PubMed Health⌕ Search

Biomedical subjects

A Lichter

Publications and source records attributed to A Lichter.

At least 19 recordsLinked to original sources

Occurrence of ochratoxin A producing fungi in wine and table grapes in Israel.

A 3-year survey was conducted to assay the number of Aspergillus Section Nigri isolates and in vitro ochratoxin A (OTA) production capacity in 10 vineyards in Israel. The survey included field sampling of two wine cultivars, 'Sauvignon Blanc' and 'Cabernet Sauvignon' as well as the table grape cultivar 'Superior'. A total of 2114 isolates were analyzed and of those 161 isolates were shown to produce OTA. The major finding was that Aspergillus carbonarius (336 tested strains) is the most consistent producer of OTA, with approximately 35% of the isolates identified as positive in vitro. In comparison, 3.1% of other isolates from the Aspergillus niger aggregate (of 1432 strains) produced OTA in vitro. In contrast, none of the 346 tested strains with a uniseriate head morphology produced OTA. The incidence of infected berries was very low before veraison, while at harvest, this frequency was twice as high. In general, the composition of black Aspergilli did not differ during berry development. Generally, more OTA-producing isolates were isolated from the surface of table grapes cv. 'Superior' compared to 'Sauvignon Blanc'. None of the samples collected at harvest contained traces of OTA in the juice. This study shows that grapes in Israel are contaminated with ochratoxigenic species which represent a risk of OTA contamination.

Aspergillus↗

Workshop on partial breast irradiation: state of the art and the science, Bethesda, MD, December 8-10, 2002.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments.

Breast Neoplasms↗

The operon for cytokinin biosynthesis of Erwinia herbicola pv. gypsophilae contains two promoters and is plant induced.

The operon for cytokinin biosynthesis in the gall-forming bacterium Erwinia herbicola pv. gypsophilae (Ehg) has been previously shown to reside on an indigenous plasmid (pPATH(Ehg)) that is mandatory for pathogenicity. This operon consists of two genes: the first open reading frame (pre-etz) is of unknown function, whereas the second one (etz) encodes for isopentenyl transferase. Northern hybridization performed with the wild-type strain Ehg824-1 grown in Luria-Bertani broth demonstrated two transcripts of which an etz-specific transcript (1.0 kb) was predominant. Fusion of upstream DNA fragments of both pre-etz and etz to the ice nucleation reporter gene inaZ in pVSP61 showed high ice nucleation activity in both cultures, confirming the presence of two independent promoters. An increase of 1-1.5 orders in transcriptional activity of these promoters was observed following inoculation of gypsophila cuttings. Mutants of Ehg824-1 were generated by insertion of inaZ into pre-etz and etz using the transposon reporter Tn3-Spice. An increase of about two orders in transcriptional activity was recorded with both mutants following inoculation of gypsophila or bean cuttings. A similar induction was also observed when the bacteria were applied to the leaf surface of these plants. Unlike other virulence genes present on the pPATH(Ehg), neither pre-etz nor etz was regulated by the adjacent hrp gene cluster.

Bacterial Outer Membrane Proteins↗

[Evaluation of radiation dose and radiation risk for dental patients].

1. The collective dental radiation dose in Israel in 1998 is 42.86 Sv. 2. The collective dental radiation is responsible for a mortality of about 2.14 people per year in Israel, and a similar number of morbidity from non-lethal cancer. 3. It seems that the quality of the picture in dental radiographs in Israel is not satisfactory, so is the dentists' level of knowledge about it. 4. Exposure to dental radiographs may be reduced by half if measures are taken to ensure the quality of the radiographs and the knowledge of dentists on the subject.

Clinical Competence↗

Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999.

BACKGROUND: Under the auspices of the College of American Pathologists, a multidisciplinary group of clinicians, pathologists, and statisticians considered prognostic and predictive factors in breast cancer and stratified them into categories reflecting the strength of published evidence. MATERIALS AND METHODS: Factors were ranked according to previously established College of American Pathologists categorical rankings: category I, factors proven to be of prognostic import and useful in clinical patient management; category II, factors that had been extensively studied biologically and clinically, but whose import remains to be validated in statistically robust studies; and category III, all other factors not sufficiently studied to demonstrate their prognostic value. Factors in categories I and II were considered with respect to variations in methods of analysis, interpretation of findings, reporting of data, and statistical evaluation. For each factor, detailed recommendations for improvement were made. Recommendations were based on the following aims: (1) increasing uniformity and completeness of pathologic evaluation of tumor specimens, (2) enhancing the quality of data collected about existing prognostic factors, and (3) improving patient care. RESULTS AND CONCLUSIONS: Factors ranked in category I included TNM staging information, histologic grade, histologic type, mitotic figure counts, and hormone receptor status. Category II factors included c-erbB-2 (Her2-neu), proliferation markers, lymphatic and vascular channel invasion, and p53. Factors in category III included DNA ploidy analysis, microvessel density, epidermal growth factor receptor, transforming growth factor-alpha, bcl-2, pS2, and cathepsin D. This report constitutes a detailed outline of the findings and recommendations of the consensus conference group, organized according to structural guidelines as defined.

