Experimental renal papillary necrosis in the rat: The selective vulnerability of medullary structures to injury

Summary Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Although the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability of renal medullary structures to injury by the toxic agent studied.     

Comparative light and electron microscopic studies of cystic and papillary tumors of the peritoneum

Summary Using a cystic lymphangioma of the greater omentum and a benign cystic mesothelioma as examples, the distinguishing characteristics of cystic peritoneal tumors are shown, using light microscopic and ultrastructural findings. A benign papillary mesothelioma is used for comparison. The cellular structures and growth rate of the mesotheliomas are contrasted with the tissue reactions which are typical for irritated serosa. The diffusely growing papillary mesothelioma is a very rare tumor, the cells of which are similar to normal serosa cells, but also show characteristics of other benign or malignant mesothelial tumors and of reactive proliferated mesothelial cells. The diffusely growing benign cystic mesothelioma has only been described in isolated cases and is characterized by cysts grouped in acini with mainly flat, localized cuboidal cell lining. The histochemical properties and cytological findings correspond closely to those of the papillary tumor or normal peritoneal lining cells. In contrast, the cystic lymphangioma probably represents a congenital defect with a slow growth rate. The structure is characterized by a sponge-like arrangement of smooth-walled cysts, in the walls of which smooth muscle cells and lymph follicles are embedded. The endothelium is also flat and ultrastructurally resembles that of lymph vessels.     

Genotoxic effects of gossypol acetic acid on cultured murine erythroleukemia cells

Gossypol acetic acid, a male anti-fertility drug, was evaluated for its effects on cell multiplication, chromosomes, scheduled and unscheduled DNA synthesis, and the surface ultrastructure in cultured murine erythroleukemia cells (clone 6A11A). Gossypol treatments inhibited cell multiplication at 10 and 20 micrograms/ml concentrations and this inhibitory effect increased with elevated dosage and prolonged treatment. Gossypol significantly depressed the mitotic index but did not alter chromosome numbers or increase the frequency of chromosomal structural abnormalities. Cell fraction techniques revealed that gossypol induced a negative effect on cellular DNA synthesis at concentrations as low as 3.3 micrograms/ml after 24 hr of treatment. The number of cells undergoing DNA synthesis decreased with increasing dosages and durations of drug exposure. An unscheduled DNA synthesis assay (UDS) found gossypol to be an active UDS-inducing agent at certain dose levels and treatment times, as measured by increase in net nuclear gain and percentage of UDS cells (ANOVA, Bonferroni test, P less than 0.05). A scanning electron microscope study revealed that 10 micrograms/ml treatment with gossypol caused changes in mouse erythroleukemia cell surface ultrastructure characterized by general balding and the appearance of holes, often after 48 hr of treatment.     

The many faces and mimics of papillary thyroid carcinoma

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto’s thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.     

A study on renal papillary necrosis experimentally produced by the Shwartzman mechanism in rabbits

To produce renal papillary necrosis experimentally by means of the Shwartzman mechanism in rabbits, E. coli endotoxin was injected into the renal pelvis unilaterally through the ureter as a preparative procedure after pretreatment by local administration of alcohol, and the same endotoxin was given again 24 hours later, but intravenously this time via the ear vein, as a provocation. Marked necrosis was produced in the renal papillae, where many intravascular fibrin thrombi were found histologically. Such papillary necrosis was largely prevented by heparin administration, and this lesion was considered to be the univisceral Shwartzman reaction occurring in the renal papillae. The lesion produced in the new experimental system of renal papillary necrosis described here has a good similarity to that of human cases in etiology, pathogenesis and morphology. The present system may therefore be a good model of human renal papillary necrosis, and should be useful for future studies.     

