Mobile phones and your health.
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Animals↗
Biomedical subjects
V K Lee
Publications and source records attributed to V K Lee.
The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding.
We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis called HFE. The gene product, a member of the major histocompatibility complex class I-like family, was found to have a mutation, Cys-282 --> Tyr (C282Y), in 85% of patient chromosomes. This mutation eliminates the ability of HFE to associate with beta2-microglobulin (beta2m) and prevents cell-surface expression. A second mutation that has no effect on beta2m association, H63D, was found in eight out of nine patients heterozygous for the C282Y mutant. In this report, we demonstrate in cultured 293 cells overexpressing wild-type or mutant HFE proteins that both the wild-type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR). The C282Y mutation nearly completely prevents the association of the mutant HFE protein with the TfR. Studies on cell-associated transferrin at 37 degrees C suggest that the overexpressed wild-type HFE protein decreases the affinity of the TfR for transferrin. The overexpressed H63D protein does not have this effect, providing the first direct evidence for a functional consequence of the H63D mutation. Addition of soluble wild-type HFE/beta2m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. Furthermore, at 4 degrees C, the added soluble complex of HFE/beta2m inhibited binding of transferrin to HeLa cell TfR in a concentration-dependent manner. Scatchard plots of these data indicate that the added heterodimer substantially reduced the affinity of TfR for transferrin. These results establish a molecular link between HFE and a key protein involved in iron transport, the TfR, and raise the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis.
Amino Acid Sequence↗
The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin interaction and cell surface expression.
We recently reported the positional cloning of a candidate gene for hereditary hemochromatosis (HH), called HLA-H, which is a novel member of the major histocompatibility complex class I family. A mutation in this gene, cysteine 282 --> tyrosine (C282Y), was found to be present in 83% of HH patient DNAs, while a second variant, histidine 63 --> aspartate (H63D), was enriched in patients heterozygous for C282Y. The functional relevance of either mutation has not been described. Co-immunoprecipitation studies of cell lysates from human embryonic kidney cells transfected with wild-type or mutant HLA-H cDNA demonstrate that wild-type HLA-H binds beta2-microglobulin and that the C282Y mutation, but not the H63D mutation, completely abrogates this interaction. Immunofluorescence labeling and subcellular fractionations demonstrate that while the wild-type and H63D HLA-H proteins are expressed on the cell surface, the C282Y mutant protein is localized exclusively intracellularly. This report describes the first functional significance of the C282Y mutation by suggesting that an abnormality in protein trafficking and/or cell-surface expression of HLA-H leads to HH disease.
Base Sequence↗
A 1.1-Mb transcript map of the hereditary hemochromatosis locus.
In the process of positionally cloning a candidate gene responsible for hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination of three gene-finding techniques, direct cDNA selection, exon trapping, and sample sequencing, were used initially for a saturation screening of the 1.1-Mb region for expressed sequence fragments. As genetic analysis further narrowed the HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final measure to identify all genes. Besides the novel MHC class 1-like HH candidate gene HLA-H, we identified a family of five butyrophilin-related sequences, two genes with structural similarity to a type 1 sodium phosphate transporter, 12 novel histone genes, and a gene we named RoRet based on its strong similarity to the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger protein. Several members of the butyrophilin family and the RoRet gene share an exon of common evolutionary origin called B30-2. The B30-2 exon was originally isolated from the HLA class 1 region, yet has apparently "shuffled" into several genes along the chromosome telomeric to the MHC. The conservation of the B30-2 exon in several novel genes and the previously described amino acid homology of HLA-H to MHC class 1 molecules provide further support that this gene-rich region of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four approaches for gene finding and conclude that direct selection provides the most effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1-Mb region may be derived from noncoding genomic DNA.
Amino Acid Sequence↗
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.
Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.
Alleles↗
Psychological effects of severe burn injuries.
Severe burn injuries provide researchers with an opportunity to study the effects of painful but usually transient trauma on psychological functioning. To that end, this article presents a review of the 3 main areas of this body of literature: (a) premorbid characteristics of people who sustain severe burn injuries, (b) psychological reactions during hospitalization, and (c) long-term adjustment. The general implications of these studies are discussed and then used to illuminate the circumstances under which individuals suffer the most from this type of trauma, the effects of such injuries on personality function, and how meaningful units of measurements can be defined. Potential clinical applications are also described.