Breast Neoplasms↗

Control of pigmentation of Ustilago hordei: the effect of pH, thiamine, and involvement of the cAMP cascade.

The intensely pigmented teliospores of Ustilago hordei that are produced on susceptible barley cultivars contain nondiffusible deposits of a melanin-like pigment. Expression of pigmentation differed among haploid sporidial cultures and could be shown to be influenced by culture conditions. Pigmentation of strain 8.2a was black at acidic pH and repressed in medium adjusted to neutral or basic pH, and growth at elevated pH triggered a concomitant accumulation of a diffusible red pigment. Pigment formation by some strains was also determined to be under the control of thiamine and was completely inhibited when thiamine was present at levels above 0. 02 microM. The second messenger, cAMP, transiently repressed pigment formation, whereas the cAMP phosphodiesterase inhibitor isobutryl-3-methyl xanthine completely repressed pigment formation. Like cAMP, the expression of the Galpha subunit gene FIL1 from a multicopy vector resulted in transient inhibition of pigment formation. However, pigment formation was not observed in cells expressing the mutant allele FIL1(Q206R), which ostensibly renders the gene constitutively active. The means by which pigment formation is repressed suggested that numerous genes were involved. Upon examination of a wild-type strain transformed with random cosmid clones of a genomic library, it was estimated that approximately 30 cosmid members per genome equivalent caused repression of the melanin-like pigments, whereas approximately 6 cosmid members induced pigment formation.

1-Methyl-3-isobutylxanthine↗

Fil1, a G-protein alpha-subunit that acts upstream of cAMP and is essential for dimorphic switching in haploid cells of Ustilago hordei.

A constitutive mutation, fil1, that causes filamentous growth in the haplophase of the dimorphic smut fungus Ustilago hordei, was previously shown to be genetically associated with a 50-kb deletion within a 940-kb chromosome. Physiological studies suggested that a gene that functions upstream of adenylyl cyclase was deleted in the mutant. Representational difference analysis of isolated chromosomes was used to obtain deletion-specific DNA probes and corresponding genomic cosmid clones. Complementation analysis identified a cosmid clone and subsequently a 2.1-kb insert that converted transformants of the mutant strain 10.1a(fil1) from the filamentous to the sporidial cell type. A single open reading frame of 354 codons that encodes a putative alpha-subunit of the heterotrimeric G-proteins was identified. Fil1 displayed a high degree of sequence identity to Gpa1 from the basidiomycete Cryptococcus neoformans and CPG-2 from the ascomycete Cryphonectria parasitica. FIL1, when introduced on a self-replicating vector, was found to suppress filamentous growth of starved haploid wild-type strains and restore normal mating response to the fil1 mutant, but did not suppress sexual dimorphism of either strain. Fil1 appears to function analogously to mammalian G alpha proteins, which are coupled to cAMP production via adenylyl cyclase, to regulate dimorphic switching in U. hordei.

Amino Acid Sequence↗

The presence of hrp genes on the pathogenicity-associated plasmid of the tumorigenic bacterium Erwinia herbicola pv. gypsophilae.

The pathogenicity-associated plasmid (pPATH) of Erwinia herbicola pv. gypsophilae (Ehg), which is present only in pathogenic strains, contains a gene cluster encoding indole-3-acetic acid and cytokinin biosynthesis. The transposon-reporter Tn3-Spice was used to generate nonpathogenic mutants on two overlapping cosmids, pLA150 and pLA352, of the pPATH. A cluster of such mutations, which spanned 16 kb, mapped approximately 15 kb from the gene cluster involved in phytohormone biosynthesis. Non-pathogenic mutants also failed to elicit the hypersensitive reaction (HR) on tobacco. Pathogenicity and HR were restored concomitantly to these mutants by in trans complementation with wild-type Ehg DNA. A 3.8-kb HindIII DNA fragment that complemented the hrp mutants was sequenced and six complete and two partial open reading frames (ORFs) were identified. Comparison of the deduced amino acid sequences of the eight ORFs showed striking homology and co-linearity with hrp genes of E. amylovora as well as with other plant and mammalian pathogenic bacterial genes encoding proteins of the type III secretion system. Limited DNA sequencing at various sites on the remaining 11-kb region of pLA352 also showed high identity to Hrp proteins of E. amylovora, E. stewartii, and Pseudomonas syringae. These results suggest that hrp genes are mandatory for gall formation by E. herbicola pv. gypsophilae.

