Parathyroid hormone-related protein production by breast cancers, improved survival, and reduced bone metastases.
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Adult↗
Biomedical subjects
T Martin
Publications and source records attributed to T Martin.
Natural autoreactive B cells in transgenic mice reproduce an apparent paradox to the clonal tolerance theory.
Naturally occurring autoreactive B cells are thought to be physically eliminated or rendered functionally silent through different mechanisms of tolerance. However, multireactive low affinity natural autoantibody-producing B cells seem to escape these mechanisms in normal adults and could constitute the B cell pool from which pathological autoantibodies can emerge. To analyze this apparent paradox to the clonal tolerance theory, we have made two transgenic mouse lines (mu(k), mudelta(k)) producing a natural low affinity multireactive human autoantibody. These models enable us to test both the central tolerance mechanisms (reactivity with single-stranded DNA) and the peripheral tolerance mechanisms after Ag administration. Not only are the multireactive B cells not deleted in the bone marrow, they circulate and remain in the periphery even after the prolonged administration of Ag, the presence of membrane IgD increasing the number of mature autoreactive B cells. Self-reactive B cells are shown to be autoantigen ignorant both in vivo and in vitro, but they are not anergic because they can be easily activated through both B cell receptor-dependent and -independent pathways. Thus, these mouse lines reproduce an apparent paradox to the clonal tolerance theory meriting further investigation of the biological significance of this phenomenon.
Animals↗
Plastid redox state and sugars: interactive regulators of nuclear-encoded photosynthetic gene expression.
Feedback regulation of photosynthesis by carbon metabolites has long been recognized, but the underlying cellular mechanisms that control this process remain unclear. By using an Arabidopsis cell culture, we show that a block in photosynthetic electron flux prevents the increase in transcript levels of chlorophyll a/b-binding protein and the small subunit of Rubisco that typically occurs when intracellular sugar levels are depleted. In contrast, the expression of the nitrate reductase gene, which is induced by sugars, is not affected. These findings were confirmed in planta by using Arabidopsis carrying the firefly luciferase reporter gene fused to the plastocyanin and chlorophyll a/b-binding protein 2 gene promoters. Transcription from both promoters increases on carbohydrate depletion. Blocking photosynthetic electron transport with 3-(3', 4'-dichlorophenyl)-1,1'-dimethylurea prevents this increase in transcription. We conclude that plastid-derived redox signaling can override the sugar-regulated expression of nuclear-encoded photosynthetic genes. In the sugar-response mutant, sucrose uncoupled 6 (sun6), plastocyanin-firefly luciferase transcription actually increases in response to exogenous sucrose rather than decreasing as in the wild type. Interestingly, plastid-derived redox signals do not influence this defective pattern of sugar-regulated gene expression in the sun6 mutant. A model, which invokes a positive inducer originating from the photosynthetic electron transport chain, is proposed to explain the nature of the plastid-derived signal.
Arabidopsis↗
Enhancers and core promoter elements are essential for the activity of a cryptic gene activation sequence from tobacco, tCUP.
Cryptic gene regulatory elements are sequences that are inactive at their native locations in the genome but have the ability to become functional when positioned adjacent to genes. We have recently isolated such a cryptic sequence from tobacco, tCUP, that can act as a promoter. A 135-bp fragment spanning extending from position -197 to -62, relative to the transcription start site, was found to promote GUS expression in all of the major organs of transgenic Arabidopsis plants. Furthermore, this 135-bp fragment complemented the -46 minimal promoter of CaMV 35S and conferred constitutive expression on transgenic Arabidopsis plants. An electrophoretic mobility-shift assay showed that nuclear proteins prepared from tobacco leaves interact with the 135-bp fragment. tCUP has a core promoter that lacks the TATA consensus sequence but addition of a TATA-box sequence increased the core promoter activity by three-fold. The sequence surrounding the transcription start site of tCUP has sequence similarity with the initiator element (Inr), and deletion of this sequence significantly reduced promoter activity, suggesting that an essential Inr element may exist in the tCUP core promoter. Fusion of the GCC-box enhancer element from pathogenesis-related genes to the core promoter elevated tCUP core promoter activity. Our study indicates that cryptic promoters are similar in composition and organization to promoters associated with expressed genes and that their promoter elements can be combined to create composite promoters that are fully functional. This data provides direct evidence that the expression pattern of plant genes can be influenced by cryptic gene regulatory elements when they are brought into juxtaposition with genes through DNA rearrangements.
Arabidopsis↗
Clinical characteristics of neuroleptic-induced parkinsonism.
