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Paenibacillus sp.Y412MC10 was one of a number of organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. The isolate was initially classified as a Geobacillus sp. Y412MC10 based on its isolation conditions and similarity to other organisms isolated from hot springs at Yellowstone National Park. Comparison of 16 S rRNA sequences within the Bacillales indicated that Geobacillus sp.Y412MC10 clustered with Paenibacillus species, and the organism was most closely related to Paenibacillus lautus. Lucigen Corp. prepared genomic DNA and the genome was sequenced, assembled, and annotated by the DOE Joint Genome Institute. The genome sequence was deposited at the NCBI in October 2009 (NC_013406). The genome of Paenibacillus sp. Y412MC10 consists of one circular chromosome of 7,121,665 bp with an average G+C content of 51.2%. Comparison to other Paenibacillus species shows the organism lacks nitrogen fixation, antibiotic production and social interaction genes reported in other paenibacilli. The Y412MC10 genome shows a high level of synteny and homology to the draft sequence of Paenibacillus sp. HGF5, an organism from the Human Microbiome Project (HMP) Reference Genomes. This, combined with genomic CAZyme analysis, suggests an intestinal, rather than environmental origin for Y412MC10.

The evaluation of decisions in treating endometrial cancer according to levels of evidence and grades for recommendation is gaining importance. This can help to evaluate results of studies and publications for guidelines and standards in treating endometrial cancer. - Concerning endometrial cancer there are some publications with a high level of evidence especially in early stages whereas data of treating progressive and advanced disease with a high level of evidence is lacking. - There are some studies with an acceptable level of evidence evaluating radiation and surgical treatment in stages I and II. In stages III and IV further data concerning evaluation of hormonal treatment and chemotherapy is pending.

Purpose: Breast cancer (BC) is the most frequent female carcinoma and the major cause of death in women aged 35--50 years. The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years. As a consequence, the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing. At present, hormone replacement therapy (HRT) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms (PMS) experienced by these patients., Patients and Methods: In a retrospective study (total n = 185 BC patients, 64 with and 121 without HRT), the effect of HRT during or after adjuvant therapy [chemotherapy and/ or (anti-) hormonotherapy] has been investigated. The surveillance period was up to 60 months. Evaluated were HRT effects on (1) PMS measured by a comprehensive life quality questionnaire, (2) bone mineral density (BMD) measured by osteodensitometry and (3) morbidity as well as mortality rates., Results: Both groups did not differ with regard to tumor stage, lymph node involvement, metastasis, grading, and steroid hormone receptor status. A reduction in PMS was significant in women taking HRT (p < 0.001), especially in the subgroup of women < or =50 years (p < 0.0001). For both age groups, the median reduction in BMD (z-score) was less in women receiving HRT (< or =50 years: without HRT -1.99 vs. with HRT -0.95, p < 0.05; >50 years: without HRT -2.29 vs. with HRT -1.19, p < 0.01). There were no statistically significant differences regarding morbidity and mortality (p = 0.29)., Conclusion: In this study of BC patients, the use of HRT shows positive effects on PMS and BMD. There was no significant influence on morbidity or mortality. However, a reevaluation of HRT in the routine management of BC patients should await the results of prospective randomized trials., (Copyright 2001 S. Karger AG, Basel)

Unlabelled: PURPOSE/METHODS/PATIENTS: This work retrospectively analysed 252 synovectomies performed on 153 patients from 1958 to 1995 at the Balgrist University Orthopaedics Clinic, and evaluated the short-term and long-term benefits of open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis., Results: Rheumatoid arthritis (n = 182) was by far the most common of the 21 different diagnoses involved, and the metacarpo-phalangeal joint (n = 101) was by far the most frequently operated of the 7 different joint types in question. In the short tenn (n = 97), after a mean of 5.5 months, open synovectomy of a metacarpo-phalangeal joint in rheumatoid arthritis patients provided a benefit in terms of mobility in 85% of cases and in terms of joint swelling and pain in 93% of cases. Among one-third of the originally operated cases (n = 38), long-term benefit, i.e. after a mean of 6.9 years, was obtained in 89% of cases with regard to joint mobility, 87% with regard to swelling and 97% with regard to pain relief. Two-thirds of the joints presented normal mobility and swelling, and three-quarters were pain-free., Conclusions: The metacarpo-phalangeal joint is very important for maintaining the independence of a patient (gripping). Open synovectomy of the metacarpo-phalangeal joint in rheumatoid arthritis patients is an effective therapeutic procedure with little morbidity and very good long-term benefit in the management of metacarpo-phalangeal pain, swelling and stiffness refractory to conservative therapy.

