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Biomedical subjects

A Minassian

Publications and source records attributed to A Minassian.

17 recordsLinked to original sources
PubMed2005

Adaptive gain interferometry: a new mechanism for optical metrology with speckle beams.

We describe, for the first time to our knowledge, the use of a saturable laser gain medium to implement an adaptive gain interferometer for performing optical metrology with speckle-distorted beams. We show that interferometric formation and replay of a saturable gain hologram permit coherent extraction of fast vibrational information about an object in real time and removal of slowly varying spatial distortion. An experimental characterization of the frequency response of the adaptive gain interferometer is made by use of a diode-pumped solid-state laser amplifier, and a new theoretical formulation of the gain interferometer is also developed for the first reported time.

Journal Article↗
PubMed2001

Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania.

BACKGROUND: Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) and habituation of the human startle response have been noted in schizophrenia and other patients with known dysfunction in the brain substrates that regulate PPI. During acute mania, bipolar disorder (BD) and schizophrenia patients present with symptoms that are similar. To determine if these clinical similarities extend to neurophysiologic domains, PPI and startle habituation were assessed in BD patients with acute psychotic mania and compared with a sample of acutely psychotic schizophrenia patients and a normal comparison group. METHODS: Fifteen BD patients, 16 schizophrenia patients, and 17 control subjects were assessed on PPI and startle habituation. RESULTS: The BD patients had significantly lower PPI than did the control subjects in two of the three PPI conditions (60- and 120-msec interstimulus intervals) as well as less startle habituation. The BD patients did not statistically differ from the schizophrenia patients in PPI or habituation. CONCLUSIONS: These findings of sensorimotor gating deficits among bipolar disorder patients are consistent with other findings using different measures of information processing and suggest that the neurobiological substrates underlying sensorimotor gating may be dysregulated during acute manic and psychotic states.

Acute Disease↗
PubMed2001

Working memory in schizophrenia: transient "online" storage versus executive functioning.

Working memory has been described as the temporary "online" storage and the subsequent manipulation and retrieval of information. It has been suggested that the prefrontal cortex is a primary site of working memory. Schizophrenia patients, who are thought to have prefrontal cortical dysfunction, have demonstrated inconsistent deficits on a variety of verbal and spatial working memory tests. This has led to questions about how to define and measure working memory, whether these deficits are distinct to one cognitive domain, and what role factors such as intelligence and symptoms play in working memory performance. We compared schizophrenia patients to normal comparison subjects in four separate studies. Based upon the results we recommend that working memory tests be characterized as either transient "online" storage and retrieval tasks (where short-term storage and retrieval of information is required) or executive-functioning working memory tasks (where storage, manipulation, and retrieval of information is required). The importance of clearly identifying which distinct aspects of working memory are assessed is discussed.

Adolescent↗
PubMed2000

The deficit in cataract surgery in England and Wales and the escalating problem of visual impairment: epidemiological modelling of the population dynamics of cataract.

BACKGROUND: The pool of old cases of cataract, the expected new cases, and the shortfall in cataract surgery and consequently the numbers dying with poor vision without the benefit of cataract surgery are regarded as escalating problems worldwide. Successive governments and the professional ophthalmic bodies have not had the wherewithal to estimate the magnitude or interaction of these elements in the population of the UK. This study has collected and applied the best available epidemiological data on cataract prevalence, incidence and service utilisation, and demography to address the problem of control of the cataract pool in the population of England and Wales. METHODS: Data from recent surveys undertaken by the authors, both on prevalence of vision impairing cataract and on patterns of cataract surgery, were used together with demographic and service utilisation information obtained from government departments. These were integrated within a holistic model, which was run under varied assumed levels and patterns of service provision. RESULTS: The study shows that there is a serious pool of unoperated vision impairing cataract in the population aged 65 and older, reflecting a shortfall in cataract surgery. Continuing with the present level and pattern of service provision, the pool will increase to over 2.5 million by the year 2001. In addition, more than 700 000 will die with unoperated impaired vision. CONCLUSIONS: Targeting of existing or new additional operations to those below the visual acuity of 6/12 will have relatively little effect on numbers dying without surgery, but should have a substantial controlling effect on the pool of vision impairing cataract in the population.

Age Factors↗
PubMed2000

Utility of predictive equations for estimating the prevalence and incidence of primary open angle glaucoma in the UK.

