Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma

Ki-67 expression in tumours has been shown to be associated with prognosis in patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples were obtained from 67 patients undergoing surgical resection. None of these patients had been subjected previously to any other form of therapy, such as arterial embolization or chemotherapy. Histologically normal liver tissues from liver resection for metastatic colon cancer were taken as controls (n= 8). Monoclonal antibody against Ki-67 was used for immunostaining and ?ow cytometry was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage of Ki-67-positive cells) of the HCC (26 ± 22%; range 0.1–89%) was signi?cantly higher than that of the normal controls (39 ± 0.8%, P < 0.05). The mean Ki-67 labelling index (19 ± 15%; n= 28) of the tumours with diploid DNA pattern was signi?cantly lower than those with aneuploid DNA pattern (32 ± 25%, n= 39; P= 0.01). Hepatocellular carcinoma patients (n= 47) with Ki-67 index >10% had a signi?cantly lower disease-free and overall survival than those (n= 20) with Ki-67 index ≤10% (P= 0.0009 and P= 0.02, respectively). Multivariate analysis showed that Ki-67 expression and tumour node metastasis stage were two independent prognostic factors for disease-free and overall survival rates. Our results suggest that the expression of Ki-67 is an independent prognostic indicator for patients with HCC after resection and could be of assistance in the decision-making of adjuvant therapy.     

Rapid excretion of gallium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine

A 23 year-old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga-67), which was initially nondiagnostic because of Ga-67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney. To our knowledge the unusual interaction in vivo of DFO with Ga-67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga-67 scanning in this clinical situation, or an alternative isotopic scan, such as indium-labelled white cells, should be considered.     

烟碱型乙酰胆碱受体的表达

作介绍利用ＴＥ６７１细胞株表达乙酰胆碱受体（ＡＣｈＲ）的方法，并用α－ＢｕＴｘ特异性、不可逆地与ＡＣｈＲ结合的特点，观察验证ＴＥ６７１细胞表面表达的ＡＣｈＲ数量与细胞培养时间和细胞培养数量之间的关系。结果表明细胞表面表达的ＡＣｈＲ数量的多少与细胞培养数量和细胞培养时间密切相关。中简要地探讨了影响ＡＣｈＲ表达的几种因素，认为选择适宜的细胞培养时间及培养数量具有重要意义。     

Role of Dopamine in the Plasticity of Glutamic Acid Decarboxylase Messenger RNA in the Rat Frontal Cortex and the Nucleus Accumbens

The modulatory role of dopamine (DA) on the expression of mRNA encoding the large isoform of glutamic acid decarboxylase (GAD67), the biosynthesis enzyme of gamma aminobutyric acid (GABA), was examined in GABA neurons of two structures innervated by DA neurons originating from the ventral tegmental area (VTA): the medial frontal cortex (MFC) and the nucleus accumbens (NAcc). A bilateral electrolytic lesion of VTA was performed in rats to produce a DA denervation of both the MFC and NAcc. The efficacy of VTA lesions was verified by measurement of locomotor activity and by immunohistochemical detection of tyrosine hydroxylase in the mesencephalon. GAD67 mRNA was detected by in situ hybridization histochemistry using a ³⁵S-labelled cDNA probe. Densitometric analysis of GAD67 mRNA hybridization signals revealed in VTA-lesioned rats a significant decrease (-24%) in GAD67 mRNA levels in the prelimbic area of the MFC and no significant effect in the anterior cingulate area or the frontoparietal cortex. Single cell analyses by computer-assisted grain counting showed that the decrease in GAD67 mRNA levels in prelimbic MFC was due to a change in GAD67 mRNA expression in a subpopulation of GABA interneurons located in the deep cortical layers (V-VI). By contrast, in the NAcc of VTA-lesioned rats, GAD67 mRNA levels were significantly increased in the anterior part and in the core but were unchanged in the shell part. These results suggest that in two target structures of VTA DA neurons, GAD67 mRNA expression is, in normal conditions, under a tonic stimulatory and a tonic inhibitory DA control in the MFC and the NAcc respectively. A schematic diagram is proposed for functional interactions between these structures.     

67Ga scan for evaluating response to therapy in malignant lymphoma

⁶⁷Ga scintigrams in a patient with malignant lymphoma before and after chemotherapy are presented. ⁶⁷Ga did not accumulate in the mostly necrotic mass with some viable cells. Negative uptake of ⁶⁷Ga might reflect necrosis of the tumor; however, it is difficult to detect some residual tumor cells. Therefore, negative uptake of ⁶⁷Ga in the mass seen in X-ray CT may not be totally reliable evidence of eradication of viable tumor cells.     