Ovarian cancer arises mostly from the ovarian surface epithelium. The aim of our study was to compare the effects of cytokines in ovarian surface epithelial (OSE) cells and in ovarian carcinoma cells. Proliferation and expression of surface antigens (CA-125 and classes I and II antigens of the major histocompatibility complex [MHC]) were measured in OSE cells obtained from 7 different patients and 7 ovarian carcinoma cell lines. Proliferation of OSE cells remained unaffected by interferon (IFN)-alpha or IFN-gamma, whereas interleukin-1 (IL-1) and tumor necrosis factor (TNF) increased cell growth. Proliferation of ovarian carcinoma cells was reduced by both types of IFN as well as TNF but was not affected by IL-1. Expression of the tumor marker CA-125 was increased by IFN-gamma in ovarian carcinoma cells but not by any other treatment. None of the cytokines affected CA-125 surface expression in OSE cells. Expression of MHC-I was augmented in OSE and in carcinoma cells by both IFNs but not by the other cytokines. Both types of cell were negative for MHC-II, but IFN-gamma induced its expression in both OSE and carcinoma cells. Significant concentrations of the cytokines evaluated here have been measured in blood and follicular fluid by several authors. The different actions of these cytokines in OSE and carcinoma cells could therefore be important in understanding the role of such molecules in the regulation of physiological and pathological processes in the ovary, such as ovulation or malignant proliferation.

In 250 patients with node-negative breast cancer and no systemic adjuvant therapy the impact on the prognosis of the variables age, histological tumour type, tumour size, histological grade, receptor status and localisation of the tumour within the breast, was studied. Patients were followed over a mean period of 60 (range 7-164) months. In a subset of 124 cases additional examination of the growth fraction rate, detected by immunohistochemical determination of antibody Ki-67 and semiquantitative measurement of the stained tumour cell nuclei was performed. In 43 cases, measurement of S-phase fraction by flow cytometry was also performed. By univariate analysis, the histological tumour type (ductal/non-ductal), histological grade and growth fraction rate (< = 20%/> 20% tumour cell nuclei stained by antibody Ki-67) were found to exert a significant influence on distant disease-free and overall survival. Cox' multivariate regression exhibited histological tumour type and growth fraction rate to be independent predictors of distant disease-free and overall survival. Additionally, age was found to be an independent variable of distant disease-free survival. Measurement of growth fraction rate by immunohistochemical detection of Ki-67 antigen is a fairly simple and easily applicable procedure. It should be discussed whether a growth fraction rate of more than 20% could be an indication for adjuvant chemotherapy in patients with node-negative breast cancer.

The occurrence of the p 53 gene mutation in breast carcinoma tumour cells, leads to the accumulation of mutant p 53 protein types, whose consequence is the loss of the negative regulation normally exercised by the p 53 gene, which is considered to act as a tumour suppressor. It is possible to demonstrate the presence of mutant p 53 protein types in tumour cell nuclei by applying immunohistochemical procedures to paraffin sections (Clon DO 1, Dianova). We tested 482 primary breast carcinomas for the presence of these proteins, and positive immunohistochemical findings for mutant p 53 proteins were recorded in 21.6% of the cases. In another 14.3% of these breast carcinomas, less than 10% of the tumour cells exhibited positive staining. In the other 64.1% of cases, the immunohistochemical findings for p 53 proteins were entirely negative. Independent of the immunohistochemical staining results, we performed a retrospective analysis of the disease course of this group of primary breast carcinomas: it emerged, that p-53-positive breast carcinomas had a significantly less favourable prognosis as compared to primary tumours, which were negative or weakly positive for this protein group. The accumulation of p 53 proteins in tumour cell nuclei is correlated with negative oestrogen- and progesterone-receptor status, as well as with the degree of proliferation exhibited by the breast carcinoma. Such accumulation is, in contrast, unaffected by the tumour stage, its histological grading, menopausal status, and the overexpression of c-erb B2.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: Are newer histologic investigations helpful in the evaluation of the prognosis of vulvar carcinoma?, Methods: 147 primary squamous cell carcinomas of the vulva were examined for overall- and disease-free survival (mean observation 59.6 months)., Results: A significance in prognosis was found for FIGO-stage, a new-created histologic grade, p53- and vimentin-expression and amount of T-lymphocytes in tumoral stroma. Unfavourable prognosis was detected for tumors with elevated growth fraction, high proliferating cell-compartment (S + G2 + M) and increased cytokeratin-8-expression., Conclusions: These investigations are able to describe the malignant potential of a vulvar carcinoma and should therefore influence the decision for a modified radical therapy.

