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Biomedical subjects

P Berman

Publications and source records attributed to P Berman.

At least 73 records · Page 4Linked to original sources
PubMed1989

Recognition of HIV glycoprotein gp120 by T cells. Role of monocyte CD4 in the presentation of gp120.

The HIV envelope glycoprotein gp120 binds with high affinity to CD4 and is responsible for the tropism of HIV for CD4+ T cells and monocytes. Efforts to develop HIV vaccines have focused on gp120 and, therefore, a detailed molecular understanding of human immune responses to gp120 is essential. In this report, we have used human T cell clones specific for gp120 to examine the processing and presentation of gp120 to T cells. In particular, we examined the role of the CD4 that is expressed at low levels on the surfaces of human monocytes in the presentation of gp120 by monocytes. The presentation of gp120 to gp120-specific human T cell clones was blocked by pretreatment of monocytes with anti-CD4 mAb. Blocking of monocyte CD4 with anti-CD4 did not inhibit presentation of other Ag or of synthetic peptides representing epitopes within gp120 recognized by gp120-specific T cell clones. These results indicated that the anti-CD4-mediated inhibition occurred at the level of the monocyte, was specific for the gp120 response, and was operative at the initial Ag uptake phase of the Ag-processing pathway. Definitive confirmation that monocyte CD4 functions in the initial uptake step of the gp120-processing pathway was obtained by using soluble CD4 to block the interaction of gp120 with monocyte CD4. These results demonstrate that gp120 expressed by human monocytes plays an important role in the initial uptake of gp120 by monocytes and that gp120 taken up via CD4 is subsequently processed to allow for exposure of epitopes recognized by gp120-specific human T cells. At limiting gp120 concentrations, uptake via CD4 is essential for the presentation of gp120.

Antigen-Presenting Cells↗
PubMed1989

Geriatric outpatient clinics: an audit of clinical action, transport and general practitioners' views.

An audit was performed of patients attending geriatric outpatient clinics for review during a calendar month. Patients were asked to complete a brief questionnaire and 93% of case notes were available for study. In 97 attendances, management was altered in 36, a new medical problem found in 16, and 49 patients were discharged. Forty-seven attendances followed recent discharge from hospital; 19 of these patients had no evident clinical benefit from attendance, although the majority were discharged. There may be scope for a liaison nurse to take over the follow-up of some patients to save their attending a clinic. A survey of local general practitioners suggested they would welcome this.

Aged↗
PubMed1989

The costs of public primary health care services in rural Indonesia.

Described are the results of a cost study of national rural health services carried out in Indonesia between November 1986 and March 1987. Detailed costings of government inputs to all public health services below the district hospital level were made for 41 subdistricts in five provinces that were representative of the different regions of the country. The total costs of services as well as the average costs for specific service functions were estimated for the whole country as well as for the different provinces. The results indicate a low overall level of government spending on rural primary health care. Regional differences in this respect were not significant, suggesting that the government policy of encouraging regional balance in allocations has been successful. The average costs for most services were much greater than the charges made to patients, and this provided information on the current level of government subsidies. There was a large variability in the average costs, indicating that the existing system is inefficient, that some districts were able to attain much higher levels of efficiency than others within the existing constraints, and that improvements in this respect are possible.

Community Health Services↗
PubMed1988

Characterization of GP120 binding to CD4 and an assay that measures ability of sera to inhibit this binding.

