acquired immune deficiency virus (AIDS) and related disorders. Anti-idiotypic antibodies were generated in rabbits against a murine monoclonal antibody identifying an epitope on the p24 gag core protein of HIV. After extensive absorption on affinity columns to remove isotype- and allotype-specific antibodies, the purified anti-idiotypic antibody preparation was shown to have specific complementarity with the immunizing mouse monoclonal antibody. This anti-idiotypic antibody was also shown to recognize a common idiotype associated with HIV-specific antibodies from both humans and chimpanzees infected with the AIDS virus. In addition a group of rats immunized with the anti-Id responded with significant antibody titers to recombinant derived p24 gag. These data indicate that at least a subpopulation of these polyclonal anti-Id antibodies structurally mimics an HIV gag region epitope and suggest that immunoregulation by anti-idiotypic antibodies may have therapeutic utility for the AIDS epidemic.

Animals↗

Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120.

Amino acid sequences inducing neutralizing antibodies to HIV-1 were sought. Murine monoclonal antibodies (MAbs) were characterized by their reactivity with the envelope precursor gp160 or the Escherichia coli recombinant DNA products pB1 and pE3 representing the carboxy- and amino-terminal halves of mature envelope gp120. Fine mapping of the MAb determinants was performed using defined 15-mer synthetic peptides spanning the entire envelope gp120 region of HIV-1. One group of MAbs recognizes epitopes (amino acids 304-323) occurring in a small region with variable and conserved amino acid sequences of gp120. These MAbs mediate neutralization of the HIV-1 strain HTLV-IIIB (HIV-1IIIB) which was used for immunization. Nine out of 11 primary HIV-1 isolates were neutralized well or moderately well. In addition, prominent serological reactivity was noted with peptide sequences of strains of various European or American origins, but not with two HIV-1 strains of African origin. The cross-reactivity contrasts with previously described type-specific reactions to other sequences of this region. The reactivity to the short conserved site GPGR with its flanking amino acids may explain the broad sequence cross-reactivity seen with our neutralizing MAbs. Two other MAbs recognize conserved epitopes (amino acids 79-103) situated in the amino-terminal region of gp120. These MAbs did not neutralize HIV-1IIIB.

Amino Acid Sequence↗

Accommodative responses to naturalistic stimuli.

Steady-state accommodative responses to a wide range of commonly encountered textural and graphic stimuli were investigated in 12 young, visually normal subjects. Details of two experiments are described. In the first experiment, stimuli were varied in terms of size, contrast, spatial frequency, colour and intellectual demand. In the second experiment, only the colour of the targets was systematically altered. In both experiments the stimulus demand was maintained at 3 D, and accommodation was measured subjectively using a Hartinger coincidence optometer. No significant difference in mean accommodative response was observed between the widely differing targets adopted in either experiment. These findings suggest that an overall threshold exists for accommodative stimuli, with supra-threshold targets of low to moderate contrast being capable of initiating and sustaining an appropriate accommodative response.

Accommodation, Ocular↗

Antipsychotics in the elderly.

Neuroleptics are commonly prescribed medications in the geriatric population and have a broader spectrum of indications than in younger patients. In spite of the frequent use of neuroleptics in elderly patients with organic brain syndromes, there are relatively few studies that use double-blind, placebo-controlled methodology. The results of these studies are conflicting; however, there is sufficient evidence that symptoms of agitation, behaviourial dyscontrol, and psychosis are often responsive to neuroleptic treatment. Elderly patients with schizophrenia or other psychotic disorders may also benefit from neuroleptic treatment. As there is a potential for overuse of these medications among the elderly, clear definition of checklist symptoms is imperative. Furthermore, periodic reduction of dose and possible discontinuation of the drug should be considered since many of the checklist symptoms in this age group are environmentally related and time-limited. There has so far been little evidence to support the use of one neuroleptic over another. Side-effect profiles suggest that low doses of the high potency agents are safer and better tolerated in the elderly. Both therapeutic effects and side effects should be assessed at regular intervals.

Aged↗

Management of malignant obstructive jaundice.

This study compares the efficacy of percutaneous transhepatic drainage (PTD) versus operative biliary decompression for patients with malignant obstructive jaundice. The utilization of preoperative PTD as a surgical adjuvant is also examined. The records of 90 patients with obstructed jaundice from two large community hospitals were reviewed. In the group of patients undergoing curative resections, no advantage was noted for the patients who received preoperative PTD. The patients receiving only surgery left the hospital 8 days sooner. For the patients undergoing palliative treatment, the group receiving only the surgery had the lowest morbidity and mortality and the longest survival rates. The patients receiving only PTD had the shortest hospital stay, but also had many complications, the highest mortality rate, and the shortest survival rate. The group receiving preoperative PTD followed by surgical decompression had more complications and stayed in the hospital longer, with no change in postoperative mortality.

Aged↗

Clonidine treatment of schizophrenia: can we predict treatment response?

