Relationship of standardized mitotic indices to other prognostic factors in breast cancer

OBJECTIVE: To examine the relationship between mitotic index (MI), calculated from direct microscopic counts, and other prognostic features in breast cancer. DESIGN: Mitotic index was based on direct microscopic observations of mitotic figures in 10 consecutive microscopic fields, and the average cell number was determined by counts of population density in three of those fields. Tumor grade and type were established from tissue sections, whereas metastases were detected in lymph node biopsy, chest roentgenograms, and bone scan. Estrogen receptor (ER) and progesterone receptor (PgR) levels were determined by flow cytometry. RESULTS: The MI for 242 patients ranged from 0.2 to 37.6, with a mean of 5.8 mitoses per 1000 cells. More than 85% of the tumors with an MI below 1.0 were diploid and contained an S-phase fraction of 6.7% or less. In contrast, more than 75% of tumors with an MI above 5.0 were aneuploid with more than 6.7% of cells in S-phase. There was an inverse relationship between ER and PgR status and MI. Eighty percent of tumors with an MI less than 1.0 were both ER and PgR positive while only 25% of those with an MI above 10.0 were both ER and PgR positive. Receptor-positive tumors with high S-phase and MI values had ER and PgR levels below 100 fmol/mg. CONCLUSIONS: Lower MI values calculated from direct cell counts are correlated with negative node status, diploid DNA content, low S-phase fraction, and positive receptor status. Thus, there is a significant relationship between objective MI values and several other factors that predict the probability of breast tumor recurrence.     

Comparison of laparoscopic and minilaparotomy pelvic lymphadenectomy for prostate cancer staging in a community practice

OBJECTIVES: To compare the cost-effectiveness and morbidity of minilaparotomy (MINILAP) and laparoscopic pelvic lymphadenectomy (LAP) in a community practice setting. METHODS: We reviewed our experience with 44 consecutive patients with prostate cancer who had staging pelvic lymphadenectomy from January 1992 through April 1995 in a general health maintenance organization urology practice. Of this group, 22 men had LAP and 22 men had MINILAP. RESULTS: MINILAP and LAP groups were similar in age (mean 67 years). Gleason score (mean 7.2 and 6.8), prostate-specific antigen level (mean 46 and 49 ng/mL), and clinical stage (T1 to T3). Operative time was statistically significantly shorter for MINILAP (mean 1.2 hours) than for LAP (mean 2.9 hours). Complication rate was 9.1% for MINILAP and 31.8% for LAP. Lymph node metastasis was found in 45% of MINILAP patients and in 27% of LAP patients. Mean initial hospital stay was 1.0 day for MINILAP and 1.6 days for LAP. Total hospital stay including hospital readmission for complications was 1.5 days for MINILAP and 2.6 days for LAP. Cost of MINILAP was at least $1900 less than that of LAP because of shorter total hospital stay, shorter operation time, and lower equipment cost. CONCLUSIONS: Compared with LAP, MINILAP was more cost-effective and produced less morbidity. Patient satisfaction with the procedures was similar. MINILAP is an excellent alternative to LAP for prostate cancer staging in general urology practice.     

The dependence of the differentiation potentials of fragments of the marginal zone in early gastrulas of the clawed toad on their morphogenetic movements

Using Xenopus early gastrulae, we studied the dependence of differentiation potential of tissue fragments explanted from different regions of the marginal zone on the conditions promoting or preventing convergent-intercalation movements (CIM). Previously it has been shown that CIM are stimulated by surface tension usually produced in the embryo by folding (involuting) edge of cell layer. In the first experimental series, we prevented involution of tissue explanted from the region above blastopore by enveloping it in ectoderm of more advanced developmental stages. As the result, percentage of axial organs developed in such explants drastically decreased, whereas that of more ventral structures increased. In the second experimental series, an increase in percentage of axial structures that differentiated in tissue fragments explanted from the lateral part of marginal zone was achieved by stimulating involution of its dorsal edge. In the third series, it was shown that percentage of axial structures formed in ventral halves of embryos becomes significantly greater under the conditions that stimulate stretching of the surface and involution of the free edge of explants. A conclusion is drawn that regional specificity of differentiation potential, which is observed within the marginal zone, greatly depends on surface tension in the explants and, therefore, on morphogenetic movements proceeding in them.     

Organizational problems of the production of biological preparations of blood

The trend of the incidence of tick-borne encephalitis makes one pay attention to the production of blood biological preparations. A detailed programme for improving the production process, which is included into the federal and republican programmes, is outlined.     