Bacterial Proteins↗

Breast conservation and prolonged chemotherapy for locally advanced breast cancer: the University of Michigan experience.

PURPOSE: To determine whether breast conservation and prolonged neoadjuvant chemotherapy have efficacy in locally advanced breast cancer (LABC), as measured by survival and rate of breast conservation. MATERIALS AND METHODS: Eighty-nine patients with stage III disease were enrolled at the University of Michigan (UM) onto a prospective nonrandomized trial. Patients received nine 21-day cycles of neoadjuvant chemohormonal therapy that consisted of doxorubicin 30 mg/m2 and cyclophosphamide 750 mg/m2 intravenously on day 1, conjugated estrogens 0.625 mg orally twice daily on days 6 to 8, methotrexate 40 mg/m2 and fluorouracil 500 mg/m2 intravenously on day 8, and tamoxifen 10 mg orally twice daily on days 9 to 14. Patients with a negative biopsy received radiation only, while those with residual disease underwent mastectomy and postoperative radiotherapy. Eight more cycles of chemohormonal therapy were administered after local-regional therapy. RESULTS: The clinical response rate to neoadjuvant therapy was 97%, 28% of patients had a complete pathologic response evaluated at biopsy. Five-year overall and disease-free survival probabilities were 54% and 44%, respectively. The median disease-free survival time was 2.4 years. The 5-year actuarial rates of local-regional control with local failure as only first failure were 82% and 78% following radiotherapy, and mastectomy and radiotherapy, respectively (P = .99). CONCLUSION: Prolonged neoadjuvant chemohormonal therapy and biopsy-driven local therapy have efficacy in LABC, with 28% of patients being candidates for breast conservation and a 5-year overall survival rate of 54%.

Antineoplastic Combined Chemotherapy Protocols↗

Kinetic evidence for protein complexes between thioredoxin and NADP-malate dehydrogenase and presence of a thioredoxin binding site at the N-terminus of the enzyme.

The kinetics of activation of NADP-malate dehydrogenase (MDH; EC 1.1.1.82) from soybean and spinach leaves by the chloroplast thioredoxins isolated from the same plants, by the corresponding storage forms of the soybean chloroplast thioredoxins from soybean seeds, and by the bacterial Escherichia coli thioredoxin have been studied. The Hill equation has been applied to evaluate the saturation kinetics. The observed variable thioredoxin saturation characteristics (Vmax 0.37-14.5 mumol NADPH min-1 mg enzyme-1; K0.5 0.15-1.33 microM; Hill coefficient h 0.90-3.04) indicate that the activation of NADP-MDH depends strongly on the individual thioredoxin used. Thus, thioredoxin action is not solely due to simple reductive activation of the NADP-MDH. Specific thioredoxin complex formation between thioredoxin and NADP-MDH must be included into the mechanism of the activation process. To study the regulatory consequences of the specific thioredoxin/NADP-MDH complexes we investigated the saturation kinetics of the substrates NADPH and oxaloacetate in presence of different concentrations of each individual thioredoxin species. The kinetic characteristics of the substrates (S0.5, Vmax, and Hill coefficients h) varied individually in response to the different thioredoxin species substantiating our model of thioredoxin/ NADP-MDH complex formation. Aminopeptidase-K-truncated pea NADP-MDH has been used to demonstrate that the N-terminal 37 amino residues are involved in providing a specific thioredoxin binding site. The fact that the versatile light-dependent regulation of numerous enzyme activities by only two thioredoxin species in chloroplasts cannot be accomplished without the formation of thioredoxin/target enzyme complexes is discussed in detail.

Bacterial Proteins↗

The use of mammography in breast preservation in locally advanced breast cancer.