In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.
Activities of Daily Living↗
Computerized weight loss intervention optimizes staff time: the clinical and cost results of a controlled clinical trial conducted in a managed care setting.
OBJECTIVE: To evaluate the costs and effects of incremental components of a weight-loss program. DESIGN: A 3-arm, 12-month randomized controlled clinical trial to evaluate 3 incremental levels of intervention intensity. SUBJECTS/SETTING: The study included 588 individuals (BMI > 25 kg/m2) in a freestanding health maintenance organizalion and achieved an 81% completion rate. INTERVENTION: Using a cognitive behavioral approach for tailoring lifestyle modification goals, the incremental levels of intervention included a) a workbook alone, b) the addition of computerized tailoring using onsite computer kiosks with touch screen monitors, and c) the addition of both computers and staff consultation. MAIN OUTCOME MEASURES: Endpoints included weight parameters, lipid profile, plasma glucose, blood pressure, intervention costs, dietary intake, and physical activity. STATISTICAL ANALYSIS PERFORMED: Study endpoints were analyzed using analysis of variance for normally distributed variables and analysis of covariance to control for any baseline differences. Regression and correlation analysis assessed the relationship between weight loss and other variables. RESULTS: For the increasing levels of intervention intensity, the mean 12-month weight losses were 2.2, 4.7, and 7.4 pounds, with the respective cost per participant being $12.33, $41.99, and $133.74. The decreases in mean BMIs for these respective intervelation levels were 0.4, 0.9 and 1.2. All groups reported a decrease in energy and fat intake and an increase in blocks walked (P<.01). Intervention variables that correlated with weight loss included more computer log-ons, achieving computer-selected goals, more self-monitoring, increased walking, and decreased energy and fat intake, as well as higher attendance in staff consultation group sessions for that treatment condition. Weight loss correlated with decreases in fasting glucose and blood pressure. APPLICATIONS/CONCLUSIONS: In a weight-loss program, computers can facilitate selecting behavioral change goals. More frequent usage resulted in greater weight loss. Staff counseling to augment the computer intervention achieved the most weight loss.
Analysis of Variance↗
Long-Term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation.
Donor lymphocyte infusions (DLIs) are an effective treatment for relapsed Chronic myeloid leukemia (CML) after allogeneic transplantation but are limited by the occurrence of GVHD. CD8+ T lymphocytes are involved in the pathogenesis of GVHD but may not be essential for the graft-versus-leukemia (GVL) effect in CML. We have treated 26 CML patients with posttransplantation relapse with CD8-depleted DLI. Thirteen of 15 patients (87%) who relapsed in early-phase CML achieved complete cytogenetic response, but only 1 of 11 who relapsed in advanced-phase disease achieved complete response. Acute GVHD occurred in 2 patients (8%), and extensive chronic GVHD occurred in 2 patients (11%). Treatment-related mortality was 11.5%. Responses were durable; with a median follow-up of 4.2 years (1-7.5 years), only 1 responding patient relapsed (7%). CD8-depleted DLI was equally effective and safe after unrelated donor transplants and sibling transplants. Cytogenetic clonal evolution at the time of DLI was not predictive of treatment failure unless associated with hematologic criteria for disease acceleration. CD8 depletion is an effective method to separate GVL from GVHD for posttransplantation relapsed CML. This strategy is associated with durable complete remissions and a low rate of complications and therefore merits further investigation in larger-scale comparative trials.
Adult↗
Activation of tomato PR and wound-related genes by a mutagenized tomato MAP kinase kinase through divergent pathways.
A mitogen-activated protein kinase kinase (MAPKK) gene, tMEK2, was isolated from tomato cv. Bonny Best. By mutagenesis, a permanently active variant, tMEK2MUT, was created. Both wild-type tMEK2 and mutant tMEK2MUT were driven by a newly described strong plant constitutive promoter, tCUP, in a tomato protoplast transient gene expression system. Pathogenesis-related genes, PRlb1, PR3 and Twi1, and a wound-inducible gene, ER5, were activated by tMEK2MUT. Specific inhibitors of p38 class MAPK inhibited tMEK2MUT-induced activation of PR3 and ER5 genes but not that of the PRlb1 or Twi1 gene. Arabidopsis dual-specificity protein tyrosine phosphatase 1 (DsPTP1) and maize protein phosphatase 1 (PP1) inhibited tMEK2MUT-induced activation of the ER5 gene and the Twi1 gene, respectively, whereas PRlb1 and PR3 were not affected by either AtDsPTP1, or maize PP1, or Arabidopsis protein phosphatase 2A (PP2A). We have demonstrated for the first time that a single MAPKK activates an array of PR and wound-related genes. Our observation indicates that the activation of the genes downstream of tMEK2 occurs through divergent pathways and that tMEK2 may play an important role in the interaction of signal transduction pathways that mediate responses to both biotic (e.g. disease) and abiotic stresses (e.g. wound responsiveness).