There is evidence that the initial interaction between HIV-1 and the host that is essential for infection is the specific binding of the viral envelope glycoprotein, gp120, to the CD4 molecule found on certain T cells and monocytes. Most individuals infected with HIV develop antibodies against the gp120 protein. Although in vitro treatment of CD4+ T cells with mAb to a specific epitope of the CD4 molecule (T4a) blocks virus binding, syncytia formation, and infectivity, it is unclear if antibodies to gp120 from an infected individual that can inhibit the binding of gp120 to CD4 is in any way related to the clinical course of disease. Our present study characterizes the binding of 125I-labeled rgp120 to CD4+ cells, and describes an assay system that measures a potentially relevant form of immunity to HIV infection, i.e., the blocking of HIV binding to CD4+ cells. Optimal binding conditions included a 2-h incubation at 22 degrees C, 4 x 10(6) CD4+ cells, and 1 nM gp120. The dissociation constant (KD) for gp120 binding to cell surface CD4 was 5 nM, and was inhibited by soluble CD4 and by mAb to T4a but not to T3 or T4. For the binding inhibition assay, negative controls included healthy seronegatives, seronegatives with connective tissue diseases, patients with HTLV-1 disease, and patients infected with HIV-2. In studying over 100 sera, the assay was highly sensitive (98%) and specific (100%). The majority of HIV+ sera could inhibit binding at dilutions of 1/100 to 1/1000. No correlation was noted between binding inhibition (BI) titer in this assay and clinical stage of HIV infection. In addition, there was no correlation between BI titer and HIV neutralizing activity. The BI titer was correlated with the titer of anti-gp160 (r = 0.63) and the titer of anti-gp120 (r = 0.52) antibodies determined by Western blot dilution. As with neutralizing antibodies and other forms of immune response to HIV, it is unclear what role antibody blocking of HIV binding to CD4+ cells may play in active immunity to HIV in infected individuals. This activity may prove to have some value in protection against initial HIV infection and, thus, the assay may be of use in monitoring vaccine trials.

Animals↗
PubMed1988

Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: effect of HIV sequence variation and a mechanism for CD4+ cell depletion.

The primary human T cell response to HIV was analyzed by isolating from seronegative donors T cell clones specific for HIV gp120. T cell epitopes restricted by different MHC elements were identified within gp120, and synthetic peptides were used to address the fundamental problem of how HIV sequence variability affects T cell recognition. Even one conservative substitution can drastically reduce recognition; thus the interaction of gp120 epitopes with T cell receptors and MHC is precise and poorly crossreactive. Importantly, a subset of CD4+ gp120-specific clones manifest cytolytic activity and lyse uninfected autologous CD4+Ia+ T cells in the presence of gp120 in a process that is strictly dependent upon CD4-mediated uptake of gp120 by T cells. Assuming gp120 is shed from HIV-infected cells in vivo, this novel CD4-dependent autocytolytic mechanism may contribute to the profound depletion of CD4+ cells in AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

T cells can present antigens such as HIV gp120 targeted to their own surface molecules.

To trigger class II-restricted T cells, antigen presenting cells have to capture antigens, process them and display their fragments in association with class II molecules. In most species, activated T cells express class II molecules; however, no evidence has been found that these cells can present soluble antigens. This failure may be due to the inefficient capture, processing or display of antigens in a stimulatory form by T-cells. The capture of a soluble antigen, which is achieved by nonspecific mechanisms in macrophages and dendritic cells, can be up to 10(3) times more efficient in the presence of surface receptors, such as surface immunoglobulin on B cells that specifically bind antigen with high affinity. We asked whether T cells would be able to present soluble antigens that bind to their own surface molecules. Here we show that such antigens can be effectively processed and presented by both CD4+- and CD8+-bearing human T cells. This indicates that T cells are fully capable of processing and displaying antigens and are mainly limited in antigen presentation by their inefficiency at antigen capture.

Antibodies, Monoclonal↗
PubMed1988

Acute extrapyramidal syndrome in methylmalonic acidemia: "metabolic stroke" involving the globus pallidus.

We report four patients with methylmalonic acidemia who developed acute extrapyramidal disease after metabolic decompensation. The neurologic findings resulted from bilateral destruction of the globus pallidus with variable involvement of the internal capsules. This complication was unrelated to a specific gene defect responsible for methylmalonic acidemia or to cyanocobalamin administration. These lesions constitute a "metabolic stroke," probably because of the accumulation of toxic organic acid metabolites, because they cannot be accounted for by hypoxemia or vascular insufficiency.

Adolescent↗
PubMed1987

Sequence analysis, cellular localization, and expression of a neuroretina adhesion and cell survival molecule.

