[Evolution of management of penetrating brain wounds--lessons learned from wars since Israel's independence].
Explore the source record for details and available documents.
Brain Injuries↗
Biomedical subjects
L Levy
Publications and source records attributed to L Levy.
The use of transgenic fruit trees as a resistance strategy for virus epidemics: the plum pox (sharka) model.
Sharka or plum pox, caused by Plum pox virus (PPV: genus Potyvirus; Family Potyviridae), is the most serious disease of Prunus. Most cultivated Prunus species are highly susceptible and conventional breeding has not produced highly resistant and commercially acceptable varieties. Success in developing virus-resistant herbaceous crops through genetic engineering led us to investigate this approach for resistance to PPV. Our programme aims to develop a biotechnological approach to PPV control that is effective and shown to be environmentally safe. The programme began with the cloning of the PPV coat protein (CP) gene and the development of a transformation system for plum (Prunus domestica). The CP construct was first tested in Nicotiana benthamiana in which it proved effective in producing transgenic plants with varying levels of CP expression. Some of these plants, particularly low PPV CP expressers, were resistant to PPV, or recovered from initial infection. Based on these results plum was transformed using the Agrobacterium tumefaciens system and both low and high PPV CP-expressing transgenic plum lines were obtained. These were inoculated with PPV by bud grafts in the greenhouse. Line C-5 proved to be highly resistant. It contained multiple copies of the insert, produced low levels of PPV CP mRNA, no detectable CP and the insert appeared to be methylated. These characteristics all suggest that the resistance of the C-5 clone is based on post-transcriptional gene silencing (PTGS). Field tests of C-5 and other transgenic lines in Poland, Romania and Spain have demonstrated that such trees when inoculated by bud-grafts allow a low level of PPV multiplication, from which they rapidly recover. C-5 plants exposed to natural infection for 3 years did not become infected, whereas control trees were infected in the first year. Hybrid plums having the C-5 PPV CP insert inherited from C-5 are virus-resistant, demonstrating the usefulness of C-5 as a parent in developing new PPV-resistant plum varieties. Research is in progress on the biorisks of PPV CP transgenic plants. Gene constructs that either produce no CP or CP that cannot be transmitted by aphids have been developed, tested in N. benthamiana and transferred to plum. Studies have begun on the potential for synergistic interactions between the PPV CP gene and the other common viruses of Prunus spp. In the future we will be participating in investigating the toxicity or/and the allergenicity of transgenic fruit products and, more importantly, transgenic lines will be developed that express transgenes only in vegetative parts of the plant and not in the fruit.
Capsid↗
beta1 integrins regulate keratinocyte adhesion and differentiation by distinct mechanisms.
In keratinocytes, the beta1 integrins mediate adhesion to the extracellular matrix and also regulate the initiation of terminal differentiation. To explore the relationship between these functions, we stably infected primary human epidermal keratinocytes and an undifferentiated squamous cell carcinoma line, SCC4, with retroviruses encoding wild-type and mutant chick beta1 integrin subunits. We examined the ability of adhesion-blocking chick beta1-specific antibodies to inhibit suspension-induced terminal differentiation of primary human keratinocytes and the ability of the chick beta1 subunit to promote spontaneous differentiation of SCC4. A D154A point mutant clustered in focal adhesions but was inactive in the differentiation assays, showing that differentiation regulation required a functional ligand-binding domain. The signal transduced by beta1 integrins in normal keratinocytes was "do not differentiate" (transduced by ligand-occupied receptors) as opposed to "do differentiate" (transduced by unoccupied receptors), and the signal depended on the absolute number, rather than on the proportion, of occupied receptors. Single and double point mutations in cyto-2 and -3, the NPXY motifs, prevented focal adhesion targeting without inhibiting differentiation control. However, deletions in the proximal part of the cytoplasmic domain, affecting cyto-1, abolished the differentiation-regulatory ability of the beta1 subunit. We conclude that distinct signaling pathways are involved in beta1 integrin-mediated adhesion and differentiation control in keratinocytes.
Amino Acid Motifs↗
Histoplasmosis of the small bowel in patients with AIDS.