AIMS: To assess the Tuck-Crick and the Quigley-Vitale predictive regression equations against fresh independent real world data for estimating the prevalence of primary open angle glaucoma (POAG) in the UK. To apply the equations to the elderly population of England and Wales, for which there is sample survey data on glaucoma, and demographic data. METHODS: Directly measured actual prevalence of POAG in a population sample of 1530 people was compared with the predicted prevalence derived by applying the Tuck-Crick and the Quigley-Vitale equations to the sample data. The two equations were applied to the demographic data of the population to project POAG prevalence and to derive 5 year cumulative incidence for the elderly population. These were compared with estimates derived from the local survey data. RESULTS: The actual directly measured prevalence of POAG in the local sample was 3.01%. The Tuck-Crick estimate was 2. 74% (difference 0.27%), and the Quigley-Vitale was 3.50% (difference -0.49%). The three methods-projection from local survey data, Tuck-Crick, and Quigley-Vitale-gave point estimates of 2.85% (228 526 cases), 2.71% (217 375 cases), and 3.50% (280 364 cases) respectively for the prevalence of POAG in the elderly population of England and Wales (8 008 705 people aged 65 or older). Calculation of incidence from age specific prevalence gave the following results: the numbers of new cases of POAG expected (5 year cumulative incidence) in the elderly population were 71 146 and 94 485 for methods 2 and 3 respectively. CONCLUSIONS: The Tuck-Crick predictive equation performed well when applied to fresh (independent) actual data from a local sample survey using a particular definition for POAG, and its usefulness for estimation of prevalence of POAG in England and Wales has been demonstrated. The work on development of predictive equations has been very promising and further refinements could be made when more fresh survey data become available.

Age Distribution↗
PubMed1998

Measurement of the charge properties of articular cartilage by an electrokinetic method.

The charge structure of the surface of articular cartilage determines its interactions with the macromolecules and cells of synovial fluid. It may thereby be important to the physiological function and pathological degeneration of the tissue. To determine whether the electrokinetic properties of the surface differ from those of the bulk tissue, we measured the streaming potential generated by the flow of electrolyte over the surface of a cartilage plug mounted in a chamber built for that purpose. We then calculated the effective surface charge density. In nonfibrillated cartilage from the human femoral head, the surface charge density, 0.037+/-0.004 Cm(-2) (mean+/-SD), was approximately half that measured at the surface of slices cut from the middle and deep zones. In addition, the surface charge density fell relatively little at low pH; this is consistent with a higher proportion of strongly acidic groups. The variations in surface charge density were found to be similar to those in total fixed charge density in the slices by the tracer cation method. Therefore, no evidence exists that the actual surface differs in composition from the immediately underlying matrix. The addition of synovial fluid (0.0025 ml/ml) to the superfusing solution reduced the surface charge density by 25+/-9% (n=5), and we attributed this to the binding of synovial-fluid macromolecules.

Animals↗
PubMed1997

Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope.

Immunodominant epitopes are known to suppress a primary immune response to other antigenic determinants by a number of mechanisms. Many pathogens have used this strategy to subvert the immune response and may be a mechanism responsible for limited vaccine efficacies. HIV-1 vaccine efficacy appears to be complicated similarly by a limited, immunodominant, isolate-restricted immune response generally directed toward determinants in the third variable domain (V3) of the major envelope glycoprotein, gp120. To overcome this problem, we have investigated an approach based on masking the V3 domain through addition of N-linked carbohydrate and reduction in net positive charge. N-linked modified gp120s were expressed by recombinant vaccinia virus and used to immunize guinea pigs by infection and protein boosting. This modification resulted in variable site-specific glycosylation and antigenic dampening, without loss of gp120/CD4 binding or virus neutralization. Most importantly, V3 epitope dampening shifted the dominant type-specific neutralizing Ab response away from V3 to an epitope in the first variable domain (V1) of gp120. Interestingly, in the presence of V3 dampening V1 changes from an immunodominant non-neutralizing epitope to a primary neutralizing epitope with broader neutralizing properties. In addition, Ab responses were also observed to conserved domains in C1 and C5. These results suggest that selective epitope dampening can lead to qualitative shifts in the immune response resulting in second order neutralizing responses that may prove useful in the fine manipulation of the immune response and in the development of more broadly protective vaccines and therapeutic strategies.

AIDS Vaccines↗
PubMed1997

Familial incidence of late ventricular potentials and electrocardiographic abnormalities in arrhythmogenic right ventricular dysplasia.

Familial forms of arrhythmogenic right ventricular dysplasia (ARVD) have been described. Signal-averaged electrocardiograms (SAECGs) and standard electrocardiograms have been used to detect ARVD. The purpose of this prospective study, for a given family member, was to evaluate the risk of having ARVD or only belonging to an affected family. To address these issues, we assessed the incidence of late ventricular potentials and electrocardiographic (ECG) abnormalities in the families of our patients with ARVD. SAECGs and electrocardiograms were recorded in 101 eligible family members and compared with those recorded in ARVD patients with sustained ventricular tachycardia (13 patients in 12 families), and in 37 control subjects with a normal electrocardiogram. The incidence of late ventricular potentials was significantly higher in family members than in control subjects (16% vs 3%, p <0.05). The incidence of ECG abnormalities was 34% in family members. When the incidence of late ventricular potentials and/or ECG abnormalities were added up, results were 38% abnormal findings in family members. Late ventricular potentials and/or ECG abnormalities were found in members of all 7 families; these abnormalities were initially thought to be sporadic forms, and thereafter were classified as familial forms. Thus, SAECGs and standard ECG recordings in ARVD family members showed 38% abnormal findings, and that all cases of ARVD could be classified as familial forms. The incidence of familial forms of ARVD was greater than was previously believed, which is highly suggestive of a genetic transmission of the disease in our geographic area.

