Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

International travels are increasingly frequent. Beside malaria prophylaxis, the general practitioner will review several vaccinations.e Tetanus and poliomyelitis vaccines should be administered once every ten years. It will often be useful to give a protection against hepatitis A, and less often, against typhoid fever. The yellow fever vaccine, which may be required or recommended to visit several African and South American countries, is injected only by officially recognised centres. For some travels, vaccination against hepatitis B, meningococcal meningitis or, rarely, against rabies may be considered. The vaccine against cholera will never be administered, due to its lack of efficacy and high frequency of side effects. Travellers diarrhoea will be discussed, and a "pocket" treatment prescribed. Finally, general information will be provided, including those on STD.
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PMID:[Vaccinations and useful advice for travelers]. 793 82

X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of B lymphocytes due to an arrest in B lymphocyte development, is caused by mutations in the gene encoding Btk (Bruton tyrosine kinase). The BTK gene has been cloned and the genomic organization determined. BTK codes for 19 exons and is expressed in all hematopoietic cell lineages but is selectively down-regulated in T lymphocytes and plasma cells. The different Btk domains include PH, TH, SH3, SH2, and the kinase (SH1) domains. Btk, a cytoplasmic protein tyrosine kinase, is involved in cell signaling, although the precise pathway remains elusive. Mutation analysis has been performed in 236 families representing 282 patients. Mutations are scattered throughout the gene and consist of missense, nonsense, and splice site mutations as well as deletions and insertions. The major consequence of nonfunctional Btk appears to be a delay or block of the development of pro-B cells to pre-B cells and then to mature lymphocytes. Because IgG is actively transported across the placenta, affected newborns have normal levels of serum IgG at birth followed by gradually decreasing IgG levels and development of hypogammaglobulinemia and increased susceptibility to infections. Bacterial infections are the most common clinical manifestation. Resistance to viral infection is intact, except for an unusual susceptibility to infections with enteroviruses that may result in vaccine-related paralytic poliomyelitis or a dermatomyositis-meningoencephalitis syndrome. The diagnosis of XLA is based on the presence of lymphoid hypoplasia, markedly reduced serum levels of all 3 major classes of immunoglobulins, failure to make antibody to antigenic stimulation, and almost complete absence of B lymphocytes in the peripheral blood. Carrier detection and prenatal diagnosis are possible. The prophylactic infusion of high-dose intravenous immunoglobulin (IVIG) and the use of antibiotics have markedly improved the long-term prognosis of patients with XLA.
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PMID:X-linked agammaglobulinemia. A clinical and molecular analysis. 898 47

As more than 15,000 new HIV infections occur daily, mainly in developing countries, social and political will is growing to develop a safe and effective vaccine against the virus and subsequent AIDS disease. The worldwide successes in developing and disseminating vaccines against smallpox and polio raise hopes of the possibility of developing vaccines capable of blocking the transmission of HIV-1. Early attempts to develop HIV-1 vaccines, HIV-1 efficacy trials, immune correlates of protection from HIV-1, live vector-based vaccines, deoxyribonucleic acid (DNA) vaccines, and live attenuated vaccines are discussed. Enthusiasm was renewed at the recent world AIDS conference in Geneva for ongoing research towards a HIV-1 vaccine. However, the polarity of the HIV-1 epidemic, generally affecting countries which cannot afford more than basic health care, has forced the re-examination of research priorities. Many western governments have made at least a verbal commitment to increase funding for HIV-1 vaccine research. Funding agencies such as the World Bank are considering ways to fund and deliver a vaccine if and when one becomes available, and the International AIDS Vaccine Initiative in the US is increasing awareness of the urgent importance of the issue. An AIDS vaccine is still many years away.
Int J STD AIDS 1998 Dec
PMID:Preventive HIV-1 vaccines: where are we going? 987 16