Two cases of jejunal strictures caused by Histoplasma capsulatum in AIDS patients are presented. Both patients were intravenous drug abusers. One patient, who was being treated for Pneumocystis carnii pneumonia, presented with jejunal perforation and the other presented with lower gastrointestinal bleeding and intestinal obstruction. On exploration, both patients were found to have jejunal strictures; one had intestinal perforation, and the other had intestinal obstruction with ulcers and strictures resulting in gastrointestinal bleeding. In areas where it is endemic, histoplasmosis is rarely disseminated. Dissemination is most commonly seen in immunosuppressed patients. Dissemination and extrapulmonary histoplasmosis is now included in the case definition of AIDS.
AIDS-Related Opportunistic Infections↗
Leprosy chemoprophylaxis in Micronesia.
A programme of chemoprophylaxis was introduced as a component of the leprosy control programme in the Federated States of Micronesia (FSM), beginning in 1996. The entire population of the country was to be screened, and a single dose of 600 mg rifampicin, 400 mg ofloxacin and 100 mg minocycline (ROM) was to be administered to the entire population. Two rounds of screening the entire population were carried out, approximately 1 year apart, and chemoprophylaxis was administered at the time of each screening. Ninety percent of the population were screened at least once, and 55% were screened in both rounds; 87% of the population received at least one dose, and 54% received two doses. In the course of the first round, 322 new cases were detected, whereas only 80 new cases were detected during the second round, of whom only 12 had received chemoprophylaxis in the course of the first round. A third round of screening, confined to a small number of villages in both Chuuk and Pohnpei, in which states leprosy endemicity was high, was carried out approximately 2 years after the second. Only 16 new cases were detected during the third round of screening, whereas 102 new cases had been detected in this same population during the first round of screening, and 32 new cases during the second. Six of the 16 newly detected cases stated that they had been administered chemoprophylaxis at least once; however, this information may not be reliable.
Drug Therapy, Combination↗
Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma.
To identify strategies that enhance tumor-specific immunity in patients with ovarian carcinoma, 22 patients received four to six doses of i.p. recombinant IFN-gamma (rIFN-gamma), 200 microg/m2 on days 1, 3, 5, 8, 10, and 12, and i.p. recombinant interleukin 2 (rIL-2), either 6.0 x 10(5) IU/m2 (group A) or 1.0 x 10(5) IU/m2 (group B), on days 9, 10, and 11. Two patients in group A also received T-cell lines expanded from peritoneal tumor-infiltrating lymphocytes (TILs) obtained after i.p. rIFN-gamma/rIL-2 administration. Toxicity was manageable and included five nonhematological grade 3 or 4 events in 22 patients (23%). A patient had normalization of CA-125 values and a progression-free interval of 18 months, after receiving i.p. rIFN-gamma/rIL-2 without TILs. Another patient who received i.p. rIFN-gamma/rIL-2 plus TILs had stabilization of ascites and intra-abdominal tumors and >50% reduction in serum CA-125 values over 6 months. A third patient who received i.p. rIFN-gamma/rIL-2 had stabilization of intra-abdominal tumors and ascites accompanied by CA-125 values of 50 to 100 units over 6 months. T-cell lines for adoptive immunotherapy were developed for only 3 of 20 patients who were treated with rIFN-gamma/rIL-2. Large numbers of CD3- CD56+ adherent cells were expanded in rIL-2 in the remaining patients, precluding the development of T-cell lines. i.p. rIFN-gamma, either alone or followed by rIL-2, increased proportions of human leukocyte antigen (HLA) class I+ and class II+ tumor cells and increased HLA class I staining intensity on peritoneal carcinoma cells. i.p. rIFN-gamma plus rIL-2 also enhanced cytotoxic activity against Daudi and K562 cells and against allogeneic ovarian tumor cells. Increased cytotoxic activity was associated with an increase in the proportion of CD56+ cells. IFN-gamma and IL-2 transcripts were expressed more frequently after rIFN-gamma and rIL-2 treatment. In addition, the proportions of CD45RA+ (naive lymphocytes) were increased, and CD8+ DR+ lymphocytes were increased relative to CD8+ CD69+ cells, which were decreased. IL-10 concentrations in peritoneal fluids were increased after treatment with rIFN-gamma and the higher rIL-2 dosing (group A) but not in those treated with rIFN-gamma and the lower rIL-2 dosing (group B). These results demonstrated that patients with ovarian carcinoma can tolerate treatment with rIFN-gamma and rIL-2 and that rIFN-gamma alone or rIFN-gamma combined with rIL-2 enhances the expression of HLA class I and class II antigens on ovarian tumor cells, although immunosuppressive cytokines, such as transforming growth factor-beta and IL-10, may persist. Treatment with rIFN-gamma/rIL-2 i.p. did not facilitate the production of TIL-derived T-cell lines ex vivo.
