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Biomedical subjects

J Rosen

Publications and source records attributed to J Rosen.

At least 109 records · Page 6Linked to original sources
PubMed1993

Interleukin-3/erythropoietin fusion proteins: in vitro effects on hematopoietic cells.

Erythropoietin (Epo) acts synergistically with interleukin-3 (IL-3) to induce proliferation and differentiation of erythroid progenitors. This synergy occurs at IL-3 concentrations that have little or no effect alone. To determine whether optimal expansion of erythroid cells results when they are targeted by a molecule with both IL-3 and Epo activities, fusion proteins were generated and analyzed. Expression vectors were constructed in which the coding regions of human IL-3 and Epo cDNAs were joined by either a short (2 to 3 amino acids) or long (23 amino acids) linker sequence and expressed in Chinese hamster ovary (CHO) cells. Analysis of equilibrium binding properties of the IL-3 and Epo moieties revealed that in all fusion proteins each retained the ability to bind receptor. When IL-3 was connected to Epo by a short linker, the binding affinity of the IL-3 moiety was lower. In vitro proliferative activity of each moiety was observed on cell lines responsive to IL-3, Epo or a combination of the two cytokines. Fusion of IL-3 to Epo through its amino terminus was found to result in partial loss of its function. All the fusion proteins were biologically active on human bone marrow. When IL-3 was located at the amino domain of the protein, induction of erythroid colonies was similar to that of a mixture of IL-3 and Epo. These results indicate that biological integrity of both IL-3 and Epo can be maintained when these cytokines are fused, but that enhancement of erythropoiesis over that observed with a mixture of the two cytokines cannot be achieved by their fusion alone. Other requirements such as the coexpression of the IL-3 and Epo receptors and the sharing of a receptor subunit are likely to be needed for an optimal cell response to the fusion growth factors.

Animals↗
PubMed1992

Identification of human neutralization-inducing regions of the human immunodeficiency virus type 1 envelope glycoproteins.

Four major neutralizing regions of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein were identified and characterized with a panel of 80 HIV-1 antibody-positive human sera. Levels of neutralizing antibodies against the HIV-1 strains IIIB, SF2, and RF were compared with reactivity in ELISAs against peptides that correspond to certain regions of the HIV-1 envelope. A correlation between high neutralizing activity and strong seroreactivity against specific peptides suggested that the corresponding regions might be involved in neutralization. This was further substantiated by using peptides to inhibit neutralization by a panel of 10 HIV-1 antibody-positive sera. The positions of three neutralizing sites, defined earlier mostly by antisera from animals, were confirmed in the present study. Human sera thus recognize the strain-specific third variable region of gp120 (amino acids 304-318), the C-terminal end of gp120 (amino acids 489-508), and the conserved region in the intracellular part of gp41 (amino acids 732-746). It is likely that these different regions mediate help rather than self-sufficient neutralization. Furthermore, a human neutralizing region was detected in a conserved part of gp41 (amino acids 647-671). Accordingly, neutralizing antibodies directed to this region were found to be cross-reactive between HIV-1 strains. Peptides corresponding to these four regions were able to inhibit neutralization mediated by serum from HIV-1 antibody-positive individuals. These results indicate that this conserved B-cell epitope of the HIV-1 envelope elicits a virus-neutralizing antibody response during natural infection in humans and may therefore be considered for inclusion in a vaccine against HIV-1.

Amino Acid Sequence↗
PubMed1992

Immunoglobulin V regions and epitope mapping of a murine monoclonal antibody against p24 core protein of HIV-1.

The nucleotide sequence of a murine monoclonal antibody (CB-mab-p24/13-5) against p24 core protein of the human immunodeficiency virus (HIV-1) was determined for variable regions of the heavy and light chain, respectively. Genetic elements encoding the VDJH- and VJL-regions of the antibody were generated from RNA by the polymerase chain reaction, cloned into the vector pICEM 19R and sequenced. Synthetic peptides, 10 amino acids overlapping served for the localization of the epitope. The residues 152-156 within the p24 sequence contain the epitope.

Amino Acid Sequence↗
PubMed1992

Impact of psychiatric hospitalization on behavioral complications of Alzheimer's disease.

OBJECTIVE: The authors conducted a prospective study of the clinical utility of the four DSM-III-R subtypes of primary degenerative dementia of the Alzheimer type (with delirium, with delusions, with depression, or uncomplicated) and acute psychiatric hospitalization for treatment of these subtypes. METHOD: The subjects were 120 consecutive inpatients with Alzheimer's disease, most of whom had behavioral abnormalities. Each subject received detailed physical, neurological, psychiatric, and mental status examinations. The presence or absence of specific behavioral problems was also documented. Patients were treated with medication, psychotherapy, and behavioral techniques. RESULTS: While all patients could be assigned to one of the four DSM-III-R behavioral subtypes, the uncomplicated subtype did not accurately reflect the burden of behavioral symptoms in the patients who did not have delirium, delusions, or depression. Each behavioral subtype responded in a characteristic way to inpatient treatment, as reflected by changes in scores on four psychometric scales used to assess cognitive impairment, psychiatric symptoms severity, and level of functioning at admission and at discharge, as well as by changes in residential setting following hospitalization. Half of all patients admitted from their homes and two-thirds of those with depression were able to go home following discharge. CONCLUSIONS: Behavioral syndromes in Alzheimer's disease should not be overlooked, because they have both clinical and prognostic significance. Short-term psychiatric hospitalization is effective and efficient for achieving the goal of returning patients to their homes and for safely implementing specific treatments in this frail population, and it may reduce the need for institutionalization.