Amino Acid Sequence↗
Transplantation of a fetus with paternal Thy-1(+)CD34(+)cells for chronic granulomatous disease.
A fetus diagnosed with X-linked chronic granulomatous disease was transplanted with Thy-1(+)CD34(+) cells of paternal origin. The transplant was performed at 14 weeks gestation by ultrasound guided injection into the peritoneal cavity. The fetus was delivered at 38 weeks gestation after an otherwise uneventful pregnancy. Umbilical cord blood was collected and used to determine the level of peripheral blood chimerism as well as levels of functional engrafted cells. Flow cytometry was used to detect donor leukocytes identified as HLA-A2(-)B7(+) cells, whereas recipient cells were identified as HLA-A2(+)B7(-) cells. No evidence of donor cell engraftment above a level of 0.01% was found. PCR was used to detect HLA-DRB1*15(+) donor cells among the recipient's HLA-DRB1*15(-) cells, but no engraftment was seen with a sensitivity of 1:1000. The presence of functional, donor-derived neutrophils was assessed by flow cytometry using two different fluorescent dyes that measure reactive oxygen species generated by the phagocyte NADPH oxidase. No evidence of paternal-derived functional neutrophils above a level of 0.15% was observed. Peripheral blood and bone marrow samples were collected at 6 months of age. Neither sample showed engraftment by HLA typing using both flow cytometry and PCR. Functional phagocytes were also not observed. Furthermore, no indication of immunological tolerance specific for the donor cells was indicated by a mixed lymphocyte reaction assay performed at 6 months of age. While there appears to be no engraftment of the donor stem cells, the transplant caused no harm to the fetus and the child was healthy at 6 months of age. Analyses of fetal tissues, obtained from elective abortions, revealed that CD3(+) T cells and CD56(+)CD3(-) NK cells are present in the liver at 8 weeks gestation and in the blood by 9 weeks gestation. The presence of these lymphocytes may contribute to the lack of donor cell engraftment in the human fetus.
Adult↗
Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth.
The variable regions of the immunoglobulin (Ig) expressed on the surface of a malignant B cell can be considered tumor-specific antigens and, as such, could be targets for immunotherapeutic approaches. However, because until now the immunization procedures have been complex and have given only partial protection, it was necessary to find new methods of immunotherapy. Here, we present a successful method of vaccination against B-cell tumors in a murine model. We produced recombinant vaccinia viruses (rVV) expressing the heavy and the light chain of surface Ig of a patient's malignant B cells and we tested the ability of these rVV to protect immunized mice against tumor growth of transfectomas producing the same human Ig. The protection of the mice was complete and specific to the variable region of the immunizing heavy chain although specific lymphoproliferative and cytotoxic responses were not detectable in vitro. The protection was strictly dependent on the presence of CD4 T cells and asialo GM1+ cells. Furthermore, tumor protection clearly required gamma-interferon and was partially inhibited by blocking the Fas-Fas ligand interaction. We also show, in a murine syngeneic model, that rVV expressing a poorly mutated Ig protects against the growth of Ig-producing tumor.
Amino Acid Sequence↗
Something special: forensic psychiatric nursing.
In this paper the claims that forensic psychiatric nursing has achieved the status of a specialist area of nursing are refuted. An examination of the literature demonstrates that specialist knowledge and skills have not been documented. It is suggested that three requirements are necessary if forensic psychiatric nurses wish to achieve specialty status. Forensic nurses have to consolidate their role in the containment and care of patients, they have to return to the nurse-patient relationship as the foundation of psychiatric nursing practice, then, within that relationship, nurses must expand their practice to include dealing with offence issues.
Antisocial Personality Disorder↗
Undergraduate nursing students' views of mental health nursing in the forensic environment.
The literature clearly demonstrates that mental health nursing tends to be viewed negatively by undergraduate nursing students. While positive clinical experiences have been found to encourage more favourable attitudes towards mental health nursing, suitable placements are becoming scarce. An evaluation of clinical placements at the Victorian Institute of Forensic Mental Health (VIFMH) was undertaken to determine whether appropriate learning opportunities were offered, and identify the impact of the placement on students' attitudes to mental health nursing. The results suggest that VIFMH provides valuable learning experiences to increase students' understanding of mental health nursing and is effective in producing more positive attitudes towards this area of practice.