Adaptation, Psychological↗
T cells from tumor-immune mice nonspecifically expanded in vitro with anti-CD3 plus IL-2 retain specific function in vitro and can eradicate disseminated leukemia in vivo.
The therapeutic efficacy of adoptive immunotherapy of cancer has been shown to positively correlate with the dose of tumor-immune T cells transferred. Therefore, the success of this therapy is critically dependent on the ability to procure large numbers of functionally active T cells. Previous studies in animal models have shown that the limited therapeutic efficacy of a small number of immune T cells can be greatly enhanced by expansion of T cells in vitro to greater numbers before transfer in vivo. Optimal regimens for T cell expansion in vitro have generally employed the use of intermittent stimulation of the TCR with specific Ag followed by exogenous IL-2. The use of IL-2 alone does not provide for requisite episodic up-regulation of IL-2R. Stimulation of the invariant CD3 portion of the TCR/CD3 complex with antibody to CD3 (anti-CD3) represents an alternative method of up-regulating IL-2R and has been used to nonspecifically induce the growth of Ag-specific T cell lines and clones long-term in vitro with maintenance of function and specificity. The current study examined whether resting T cell populations containing small numbers of memory tumor-specific T cells could be rendered more effective in tumor therapy by nonspecific expansion in vitro with anti-CD3 plus IL-2. Spleens from C57BL/6 mice previously immunized to FBL-3, a syngeneic virus-induced leukemia, were nonspecifically stimulated with anti-CD3 plus IL-2. The resultant T cells were expanded in number, were nonlytic to FBL-3 but retained the ability to become lytic upon specific stimulation by FBL-3, and were effective in specific tumor therapy. The Ag-specific anti-tumor immune function declined on a per cell basis after each cycle of anti-CD3-induced T cell expansion. However, the approach resulted in a substantial increase in total T cell number and an overall net increase in the function of the effector T cell population. Thus, stimulation of tumor-immune T cell populations with anti-CD3 plus IL-2 represents a nonspecific method for expanding the number of specific effector T cells for cancer therapy.
Animals↗
Language changes and Alzheimer's disease: a literature review.
1. In Alzheimer's disease, the effect of cognitive changes on language and the ability to communicate and interact with others is profound. 2. Communication difficulties are a common problem identified by caregivers of demented individuals. Breakdown of communication can be frustrating and overwhelming for both patient and caregiver. 3. The deterioration of different linguistic features of language occurs at different rates, making it harder to identify deficits in the early phases of the disease. Mental status testing can give some objective measure of deficits. 4. Research is identifying explicit changes that occur in the language of Alzheimer's disease victims. Knowledge of these changes suggests strategies that can enhance communication.
Aged↗
Tumor-specific idiotopes on suppressor factors and suppressor cells revealed by monoclonal anti-idiotope antibodies.
Two monoclonal anti-idiotope antibodies, previously found to induce tumor-specific cell-mediated immunity in mice, were examined for their relationship to tumor-associated suppressor factors (SF), produced in culture by spleen cells from tumor-bearing mice or present in sera from such mice. A leukocyte adherence inhibition assay was used to detect cellular immunoreactivity to tumor antigens and its inhibition by SF, using peritoneal cells from mice bearing tumor or sensitized with anti-idiotope antibody. The SF were specifically absorbed by the corresponding anti-idiotope antibodies coupled to a solid phase and were recovered by elution. They were also specifically neutralized by the addition of the respective antibodies to the assay system. Anti-idiotope antibody, used with complement to pretreat spleen cells from tumor-bearing mice, prevented these cells from producing SF in culture. Tumor antigen-reactive effector cells, suppressor cells, and SF thus share similar idiotopes, permitting their respective functions to be modulated by appropriate anti-idiotopes.
Animals↗
Idiotypic interactions in immune responses to tumor-associated antigens.
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Animals↗
Monoclonal antiidiotypic antibodies related to a murine oncofetal bladder tumor antigen induce specific cell-mediated tumor immunity.