We determined the growth fraction in 549 primary breast carcinomas using monoclonal antibody Ki-67. With respect to the course of disease, significant differences emerged for the whole collective as well as among the node-positive tumors. We paid special attention to the node-negative (N0) carcinomas in the group, the aim being to differentiate a prognostically unfavorable subgroup in this otherwise favorable collective. Owing to the comparative rarity of clinical events, our findings for such tumors failed to attain statistical significance; however, a strong clinical trend indicating an adverse prognosis for both overall and disease-free survival emerged for tumors exhibiting a high growth fraction. One-quarter of these patients had received adjuvant treatment. In the group exhibiting high levels of Ki-67 reactivity, significantly less favorable findings with respect to overall survival were observed among the untreated patients. The present results seem to confirm previous indications that antibody Ki-67 is of value in assessing the prognosis of N0 breast cancer.

In a prospective study conducted since 1983, the hormone-receptor status of primary breast carcinomas was investigated using immunohistochemical (ER-ICA, PgR-ICA) and biochemical (DCC) methods. The degree of immunohistochemical staining was evaluated according to the immunoreactive score (IRS) devised by Remmele and Stegner [Frauenarzt 28, 41-43 (1987)]. The findings obtained using the biochemical radioactive-ligand-binding assay (cutoff level, 20 fmol/mg) and those obtained using qualitative immunohistochemical methods were in agreement in 72.5% (ER-ICA) and 72.2% (PgR-ICA) of cases. For the 789 cases of primary breast carcinoma examined, postoperative data were available for a mean follow-up period of 48 months. Using the statistical procedure of Kaplan-Meyer to analyze the probability of disease-free and overall survival, it emerged that ER-ICA- and PgR-ICA-positive breast carcinomas exhibited the most favorable course of disease. Breast carcinomas with negative immunohistochemical findings for both types of receptor were found to have a significantly less favorable disease course. Semiquantitative evaluations of the staining results using the IRS failed to yield significant differences among the 12 IRS groups. Neither the percentage of positive tumor cells nor the immunohistochemical staining intensity proved to be prognostically useful parameters for predicting the course of disease. In comparison to the established biochemical method for the demonstration of hormone receptors, however, the immunohistochemical procedure was found to be superior with respect to prognostic meaningfulness, particularly in the group with conflicting biochemical and immunohistochemical findings with respect to hormone-receptor status. Using Cox analysis, the prognostic usefulness of the immunohistochemical test was compared with that of certain established prognosis parameters (pT, pN, grading, Ki-67), from which it became apparent that PgR-ICA has the greatest prognostic value, with the most lasting influence on the course of disease. The results of the present study demonstrate that, with respect to the prognostic value of its findings, the immunohistochemical test for hormone receptors is superior to the biochemical procedure.

Between March 1989 and December 1992, a total of 85 pelvic exenterations were performed in the Department of Gynaecology and Obstetrics of the University of Mainz. To assess the accuracy of preoperative Magnetic Resonance Imaging (MRI) and Computer Tomography (CT) with regard to tumour localisation and spread, the results of 28 MRI and 14 CT examinations were compared with the postoperative histological findings. For this widely varying patient group that had undergone a broad range of previous treatments, MRI produced an accurate forecast in 56% of cases (CT, 36%). In 33% of the patients tested, the diagnosis based on MRI was partially correct (CT, 43%), whereas the MRI results fundamentally disagreed with the actual findings in 11% of cases (CT, 21%). We conclude that both MRI and CT are of great value in the planning of operations and for informing patients about their condition; however, in individual cases, an intraoperative quick-section diagnosis is necessary to provide details of tumour spread. If the extent of tumour spread is uncertain, the results of CT and/or MRI should not deter the surgeon from the radicality of the planned operative intervention.