Adult↗
PubMed1996

Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.

To identify disease-specific T cell changes that occur in Crohn's disease (CD), the T cell receptor BV repertoires of lamina propria lymphocytes (LPL) isolated from both the inflamed and "disease-inactive" colons of seven CD patients were compared by the quantitative PCR and DNA sequence analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon from the same individual were very different. Furthermore, nearly all of the differences occurred in CD4+ LPL, with very few differences in the CD8+ population of LPL. Although the pattern of BV segments that was increased in disease-active tissue relative to disease-inactive tissue was different for all seven CD patients, there were several BV segments that increased uniformly in the disease-active tissue of all seven individuals. CDR3 length analysis and DNA sequencing of these BV segments revealed that in six of the seven CD patients there was a striking degree of oligoclonality that was absent from disease-inactive tissue of the same individual. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens. The isolation of such inflammation-specific CD4+ T cells may make it possible to identify the antigens that are responsible for the inflammatory process in CD and provide a better understanding of its pathogenesis.

Adolescent↗
PubMed1995

Amphetamine on Rorschach measures in normal subjects.

Twenty-two normal undergraduate men were administered either d-amphetamine (0.2 mg/kg or 0.4 mg/kg) or placebo in a double-blind, counterbalanced design. The test sessions were exactly three weeks apart and included, among other measures, the Rorschach test. Rorschach anxiety and thought disorder variables were measured under drug and placebo conditions. The results suggest that amphetamine causes an increase in Rorschach anxiety indices but does not elevate Rorschach indices of thought disorder. The observed dissociation of anxiety and thought disorder on the Rorschach has implications for the role of the Rorschach in studying anxiety disorders and schizophrenic disorders.

Adult↗
PubMed1993

Construction of an HIV-1 peptide vaccine containing a multideterminant helper peptide linked to a V3 loop peptide 18 inducing strong neutralizing antibody responses in mice of multiple MHC haplotypes after two immunizations.

Peptide constructs comprised of multideterminant Th peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52 to 73% of HIV positive, Ag-responsive patients, were colinearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB. The segments containing clusters of overlapping Th epitopes were called cluster peptides. Cognate help for peptide 18 antibody was elicited after a single immunization in all strains of mice that had previously responded to a T cell epitope encompassed by the cluster peptides. Animals boosted with cluster peptide-peptide 18 constructs 36 to 52 wk later displayed secondary antibody responses. Cluster peptide 3-peptide 18 induced antibody that neutralized homologous virus in one strain of mice although strong peptide 18 antibody responses were detected in all four strains of mice. The most promising construct, cluster peptide 6-peptide 18, induced neutralizing antibody in all strains of mice tested, and in two strains the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, antibody titers for 90% neutralization in the range of 1/1000 to 1/16,000 were achieved. These neutralizing titers against the homologous viral strain, after just two immunizations, are at least four- to eightfold higher than the highest titered other polyclonal V3-specific immune sera we have ever observed in our laboratories. We also asked why some sera neutralized and others with similar ELISA titers did not. No correlation was found between neutralization and isotype or affinity for peptide or gp 120. We could not account for neutralization by antibodies to the helper sites. Substitutions made in the central loop region of peptide 18, amino acid residues PGRAF, dramatically reduced binding of both neutralizing and non-neutralizing sera although some fine specificity differences between neutralizing and nonneutralizing sera were noted. These results have implications for the design of synthetic peptide vaccines for HIV.

AIDS Vaccines↗
PubMedDate not supplied

CD4+ cell oligoclonality in Crohn's disease: evidence for an antigen-specific response.

To identify disease-specific T cell changes that occur in Crohn's disease (CD) the T-cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) from both disease-active and disease-inactive colonic tissue of three CD patients were compared by a quantitative polymerase chain reaction (qPCR) and CDR3 length analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon of the same individual were different, and most of the differences occurred in CD4+ LPL with very few differences in the CD8+ populations of LPL. Although the pattern of BV segments that was increased in disease-active relative to disease-inactive tissue was different for all three CD patients, there was an increase in the levels of BV11, 13S2, 15, 16, and 17 segments in the disease-active tissue of all three patients. Standard CDR3 length analysis of BV11, 13S2, 15, 16, and 17 segments revealed that in two of the three CD patients there was a striking degree of TCR oligoclonality in the disease-active tissue that was absent from disease-inactive tissue of the same individual. Additional differences between the disease-active and disease-inactive tissues were observed using a more refined method of CDR3 length analysis, which employs BV- and BJ-specific primers. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens.

Adolescent↗