Rat monoclonal antibody 6.10 recognizes a 175-kDa protein expressed in all BALB/c mouse transitional cell bladder carcinomas tested, in epithelial cells of the mouse embryo, and in a few epithelial cells of adult mice. The antibody was used as an immunogen to generate two mouse monoclonal antibodies, 21D9 and 43A10, which bind to idiotopes on antibody 6.10 associated with the binding site for the 175-kDa antigen. The antiidiotypic antibodies induced bladder tumor-specific, cell-mediated immunity when injected into syngeneic mice, as shown by delayed-type hypersensitivity reactions in vivo and leukocyte adherence inhibition reactions in vitro. Tumor specificity was demonstrated by employing as controls a chemically induced BALB/c fibrosarcoma, MCA-1511 (MCA, 3-methylcholanthrene), and its corresponding antiidiotypic antibody, 5.96. Lymphocytes from mice sensitized with antibody 21D9 or 5.96 specifically recognized antigens in extracts of BALB/c bladder carcinoma BTCC-1660 (BTCC, bladder transitional cell carcinoma) and sarcoma MCA-1511, respectively, as shown by leukocyte adherence inhibition reactivity. This reactivity was selectively abrogated by prior treatment of the sensitized cells with the appropriate antiidiotypic antibodies and complement. An antigen recognized in vitro by antibody 21D9-sensitized lymphocytes could be separated from BTCC-1660 extract by immunoabsorption with antibody 6.10 and elution with acidic buffer. Our findings indicate that the oncofetal antigen defined by antibody 6.10 is recognized by the immune system of syngeneic mice and suggest that antiidiotypic antibodies related to certain oncofetal antigens can be used to immunize against syngeneic tumors.
Animals↗
Monoclonal antibodies to cell surface antigens shared by chemically induced mouse bladder carcinomas.
Rats were immunized with cultured cells from chemically induced transitional cell carcinomas of the mouse urinary bladder, and their spleen cells were hybridized with NS-1 mouse myeloma cells. Following initial screening of antibodies made by hybridoma clones, the tissue distribution of antigens defined by the antibodies was established by using a peroxidase-antiperoxidase technique with frozen sections of a variety of mouse tumors, as well as normal adult and embryonic tissues. Two antibodies were identified which detected antigens with bladder carcinoma specificity. One antibody (3B12) reacted weakly with epithelial cells from several sources, including normal bladder, while the second antibody (6.10), which bound strongly to bladder carcinoma cells, was negative on bladder epithelium and bound (weakly) to only a small fraction of all epithelial cells tested except for epidermal cells and periosteum from embryos. Both antibodies should be useful to assess the immunotherapeutic and immunoprophylactic effects of monoclonal antibodies to tumor-type specific oncofetal antigens.
Animals↗
A case report: special needs of hospitalized elders.
A case report is used to discuss common problems and complications of hospitalized elders. The report also illustrates the need for proactive hospital staff who are knowledgeable about the special needs of the aging population if this group is to be cared for successfully. The geriatric resource nurse model involves informal unit-based education aimed at expanding staff nurses' geriatric knowledge and is one of several models sponsored by the Hartford Foundation to improve care of the hospitalized elderly. Teaching rounds between geriatric resource nurses and advanced practice nurses are a primary feature of this model.
Aged↗
Herpes zoster and postherpetic neuralgia in the elderly.
This article describes herpes zoster (HZ), its cause, diagnosis, treatment, and associated complications. Postherpetic neuralgia (PHN), the most common complication of HZ, is the primary focus of the discussion. PHN is defined broadly as chronic pain that persists after the characteristic vesicular rash of HZ has resolved.
Aged↗
Faculty as primary nurses on a model inpatient unit.
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Education, Nursing↗
Clinical and radiological aspects in Melnick-Needles syndrome.
Melnick-Needles syndrome is an X-linked dominant bone dysplasia, lethal in males, characterized by a typical facies and characteristic radiological findings: including sclerosis of skull base and mastoids. S-shaped appearance of tibia; cortical irregularities with a ribbon appearance of the ribs. About 48 well-documented cases have been reported, most of them were sporadic. Parental transmission has been published in only 11 kindreds. We are presenting the first Brazilian family with mother-daughter transmission. The proposita presented the typical clinical and radiological features with characteristic facies, severe thoracic cage restriction and pulmonary hypertension. Her mother was more mildly affected.
Adolescent↗
Drug therapy for osteoporosis management in nursing home residents.
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Calcitonin↗