The effects of temperature on the energetics of rat papillary muscle

The mechanical and myothermic responses of left ventricular papillary muscles from adult rats have been examined at 20° and at 27°C. Contraction trains of six isometric or isotonic twitches at 1/6 Hz were used to establish the heat-stress and load-enthalpy relations respectively. Peak isometric stress was slightly higher at 20° than at 27°C (45 vs. 41 mN/mm²) and was inversely related to muscle cross-sectional area. The stressindependent heat component, identified with the activation heat, was 75% greater at the lower temperature. The stress-dependent heat component, identified with the heat of actin-myosin interaction, was unaffected by temperature. In isotonic experiments the external work performance was similar at both temperatures but the heat liberation was significantly enhanced at the lower temperature so that mechanical efficiency (external work/enthalpy) was reduced. Evidence is presented suggesting that the preparations were not O₂-diffusion limited at either temperature. The results are discussed in terms of the known functional anomalies of rat cardiac tissue.     

Studies on subcutaneous fat necrosis of the newborn

Summary Biopsy specimens from the skin and subcutaneous fat tissue of four cases with neonatal subcutaneous fat necrosis were made and investigated by light and electron microscopy at 2, 4, and 6 weeks, and 5 months (Case 2) from the onset of the disease. Three stages of ultrastructural change of fat cells were observed. The evolution of crystal formation in the fat cells was seen and phagocytosis of crystals and fat droplets by macrophages and foreign-body giant cells was also noted. In the light microscope accumulation of calcium concretions in the spaces between and inside the fat cells was found. In the electron microscope we detected foci of highly electrondense granules, which were similar in distribution and structure to calcium salts stained with the von Kossa method. Changes in small and medium size blood vessels were observed.This work was written during a stay supported by Max-Planck-Gesellschaft from Dec. 1. 1973 to March 31. 1975 in the Max-Planck-Institut für Klinische und Physiologische Forschung (W.G. Kerckhoff-Institut), Bad Nauheim, West Germany (Director: Prof. Dr. Wolfgang Schaper)     

肿瘤坏死因子静脉注入对大鼠多器官功能影响的实验观察

虽然肿瘤坏死因子（ＴＮＦ）被认为是感染性休克和多器官功能衰竭（ＭＯＦ）过程中最重要的化学介质之一，但最新资料表明，ＴＮＦ对机体的损伤作用依赖于内毒素和其它因子的存在。本研究旨在观察单独静脉注射ＴＮＦ对大鼠多器官有无损伤作用。采用人重组肿瘤坏死因子（ｒｈＴＮＦα）６×１０５Ｕ／ｋｇ·ｄ持续静脉泵入，分别于２４ｈ，７２ｈ活杀，观察肺系数，血气和肝肾功能，白细胞吞噬发光，血液及组织ＴＮＦ水平，超氧化物歧化酶（ＳＯＤ）活性，丙二醛（ＭＤＡ）含量，血浆内毒素水平及血培养。实验结果显示静脉注射ＴＮＦ单独作用２４ｈ和７２ｈ，各主要器官功能无严重损害，也未诱发内源性感染，白细胞吞噬功能无明显变化，但ＴＮＦ可使机体自由基产生增加。     

The diagnostic significance of periportal hepatic necrosis and inflammation

In this review the several types of cell damage and cell death which may be found in liver biopsy specimens are defined. We describe the different processes which occur at the portal/parenchymal or septal/parenchymal interface, viz. periportal spillover, periportal hepatitis, classic or lymphocytic piecemeal necrosis and biliary piecemeal necrosis. The diagnostic implications of these lesions in relation to the clinicopathological diagnosis and prognosis in various liver diseases are discussed.     