High-speed rotational atherectomy: six-month serial quantitative coronary angiographic follow-up

One hundred twenty-three patients treated with high-speed rotational atherectomy (HSRA) were restudied 6.9 +/- 1.2 months later. At the follow-up, the number of focal concentric lesions increased from 32.2 percent to 63.0 percent, p<0.01, with decrease of type C lesions from 54.8 percent to 30.8 percent, p<0.05. Comparison of the degree of the net gain (NG) showed more severe baseline lesions in the high-gain group (NG >20 percent) compared with the moderate-gain group (20 percent > NG > 0 percent) and to the loss group (minimal luminal diameter [MLD] 0.8 +/- 0.4 mm vs 1.0 +/ 0.4 mm, p<0.05; and 1.2 +/- 0.5 mm; p<0.01, respectively). Highest initial gain (36.5 percent +/- 26.2 percent vs 24.5 percent +/- 18.1 percent; p<0.015; and 19.0 percent +/- 23.2 percent; p<0.001) as well as lowest late loss (1.8 percent +/- 21.7 percent vs 14.0 percent +/-18.4 percent; p<0.01 and 28.1 percent +/- 25.0 percent; p<0.01) were found in the high NG group. A higher interaction between burr and atheroma resulted in the lowest restenosis rate of 6 percent.     

Developmental regulation of cAMP signaling pathways in thymocyte development

Major developmental transitions in thymocyte differentiation are accompanied by sharp alterations in cAMP metabolism. We have analyzed the cAMP accumulation responses of cell populations representing successive stages of T-cell development, namely: immature TcR- thymocytes from SCID mice, proliferating cortical blasts, small cortical thymocytes, medullary thymocytes and peripheral T cells. We find that all classes of thymocytes exhibit higher cAMP synthesis in response to forskolin than peripheral T cells. In immature TcR- thymocytes, this high capacity is buffered by efficient phosphodiesterase activity, but in CD4+CD8+TcRlow thymocytes, phosphodiesterase activity becomes much less effective. Phosphodiesterase activity then rises again after positive selection. The ability of thymocytes to respond to prostaglandin E is regulated distinctly from their ability to respond to forskolin. Unlike forskolin, PGE1 induces cAMP synthesis to similar levels in all classes of thymocytes, possibly due to partial activation of phosphodiesterase in cortical thymocytes by PGE1. Finally, we report a novel effect of Ca2+/protein kinase C signaling on cAMP accumulation, which occurs selectively in the proliferating cortical blasts.     

The effects of high salt concentrations on the regulation of the substrate specificity of human recombinant deoxycytidine kinase

Deoxycytidine kinase (dCK) is a salvage pathway enzyme with broad substrate specificity that can phosphorylate both pyrimidine and purine deoxynucleosides, including important antiviral and cytostatic agents. The kinetic behaviour of dCK is complex with saturation curves showing negative cooperativity. In this study, we have expressed and affinity purified recombinant dCK, using the pET 9d vector system with a histidine tag-sequence and a thrombin cleavage site fused to the N-terminus of the dCK coding sequence. The His-tagged protein showed essentially the same kinetic properties as the protease cleaved protein and the purified protein isolated from human spleen. However, addition of 0.2-0.4 M NaCl during the dCK reaction caused a stimulation of 2'-deoxycytidine (dCyd), and the antileukemic analog 2-chlorodeoxyadenosine (CldAdo) phosphorylation, but an inhibition of the 2'-deoxyguanosine (dGuo) phosphorylation, both with His-tagged and protease cleaved dCK. The negative cooperativity observed with dCyd was eliminated by the presence of 0.4 M NaCl so that the Hill coefficient changed from 0.6 to 1.4. In contrast, dGuo phosphorylation that initially followed Michaelis-Menten kinetics showed negative cooperativity after addition of 0.4 NaCl. The alterations in kinetic properties were not accompanied by any apparent changes in subunit structure as revealed by gel filtration. The major form of dCK eluted in the position corresponding to a dimer in the presence or absence of salt, but a minor fraction of dCK, eluting in the position of a tetramer, was diminished in the presence of salt. The mechanism for the effects of 0.4 M NaCl on dCK kinetic behaviour is not known but it is most likely due to alterations in the conformation of the active site of the enzyme. The effects described here also may explain some of the discrepancies reported in the literature on the substrate specificity of this complex enzyme.     

Structure of the O-specific polysaccharide of Citrobacter freundii O3a,3b,1c

The following structure of the O-specific polysaccharide of Citrobacter freundii O3a,3b,1c containing D-mannose and D-rhamnose was established using sugar analysis and NMR spectroscopy, including computer-assisted analysis of the 13C NMR spectrum, 2D COSY, H,H-relayed COSY, heteronuclear 13C, 1H correlation (HETCOR), and rotating-frame NOE spectroscopy (ROESY):-->4)-alpha-D-Manp-(1-->3)-beta-D-Rhap-(1-->4) -beta-D-Rhap-(1-->.