Ascitic Fluid↗
Malingering and symptom magnification: a case report illustrating the limitations of clinical judgement.
Explore the source record for details and available documents.
Chronic Disease↗
Motivations for using vitamin and mineral supplements.
Explore the source record for details and available documents.
Adult↗
Evaluation of a simplified vitamin supplement inventory developed for the Women's Health Initiative.
OBJECTIVE: To evaluate the accuracy of a simplified inventory procedure for assessing nutrient intake from vitamin and mineral supplements. DESIGN: Participants brought their supplements to a clinic. An interviewer conducted the supplement inventory procedure, which consisted of recording data on the type of multiple vitamin and single supplements used. For the multiple vitamins, the interviewer recorded the exact dose for a subset of nutrients (vitamin C, calcium, selenium). For other nutrients, we imputed the dose in multiple vitamins. The dose of all single supplements was recorded. Labels of the supplements were photocopied and we transcribed the exact nutrient label data for the criterion measure. Spearman correlation coefficients were used to assess precision of nutrient intakes from the simplified inventory compared to the criterion measure. SETTING/SUBJECTS: Data are from 104 adult vitamin supplement users in Washington state. RESULTS: Correlation coefficients between nutrient intake estimated from the simplified inventory compared to the criterion measure were high (0.8-1.0) for those nutrients (vitamin C, calcium, selenium) for which the interviewer recorded the exact dose contained in multiple vitamins. However, for nutrients for which imputations were made regarding dose in multiple vitamins, correlation coefficients ranged from good (0.8 for vitamin E) to poor (0.3 for iron). CONCLUSIONS: The simplified inventory is rapid (4-5 min) and practical for large-scale studies. The precision of nutrient estimates using this procedure was variable, although excellent for the subset of nutrients for which the dose was recorded exactly. This study illustrates many of the challenges of collecting high quality supplement data.
Adult↗
Essential drugs for cancer therapy: a World Health Organization consultation.
The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible.
Antineoplastic Agents↗
Touch imprint cytological analysis of sentinel lymph nodes for detecting axillary metastases in patients with breast cancer.
BACKGROUND: Sentinel lymph node biopsy is a procedure that examines the first tumour-draining lymph node. Touch imprint cytology may provide a quick method for intraoperative screening of sentinel lymph nodes for the presence of metastases. METHODS: Touch imprint cytological analysis of sentinel lymph nodes was compared prospectively with the findings obtained on routine paraffin sections. Touch imprint slides from 55 patients with breast cancer were prepared during operation from multiple sections of sentinel lymph nodes, stained with haematoxylin and eosin. A cytopathologist blinded to the histological results interpreted the smears. RESULTS: The concordance between touch imprint and paraffin sections of sentinel lymph nodes was 98 per cent (54 of 55). When touch imprint analysis of sentinel lymph nodes was compared with paraffin sectioning of all lymph nodes from the axillary node dissection, the concordance was 95 per cent (52 of 55). The sensitivity and specificity of sentinel lymph node touch imprints in detecting metastases were 82 and 100 per cent respectively. The positive and negative predictive values were 100 and 93 per cent respectively. CONCLUSION: Touch imprint cytology is potentially useful for the intraoperative evaluation of sentinel lymph nodes in patients with breast cancer.
Axilla↗
A P element has induced intron formation in Drosophila.
We report evidence supporting the hypothesis that some introns could be originated from transposable elements. In the Drosophila montium species subgroup, we recently described a novel example of domestication by the host genome of a P transposable element. The element is a unique truncated P sequence transcribed into a polyadenylated RNA encoding a putative 66-kDa transposition repressor-like protein. Here, we analyze the genomic modifications associated with this transition of a transposable element into a stationary gene that is useful for the host. Study of the transcription modalities of this neogene reveals that the new transcriptional unit harbors a de novo synthesis of a new exon and a new intron upstream of the original P sequence initiation site. The new exon was constructed from the genomic flanking sequence of the P sequence, whereas the first half of the new intron is composed of genomic flanking sequence and the second half is composed of P sequence. This domestication event has involved the capture of a new promoter. An investigation of a large number of species belonging to the melanogaster species group revealed that this P element domestication is restricted to the species of the montium subgroup and that the new exon-intron structure is present in at least three other species. From sequence data, we hypothesize that cryptic acceptor and donor splicing sites present on the P element and flanking sequences have been under selective constraints which have led to the emergence of a new intron.
Animals↗
Vaccination of mice against the leprosy bacillus with skin-test antigens.
Explore the source record for details and available documents.
Aluminum Hydroxide↗
Validity of methods used to assess vitamin and mineral supplement use.
Assessing vitamin and mineral supplement use is important because supplement use per se is an exposure of interest for the risk of several chronic diseases and because supplements contribute a large proportion of total (diet plus supplement) micronutrient intake, another important exposure in epidemiologic research. Unfortunately, little is known about methods for obtaining valid information about supplement use. The authors conducted a validation study in 1996 comparing supplement data collected in a telephone interview and from a self-administered questionnaire with data derived from a detailed, in-person interview and transcription of the labels of supplement bottles (i.e., a gold standard) among adult supplement users in Washington State (n = 104). Spearman correlation coefficients comparing average daily supplemental vitamin and mineral intake from the interview or questionnaire with the gold standard ranged from 0.76 (95% confidence interval 0.66-0.83) for vitamin C to 0.08 (95% confidence interval -0.14 to 0.29) for iron, with a mean of about 0.5. The principal sources of error were inaccurate assumptions about the micronutrient composition of multiple vitamins and respondent confusion regarding the distinction between multiple vitamins and single supplements. These results suggest that commonly used epidemiologic methods of assessing supplement use may incorporate significant amounts of error in estimates of some nutrients.
Adult↗
Ovarian serous borderline tumors with invasive peritoneal implants.
BACKGROUND: The objective of the current study was to update the authors' experience with patients with ovarian serous borderline tumors with invasive peritoneal implants to gain additional insight into the biologic behavior of these tumors and a better understanding of the effect of postoperative treatment. METHODS: Thirty-nine patients with ovarian serous borderline tumors with invasive peritoneal implants were identified through a retrospective review. Major endpoints selected for analysis were surgicopathologic response, time to recurrence, type of recurrence, progression free survival, and overall survival. Univariate and multivariate regression analyses also were performed. RESULTS: Median follow-up time was 111 months. Four of 7 evaluable patients who had second-look surgery (57%) had a response to chemotherapy. Twelve of 39 patients (31%) either developed progressive disease or had a recurrence. The median time from date of diagnosis to recurrence was 24 months. In 10 of these 12 patients with a recurrence, tissue was available; 9 had invasive low grade serous carcinoma and 1 had a recurrent borderline tumor. Macroscopic residual disease was the only factor studied that had a significant effect on survival; patients with no macroscopic residual tumor had a significantly better survival than those with any macroscopic residual tumor (P < 0.01). In univariate regression analysis, macroscopic residual disease and the presence of frankly invasive implants were significant predictors of progression free survival. Platinum-based chemotherapy was associated with a significantly shorter progression-free survival. Only macroscopic residual tumor was a significant predictor of survival. CONCLUSIONS: Greater than 30% of patients with ovarian serous borderline tumors with invasive peritoneal implants will develop progressive or recurrent tumor, most commonly serous carcinoma. The presence of macroscopic residual disease appears to be the major predictor of recurrence and survival. However, in this study, the authors were unable to elucidate the role of postoperative therapy or the criteria for selection of patients for such therapy.