A cDNA for purpurin, a secreted 20,000 dalton neural retina cell adhesion and survival protein, has been sequenced and expressed in mammalian cells. Purpurin mRNA is found in both embryonic and adult retina, but not the brain, heart, or liver. The protein is highly concentrated in the neural retina between the pigmented epithelium and the outer segments of the photoreceptor cells; it is synthesized by photoreceptor cells. The predicted purpurin sequence contains 196 residues, has approximately 50% sequence homology with serum retinol binding protein, and is a member of the alpha-2 mu-globulin superfamily. Purpurin binds retinol and may play a major role in retinol transport across the interphotoreceptor cell matrix.

Amino Acid Sequence↗
PubMed1987

Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor.

The primary event in the infection of cells by HIV is the interaction between the viral envelope glycoprotein, gp120, and its cellular receptor, CD4. A recombinant form of gp120 was found to bind to a recombinant CD4 antigen with high affinity. Two gp120-specific murine monoclonal antibodies were able to block the interaction between gp120 and CD4. The gp120 epitope of one of these antibodies was isolated by immunoaffinity chromatography of acid-cleaved gp120 and shown to be contained within amino acids 397-439. Using in vitro mutagenesis, we have found that deletion of 12 amino acids from this region of gp120 leads to a complete loss of binding. In addition, a single amino acid substitution in this region results in significantly decreased binding, suggesting that sequences within this region are directly involved in the binding of gp120 to the CD4 receptor.

Antibodies, Monoclonal↗
PubMed1987

4-Aminosalicylic acid retention enemas in treatment of distal colitis.

Forty-five of 47 patients with distal ulcerative colitis completed a two-week double-blind, randomized, controlled trial to determine if 4-aminosalicylic acid (4-ASA) enemas, 1 g bid or 2 g bid, were therapeutically effective compared to placebo. Forty-one patients enrolled because they were refractory to or had side effects during conventional therapy with sulfasalazine or corticosteroids. Proctoscopic examination was done before and after two weeks of treatment. Patients kept daily diaries assessing: blood in stools, mucus in stools, tenesmus, abdominal pain, loss of appetite, fatigue, weight loss, and malaise. Severity of each symptom ranged from 0 (absent) to 3 (severe). A total severity score was calculated from the above for each patient. At the end of the two-week study, 35 patients elected to take 4-ASA in an open-label trial for one year. 4-ASA enemas in the 1-g bid but not the 2-g bid dosage were significantly more effective in improving symptoms than placebo: P less than or equal to 0.05. Neither dose of 4-ASA enema was better than placebo in improving the sigmoidoscopic appearance at the end of two-weeks. Forty-six percent of patients had complete resolution of all signs and symptoms in the open-label trial and 31% were better but still had sigmoidoscopic evidence of disease, a total response rate of 77%. Side effects were similar in the placebo and 4-ASA groups. We conclude that 4-ASA enemas in a dose of 1 g bid are safe and effective in the treatment of distal ulcerative colitis.

Adult↗
PubMed1987

The atypical presentation of infection in old age.

A study was designed to determine the incidence of atypical or geriatric presentation of infection in a long-term-care-hospital population of aged veterans. During the 6-month period of surveillance there were 65 instances of functional decline among the 143 veterans, with 50 episodes of infection. Although the symptoms and signs of infection were attenuated in many patients, a diagnosis was reached by careful examination and investigation. The majority of patients had a temperature of at least 38 degrees C in the presence of infection and it is concluded that the afebrile response to infection is rare in this population. During the course of this study the death rate in this institution dropped to about half of what was anticipated, and returned to previous levels following completion of the study. Infection can be recognized at a very early stage despite an atypical geriatric presentation and early treatment reduces morbidity and mortality.

