Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait.

We studied 21 patients with Sanjad-Sakati syndrome (SSS) from 16 families. Parental consanguinity was recorded in 2 families (12.5%). All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp (155-166del) in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers.

Thrust and torque force analysis in the drilling of aramid fibre-reinforced composite laminates using RSM and MLPNN-GA.

Aramid Fibre Reinforced Plastic composites are difficult to be drilled due to anisotropic material properties. Currently, soft computing techniques are used as alternatives to conventional mathematical models, which is robust and can deal with inaccuracy and uncertainty. In this paper, drilling of Aramid Fibre Reinforced Plastics (AFRPs) was carried out using Taguchi L54 experimental layout. Drilling tool used in this experiment was solid carbide. The purpose of this study was to find optimum combination of drilling parameters to obtain minimum thrust and torque force to reduce the delamination. Also, this paper proposed a prediction model of Multilayer Perception Neural Network optimized by Genetic Algorithm (MLPNN-GA). Moreover, RSM technique was used to evaluate the influence of process parameters (spindle speed, feed rate, drill point angle and drill diameter on thrust force and torque. The prediction capability of both RSM and MLPNN-GA was compared with Response optimizer for thrust force and torque. The investigation demonstrated that drill point angle is the primary factor affecting thrust force and drill diameter influences the torque force on the drill bit. Overall, this study recommends the use of high speed and low feed combination and drill point angles of 90°-118° to reduce the delamination of the materials in the drilling of AFRP composites.

Trisomy 18 in Kuwait.

BACKGROUND: Trisomy 18 (Edwards' syndrome, T18) is the second most common trisomy in man. We describe 118 children with regular T18 who were ascertained clinically and cytogenetically in the Kuwait Medical Genetics Centre during 1980-1997. METHODS: Ascertainment of T18 cases was performed shortly after birth. Chromosomal studies were carried out in addition to other relevant investigations. To investigate the factors associated with T18, a case-control study was carried out with 131 normal healthy newborns. Studied factors included maternal and paternal age, birth order, abortion, associated malformation, and survival. Multiple logistic regression analysis was used to adjust for confounding between variables. RESULTS: There was a preponderance of females among T18 cases (female:male ratio 2.1:1). The majority of T18 cases (53%) died before the second week of life. The most common associated anomalies were: congenital heart (38.1%) and gastrointestinal (25.4%). Multiplicity of malformations was also observed. Significant seasonal variation in T18 cases was detected with a peak in spring. Of the 118 T18 cases, 59 were delivered during 1994-1997 (average overall T18 birth prevalence rate 8.95 per 10 000 live births [95% CI: 6.66-11.23]). Concerning maternal age, 30.5% of the T18 cases' mothers were > or =35 years compared to 10.7% in the control group. The difference was statistically significant, P = 0.002. Logistic regression analysis showed that maternal age >30 years was a significant risk factor for T18, after adjusting for confounding with paternal age. Paternal age and abortion were not found to be significant risk factors. CONCLUSION: Trisomy 18 birth prevalence rate is high in Kuwait with advanced maternal age as a significant risk factor.

PIP: This paper describes associated factors of trisomy 18 (T18) or Edwards' syndrome among infants in Kuwait. A case control study of 131 normal newborn controls was undertaken. The study included information about gender, maternal age, paternal age, birth order, reproductive history, consanguinity, survival, and associated anomalies. Results showed a preponderance of females among T18 cases (female/male ratio, 2.1:1). The difference between the T18-case mothers and the control-group mothers was statistically significant (P = 0.002); however, there was no significant difference with regard to paternal age. The logistic regression analysis showed that the odds ratio for 2 abortions with reference to (0/1) abortion was 1.086, which is statistically significant as a risk for T18. The majority of children with T18 died before the second week of life. With regard to malformations, the most common associated anomalies were congenital heart and gastrointestinal abnormalities. Thus, the prevalence of T18 is high in Kuwait, with advanced maternal age as a significant risk factor.

[In situ detection of Epstein-Barr virus in the non-neoplastic gastric glands and infiltrated lymphocytes].