Attitude of Health Personnel↗
Long-term effects on the intelligence of children treated for acute lymphoblastic leukemia.
The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.
Adult↗
Effect of NASA light-emitting diode irradiation on wound healing.
OBJECTIVE: The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. BACKGROUND DATA: Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. MATERIALS AND METHODS: In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. RESULTS: LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. CONCLUSION: We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.
Animals↗
Penetrating trauma causing partial disruption of a duplicated ureter: case report.
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Abdominal Injuries↗
Sinorhizobium meliloti cells require biotin and either cobalt or methionine for growth.
Sinorhizobium meliloti is usually cultured in rich media containing yeast extract. It has been suggested that some components of yeast extract are also required for growth in minimal medium. We tested 27 strains of this bacterium and found that none were able to grow in minimal medium when methods to limit carryover of yeast extract were used during inoculation. By fractionation of yeast extract, two required growth factors were identified. Biotin was found to be absolutely required for growth, whereas previously the need for this vitamin was considered to be strain specific. All strains also required supplementation with cobalt or methionine, consistent with the requirement for a vitamin B(12)-dependent homocysteine methyltransferase for methionine biosynthesis.
Biotin↗
[Radiotherapy in vertebral hemangioma].
Vertebral hemangiomas are the most common benign spinal tumors with an incidence range of 10-12%. Approximately 1-2% of the cases develop clinically significant symptoms causing the necessity for treatment. Based on our own results and a review of the literature we discuss the role of radiotherapy in the management of symptomatic vertebral hemangiomas. A total dose of 30.0 Gy given in five weekly fractions of 2.0 Gy has been proven as effective for the primary treatment and postsurgical irradiation for the prevention of a recurrence. In the literature review the results are summarized of 59 reports in the period of 1929-2000 for a total of 327 cases. The analysis of 55 studies reporting results in 210 cases which underwent primary radiotherapy or combinations with other methods of treatment demonstrated that in 54% occurred a complete relief of symptoms (CR), in 32% a partial relief (PR), and 11% were non-responders (NR). The analysis of 21 reports of 63 cases which were treated with radiotherapy as the sole measure of treatment demonstrated that 57% had a complete remission of symptoms (CR), 32% a partial remission (PR), and 11% did not respond to radiotherapy (NR). We conclude that radiation therapy is very effective in the management of symptomatic vertebral hemangiomas. With regard on the delayed effects of the irradiation, cases with an acute compression of the spinal cord should be treated primarily with a surgical procedure and a postsurgical irradiation is recommended to prevent a relapse of symptoms. In order to minimise acute or late toxicity and the risk of radiation-induced neoplasms the total dose should not exceed 30 Gy.
Adult↗
Hypofractionated radiotherapy for Graves' orbitopathy.
BACKGROUND: Radiotherapy (RT) has been proven effective in the management of Graves' orbitopathy in numerous studies. Most commonly is the use of conventional fractionated RT and the value of hypofractionated irradiation has not been investigated. MATERIALS AND METHODS: The results in 33 euthyroid cases who underwent RT with a total dose of 21.0 Gy given in three weekly fractions of 3.0 Gy are retrospectively analyzed. The duration of symptoms ranged from 1-84 months and all of the cases had treatment failure after previous administration of corticosteroids. After a mean follow-up period of 33.6 months the overall results were assessed according to the criteria by Donaldson et al. and for evaluation of the clinical outcome a classification with the main criteria being eye-lid changes, exophthalmos, myopathy and eye nerve involvement was used. RESULTS: At follow-up, the overall response to RT was 84.8% (28/33 cases). The analysis with the clinical classification demonstrated that in 19/33 (57.6%) cases occurred a decrease of eye lid changes and exophthalmos and 12/33 (36.4%) had a relief of myopathy. 2/33 cases (6.0%) developed an eye nerve compression causing the necessity of surgical decompression. 3/33 cases (9.0%) had a progression of at least of one of the single criteria of the score and therefore they were classified as non-responders. CONCLUSIONS: Hypofractionated RT has been proven effective for treatment of severe cases of Graves' orbitopathy in cases with a prolongated duration of symptoms. The comparison with literature data demonstrate that the results after hypofractionated RT are comparable to those obtained after conventional fractionated RT.
Adult↗