Determination of Proliferation Index By MIB-1 Immunostaining in Early Stage Breast Cancer Using Quantitative Image Analysis

Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the stratification into favorable and unfavorable groups. The monoclonal antibody MIB-1 reacts with the same antigen site, not epitope, as recognized by the Ki-67 antibody. Like Ki-67, MIB-1 reacts with cells in the late G₁, S, M and G₂ phases of the cell cycle, but MIB-1 has the advantage of reacting with formalin-fixed, paraffin-embedded material. The authors investigated the feasibility of using image analysis to quantitate the MIB-1 antibody staining (proliferation index [PI]) and predict survival in a series of 230 patients with stage I and stage II breast cancer. In a univariate Cox regression model, larger values of MIB-1 were related to shorter survival times (p < 0.001). Exploratory statistical procedures were used to categorize the patients into good, intermediate, and poor survival groups using the following proliferation indices as cut-points: <5%, 5–11%, and >11 %, respectively. Higher clinical stage was associated with higher MIB-1 values and shorter survival (p = 0.01, and p = 0.003, respectively). Tumor size (p = 0.02) and nodal status (p = 0.05) were also associated with higher values of MIB-1. After adjusting for age, clinical stage, nodal status, and tumor size in a multivariate analysis, MIB-1 retained its prognostic significance (p < 0.0001) when considered as either a continuous or categorical variable. There were no significant associations between MIB-1 determined proliferation index and age (p = 0.54), histologic grade (p = 0.69), nuclear grade (p = 0.06) or the presence of vascular invasion (p =.66). There is a strong statistical relationship between cell proliferative activity, as determined by MIB-1 expression, and survival in early stage breast cancer.     

槲寄生化学成分的研究——Ⅷ.2,3-丁二醇单葡萄糖甙的分离和结构

From the ethanol extract of Viscum coloratum (Kom.) Nakai , a giucoside ofaliphatic diol and three other glucosides were isolated. Based on chemical and spectroscopic analysis,the structures have been elucidated as 2-β-D- glucosyl-3- methylpropanol (Ⅷ), syringin (Ⅸ),eleatheroside E(Ⅹ) and syringenin-4'-O-D-apiosylglucoside (Ⅺ). Ⅷ is a new glucoside of aliphaticdiol and named 3-β-D-glucopyranosyloxy-butanol-2. Three other compounds (Ⅸ～-Ⅺ) were foundfor the first time in this plant.     

An outbreak of pyodermas among neonates caused by ultrasound gel contaminated with methicillin-susceptible Staphylococcus aureus.

OBJECTIVE: To investigate an outbreak of methicillin-susceptible Staphylococcus aureus (MSSA) infections in a neonatal clinic. DESIGN: Prospective chart review, environmental sampling, and genotyping by two independent methods: pulsed-field gel electrophoresis (PFGE) and randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). A case-control study was performed with 31 controls from the same clinic. SETTING: A German 1,350-bed tertiary-care teaching university hospital. RESULTS: There was a significant increase in the incidence of pyodermas with MSSA; 10 neonates in good physical condition with no infection immediately after birth developed pyodermas. A shared spatula and ultrasound gel were the only identified infection sources. The gel contained MSSA and was used for hip joint sonographies in all neonates. PFGE and RAPD-PCR patterns from 6 neonates and from the gel were indistinguishable and thus genetically related clones. The case-control study revealed no significant risk factor with the exception of cesarean section (P=.006). The attack rate by days of hip-joint sonography between April 15 and April 27, 1994, was 11.8% to 40%. CONCLUSIONS: Inappropriate hygienic measures in connection with lubricants during routine ultrasound scanning may lead to nosocomial S. aureus infections of the skin. To our knowledge this source of S. aureus infections has not previously been described.     

Inter- and intrasensory modality matching in children with hand-eye coordination problems: exploring the developmental lag hypothesis

This study set out to explore the suggestion that the problems experienced by 8-year-old children diagnosed as clumsy in the area of hand-eye coordination (HECP) might be attributed to a developmental lag. The performances of this group of HECP children were compared with those of groups of 5-year-old and 8-year-old controls without such deficits, when required to carry out a task involving pointing, without vision, to targets located, visually, visually/proprioceptively, or proprioceptively, the dependent variable being the distance error score from the centre of the target. The performances of the HECP children, when vision or vision/proprioception was used to locate the targets, were shown to be inferior to those of the two control groups of children thereby supporting a visual deficit hypothesis. When the targets had to be located proprioceptively, the performance of the HECP children was shown to be similar to that of the 5-year-olds, while both groups were inferior to the 8-year-olds, thereby supporting a developmental lag hypothesis in proprioceptive terms. However, when the scores for the preferred and non-preferred hands were analysed separately a marked deterioration in the performances of both the 5-year-old controls and the HECP children was observed while the 8Jyear-old controls were unaffected. While this finding supports a developmental lag explanation of the inferior performances of the HECP children, it was necessary to qualify such an explanation when the within-group performances using the preferred and non-preferred hands were compared. Only the HECP children, under the visual/proprioceptive or proprioceptive conditions, showed significant performance differences, in. favour of the preferred hand. This finding was taken as a suggestion that the developmental lag exhibited by the HECP children might have pathological overtones possibly related to the development of the corpus callosum.     

Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery.