Recently, clonal EBV-DNA and/or EBV-encoded small RNA(EBER1) have been detected in some gastric carcinomas. We reported the first observation of EBV infection in gastric glands with intestinal metaplasia, and characterized the EBV-infected lymphocytes which infiltrated in gastric mucosa. To determine the cellular location of EBV, EBER1 in situ hybridization(ISH) with an EBER1 oligonucleotide probe was applied to paraffin sections of the non-neoplastic gastric mucosa in 80 cases of gastric carcinoma and 49 cases of gastric ulcer. Not only was EBER1 expression detected in the nucleus of gastric cancer cells(5 cases) but also in non-neoplastic gastric epithelial cells(3 cases) and in infiltrated lymphocytes(40 cases). A single or a few shedding non-neoplastic epithelial cells in 2 cases of EBV-associated gastric cancer showed EBER1 expression. In one case, EBER1 was observed in all of the epithelial cells of a few gastric glands with intestinal metaplasia, suggesting that the stem cells of the metaplastic gastric glands were infected with EBV. EBV DNA was also detected in the EBER1-positive metaplastic glands scratched from the paraffin section by a single cell PCR method with a BamHI W primer pair. However, immunohistochemical examination showed that these metaplastic glands lacked expression of EBNA2 and LMP-1. The observation of these rare EBV-infected metaplastic glands reinforces the pre-transformation EBV infection hypothesis for EBV-associated gastric carcinoma. The double staining using ISH and immunohistochemistry revealed that EBER1 positive lymphocytes showed a B cell marker of L26(< 50%) but not T cell markers of UCHL1 and OPD4.

Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patients.

Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI.

Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl.

Complete T cell activation requires not only the first signal via TCR-CD3 engagement, but also a co-stimulatory signal through accessory receptors such as CD2, LFA-1 and CD28. However, the pathway of co-stimulatory signaling through accessory receptors is incompletely understood. We report here that CD2 provides a co-stimulus for activation of CD3-mediated syk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Although cross-linking of CD2 alone or any combination of CD2 with LFA-1alpha, LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk, co-cross-linking of CD2 with CD3 enhanced CD3-mediated tyrosine phosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk by CD2 co-stimulation was CD2 antibody concentration-dependent, and time course studies showed that CD2 co-stimulation enhanced Syk tyrosine phosphorylation by 30 s and through 5 min stimulation compared with the control. In vitro kinase assay revealed that co-cross-linking of CD2 with CD3 augmented Syk kinase activity using myelin basic protein as a substrate. Furthermore, CD2 co-stimulation with CD3 resulted in enhanced tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an antibody concentration-dependent manner. Finally, CD2 provided a co-stimulatory signals for synthesis of IL-2 in Jurkat cells and phytohemagglutinin (PHA)-activated T cells and for proliferation of PHA-activated T cells. Taken together, these results indicate that CD2 is an important co-stimulatory receptor for CD3-mediated T cell activation and functions in concert with CD3.

Beta2-integrin, LFA-1, and TCR/CD3 synergistically induce tyrosine phosphorylation of focal adhesion kinase (pp125(FAK)) in PHA-activated T cells.

Complete T cell activation requires not only a first signal via TCR/CD3 engagement but also a costimulatory signal through accessory receptors such as CD2, CD28, or integrins. Focal adhesion kinase, pp125(FAK) (FAK), was previously shown to be localized in focal adhesions in fibroblasts and to be involved in integrin-mediated cellular activation. Although signaling through beta1- or beta3-integrins induces tyrosine phosphorylation of FAK, there has been no evidence that activation of T cells through the beta2-integrin, LFA-1, involves FAK. We report here that crosslinking of LFA-1 induces tyrosine phosphorylation of FAK in PHA-activated T cells. Moreover, cocrosslinking with anti-LFA-1 mAb and suboptimal concentration of anti-CD3 mAb markedly increases tyrosine phosphorylation of FAK in an antibody-concentration-dependent and time-kinetics-dependent manner compared with stimulation through CD3 alone, which correlates well with enhanced proliferation of PHA-activated T cells. Furthermore, LFA-1beta costimulation with CD3 induces tyrosine phosphorylation of Syk associated with FAK. These results indicate, for the first time, that signals mediated by LFA-1 can regulate FAK, suggesting that LFA-1-mediated T cell costimulation may be involved in T cell activation at least partially through FAK.

Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait

We studied 21 patients with Sanjad-Sakati syndrome [SSS] from 16 families. Parental consanguinity was recorded in 2 families [12.5%]. All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp [155-166del] in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers