The morphofunctional characteristics of proteins of nucleolar organizers in uterine smooth muscle tumors

The authors have shown the activity of argyrophylic nucleolar organizer region proteins (Ag-NOR-proteins) in the uterine leiomyomas of varying histological structure and determined their relationship to the growth rate, size, and site of a node and endometrial pathology. The investigation indicat yomas with significant sclerosis, 4.32 +/- 0.1 in simple leiomyomas, and 6.2 +/- 0.2 in cell leiomyomas (r = 0.58). In menopause, myomas with significant sclerosis and hyalinosis were characterized with a small number of Ag-NOR (1.44 +/- 0.04). Thus, the organizers numbered 12.1 +/- 0.5 and 21.7 +/- 1.0 in high- and low-grade sarcomas, respectively, which may be used in the differential diagnosis of cellular, bizarre, mitotically active leiomyomas and leiomyosarcomas.     

Molecular pathogenesis of malignant glial tumors

Malignant glial tumors are the most aggressive and difficult to treat neoplasms arising in the brain. More than 22,000 people in the United States are diagnosed with a malignant glioma annually, and most will die within the first two years from diagnosis. Traditionally, gliomas have been categorized based solely on tumor histological features. However, expression studies have found that molecular signatures can be used to categorize these tumors into subclasses that more effectively predict patient outcome. The heterogeneity between tumors as well as within individual tumors makes understanding the molecular aspects of tumorigenesis extremely important. Several genetically engineered mouse models (GEMMs) of glioma have been developed that recapitulate the molecular alterations observed in the human disease. GEMMs of glioma have allowed researchers to more closely study the role of cancer stem cells (CSC) in gliomagenesis as well as the relevance of signaling within the CSC microenvironment. Knowledge of the underlying molecular signatures of malignant glial tumors coupled with the existence of a variety of human disease-relevant GEMMs of this tumor type provide researchers and clinicians with valuable resources for the discovery of new drug targets.     

Value of counting positive PHH3 cells in the diagnosis of uterine smooth muscle tumors

The diagnosis of uterine smooth muscle tumors including leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), bizarre (atypical) leiomyoma (BLM), mitotically active leiomyoma (MAL) and leiomyoma (LM) depends on a combination of microscopic features, such as mitoses, cytologic atypia, and coagulative tumor cell necrosis. However, a small number of these tumors still pose difficult diagnostic challenges. The assessment of accurate mitotic figures (MF) is one of the major parameters in the proper classification of uterine smooth muscle tumors. This assessment can be hampered by the presence of increased number of apoptotic bodies or pyknotic nuclei, which frequently mimic mitoses. Phospho-histone H3 (PHH3) is a recently described immunomarker specific for cells undergoing mitoses. In our study, we collected 132 cases of uterine smooth muscle tumors, including 26 LMSs, 16 STUMPs, 30 BLMs, 30 MALs and 30 LMs. We used mitosis specific marker PHH3 to count mitotic indexes (MI) of uterine smooth muscle tumors and compared with the mitotic indexes of hematoxylin and eosin (H&E). There is a positive correlation with the number of mitotic figures in H&E-stained sections and PHH3-stained sections (r=0.944, P<0.05). The ratio of PHH3-MI to H&E-MI has no statistically significant difference in each group except for LMs (P>0.05). The counting value of PHH3 in LMSs have significantly higher than STUMPs, BLMs, MALs and LMs (P<0.001) and the counting value of PHH3 is 1.5±0.5 times of the number of mitotic indexes in H&E. To conclude, our results show that counting PHH3 is a useful index in the diagnosis of uterine smooth muscle tumors and it can provide a more accurate index instead of the time-honored mitotic figure counts at a certain ratio.     

Ultrastructural observations on smooth muscle tumors

The ultrastructure of a series of primary and metastatic smooth muscle tumors is reviewed. Myofilaments and other smooth muscle features were present in all primary leiomyosarcomas of the soft tissues and uterus. They were also present but were less plentiful in most of the metastatic leiomyosarcomas. Electron microscopy is therefore a useful method to establish the diagnosis of a suspected leiomyosarcoma. Stromal tumors of the gastro-intestinal tract may require correlated immunocytochemical and ultrastructural studies for their identification: 9 of the 50 cases examined were positive with immunostaining for S-100 protein, and 16 tumors with epithelioid transformation did not show evidence of smooth muscle differentiation by electron microscopy.     

P16免疫染色可以提高子宫平滑肌肿瘤的组织学分类

子宫平滑肌肿瘤根据核分裂像、细胞学异型性和凝固性肿瘤细胞坏死可分为平滑肌瘤和平滑肌肉瘤。平滑肌瘤和平滑肌肉瘤是不同的肿瘤，不属于一个生物学谱系。然而，恶性潜能未定的子宫平滑肌肿瘤（STUMP）因缺乏临床经验而不能明确归人平滑肌瘤或平滑肌肉瘤。作者研究了p16在各种子宫平滑肌肿瘤（平滑肌肉瘤15例、平滑肌瘤22例、STUMP8例和10例正常子宫肌层）中的表达，结果显示12／15例平滑肌肉瘤强烈而弥漫性表达p16，     

Ionic currents in the uterine smooth muscle.

1. Short segments of isolated longitudinal myometrium from the pregnant rate uterus have been studied in a double sucrose-gap voltage-clamp arrangement. The clamped segment averaged 65 mum times 240 mum times 100 mum, has an average total capacitance of 0-14 muF, and may contain 50-200 individual myometrial cells. 2. A significant resistance exists in series with the membrane, and limits theprecision of the quantitative information. However, it is argued that some qualitative and some comparative information is useful. 3. In Krebs-bicarbonate solution, depolarizing steps produced initial transient inward currents followed by delayed outward currents. 4. When [Na+]o was reduced by 50%, the equilibrium potential Ea shifted by an average of -17-6 mV, the maximum inward current was reduced to 0-5, the time to peak of the early current was delayed by 1-1 msec, and the maximum chord conductances for the early(Ga) and late (GK) currents remained unchanged as compared with those in normal [Na+]o. 5. When [Ca2+] was reduced to 25% of normal, Ea shifted by an average of -20-3 mV, the maximum inward current was reduced to 0-5, the time to peak was delayed 3-1 msec, and Ga was significantly reduced, while GK was unaffected. 6. The early current, and its tail when repolarization was imposed, reversed direction from inward to outward when [Na+]o was reduced from 143 mM to zero, with [Ca2+]o remaining constant at 1-9 mM. 7. From the observations in 4, 5 and 6, it was concluded that Na+ is the main charge carrier for the early current, and that Ca2+ is important in regulating Ga. 8. The late current is outwards when [K+]o equals 5-9 mM, but inwards in some voltage range when [K+]o was elevated to 120 or 148 mM. K+ is the main charge carrier for the late current. 9. The equilibrium potential for the late current, EK, is about 15 mV more negative than the natural resting potential. 10. Prolonged holding of the preparations at voltages that differ significantly from the natural resting potential tends to shift EK in a way consistent with passive changes in [K+]i by the holding current. 11. The steady-state inactivation of the early current, h, is unusual. Inward current is macimum around the resting potential, and declines with both hyperpolarizing and depolarizing changes. Half-inactivation occurred with about 9 mV depolarization and 15 mV hyperpolarization. 12. The instantaneous current-voltage relations of both early and late currents are linear. The chord conductances Ga and GKare similar in form to those in other tissues.     

Ionic fluxes in rat uterine smooth muscle.