The effects of live Neisseria meningitidis and tumour necrosis factor-alpha on neutrophil oxidative burst and beta2-integrin expression

The effects of human recombinant tumour necrosis factor-alpha (TNF-alpha) on neutrophil (PMNL) oxidative burst and on CD11b/CD18 and CD14 expression after stimulation with pathogenic or nonpathogenic Neisseria meningitidis were studied using chemiluminescence and flow cytometry. PMNL oxidative burst increased more when stimulated with the apathogenic 29E strain than with the pathogenic B strain both when studied by chemiluminescence and by flow cytometry. When TNF-alpha was added to whole blood or PMNL together with bacteria a significant increase in the oxidative burst was seen for the B strain only. When whole blood was preincubated for 30 min with TNF-alpha the increase in oxidative burst was significant for both meningococcal strains. TNF-alpha caused a significant increase in PMNL CD 11b/CD18 expression after 30 min of incubation at 37 degrees C. TNF-alpha added simultaneously with the bacteria induced a significant increase in PMNL CD11b/CD18 in both strains. Incubation with the B strain alone caused a low but significant increase in CD11b/CD18 expression, but the addition of TNF-alpha increased this expression to the same high level as incubation with TNF-alpha alone or the 29E strain alone. Only TNF-alpha and the 29E strain caused significant increases in CD14 expression. In conclusion, human PMNLs react differentially when stimulated with pathogenic and nonpathogenic N. meningitidis and the activating effect of TNF-alpha is variable depending on the bacteria involved.     

An ultrastructural study of the hypertrophied human papillary muscle cell with special emphasis on specific staining patterns,mitochondrial projections and association between mitochondria and SR

Summary Biopsy material of the hypertrophied human papillary muscle has been processed according to various electron microscopical techniques in order to study the mitochondrial ultrastructure and the association between mitochondria and sarcoplasmic reticulum (SR).En bloc staining with a Cu-Pb citrate solution resulted in specifically contrasted mitochondrial and sarcotubular membranes, characterized by numerous, discrete, electron-dense particles. The differences in staining patterns between the perinuclear mitochondria and their subsarcolemmal and interfibrillar counterparts suggest differences in chemical properties and/or metabolic activities. The selectively contrasted mitochondrial particles may represent a conglomorate of extrinisic and intrinisic respiratory enzymes and other membrane-associated proteins, while the majority of the electron-dense particles of the sarcotubular membrane may represent positively stained Ca²⁺-pumps. Ultrastructural findings in the present study strongly indicate that the slender mitochondrial projections represent an initial stage in a process leading to the formation of large and pleomorphic mitochondria. Intimate contact between adjacent mitochondria as well as between mitochondria and SR are documented. In the contact regions some of the specifically contrasted particles of the adjacent membranes had fused with each other. It is suggested that these particles represent membrane-bound transport proteins providing a system for interorganelle exchanges of metabolites and/or ions.     

Apaf-1在甲状腺乳头状癌中的表达及意义

目的:探讨凋亡蛋白酶活化因子1(Apaf-1)在甲状腺乳头状癌(PTC)中的m RNA与蛋白表达及其与细胞增殖的关系。方法:分别采用real-time PCR、Western blot及免疫组化法检测并比较甲状腺乳头状癌和癌旁组织中Apaf-1的m RNA及蛋白表达情况,并分析其表达水平与PTC临床病理学特征的关系;通过下调CGTHW-3细胞中Apaf-1表达量,验证Apaf-1对细胞增殖的影响。结果:在PTC组织中,Apaf-1的m RNA和蛋白表达量均显著低于癌旁组织(P 0. 05);下调Apaf-1表达增强了CGTHW-3细胞的增殖活性(P 0. 05)。结论:Apaf-1在PTC中低表达,抑制其表达可增强CGTHW-3细胞的增殖能力。Apaf-1在甲状腺乳头状癌中可能发挥抑癌作用。     

The stiffness of parallel elastic elements in rat papillary muscle

Summary The dynamic stress-strain relationship of the parallel elastic element (PE) in rat papillary muscle has been investigated.This relationship cannot be correctly estimated by means of the classical diagram: muscle length-stable passive tension of the whole muscle. A new experimental approach has been developed by which the elastic properties of PE may be measured under dynamic conditions.After isometric stabilization of the muscle at a series of preloads, tension changes following quick release were measured. The tension-length relationships measured under these conditions were used to evaluate the elastic behaviour of the parallel elements.The results obtained show that the stiffness of PE is higher than expected and that its maximum elongation never exceeds 10% of the respectiveL _o value at all preload levels explored.Preliminary communication at: International Congress of Physiological Sciences, Munich, July 1971. This study was partially supported by a grant from the Consiglio Nazionale delle Ricerche (CNR, Rome, Italy).     

Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma

Aims: To date, only limited information is available on the prognostic significance of the presence and extent of histological tumour necrosis with regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification. Thus, the aim of this study was to evaluate the prognostic impact of these pathological features on the clinical outcome in papillary subtypes. Methods and results: The influence of histological tumour necrosis on the clinical outcome in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the presence of histological tumour necrosis was an independent negative prognostic factor for disease‐free survival (P = 0.039), and a greater extent of necrosis (>20%) was significantly associated with both poor disease‐free and overall survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2, neither the presence nor extent of histological tumour necrosis was a statistically significant negative prognostic factor. Conclusion: Our findings suggest that the presence and extent of histological tumour necrosis are independent prognosticators in papillary RCC subtype 1, but not in papillary subtype 2. Thus, previously reported conflicting data regarding the prognostic impact of tumour necrosis in papillary RCC might be explained, in part, by heterogeneous subtypes.     

Efficient preparation of plant chromosomes for high-resolution scanning electron microscopy

A highly reproducible technique to prepare plant chromosomes for high-resolution field emission scanning electron microscopy is presented. The procedure allows the production of relatively high numbers of chromosome spreads that can be viewed at high resolution, showing structural details below 10 nm. This preparation technique is not restricted to metaphase chromosomes, but also allows the observation of plant chromosomes during all stages of the cell cycle.     

Ultrastructural observations on cell necrosis during formation of the neural tube in mouse embryos

Summary Spontaneous cell death in the developing brain of 8.5–9 day old mouse embryos has been investigated with the electron microscope. Before closure of the neural tube, areas of cell death are found at the neuro-somatic junction. After closure of the neural tube degenerating cells are found in the dorsal midline of the prospective diencephalon. Ultrastructurally, cell degeneration is marked by chromatin condensation, increase in electron density of the structures in the cytoplasm and, in later stages, by a marked pycnosis of the dying cell. After fragmentation, the necrotic material as well as entire pycnotic cells are phagocytized and digested by cells of the neuroepithelium. An invasion of macrophages has not been observed. The significance of cell necrosis is discussed in relation to the normal formation of the neural tube and to the occurrence of certain induced malformations (exencephalies).     

A renal cell carcinoma with components of both chromophobe and papillary carcinoma

We report a case of a morphologically unusual renal cell carcinoma with features of both chromophobe and papillary carcinoma. Immunohistochemical analysis of high molecular weight cytokeratins (HMWCK), cytokeratin 7 (CK7), cytokeratin 19 (CK19), c-Kit, and α-methylacyl-CoA racemase (AMACR) demonstrated differential profiles for the two components of the tumor, consistent with the respective patterns commonly observed for pure chromophobe and papillary renal cell carcinomas. Specifically, the chromophobe tumor cells expressed CK7 and c-Kit weakly, while HMWCK, CK19, and AMACR were not detectable. In contrast, the papillary tumor cells expressed uniformly HMWCK, CK7, and c-Kit and focally CK19 and AMACR. Fluorescence in situ hybridization analysis of nuclei isolated from paraffin-embedded tumor tissue detected monosomy 1, disomy 7, and monosomy 17, a common and characteristic finding in chromophobe carcinomas, in a majority of, but not all tumor cells, whereas a population characterized by disomy 1, trisomy 7, and trisomy 17, a frequent finding in papillary carcinoma, was not identifiable. Electron microscopic analysis revealed numerous characteristic small cytoplasmic vesicles in the chromophobe areas, which were absent in the papillary component. This case illustrates the rare coexistence of two distinct and admixed histologic types of renal cell carcinoma.