Four out of 13 drug-free relapsed schizophrenic patients improved with double-blind clonidine treatment. All responders were paranoid schizophrenic patients. Pretreatment growth hormone (GH) response to the clonidine challenge test (CCT) correlated significantly with clonidine treatment improvement in psychosis, anxiety, and negative symptom ratings. Spontaneous GH peaks following placebo correlated significantly with the behavioral change with clonidine treatment. Our data suggest that patients with normal or high alpha 2-receptor activity and "normal" cerebrospinal fluid (CSF) norepinephrine (NE) are likely to respond to clonidine treatment. Patients with either high or low CSF NE levels did not respond to clonidine treatment. CSF NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) decreased significantly with clonidine treatment. Changes in CSF NE and MHPG did not correlate significantly with improvement in psychosis, but they correlated with changes in other behaviors.

Adult↗

Channel probability and Nd: an event-related potential sign of attention strategies.

Event-related potentials were recorded in a two-channel selective attention paradigm designed to assess the effects of channel probability on processing negativity. For channel probabilities of 70% or greater, the subtraction Nd for standard tones was greatly reduced or absent. This change was due to apparent processing negativity in the waveform of the irrelevant standards at high channel probabilities. Deviant long tones showed similar early Nds to standard tones, and also developed late attention-related negativity commencing at about 500 ms from stimulus onset. It was concluded that there was no evidence that processing negativity to the relevant tones, defined as a negative component associated with selective attention, is affected by channel probability. Changes in Nd amplitude as the channel probabilities became more unequal were attributed to changes in strategies used by subjects, which primarily altered ERPs associated with the irrelevant tones.

Adult↗

Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers.

The present study demonstrates that maternal antibodies to certain epitopes of human immunodeficiency virus 1 (HIV-1) proteins are associated with a defined outcome for at-risk pregnancies of HIV-infected women. An initial retrospective analysis of antibodies to synthetic peptides and recombinant proteins representing env, pol, and gag regions of HIV-1 was carried out. Sera studied were from 33 children who were born to HIV-infected mothers and whose clinical outcome was known at the time of analysis. Sera, collected within the first 6 months of life, of uninfected at-risk children were found to selectively contain maternal antibodies to certain peptides containing epitopes of the HIV envelope glycoprotein gp120. To confirm the predictive role of maternal antibodies to defined HIV-1 epitopes, a prospective analysis was then performed on sera from 21 HIV-seropositive mothers and their infants, whose clinical and immunological status was then followed up for a period of at least 15 months. As expected, antibodies to the same envelope protein peptides were detected almost exclusively in sera from mothers of uninfected children. Our data suggest that antibodies against select epitopes of HIV envelope protein gp120 might play an important role in preventing mother-to-child transmission of HIV-1 infection. Accordingly, site-directed serology might be used to predict the outcome of an at-risk pregnancy of an HIV-infected woman.

Amino Acid Sequence↗

Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers.

We analysed HIV-specific immunoglobulin G (IgG) responses to gag and env peptides in infants born to HIV-positive mothers. Questions of interest were whether there are early specific markers for prognosis, and whether any specific IgG is related to the prevention of vertical transmission of infection. Fifty-three children, 0-24 months old and born to HIV-1-infected mothers, were retrospectively divided into two groups based on HIV seroreactivity or non-reactivity at 15 months of age. Their sera were used to find reactivities important in diagnosis and/or prediction of the putative HIV disease. Three important findings emerged. First, a low IgG titer against the very immunodominant penv9 in newborns was found to be associated with rapid progression to AIDS. This difference was clearly reflected in the reactivity to a small peptide representing amino acid (aa) 598-606. The second interesting finding was the putative hypervariable loop on gp120 (especially aa 324-338), reactivity to which was found only in the uninfected group, and was seen in six out of 19 uninfected children under 6 months of age. This specific response was not caused by a generally high total anti-HIV reactivity, and may indicate a role of protective antibodies against vertical transmission. The response to this region in the infected group, on the other hand, was directed to the amino terminal half of the putative loop, in particular peptide 53, aa 304-318. Finally, response to a part of the amino terminal end of P17 was seen in seven out of eight infected children over 6 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

Epitope mapping of monoclonal antibodies against human immunodeficiency virus type 1 structural proteins by using peptides.

Murine monoclonal antibodies directed against the structural proteins p17 and p24 of human immunodeficiency virus type 1 were investigated in an epitope mapping system. Overlapping peptides consisting of 15 amino acids of the p17 and p24 protein, respectively, were used as competitors in an enzyme-linked immunosorbent assay. Three different immunogenic regions (A, B, and C) could be defined, one on p17 and two on p24. Twenty monoclonal antibodies reacted with the human immunodeficiency virus type 1 peptides of region B, although differences in the reactivity of these antibodies with human immunodeficiency virus type 2 and simian immunodeficiency virus strain mac were detectable. Recognized epitopes were characterized by computer analysis as described by T.P. Hopp and K.R. Woods (Proc. Natl. Acad. Sci. USA 78:3824-3828, 1981) and P.Y. Chou and G.D. Fasman (Biochemistry 13:222-245, 1974).

Amino Acid Sequence↗

Mapping of IgG subclass and T-cell epitopes on HIV proteins by synthetic peptides.