Aged↗
PubMed1992

Accommodative response during distance optometric test procedures.

The control of accommodation is an essential requirement during the clinical optometric assessment of distance vision. Accordingly, the aim of the present study was to examine the steady-state accommodative response during a number of conventional clinical procedures carried out at a viewing distance of 6m (20 feet). Accommodation was measured subjectively to Snellen letters using a Hartinger coincidence optometer during distance viewing, simulated retinoscopy and following the introduction of cylindrical and prismatic lenses in 13 visually-normal, young adults. No significant change in the mean accommodative response was induced by any of the techniques described, with subjects exhibiting a lead of accommodation of approximately 0.25D for all conditions. The results demonstrate the robustness of accommodation to apparently substantial changes in stimulus conditions.

Accommodation, Ocular↗
PubMed1991

Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease.

Prospective psychiatric evaluations were performed as part of a longitudinal study of 32 demented patients who met criteria for the histopathological diagnosis of Alzheimer's disease at the time of death. Psychosis and major depressive disorder emerged in 15 (47%) and 7 (22%) patients, respectively, none of whom had a history of either behavioral disorder prior to the onset of dementia. The prevalence of psychosis increased with increasing dementia severity, was associated with more rapid cognitive decline, and once present was often persistent. In this regard, the emergence of psychosis in the context of Alzheimer's disease appears to be a poor prognostic sign. In contrast to its relationship to cognitive impairment, psychosis was not associated with an increased mortality rate.

Aged↗
PubMed1991

Neuropathologic and neurochemical correlates of psychosis in primary dementia.

Neuropathologic and neurochemical correlates of psychosis were determined using brain tissue from 27 autopsy-confirmed cases of Alzheimer's disease. The densities of senile plaques and neurofibrillary tangles were determined in the middle frontal and superior temporal cortex, the prosubiculum, and the entorhinal cortex of the hippocampus. The concentrations of norepinephrine, dopamine, and serotonin, the metabolites of these biogenic amines, and the specific activity of choline acetyltransferase were also determined in these four cortical regions as well as in the substantia nigra, thalamus, amygdala, and caudate nucleus. Psychosis was associated with significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, with trends toward increased densities of these lesions in the other areas examined. This finding is consistent with the increased rate of cognitive decline that accompanies this behavioral disorder. Psychosis was also associated with the relative preservation of norepinephrine in the substantia nigra, with trends in this direction for five of the remaining seven brain regions examined, and a significant reduction of serotonin in the prosubiculum that was accompanied by trends toward reduced levels of serotonin and 5 hydroxyindoleacetic acid in the remaining regions. The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.

Aged↗
PubMed1991

Sleep disturbances in survivors of the Nazi Holocaust.

OBJECTIVE AND METHOD: Sleep disturbances are commonly reported by victims of extraordinary stress and can persist for decades. This study was designed to test the hypothesis that survivors of the Nazi Holocaust would have significantly more and different sleep problems than depressed and healthy comparison subjects and that the severity of the survivors' problems would be correlated with length of time spent in a concentration camp. Forty-two survivors, 37 depressed patients, and 54 healthy subjects of about the same age, all living in the community, described their sleep patterns over the preceding month on the Pittsburgh Sleep Quality Index, a self-rating instrument that inquires about quality, latency, duration, efficiency, and disturbances of sleep, use of sleep medication, and daytime dysfunction. RESULTS: The survivors had significantly greater sleep impairment than the healthy comparison subjects, as measured by all subscales of the index, but had less impairment than the depressed patients except on the sleep disturbances and daytime dysfunction subscales. However, for specific items within these subscales, survivors had significantly more frequent awakenings due to bad dreams and had less loss of enthusiasm than the depressed subjects. Sleep disturbances and frequency of nightmares were significantly and positively correlated with the duration of the survivors' internment in concentration camps. CONCLUSIONS: These findings suggest that for some Holocaust survivors, impaired sleep and frequent nightmares are considerable problems even 45 years after liberation.

Aged↗
PubMed1991

Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates.

We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality.

Aged↗
PubMed1991

Identification of amino acids in the V3 region of gp120 critical for virus neutralization by human HIV-1-specific antibodies.

