Pemphigus Vulgaris Autoantibody Response is Linked to HLA-DQB10503 in Pakistani Patients

ABSTRACT: Pemphigus vulgaris (PV) is an autoimmune disease of the skin and mucous membranes characterized by an autoantibody response against an epidermal cadherin. We performed high resolution HLA class II typing in 19 patients with PV from Rawalpindi, Pakistan and 19 non-Jewish European PV patients from Boston by sequence-specific oligonucleotide probe hybridization. The results were compared with two separate ethnically matched control populations. We found that PV patients from Pakistan had significantly increased frequencies of DRB1*1404 ( p = 0.01), DQA1*0101 ( p = 0.02), and DQB1*0503 ( p = 0.01). Among the patients of non-Jewish European ancestry, DRB1*1401 ( p < 10⁻⁶), DQA1*0101 ( p < 10⁻⁵) and DQB1*0503 ( p < 10⁻⁶), were increased in PV patients. Formal linkage analysis between the major histocompatibility complex and the PV antibody was performed in 67 relatives of the 19 Pakistani patients. The results showed strong evidence for linkage of HLA-DRB1*1404, DQA1*0101, DQB1*0503, with the presence of PV antibody in relatives’ families with a significant logarithm of the odds score of 6.06. Based on the three dimensional structure of class II molecules, we propose that HLA-DQA1*0101 and DQB1*0503, encode a negatively charged P9 peptide binding pocket of the DQ molecule and are significantly associated with susceptibility to PV in non-Jewish populations.     

Births of normal daughters after MicroSort sperm separation and intrauterine insemination, in-vitro fertilization, or intracytoplasmic sperm injection

The world's first deliveries of normal babies after use of flow cytometric separated human sperm cells (MicroSort) for preconception gender selection are reported. Offspring were of the desired female gender in 92.9% of the pregnancies. Most of these pregnancies and births were achieved after simple intrauterine insemination.      

Adaptive Wiener Filtering for Improved Acquisition of Distortion Product Otoacoustic Emissions

An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subjects nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR. © 1998 Biomedical Engineering Society. PAC98: 4364Jb, 4360-c, 8790+y     

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.      

Assessing lymphocyte functions in neonates for revealing abnormal prenatal development of the immune system

Because it is difficult to assess prenatally induced functional deficits of the human immune system, we developed an ex vivo method for differentiation and maturation of peripheral lymphocytes of newborn, preferentially using umbilical cord blood. Many lymphocyte subsets of newborn infants are "immature" with respect to defined surface receptors. An example of such an immaturity is the almost complete lack of "memory"-type helper T cells (also designated as helper-inducer cells), characterized by expressing the surface receptors: CD4(+)CD45R0(+)CD45RA(-)CD29(high). On the other hand, umbilical cord blood contains many "naive"-type helper T cells (often designated as suppressor-inducer cells), with the receptors: CD4(+)CD45R0(-)CD45RA(+)CD29(low). In this report, we demonstrate that the immature helper lymphocyte population of umbilical cord blood is capable of differentiating to mature cells following stimulation with pokeweed mitogen (PWM) and other stimulants ex vivo. The obtained receptor pattern is virtually indistinguishable from the one observed on the mature cells of adults. Such an extensive differentiation can only be achieved with cells of newborns. As intermediates during differentiation in culture, CD45R0(+)CD45RA(+) cells may be observed which are rather rare in vivo. Additionally, the appearance of several activation (CD25, CD69, HLA-DR) and adhesion (CD11a, CD11b, CD11c, CD18, CD49b, CD49d, CD54) receptors on CD4 cells were analyzed. With this model system evidence for the sequence of events during differentiation and maturation may be obtained. This ex vivo-model is capable of studying the capacity of lymphocytes for differentiation and activation processes barely accessible in vivo. It may also be expected to represent an interesting tool for measuring the capacity for maturation and differentiation in the blood of children of different ages under normal and pathological conditions ex vivo. In addition, substance-induced effects may be studied in vitro with this approach on immature cells from newborn, or infants during culturing. Teratogenesis Carcinog. Mutagen. 20:171-193, 2000.