X-linked agammaglobulinemia in humans and X-linked immunodeficiency (xid) in mice are both caused by mutations in Bruton's tyrosine kinase (Btk). Xid mice lack the early T cell-independent type 2 (TI-2) antibody response to polio virus and to a recombinant vaccinia virus (Vacc-IND-G) expressing the neutralizing determinant of vesicular stomatitis virus (VSV). This response could be restored by introduction of one or two copies of a murine Btk cDNA transgene driven by the Ig heavy chain promoter plus enhancer and depended crucially on a sufficient Btk expression level. Introduction of the same transgene into wild-type mice had little to no negative effect. The TI-1 antibody response to VSV and the T cell-dependent response to lymphocytic choriomeningitis virus were comparable in all mice tested. All mice analyzed eventually reached similar primary and memory antibody titers against all viruses independent of the mouse Btk genotype. These studies show that the xid mutation in mice has no dominant negative effect and that a transgene - even when not provided in the natural genetic context - may be able to restore functional defects resulting from genetic mutation.
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PMID:A Btk transgene restores the antiviral TI-2 antibody responses of xid mice in a dose-dependent fashion. 1050 72

Since the implementation of highly active antiretroviral therapy in HIV-infected children, response to scheduled vaccines may determinate future morbidity and mortality. The aims of this study have been to describe the current vaccine coverage, vaccine safety and concordance with vaccine recommendations of the 68 HIV-infected children and adolescents followed up in our Unit. Forty-four percent of the children received at least one dose of the oral polio vaccine (OPV). Only 9.1% needed and received a second set of hepatitis B virus immunization because of low vaccine response. Only 14.7% were vaccinated against varicella. Coverages of 82.3% and 100% have been reached with the 23-valent and the 7-valent pneumococcal vaccines, respectively. Meningococcal conjugated vaccine uptake was moderate (80.8%). Influenza annual vaccination coverage was poor: only 22.7% had well-documented yearly vaccines. In our experience, vaccine coverage is lower in those vaccines administered in primary care centres compared with the immunizations given at the hospital. OPV administration did not cause any adverse effect in the children or in their families. Vaccine coverage in HIV-infected children was suboptimal.
Int J STD AIDS 2007 May
PMID:HIV-infected children vaccination coverage and safety in a Western European cohort: a retrospective study. 1752 1

Oral polio vaccine (OPV) has been used safely and efficiently for more than 40 years in preventive medicine. Vaccine-associated paralytic poliomyelitis (VAPP) is a rare adverse event of OPV due to reversion of the vaccine strain virus to a neurovirulent strain. VAPP can occur in healthy recipients or their close contacts. However, persons with primary humoral immunodeficiencies are at a much higher risk. X-linked agammaglobulinemia (XLA) is a prototypic humoral deficiency caused by mutations in the Bruton's tyrosine kinase (BTK) gene. In addition to susceptibility to bacterial infections, patients with XLA are especially prone to enteroviruses. Here, we describe the occurrence of VAPP in a 15-month old Iranian boy. The child had received four doses of OPV, administered at birth, 2, 4, and 6 months of age. The patient's infectious history was unremarkable. Laboratory evaluation revealed low levels of immunoglobulin G and CD19(+) B cells of less than 1% of the lymphocyte population. A novel insertion (c.685_686insTTAC) in the SH3 domain of the BTK gene was detected as the underlying cause. Immunodeficient recipients of OPV can excrete poliovirus vaccine strains for a long period and are at risk of developing flaccid paralysis. They could also serve as a source of reverted virulent poliovirus to be reintroduced into the general population. This patient presented for the first time with VAPP, without any history of other major infections in 15 months. This suggests that a negative history for recurrent infections does not exclude the presence of a primary defect in the immune system.
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PMID:Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis. 1831 3

The purpose of this study was to determine the association between physical activity and self-reported disability in ambulatory persons with mild to moderate late effects of polio (N = 81, mean age 67 years). The outcome measures were: Physical Activity and Disability Survey (PADS), a pedometer, Self-Reported Impairments in Persons with Late Effects of Polio Scale (SIPP), Walking Impact Scale (Walk-12), Falls Efficacy Scale-International (FES-I), and self-reported incidence of falls. The participants were physically active on average 158 min per day and walked 6,212 steps daily. Significant associations were found between PADS and Walk-12 (r = -.31, p < .001), and between the number of steps and SIPP, Walk-12, and FES-I (r = -.22 to -.32, p < .05). Walk-12 and age explained 14% of the variance in PADS and FES-I explained 9% of the variance in number of steps per day. Thus, physical activity was only weakly to moderately associated with self-reported disability.
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PMID:Physical Activity and the Association With Self-Reported Impairments, Walking Limitations, Fear of Falling, and Incidence of Falls in Persons With Late Effects of Polio. 2526 8