Cardiac and skeletal muscle scintigraphy in dermato- and polymyositis: Clinical implications

To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato-and polymyositis (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate (^99mTc-PYP) and gallium-67 scans showed similar sensitivity, specificity and accuracy in the detection of skeletal muscle involvement when compared with serum enzymes (70%, 100% and 80%, respectively). Compared with the clinical parameters,^99mTc-PYP showed 70% and⁶⁷Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal⁶⁷Ga cardiac uptake was seen in only 15%. Electrocardiography was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both^99mTc-PYP and⁶⁷Ga can be useful in the detection of the active phase of muscle disease. However,^99mTc-PYP seems to be more effective than⁶⁷Ga in the early diagnosis of cardiac involvement.     

Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls, 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%); no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1+ myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.     

The influence of isotopic and nonisotopic carriers on the biodistribution and biokinetics of M3+-citrate complexes

The influence of carrier amounts of Fe, Ga, and Tm on the biodistribution of ⁶⁷Ga-, ⁵⁹Fe-, and ¹⁶⁷Tm-citrate in mice was investigated. Our results suggest that ¹⁶⁷Tm, unlike ⁶⁷Ga and ⁵⁹Fe, is not transported by transferrin in the blood. Of the three radioisotopes tested, ¹⁶⁷Tm had the highest tumor/background ratio (10 h after the injection). The application of Fe carrier led to an enhancement of the elimination of ⁶⁷Ga from the blood and muscles, resulting in a better tumor/background ratio.     

Labeling of monoclonal antibodies with a 67Ga-phenolic aminocarboxylic acid chelate

As a chelating agent for labeling antibodies (Abs) with metallic radionuclides, a propionic acid substituted ethylenediamine N,N-di-[(o-hydroxyphenyl) acetic acid] (P-EDDHA), which tighly complexes ⁶⁷Ga, was synthesized. The ⁶⁷Ga-P-EDDHA chelate was coupled in aqueous solution to IgG at a molar ratio of 1:1 via carbodiimide. The average coupling yield was 15%. A specific activity of 4 mCi/mg IgG could be obtained with commercially supplied ⁶⁷Ga. In vitro stability was evaluated in human serum at 37° C and showed a half-life of about 120 h for the release of ⁶⁷Ga from the labeled Ab during the initial phase of incubation. This in vitro halflife is similar to that measured for ¹¹¹In-DTPA labeled Abs. Because of the high stability of the ⁶⁷Ga-P-EDDHA chelate, the in vivo formation of radioactive labeled transferrin by transchelation, as described for ¹¹¹In-DTPA labeled Abs, should, however, be reduced by this labeling technique.     

Bilateral injections of a selectiveμ-receptor agonist (morphiceptin) into the medial preoptic nucleus produces a marked delay in the initiation of sexual behavior in the male rat

We examined the putative functional role of the medial preoptic nucleus67jx5k30402117p/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">-receptor population in the expression of male copulatory behavior in sexually vigorous Long-Evans rats. In the first experiment, three doses of morphiceptin (10, 500, and 1000 ng) a selective67jx5k30402117p/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0">-receptor agonist injected bilaterally into the medial preoptic nucleus, produced a marked delay in the initiation of male copulatory behavior compared to saline injected controls. These injections significantly lengthened intromission and mount latencies while having no appreciable effect on any other parameter of male copulatory behavior. In a separate experiment, the transient inhibition of the expression of male copulatory behavior was completely abolished following pretreatment of naloxone 20 minutes prior to bilateral injections of morphiceptin (1000 ng) into the medial preoptic nucleus. Collectively, these results suggest that the delay in the initiation of copulation that is commonly observed following peripheral or central injections of opioids is mediated at least in part by67jx5k30402117p/xxlarge956.gif" alt="mgr" align="MIDDLE" BORDER="0"> receptors located within the medial preoptic nucleus.Preliminary reports were given at the Society For Neuroscience, St Louis, and the Conference on Reproductive Behavior, Atlanta, in 1990Winner of 67jx5k30402117p/xxlarge8220.gif" alt="ldquo" align="MIDDLE" BORDER="0">Honorable Mention67jx5k30402117p/xxlarge8221.gif" alt="rdquo" align="MIDDLE" BORDER="0"> in the 1990 National Honor Society in Psychology, (J.P. Guilford Undergraduate Research Award Competition