Fifteen amino acid peptides, sequentially overlapping by 10 amino acids, were synthesized on the basis of the HTLV-III sequences of the gag and env proteins. They were used as antigens in IgG subclass ELISAs and T-cell stimulation assays. Sera and cells were obtained from 30 asymptomatic, HIV-infected homosexuals. In all subclasses reactivity was found to parts of the gag protein, while IgG1 dominated anti-env peptide responses. It was possible to delineate peptides showing restricted IgG subclass responses that were dominated by either IgG1, 2, 3 or 4. A negative correlation was generally observed between B-cell and T-cell reactivity, but a T-cell and B-cell co-operation was suggested by the response to two IgG1-restricted peptides. The IgG3-dominated epitopes were present in peptides previously known to be amphipathic and capable of T-cell stimulation. The analysis of subclass-restricted responses on the peptide level will assist the understanding of the subclass expression in vivo, since the peptide mapping approximates the delineation of a subclass-restricted response at the level of single epitopes.

Epitopes↗

Human monoclonal antibodies against a recombinant HIV envelope antigen produced by primary in vitro immunization. Characterization and epitope mapping.

Peripheral blood lymphocytes from healthy, HIV sero-negative blood donors have been in vitro immunized using penv9, a recombinant fragment of the envelope of HIV-1. This primary in vitro immunization followed by Epstein-Barr virus (EBV) transformation and somatic cell fusion subsequently gave rise to several specific anti-penv9 monoclonal antibodies (MO28, MO30 and MO43) of mu isotype. The hybridomas have been kept in culture for over 6 months and the antibody productivity for MO30 was measured to 18 micrograms x (24 hr x 10(6) cells)-1. The fine specificity of the antibodies was mapped by a peptide inhibition enzyme immunoassay, using overlapping synthetic pentadeca peptides covering the whole penv9. These human monoclonal antibodies exhibited a similar epitope specificity directed against a non-sequential determinant, including the amino acids 632-646, 677-681 and 687-691. This specificity is very rarely found in immune sera from seropositive patients and presently not reported in human monoclonal antibodies derived from in vivo immunized individuals, indicating that different antibody specificities can be obtained by the in vitro immunization technology. These human monoclonal antibodies did not neutralize HIV. The results presented here demonstrate the feasability of generating human monoclonal antibodies against HIV by primary in vitro immunizations, thereby avoiding the use of lymphocytes derived from infected patients when human monoclonal antibodies for therapeutic purposes are to be produced.

Antibodies, Monoclonal↗

Fine specificity of IgG subclass response to group antigens in HIV-1-infected patients.

There is an association between the clinical stage of HIV-1 infection and the presence of antibodies against viral gag proteins (p17 and p24). The IgG subclass (G1 and G3) pattern against these antigens was analysed in stable patients and HIV patients progressing to AIDS. Antibodies were analysed with whole viral or peptide ELISA (using sequentially overlapping peptides) and Western Blots. IgG1 was found to be the dominant anti-HIV-1 IgG subclass and IgG1 antibodies declined in progressing patients against all HIV antigens evaluated in Western blot, including p17, p24, p31, gp41, p64, gp120 and gp160. In contrast IgG3 antibodies, which were found to be predominantly directed against gag proteins, and which could be detected in almost all patients, remained in the circulation during disease progression. By peptide assays distinct immunogenic regions were found in p17 in contrast to more evenly distributed epitopes in p24. A decreased divergence of antibody reactivity to both p17 and p24 peptides in the group of patients who developed AIDS was seen. No reaction to any single gag epitope related to disease progression. The difference between IgG1 and IgG3 anti-gag antibodies in relation to clearance during disease progression may depend on different properties of immune complexes formed by these two IgG subclasses.

Acquired Immunodeficiency Syndrome↗

HIV-1 peptides induce a proliferative response in lymphocytes from infected persons.

In a comprehensive search for T-cell epitopes of HIV-1, several new regions were discovered. The analysis was performed with lymphocytes of HIV-1-infected persons in various stages of the infection. Peptides covering the entire group antigen (gag), and transmembrane (gp41) regions, and one-half of envelope (gp120) regions of HTLV-IIIB were studied. Both common and patient-unique responses were identified. Twelve common gag T-cell sites were discovered, as well as patient-unique activating peptides. The gag peptides elicited the most frequent cell responses and the responses remained in late stages of disease. Only 1 of the 12 T-cell activating gag peptides was reactive with specific anti-HIV IgG. Eighteen common env-representing peptides evoked T-cell responses. They could be grouped into four previously undescribed regions of gp120 and two known sites, the hypervariable stretch and part of the CD4 binding region. Cell responses to env peptides were common in early stages of disease and tended to decrease in ARC and AIDS. The gp41-representing peptides evoked a cellular response to a region close to the N-terminus of the hydrophobic transmembrane region. In addition to the T-cell activating peptides, peptides representing p15 and p19 as well as previously recognized regions of gp120 and gp41 appeared to be potent B-cell epitopes.

AIDS-Related Complex↗