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PubMedDate not supplied

Recent advances in the molecular biology, diagnosis and novel therapies for various small blue cell tumors.

Small blue cell tumors are a group of tumors that share a common histologic characteristic with H&E staining. This makes differentiation from one another difficult as they all appear small, blue and round. Even though they all appear the same, they are vastly different from each other. Several different techniques have been developed to help further delineate and classify these tumors which include: small cell lung cancer (SCLC); non-Hodgkin's lymphoma (NHL); Ewing's sarcoma; rhabdomyosarcoma; Merkel carcinoma; neuroblastoma; carcinoid tumors; and intra-abdominal desmpolastic small round cell tumor. Using immunoperoxidase staining, reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization techniques, these tumors have been successfully differentiated from one another. This separation makes staging and treatment of these tumors more effective, as not all of these tumors respond to the same modality of treatment. The following review summarizes some of the recent findings in the various small blue cell tumors and with the potential of novel therapies.

Carcinoid Tumor↗
PubMed1984

Genetic obesity and the muscle satellite cell.

The nuclear content of skeletal muscles from lean and obese (ob/ob) male mice was investigated. Four lean and four ob/ob mice were examined at 2, 3, 5, 8, and 16 weeks of age. Differences in body weight between the two phenotypes were significant after 5 weeks of age. For all ages in the soleus and after 3 weeks of age in the gastrocnemius, muscle wet weight and length were less in ob/ob mice than in lean mice. Age did not influence the incidence of myonuclei in fiber cross sections for either muscle. Compared to lean mice the incidence of myonuclei per fiber cross section was significantly lower for ob/ob mice in the soleus muscle but not in the gastrocnemius muscle. The incidence of satellite cells in fiber cross sections and the percentage of nuclei within the basal lamina that were satellite cell nuclei decreased as age increased. Muscle fibers of ob/ob mice contained fewer myonuclei either because of shorter muscle length (gastrocnemius), or because of the combined effect of shorter muscle length and fewer myonuclei per unit length (soleus). The lower apparent number of myonuclei in the muscles of ob/ob mice was associated with a lower apparent number of satellite cells.

Age Factors↗
PubMed1988

Tissue plasminogen activator in cultured human trabecular meshwork cells. Predominance of enzyme over plasminogen activator inhibitor.

Maintenance of patency of the trabecular meshwork, the major outflow channel of the anterior chamber of the eye, is necessary to prevent an excessive rise in intraocular pressure. Obstruction of flow due to clot formation results in severe glaucoma and damage to the optic nerve. We have found that human trabecular meshwork cells which have been passaged in tissue culture synthesize large amounts of tissue plasminogen activator (t-PA), based on functional, immunologic and molecular weight analysis. Trabecular cells express substantially more t-PA activity than vascular endothelium which produces t-PA for clot dissolution in the systemic circulation. Vascular cells produce excess t-PA inhibitor while trabecular cells make comparatively little. Trabecular meshwork cells are the first normal cell type reported in which the balance between t-PA and inhibitor is weighted towards the activator, indicating that fibrinolysis may be more important than clotting in the anterior chamber of the eye.

Cells, Cultured↗
PubMed1994

Comparisons between in vitro glial cell adherence and internalization of non-encapsulated and encapsulated strains of Cryptococcus neoformans.

The adherence of non-encapsulated and encapsulated strains of Cryptococcus neoformans to rat glial cells in culture was compared. Like the encapsulated strain, the adherence of the unencapsulated strain was affected by the yeast culture age and growth temperature. Yeasts grown to late stationary phase at 37 degrees C were the most adherent. Neither encapsulated nor non-encapsulated strains adhered to glial monolayers when the experiments were conducted at 5 degrees C, indicating that metabolically active mammalian cells were required for yeast adherence. Additionally, the non-encapsulated strain was consistently three times more adherent than the encapsulated strain, suggesting that the non-encapsulated strain either had more adhesins or more adhesins were exposed. Electron microscope studies indicated that both strains were internalized by glial cells, an event previously not reported for this mammalian cell type. The same carbohydrates (N-acetyl-D-glucosamine, sucrose and inositol) that inhibited adherence of the encapsulated strain the most, also inhibited adherence of the non-encapsulated strain, again indicating similar adhesin mechanisms. Both encapsulated and non-encapsulated strains were made non-adherent by treatment with pronase, papain, trypsin and amylase. Immobilized amylase appeared to remove an adhesin fragment that bound to glial cells and inhibited the adherence of intact cryptococci.

Amylases↗
PubMed1990

An enzymatic method for the isolation of mouse Leydig cells.

Mouse Leydig cells were obtained by dispersion of testes of adult animals (aged 6-15 months) with a neutral protease from B. polymxa (dispase; EC 3.4.24.4). The crude Leydig cell suspension was purified by centrifugation on a discontinuous Percoll gradient using a special centrifugation procedure similar to elutriation. The crude cell suspension obtained from 50 testes could be processed in one run. The combination of these two methods yielded 320000 +/- 53000 Leydig cells/testis (n = 554 testes). The purity of the Leydig cell fraction was greater than or equal to 95% (nucleated cells) based on morphological and histochemical (staining for naphthyl esterase) identification. The purified Leydig cells showed an excellent ultrastructural appearance. More than 98% excluded trypan blue. In the presence of NADPH, testosterone biosynthesis was increased only 1.15 +/- 0.1-fold yielding a "quality factor" of 34.8. Maximal hCG doses induced 10(6) purified Leydig cells to produce 5 nmol testosterone/hr. (40-fold stimulation in comparison to basal values). The Leydig cells showed 43100 +/- 2500 LH/hCG receptors and an association constant of Ka = 1.95 x 10(9) M-1. Due to the reproducibility of the method, to the yield as well as to the morphological and functional state of the purified Leydig cells at least 25% of laboratory animals could be saved.