Aged↗
PubMed1987

Cholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

Acetylcholinesterase (AChE) and nonspecific cholinesterase (nsChE) activities of lumbar ceresbrospinal fluid (CSF) from patients with a clinical or histological diagnosis of Alzheimer's disease have been compared with those of normal age-matched control patients and patients with dementia of non-Alzheimer aetiology. No significant differences in the AChE activity of lumbar CSF from histologically and clinically diagnosed Alzheimer's disease patients and normal age-matched controls were found, although they could be distinguished from controls and other dements by their lower lumbar CSF levels of nsChE activity and by their elevated ratio of AChE/nsChE. A lower level of AChE activity was observed in the lumbar CSF of patients with dementia of non-Alzheimer aetiology. The AChE and nsChE activities of ventricular CSF obtained at postmortem have also been examined. The AChE activity of the ventricular CSF of patients with histologically confirmed Alzheimer's disease was 66% lower than that of age-matched controls; these patients could also be distinguished from normals by their lower levels of nsChE and by the elevated ratio of AChE/nsChE activities. A molecular defect in the AChE in the ventricular CSF of Alzheimer patients is indicated by the finding that the enzyme failed to show inhibition by high concentrations of substrate. The lower level of AChE in ventricular CSF may reflect the changes in this enzyme in forebrain regions of Alzheimer patients. Although it is at present not possible to correlate the lower levels of nsChE found in CSF with any known brain pathology, the significantly altered ratio of AChE/nsChE activities in lumbar CSF may possibly form the basis for a diagnostic test of Alzheimer type dementia.

Acetylcholinesterase↗
PubMed1987

31P NMR studies in Duchenne muscular dystrophy: age-related metabolic changes.

To evaluate possible progressive metabolic changes in Duchenne muscular dystrophy, we used 31P nuclear magnetic resonance spectroscopy to measure high-energy phosphate compounds and phosphorylated diesters (PDE) in resting gastrocnemius muscle of 14 Duchenne patients and 10 normal boys. The patients had higher inorganic phosphate (Pi), intracellular pH, and PDE; and lower phosphocreatine (PCr) and PCr/Pi ratio; ATP was not significantly different. The patients showed significant age-related decreases in PCr and PCr/Pi, and increases in Pi and PDE, but ATP did not change. In normal boys, ATP increased with age, but PCr and Pi did not. These studies imply progressive metabolic deterioration in Duchenne dystrophy.

Adenosine Triphosphate↗
PubMed1985

Fever in the elderly.

Infection is an important problem in the elderly and it is not unusual for fever to be absent. This review examines our present state of knowledge of the febrile response and considers its apparent impairment in old age.

Aged↗
PubMed1985

Localization of epitopes of herpes simplex virus type 1 glycoprotein D.

We previously defined eight groups of monoclonal antibodies which react with distinct epitopes of herpes simplex virus glycoprotein D (gD). One of these, group VII antibody, was shown to react with a type-common continuous epitope within residues 11 to 19 of the mature glycoprotein (residues 36 to 44 of the predicted sequence of gD). In the current investigation, we have localized the sites of binding of two additional antibody groups which recognize continuous epitopes of gD. The use of truncated forms of gD as well as computer predictions of secondary structure and hydrophilicity were instrumental in locating these epitopes and choosing synthetic peptides to mimic their reactivity. Group II antibodies, which are type common, react with an epitope within residues 268 to 287 of the mature glycoprotein (residues 293 to 312 of the predicted sequence). Group V antibodies, which are gD-1 specific, react with an epitope within residues 340 to 356 of the mature protein (residues 365 to 381 of the predicted sequence). Four additional groups of monoclonal antibodies appear to react with discontinuous epitopes of gD-1, since the reactivity of these antibodies was lost when the glycoprotein was denatured by reduction and alkylation. Truncated forms of gD were used to localize these four epitopes to the first 260 amino acids of the mature protein. Competition experiments were used to assess the relative positions of binding of various pairs of monoclonal antibodies. In several cases, when one antibody was bound, there was no interference with the binding of an antibody from another group, indicating that the epitopes were distinct. However, in other cases, there was competition, indicating that these epitopes might share some common amino acids.

Antibodies, Monoclonal↗