1. The K+, Na+ and Cl-fluxes from the oestrogen-stimulated rat uterine smooth muscle were measured using radioactive tracers. 2. The cellular compartment contained a concentration of K+ of 173-6 mM which exchanged at a rate of 5-9 x 10(-12) mol.cm-2.sec-1. 3. Cl- exchanged at a rate of 6-9 x 10(-12) mol.cm-2.sec-1 from a cellular compartment having a concentration of 39-3 mM. 4. The methods used for the evaluation of Na+ movements over-estimate both influx and efflux values. If an average value of flux of 9-2 x 10(-12) mol.cm-2.sec-1 is considered we obtain PNa+/PK+ ratios of 2-4 (-42 mV) or 1-3 (-57-6 mV), which are too high and do not correspond to electrophysiological evidence. 5. The relative permeabilities PCl-/PK+ in the case of a membrane potential of -42-0 mV could be 0-8, or 1-3 in the case of a membrane potential of -57-6 mV. 6. Both conductances GK+ and GCl- seem to play an important role in determining membrane conductance.     

Excitation-contraction coupling in voltage clamped uterine smooth muscle

1. The relationship between ionic currents and contraction has been investigated in uterine strips of pregnant rat by means of a double sucrose gap apparatus combined with an optical method which permits the measurement of the contraction of the small muscular bundle where potential and current are recorded.2. Effects of duration, size and frequency of imposed potentials upon contraction have been studied. The uterine muscle shows summation and tetanus phenomena. Tension elicited by depolarizing pulses of different durations and amplitudes can be considered as made of two components.3. The first component of the contraction evoked by short depolarizing steps (about 50 ms) depends on the slow inward current. This contraction is abolished by manganese and lanthanum ions and by compound D 600. The amplitude of the tension can be related to the external calcium concentration and consequently to the calcium influx. The slow inward current is supposed to release a part of the bound calcium without excluding, however, a direct activation of myofibrils.4. The second component of the contraction is observed in manganese containing solution with depolarizations longer than 200 ms and without inward current. Such a component of tension suggests the possibility of release of calcium from intracellular stores which could be located in the sarcoplasmic membrane of the uterine smooth muscle.     

Phase-plane analysis of action potentials in uterine smooth muscle

Summary Action potentials were recorded by micro-electrode from narrow strips of pregnant rat uterus in vitro. The phase-plane display (V vsdV/dt) of selected action potentials was analysed by the method of Jenerick (1964) to yield the ionic current. From this membrane current data, various parameters of the action potential were calculated. In comparison to skeletal muscle action potentials, the ionic currents were 30–100 times smaller in the uterus action potential. Epinephrine hyperpolarized the resting potentials and suppressed spontaneous activity, but did not cause any significant changes in the stimulated action potential. The after-potential may have been affected by epinephrine, preventing repetitive firing, but the data were inconclusive. The phase-plane analysis results were similar to the results of the double sucrose gap voltage clamp method on the same tissue (Kao and McCullough, 1975).A preliminary report of this work has been published (Specht and Kao, 1973)     

Characteristics of histamine tachyphylaxis in rat uterine smooth muscle

OBJECTIVE AND DESIGN: To study both the desensitisation induced by short-term exposure to histamine and the mechanism responsible in the isolated rat uterus. MATERIAL: Precontracted isolated uterus (37 mM KCl) from oestrogenised Wistar rats were used. TREATMENT: Repetitive responses to histamine (10(-6), 10(-5), 10(-4), 10(-3) M), dimaprit and clonidine (10(-4) M) were tested at 15, 30, 45 and 105 min., with their modifications by (5 mg/kg, 24 h before sacrifice) reserpine, 10(-7) M propranolol, 10(-8) M atropine, and 10(-6) M indomethacin. Dose-response curves for adrenaline were carried out as standard protocol. METHODS: In vitro techniques (de Jalon's solution, 31 degrees C, carbogen, isotonic registration, resting tension 1 g). Levels of cAMP were studied in response to histamine, adrenaline and isoproterenol by radioassay. RESULTS: Repeated histamine produced a rapid loss of inhibitory uterine response depending on the number of exposures and increase in concentration. The tachyphylaxis phenomenon is not modified by the different pretreatments used. Dimaprit, but not clonidine or adrenaline, produced tachyphylaxis. The second exposition to 10(-3) M histamine produced a 38.8% reduction in cAMP production. CONCLUSION: Histamine appears to induce homologous and probably cAMP-dependent desensitisation of H2-receptors.     