Toxicosis was induced in pregnant Holstein-Friesian heifers by giving polybrominated biphenyls a in gelatin capsules at the rate of 25 g/day. Initially, this dosage was approximately 67 mg/kg of body weight. Clinical signs were anorexia, excessive lacrimation and salivation, diarrhea, emaciation, dehydration, depression, and abortion. Fever was not evident during the experiment. Values for serum glutamic-oxalacetic transaminase, lactic dehydrogenase, blood urea nitrogen, and bilirubin were increased. Changes in packed cell volume, hemoglobin content, total erythrocyte and leukocyte counts, and differential leukocyte counts were minimal and reflected dehydration and secondary infection. The principal urine changes were decreased specific gravity and moderate proteinuria. Gross necropsy findings included dehydration; subcutaneous emphysema and hemorrhage; atrophy of the thymus; fetal death with concomitant necrosis of cotyledons; kidneys that were enlarged, pale tan to gray; thickened wall of the gallbladder; inspissated bile; edema of abomasal folds; mucoid enteritis; linear hemorrhage and edema of the rectal mucosa; and secondary pneumonia. Microscopic changes were most marked in the kidneys, gallbladder, and eyelid. In the kidney, the principal changes were extreme dilatation of collecting ducts and convoluted tubules, with epithelial degenerative changes of cloudy swelling, hydropic degeneration, and separation from the basement membrane. Common changes in the gallbladder were moderate to marked hyperplasia and cystic dilatation of the mucous glands in the lamina propria. The changes in the eyelids were characterized by hyperkeratosis, with accumulations of keratin in hair follicles of the epidermis and squamous metaplasia with keratin cysts in the tarsal glands. Clinical signs and lesions of toxicosis did not develop in heifers given the polybrominated biphenyls at the rate of 0.25 mg and 250 mg/day for 60 days. Initially these rates were approximately 0.00065 mg/kg and 0.65 mg/kg of body weight, respectively.

The toxicity of a commercial blend of polybrominated biphenyls was determined in 24 pregnant Holstein heifers that were allotted randomly to one of four experimental groups given 0, .25, 250, or 25,000 mg/day of fire-Master BP-6. The polybrominated biphenyls were mixed with finely ground corn and given by bolus for 60 days or until the animal became moribund. Average body weight of heifers at onset of experiment was 381 kg. No clinical signs of toxicosis were evident in heifers fed 0, .25 or 250 mg/day. Toxicosis was induced in heifers fed 25,000 mg/day resulting in reduced dry matter intake, body weight, heart rate, and respiration rate. Clinical signs were anorexia, emaciation, dehydration, excessive lacrimation and salivation, diarrhea, depression, and abortion or fetal death. All heifers fed 25,000 mg/day became moribund within 33 to 66 days.

The toxicity of a commercial preparation of polybrominated biphenyl was determined in 24 pregnant Holstein heifers that were alloted randomly to one of four experimental groups given 0 (I), .25 (II), 250 (III), and 25,000 (IV) mg per day of fireMaster BP-6 for 60 days or until the animals became moribund. Clinicopathologic determinations were on day -1 prior to dosing, days 15, 30 and 60 during dosing, and following dosing on days 80, 110, 150, and 190 from start of dosing. In addition, samples were collected from moribund heifers of Group IV immediately prior to necropsy. Toxicity was not evident in heifers in Groups I, II, or III. Toxicity was induced in heifers in Group IV. Glutamic-oxaloacetic transaminase of serum was increased and calcium decreased as early as day 15 whereas significant increases in lactate dehydrogenase, urea nitrogen, and bilirubin, and decreases in albumin were not observed until day 30 in heifers of Group IV. Analysis of urine from moribund heifers of Group IV revealed moderate proteinuria and decreased specific gravity. Evaluation of clinicopathologic data has suggested that the polybrominated biphenyls fed were renal toxins with no clear evidence of hepatotoxicity.