In order to obtain the still lacking reference data of individual plasma steroids in the immediate postnatal period needed for the assessment of adrenocortical function in various neonatal maladaptation syndromes, aldosterone (A), corticosterone, deoxycorticosterone (DOC), progesterone (P), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone were simultaneously followed in the same human newborn in a single 250-500 microliters peripheral plasma sample obtained at constant times during the first week of life using a mechanized Sephadex LH-20 multicolumn chromatography and standardized RIAs. Mean concentrations in 12 spontaneously delivered full term newborns of either sex and in paired umbilical (UV) and peripheral maternal (MV) venous plasma are given in the table. Besides significant maternoumbilical gradients in each steroid, DOC, P, 17-OHP, and cortisone, originating predominantly from the fetoplacental unit, disappear rapidly with steadily increasing half-lives. A, corticosterone, and cortisol, however, remain elevated in comparison with later infancy, with the exception of a marked "glucocorticoid dip" in cortisol and corticosterone levels between 2 and 12 h after birth.     

The preparation of leukocyte-poor red blood cells: a comparative study

Thirteen methods of prepararing leukocyte-poor red blood cells were compared for their effectiveness in removing leukocytes. When the starting material was six to ten days old, the residual leukocyte count was three to four times lower than when fresh material was used and no granulocytes could be found. The most effective manual procedure was a single upright sedimentation of six- to ten-day-old saline-diluted red cells. Inverted sedimentation was no more effective in leukocyte depletion than upright sedimentation. Automated cell processors were no more effective than several of the better manual methods. Freezing and deglycerolizing resulted in a ten-fold improvement in leukocyte removal with less red blood cell loss but at higher cost than the nonfreezing methods. The study indicates that unless the minimal leukocyte count of frozen red blood cells is essential, a single upright sedimentation of saline-diluted, six- to ten-day-old red blood cells is currently the most effective procedure for preparing leukocyte-poor red blood cells.     

Immunohistochemically Determined Estrogen and Progesterone Receptor Levels: A Comparison of Three Antibodies with the Ligand-Binding Assay

Abstract: Traditionally, estrogen and progesterone receptor levels have been determined by biochemical ligandbinding assays, but more recently immunohistochemical techniques have become available. They have gained popularity due to their low cost, smaller sample size requirements, and direct visualization capability of reaction location. Several antibody clones are commercially available and antibodies directed against the estrogen receptor (ER) are supplied by Ventana Medical Systems (Tucson, AZ), Abbott Laboratories (Abbott Park, IL), and lmmunotech Westbrook, ME). Antibodies directed against the progesterone receptor (PgR) are supplied by Ventana Medical Systems (Tucson, AZ), lmmunotech (Westbrook, ME), and Becton-DickinsonKelI Analysis Systems (San Jose, CA). Computer-assisted image analysis using the CAS ZOOTM (Becton-DickinsonKIS, San Jose, CA) allows quantitation of immunohistochemically determined receptor levels. Correlation of quantitated immunohistochemical ER levels with values determined by ligand-binding assay revealed the Ventana antibody to most closely predict the ligand-binding results (wk = .667). The Ventana anti-progesterone antibody quantitation most closely correlated with the ligand-binding results (wk = 435) for determination of PgR. Progesterone receptor level as determined by any of the tested methods did not stratify patients into favorable and unfavorable prognostic groups. Estrogen receptor level as determined by the Ventana antibody was the most predictive of patient outcome but this relationship did not reach statistical significance (p = .09). Most discrepancies between the ligand-binding assay and the immunohistochemical assays were associated with one of three factors: (a) low volume of neoplastic cells present due either to small sample size or high stromal content, (b) premenopausal status with circulating endogenous estrogens potentially occupying receptor sites, (c) presence of benign breast epithelium resulting in a false-positive ligand-binding assay.     

Angiogenesis factor in endometrial carcinoma: A new prognostic indicator?

OBJECTIVE: Tumor angiogenesis is believed to be a prognostic indicator associated with tumor growth and metastasis. Studies of angiogenesis in breast, prostate, and lung cancer, as well as melanoma, have shown that neovascularization correlates with the likelihood of metastasis and recurrences. The purpose of this study was to evaluate microvessel density as a prognostic factor in endometrial cancer. METHODS: Between 1980 and 1991 the tumor registry identified 25 patients with a diagnosis of recurrent endometrial cancer. These patients were matched with 25 patients with nonrecurrent disease for age, stage, grade, and treatment. The histologic slides of the 50 patients were reviewed. The paraffin blocks were obtained, and the area of the deepest myometrial invasion was selected for staining. The microvessels within the invasive cancer were highlighted by means of immunocytochemical staining to detect factor VIII - related antigen. Microvessels were counted by two investigators who were blinded to the patients' clinical status. Survival data were analyzed with Kaplan-Meier survival curves. RESULTS: Microvessel count was related to likelihood of recurrence, although this trend did not reach statistical significance. Patients with tumors of low capillary density had a mean survival time of 123 months. Patients with tumors of high capillary density had a mean survival time of 75 months (p = 002). Among patients with recurrent disease, those with a low capillary count survived a mean of 64 months. Patients with recurrent disease with tumors of high capillary density survived a mean of 45 months (p = 0.002). CONCLUSION: Angiogenesis factor correlates with survival in endometrial carcinoma. (Am J Obstet Gynecol 1996;174:1879-84.)