PURPOSE: As the feasibility of breast preservation in locally advanced breast cancer is currently under evaluation, little information is available correlating mammographic changes to chemotherapy with local outcome. To evaluate the role of mammography in selecting candidates with locally advanced breast cancer for conservative local therapy, we analyzed mammographic changes in the breast to induction chemotherapy and correlated the radiologic appearance with pathologic outcome. METHODS AND MATERIALS: From 1985 through 1993, 91 patients with Stage III breast cancer were enrolled on a multimodality clinical trial using chemohormonal therapy followed by local treatment and maintenance therapy. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate,and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. After nine cycles, surgical biopsies of the breast were performed. Through 1988, clinical examination alone directed the site for postinduction biopsy; for patients treated after 1988, mammography, in addition to physical examination, determined the biopsy location. Local treatment was determined by biopsy result. Patients with a pathologic complete response received radiation only to the breast adn regional nodes, while those with pathologically proven residual disease underwent mastectomy and postoperative radiotherapy. Nine additional cycles of maintenance chemotherapy were administered. RESULTS: Fifty-five of 91 patients (58%) obtained a clinical complete response (CR) to induction chemotherapy. Twenty-eight of the 53 women with a clinical CR had both pre- and postinduction mammograms. Of these 28 women, 9 obtained a pathologic CR and 19 obtained a pathologic partial response (PR). Fifty-five percent of the pathologic complete responders had resolution of mammographic abnormalities on the postinduction mammograms. Sixty-eight percent (13) of the pathologic partial responders had abnormal mammographic findings. The positive predictive value for residual cancer using physical examination was 92%, while the negative predictive value was only 36%. Among patients with a clinical complete response, the positive and negative predictive values for residual cancer using postinduction mammography were 79% and 56%, respectively. Limitations of mammography included uncertain significance of residual microcalcifications and residual masses on postinduction chemotherapy mammograms. CONCLUSIONS: Although mammography improved the accuracy of noninvasive evaluations in patients with a clinical complete response, pathologic assessment was still required to determine appropriate local therapy. More sensitive imaging modalities or modifications of film-screen mammography may improve noninvasive detection of residual disease following induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

IS1327, a new insertion-like element in the pathogenicity-associated plasmid of Erwinia herbicola pv. gypsophilae.

The pathogenicity-associated plasmid (pPATH) of Erwinia herbicola pv. gypsophilae was previously shown to be exclusively present in pathogenic strains and to contain a gene cluster encoding phytohormone biosynthesis. Sequence analysis of the DNA region located downstream from the cytokinin biosynthetic gene (etz) revealed homology to insertion sequences (IS) of the IS6 family. Southern blot analysis performed on plasmid DNA of E. herbicola pv. gypsophilae revealed the presence of six copies of this insertion-like element, which was designated as IS1327. Only pathogenic strains contained IS1327 and restriction fragment length polymorphism was observed among gypsophilae and beet pathovars of E. herbicola. Nonpathogenic deletion derivatives of pPATH contained fewer copies of IS1327, suggesting its presence in the deleted region. One copy of IS1327 (IS1327-R) was located 2.8 kb downstream from the IS element adjacent to the etz (IS1327-L) in a direct repeat.

Amino Acid Sequence↗

Three dimensional conformal radiotherapy for the treatment of prostate cancer: low risk of chronic rectal morbidity observed in a large series of patients.

PURPOSE: Three dimensional conformal radiotherapy (3D CRT) may provide a technique to increase the dose delivered to target tissues while sparing uninvolved normal structures. To evaluate the role of 3D treatment in reducing the treatment toxicity, we analyzed the chronic rectal morbidity observed in a large group of patients undergoing radiotherapy for prostate cancer. METHODS AND MATERIALS: From 1987 through 1992, 721 prostate cancer patients were treated with 3D CRT at the University of Michigan or Providence Hospital. All had axial computed tomography (CT) specifically for RT planning, multiple structures contoured on the axial images, and beam's-eye-view conformal beams edited to provide 3D dose coverage. Using current American Joint Commission (AJCC) staging, 537 patients had T1-T2 tumors, 123 had T3-T4 tumors, and 60 were treated postprostatectomy. Pelvic lymph nodes were treated in 462 patients. Prostate boosts were delivered with four-field axial, six-field axial, or four-field oblique, nonaxial fields. The median dose was 68.40 Gy (range 59.4-80.4). Median follow-up was 20.4 months; 175 were followed more than 3 years. All complications have been graded conservatively using the RTOG system. RESULTS: Using a Cox proportional hazard's model, patient age, T-stage, prescribed dose, pelvic treatment, and boost technique were analyzed. The factor most strongly related to risk of morbidity was dose (p = 0.05); however, the boost technique was also related: the four-field oblique field had the lowest relative risk. Most episodes of rectal morbidity have been mild: 82 Grade 1 or 2. There have been only 14 more serious complications including 12 Grade 3 and 2 Grade 4. The actuarial risk of a Grade 3 or 4 complication is 3% at 3 and 5 years. CONCLUSIONS: A very small proportion of patients treated with 3D CRT had significant rectal morbidity related to RT, supporting the use of conformal treatment planning and dose delivery as a mechanism to minimize complications in the treatment of prostate cancer.

