The antigen-major histocompatibility complex-T cell receptor interaction

In summary, we wish to propose that regions on MHC molecules interact with complementary regions on processed peptide antigens, and that the resultant Ag-MHC complex forms a conformation with separate functional regions that are able to interact with similarly complementary areas on T cell receptors. It is the product of these interactions that determines whether a given peptide Ag is capable of binding the MHC molecule, and whether a given Ag-MHC complex is capable of stimulating a particular T cell. As more becomes known about the molecular aspects of MHC-restricted, Ag-specific T cell activation, it will become clear which amino acid residues on the Ag, MHC, and TCR are involved in these interactions.     

Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model

We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

Comprehensive family practice clerkship in a minority institution

A comprehensive family practice clerkship program at Howard University College of Medicine has been conducted since 1970. This institution is one of three predominantly black institutions offering a family practice program. The senior clerkship is mandatory and at least 20 to 25 percent of each class elect to participate in a four-to six- week family practice preceptorship. As a result of the clerkship''s success, over 50 percent of the program''s graduates actively practice in primary medical manpower shortage or medically underserved areas.     

Immunoblot analysis of immunoglobulin G response to the Lyme disease agent (Borrelia burgdorferi) in experimentally and naturally exposed dogs.

Immunoblots were used to study the immunoglobulin G response to Borrelia burgdorferi in experimentally and naturally exposed dogs. Adsorption studies confirmed that the antibodies were specific for B. burgdorferi. Experimentally exposed dogs were asymptomatic. Naturally exposed dogs included both asymptomatic animals and animals showing signs compatible with Lyme disease. Naturally exposed dogs were from four geographic regions of the country. No differences were detected between immunoblot patterns of naturally exposed symptomatic or asymptomatic dogs from different areas of the country. The immunoblot patterns obtained with sera from experimentally exposed dogs were different from those obtained with sera from naturally exposed dogs and were characterized by reactivity to fewer and different protein bands. Immunoblot analysis using an OspA-protein-producing Escherichia coli recombinant showed that experimentally exposed dogs produced antibodies to OspA, whereas naturally exposed dogs did not. Modifications of the immune response over time, different routes of antigen presentation, and strain variation are factors postulated to account for the observed differences.     

Immunocytochemical assay of progesterone receptors in paraffin-embedded specimens of endometrial carcinoma and hyperplasia: a preliminary evaluation

An immunohistochemical method for the detection of progesterone receptors (PgR) using the monoclonal anti-PgR antibody KD 68 was utilized to study paraffin-embedded tissue sections from women with endometrial carcinoma and hyperplasia. Stromal as well as myometrial nuclear PgR were nearly always apparent. In carcinoma, 11/24 (46%) of cases showed epithelial positivity, whereas in hyperplasia 8/9 (89%) were PgR-positive (P less than 0.05). Initial biochemical PgR assays by the dextran-coated charcoal method were compared with results of PgR-immunocytochemical assays (ICA) in the paraffin-embedded tissue and were in concordance in 92%. In the one discordant specimen, PgR-ICA-negative tumor cells were seen infiltrating PgR-ICA-positive myometrium, and the biochemical assay was thus felt to be falsely positive. Twelve additional cases of endometrial carcinoma were also studied for estrogen receptor (ER) by immunocytochemistry. Two were positive for both ER and PgR, while five were negative for both receptors. The immunocytochemical methods described allow for analysis of routinely fixed, paraffin-embedded specimens, thus permitting analysis of very small specimens and archival material.     

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.      

Genetic studies on murine susceptibility to herpes simplex keratitis

We studied the influence of lgh-linked genes on the development of keratopathy after corneal inoculation with herpes simplex virus (HSV). Using congenic strains of mice, we found that the lgh-1 gene locus, or genes closely linked to it, influence the clinical expression of HSV infection. Mice with the lgh-1e or lgh-1d allotype routinely developed severe keratopathy after HSV corneal inoculation, whereas congenic strains with lgh-1a or lgh-1b allotype were less susceptible. Cell-mediated immune responses to HSV also differed between susceptible and resistant murine strains. We interpret our results to imply a genetic influence on cell-mediated, acquired immune responses to HSV infection.