Adult↗
The CXXC Zn binding motifs of the human papillomavirus type 16 E7 oncoprotein are not required for its in vitro transforming activity in rodent cells.
The conserved region 3 (CR3) of the E7 protein of human papillomaviruses contains two CXXC motifs involved in zinc binding and in the homodimerization of the molecule. Studies have suggested that the intact CXXC motifs in the CR3 of HPV16 and HPV18 E7 are required for the in vitro transforming activity of these proteins. CR3 also contains a low affinity pRb binding site and is involved in the disruption of the E2F/Rb1 complex. E7 is structurally and functionally related to Adenovirus E1A protein, which also has two CXXC motifs in CR3. However, the Ad E1A transforming activity appears to be independent of the presence of such domains. In fact, this viral protein exists in vivo as two different forms of 289 and 243 amino acids. The shorter Ad E1A form (Ad E1A243), where both CXXC motifs are deleted by internal splicing, retains its in vitro transforming activity. We have investigated if the HPV16 E7 CR3 can be functionally replaced by the Ad E1A243 CR3, which lacks both CXXC motifs. A chimeric protein (E7/E1A243) containing the CR1 and CR2 of HPV16 E7 fused to the CR3 of Ad E1A 243 was constructed. The E7/E1A243 while not able to homodimerize in the S. cerevisiae two-hybrid system retains several of the properties of the parental proteins, HPV16 E7 and Ad E1A. It associates with the 'pocket' proteins, induces growth in soft agar of NIH3T3 cells and immortalizes rat embryo fibroblasts. These data suggest that the CXXC motifs in CR3 of E7 do not play a direct role in the transforming properties of this viral protein but probably are important for maintaining the correct protein configuration.
3T3 Cells↗
Optimised retroviral infection of human epidermal keratinocytes: long-term expression of transduced integrin gene following grafting on to SCID mice.
Previous attempts to achieve long-term gene expression in retrovirally transduced human epidermal keratinocytes in vivo have been largely unsuccessful. This has been variously attributed to a failure to target epidermal stem cells, suboptimal grafting conditions or inactivation of the retroviral vector. In an attempt to overcome these problems we expressed the chick beta 1 integrin subunit in primary human epidermal keratinocytes, which allowed us to monitor retroviral gene expression on a cell-by-cell basis. We describe optimised methods for selecting high-titre amphotropic packaging cells and for infecting keratinocytes in culture. When transduced cells were grafted into mice, graft survival was comparable in nude and SCID mice, but it was essential to combine the keratinocytes with a dermal substrate. Using these methods the majority of keratinocytes expressed the chick beta 1 integrin subunit for at least 16 weeks after grafting. We conclude that epidermal keratinocytes are attractive recipient cells for gene therapy.
3T3 Cells↗
Experience with lymphatic mapping in breast cancer using isosulfan blue dye.
Sentinel (first tumor-draining) lymph node (SLN) biopsy directed by the blue dye technique may be as accurate as complete axillary lymph node dissection (ALND) in determining whether breast cancer has metastasized to the lymph nodes and may have fewer surgical complications because it is less invasive. Breast cancer patients scheduled for ALND between February and June 1997 who did not have prior axillary surgery, prior radiation therapy, or preoperative chemotherapy were included. Isosulfan blue dye was injected around the primary tumor or the biopsy cavity just before ALND. Operations were performed in a tertiary breast center by two breast surgeons who did not have experience with the technique before this study. The results of blue stained nodes were compared to those of the ALND. Blue-stained nodes were identified in 35 of 40 patients (88%), and the results were concordant with ALND in 33 of 35 (94%), 7 patients were concordant for positive results and 26 for negative results. We identified SLNs in patients whose cancers were either in the medial or lateral halves of the breast. Average time for SLN dissection was 19 +/- 9 minutes, and there were no complications. The diagnostic accuracy of the isosulfan blue dye technique for SLN biopsy, 94%, is high enough to warrant further research. The lack of complications and the short time needed to perform the technique are attractive features. Broader experience with the technique is required to evaluate the reliability and reproducibility of this method.
Adult↗