Adenocarcinoma↗

The genes involved in cytokinin biosynthesis in Erwinia herbicola pv. gypsophilae: characterization and role in gall formation.

A locus conferring cytokinin production was previously isolated from the gall-forming bacterium Erwinia herbicola pv. gypsophilae. This locus resided in a cluster with the genes specifying indole-3-acetic acid production on the pathogenicity-associated plasmid pPATH (A. Lichter, S. Manulis, O. Sagee, Y. Gafni, J. Gray, R. Meilen, R. O. Morris, and I. Barash, Mol. Plant Microbe Interact., 8:114-121, 1995). Sequence analysis of this locus indicated the presence of a cytokinin biosynthesis gene (etz) homologous to other described cytokinin biosynthesis genes. A unique open reading frame (pre-etz) encoding 169 amino acids preceded etz and together with etz formed a region with a distinctive low G+C content. Northern (RNA) analysis indicated the presence of an etz-specific transcript of 1 kb and a common transcript for pre-etz and etz of 1.4 kb. The level of the 1-kb transcript was high in the late logarithmic phase and very low in the stationary phase. In contrast, the level of the 1.4-kb transcript was lower than that of the 1-kb transcript in the late logarithmic phase and predominant in the stationary phase. A marker exchange mutant of etz which did not produce cytokinins exhibited a reduction in gall size on Gypsophila cuttings and almost abolished disease symptoms in a whole-plant assay. Complementation of this marker exchange mutant with the intact etz gene on a multicopy plasmid resulted in overproduction of cytokinins and larger plant galls from which small shoots emerged. Insertional mutation in pre-etz resulted in a sharp decrease in both the level of the etz-specific transcript and cytokinin production. A frameshift mutation in pre-etz caused a similar reduction in the cytokinin level. A marker exchange mutation in pre-etz caused a reduction of symptoms but to lower degree than the etz mutation. In the former mutant, cytokinin production and pathogenicity could not be restored by complementation. Furthermore, attempts to complement the etz marker exchange mutant with a plasmid containing an intact etz gene and a frameshift mutation in the pre-etz gene were unsuccessful. These results suggest that the mutations in pre-etz were trans dominant.

Amino Acid Sequence↗

Sensitive and specific detection of Xanthomonas campestris pv. pelargonii with DNA primers and probes identified by random amplified polymorphic DNA analysis.

The random amplified polymorphic DNA method was used to distinguish strains of Xanthomonas campestris pv. pelargonii from 21 other Xanthomonas species and/or pathovars. Among the 42 arbitrarily chosen primers evaluated, 3 were found to reveal diagnostic polymorphisms when purified DNAs from compared strains were amplified by the PCR. The three primers revealed DNA amplification patterns which were conserved among all 53 strains tested of X. campestris pv. pelargonii isolated from various locations worldwide. The distinctive X. compestris pv. pelargonii patterns were clearly different from those obtained with any of 46 other Xanthomonas strains tested. An amplified 1.2-kb DNA fragment, apparently unique to X. campestris pv. pelargonii by these random amplified polymorphic DNA tests, was cloned and evaluated as a diagnostic DNA probe. It hybridized with total DNA from all 53 X. campestris pv. pelargonii strains tested and not with any of the 46 other Xanthomonas strains tested. The DNA sequence of the terminal ends of this 1.2-kb fragment was obtained and used to design a pair of 18-mer oligonucleotide primers specific for X. campestris pv. pelargonii. The custom-synthesized primers amplified the same 1.2-kb DNA fragment from all 53 X. campestris pv. pelargonii strains tested and failed to amplify DNA from any of the 46 other Xanthomonas strains tested. DNA isolated from saprophytes associated with the geranium plant also did not produce amplified DNA with these primers. The sensitivity of the PCR assay using the custom-synthesized primers was between 10 and 50 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Actuarial Analysis↗