The importance of the dependence on single amino acids in the V3 region of HIV-1 gp120 was evaluated for virus neutralization and antibody-dependent cellular cytotoxicity (ADCC). Synthetic overlapping 15-mer peptides and a set of omission peptides covering amino acids 301-317 were used. Sera from 29 HIV-1-infected individuals at different stages of disease were tested for neutralization, ADCC and specific IgG reactivity. Six HIV-1 neutralizing monoclonal antibodies (mAb) acted as controls. All mAb reacted with a region (amino acids 304-318) of gp120, previously shown to induce neutralizing antibodies. The amino acids essential for reactivity were identified to be within the sequence GPGR (amino acids 312-315). The importance of this region for occurrence of neutralizing antibodies in infected humans was investigated using the same set of peptides. Out of 29 individuals, 21 were found to have neutralizing antibodies in titres between 100 and 1000. Among the neutralization-positive sera, 17/21 (81%) reacted with amino acids 304-318, compared with only one of eight sera (13%) negative in neutralization. When any of the four amino acids G, P, G or R were deleted, the seroreactivity decreased considerably. The conserved sequence GPGR was therefore considered to be the most important for neutralization in this region in human sera as well. Thus, the conserved sequence GPGR in the V3 region of gp120 is critical for virus neutralization by human HIV-1-specific antibodies.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Adjunctive lithium carbonate in nortriptyline-resistant elderly depressed patients.

Recent reports supporting the use of lithium carbonate as an adjunct to tricyclic antidepressants for the treatment of refractory depression have not utilized standardized tricyclic antidepressant therapy, nor have they addressed the efficacy of lithium augmentation in a geriatric population. A 3-week open trial was added to the medication regimen of 15 elderly depressed inpatients who had already failed 4 weeks of therapeutic levels of nortriptyline. Treatment response was determined by the 17-item Hamilton Rating Scale for Depression (HAM-D). Two of 15 partial responders before lithium augmentation became complete responders. Of the remaining 13 "nonresponders" before lithium augmentation, one had a complete response, 7 had a partial response and 5 remained nonresponders. Although there was a mean HAM-D change of 8.3 points after lithium augmentation (24.7 +/- 5.9 to 16.4 +/- 6.8, p less than .001), when considering the previously reported similar efficiency of extended nonaugmented nortriptyline, these data do not strongly support lithium augmentation in elderly subjects who fail to respond after 4 weeks of nortriptyline. Further study is needed to determine what role, if any, lithium augmentation should play in the treatment of geriatric depression.

Aged↗
PubMed1991

Pentigetide nasal solution: a multicenter study evaluating efficacy and safety in patients with seasonal allergic rhinitis.

The safety and efficacy of pentigetide (Pentyde) nasal solution, administered as 1 mg into each nostril four times daily, was compared with placebo for controlling symptoms associated with seasonal allergic rhinitis. This was a randomized, multicenter, double-blind, parallel-group trial involving 431 patients divided equally between pentigetide and placebo treatment. The study was conducted during the 1986 spring allergy season and consisted of 1 week of baseline followed by 2 weeks of treatment. Physicians evaluated the frequency and severity of nasal symptoms at study entry (day 1) and the final visit (day 22). Physicians and patients assessed the global condition of the patient at the end of the study and patients also recorded the severity of symptoms in a daily diary. Pentigetide-treated patients showed a statistically significant greater reduction in the frequency (P = .004) and severity (P = .05) of total nasal symptom score (sneezing, nasal congestion, and rhinorrhea) and in the individual nasal symptom scores compared with placebo-treated patients. Diary results showed consistently lower total nasal symptom scores on each treatment day for pentigetide-treated patients (P = .02). Both the physicians and patients globally rated more pentigetide-treated patients improved than placebo-treated patients. The incidence and types of adverse experiences were similar between treatment groups and there were no reports of sedation or fatigue in the pentigetide group. No clinically significant changes occurred for laboratory tests, physical examination parameters or vital sign measurements. Pentigetide nasal solution was safe and effective for the treatment of seasonal allergic rhinitis.

Administration, Intranasal↗
PubMed1990

Epitope mapping of the HIV-1 gag region with monoclonal antibodies.

A new type of immunochemical mapping of the human immunodeficiency virus type 1 (HIV-1) gag region was performed. By use of native HIV-1 viral lysates or the gag recombinant p24-15 antigen, a new set of monoclonal antibodies (Mabs) to the gag region proteins was generated. Synthetic HIV-1 peptides covering the entire gag region were used to specifically localize the continuous epitopes by direct binding to the Mabs and by blocking the Mab immunoreactivity. The identified immunogenic epitopes were localized between the gag amino acids (aa) 108-127, 203-217, 208-222, 248-282, 273-302, 288-307, 308-322, 331-354 and 408-422. These continuous epitopes formed seven immunogenic regions. One strongly p17-reactive Mab appeared to react with a discontinuous epitope, the components of which were 110 aa distant in the linear sequence: aa 23-27 and 128-132. The synthetic peptides appeared to be more congruent with the Mab-reactive sites in solution than when coated to a solid phase.

Amino Acid Sequence↗