食管间质瘤与平滑肌肿瘤对照性研究

目的 探讨食管间质瘤与平滑肌肿瘤临床病理、免疫组织化学及分子生物学特点。方法 24例食管间叶源性肿瘤用CD117、CD34等一组抗体重新进行分类,部分病例同时测定c-kit基因11外显子序列。结果 此组肿瘤分别为间质瘤3例（交界性1例、恶性2例）,年龄71、56、60岁,均为男性,瘤体直径4、8、14cm,源于固有肌层。瘤细胞梭形,上皮样多角形及印戒样,呈交叉束状、栅栏状及弥漫片状排列,免疫表型为CD117、CD34弥漫强阳性。平滑肌瘤20例,年龄30－60岁,平均41.6岁,男性12例,女性8例,15例源于固有肌层,直径0.8-10.5cm（平均4.5cm),5例源于黏膜肌层,直径为0.2-1.0cm(平均0.6cm)。平滑肌肉瘤1例,男性,61例,瘤体直径5cm,源于黏膜肌层。平滑肌（肉）瘤胞质丰富,嗜伊红,交叉束状排列,免疫表型为平滑肌肌动蛋白、肌特异性肌动蛋白、结蛋白弥漫强阳性。恶性间质瘤有c-kit基因11外显子的突变,平滑肌瘤无突变。结论 食管间叶源性肿瘤仍以平滑肌瘤多见,可发生与胃肠道间质瘤相同形态与免疫表型的间质瘤,典型平滑肌肉瘤极为罕见,食管间质瘤与平滑肌瘤具有不同的临床病理学及分子生物学特征。     

h-Caldesmon as a specific marker for smooth muscle tumors. Comparison with other smooth muscle markers in bone tumors

Caldesmon is a protein widely distributed in smooth and non-smooth muscle cells and is thought to regulate cellular contraction. Its isoform, high-molecular-weight caldesmon (h-CD), was demonstrated to be specific for smooth muscle cells and smooth muscle tumors of the soft tissue and to never be expressed in myofibroblasts. We performed an immunohistochemical study to examine h-CD expression in the following bone tumors: conventional and non-conventional osteosarcoma, 13; malignant fibrous histiocytoma of bone, 5; giant cell tumors of bone, 5; chondroblastoma, 3; metastatic leiomyosarcoma, 2; and rhabdomyosarcoma, 1. Frequent immunoreactivity for muscle actin (alpha-smooth muscle actin or muscle-specific actin) was seen in 11 of 13 osteosarcomas and all other tumors, whereas h-CD was expressed intensely only in 2 leiomyosarcomas. h-CD is considered a specific and useful marker to distinguish smooth muscle tumor from bone tumors with myoid differentiation.     

KI-67、P53、BCL-2在子宫平滑肌肿瘤中的表达及临床意义

目的探讨KI-67、P53、BCL-2与子宫平滑肌肿瘤的关系及其临床意义。方法采用免疫组化方法检测38例子宫平滑肌瘤、36例具恶性潜能的平滑肌瘤(STUMP)和33例子宫平滑肌肉瘤中KI-67、P53、BCL-2的表达。结果①KI-67、P53在子宫肉瘤中的表达强于子宫平滑肌瘤。②BCL-2在子宫肉瘤中的表达弱于子宫平滑肌瘤。结论LMS患者BCL-2表达越强,其生存期越长。K I-67、P53、BCL-2有可能成为区别子宫平滑肌肉瘤与子宫平滑肌瘤及判断子宫平滑肌肉瘤预后的指标。