Animals↗
PubMed1993

Plasma cell tumors with calcified amyloid deposition mistaken for chondrosarcoma.

PURPOSE: To report cases of plasmacytoma with a radiologic appearance simulating that of chondrosarcoma. MATERIALS AND METHODS: The authors describe four cases of plasma cell tumors with scattered foci of calcification within their matrix, causing them to resemble chondrosarcoma radiographically. Histologic examination was performed in three of these cases. RESULTS: Biopsy specimens demonstrated that the calcification in these tumors was contained in areas of amyloid deposition. Although amyloid formation in association with plasma cell dyscrasias is well known, sufficient calcification within the amyloid to become radiographically identifiable has only rarely been reported. CONCLUSION: Calcification in amyloid produced by plasma cell tumors may at times simulate the appearance of chondrosarcoma.

Amyloid↗
PubMed2000

Shape instability of a biomembrane driven by a local softening of the underlying actin cortex.

We present a theory showing that local shape instabilities of composite biological membranes, consisting of a lipid bilayer and an underlying actin cortex, can be triggered by a local softening of the membrane-associated cytoskeleton. A membrane containing such cortical defects can form blisters or invaginations, depending on external conditions. The theoretical predictions agree with observations provided by two sets of experiments: (i) microscopic observations of shape changes of giant vesicles with underlying shells of a thin actin network show the formation of local blisters and (ii) micropipet aspiration experiments of Dictyostelium discoideum cells in which we observed the formation of blisters in the aspirated cell part. In the latter experiments, the existence of a hole in the underlying cortex is confirmed by observation of the entrance of cell organelles into the blister. Our model may also be applied to the formation of lobopodia, fast-growing cell protrusions that play an important role in the locomotion and spreading of biological cells.

Actins↗
PubMed2004

Cytokine response to infection with Bacillus anthracis spores.

Bacillus anthracis, the etiological agent of anthrax, is a gram-positive, spore-forming bacterium. The inhalational form of anthrax is the most severe and is associated with rapid progression of the disease and the outcome is frequently fatal. Transfer from the respiratory epithelium to regional lymph nodes appears to be an essential early step in the establishment of infection. This transfer is believed to occur by means of carriage within alveolar macrophages following phagocytosis. Therefore, the ability of B. anthracis to transit through the host macrophage or dendritic cell appears to be an early and critical step in B. anthracis pathogenesis. In this work, we examined the cytokine responses to spore infection in mouse primary peritoneal macrophages, in primary human dendritic cells, and during a spore aerosol infection model utilizing the susceptible A/J mouse strain. We demonstrated that both mouse peritoneal macrophages and human dendritic cells exhibited significant intracellular bactericidal activity during the first hours following uptake, providing the necessary time to mount a cytokine response prior to cell lysis. Strong tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) responses were seen in mouse peritoneal macrophages. In addition to TNF-alpha and IL-6, human dendritic cells produced the cytokines IL-1beta, IL-8, and IL-12. A mixture of Th1 and Th2 cytokines were detected in sera obtained from infected animals. In this study, we provide further evidence of an acute cytokine response when cells in culture and mice are infected with B. anthracis spores.

Animals↗
PubMed1985

Muscle growth and satellite cell proliferative activity in obese (OB/OB) mice.

Muscle growth of male obese (ob/ob) and lean mice at 2, 3, 5 and 8 wk were analyzed on the basis of weights of gastrocnemius, plantaris and soleus muscles from each hind leg. The carcasses (prepared by removing skin, viscera, head, feet and tail) were analyzed for fat content so that the effect of phenotype on the relationship between muscle weight and fat-free carcass weight could be assessed. For each age group the obese mice had less muscle relative to fat-free carcass weight than lean mice, with the difference being significant at 3 wk (P less than .05) and 8 wk (P less than .025). The proliferative activity of muscle satellite cells in 2- and 3-wk-old obese and lean mice was measured on isolated muscle fibers by autoradiography. Muscle fiber diameter and number of nuclei/unit length were unaffected by phenotype, but the proportion of muscle nuclei showing proliferative activity was lower (P less than .01) in obese than in lean mice at 2 wk (1.05 vs 1.93%, respectively) and 3 wk of age (.23 vs .59%, respectively). These results are consistent with the suggestion that muscle growth is limited by satellite-cell proliferative activity, although direct evidence for a cause and effect relationship is not provided.

Adipose Tissue↗
PubMed1980

Ultrastructure of the Herbst corpuscle from beak skin of the pigeon.

In serial sections of the lamellar sensory Herbst corpuscle from beak skin of the domestic pigeon the authors followed the change in the ultrastructural picture in sections led at different levels of the corpuscle. In the proximal part of the corpuscle the inner core is formed by only a small number of broad lamellae whose number subsequently increases so that in the middle of the length there are much more lamellae and they are quite narrow. This situation is probably given by the fact that the lamellae of the inner core gradually "unwind" from the plasma of Schwann cells in distal direction. In order to judge the ultrastructure of sensory corpuscles it is necessary to have serial sections through the whole corpuscle or at least its greater part. In cross sections of the corpuscles it is visible that as a rule projections of Schwann cells reaching up to the axon are lying between the lamellar systems, forming in this way two interlamellar spaces. However, in some sections there are only collagen fibrils in one of the spaces. Ir reminds of the cleft in Pacinian corpuscles. The authors are therefore of the opinion that this phenomenon is caused by a proximodistal shift in the arrangement of Schwann cells of both sides in non-Lamellirostres. This space probably represents the boundary between the lamellar systems of neighbouring Schwann cells of one side. The study further confirmed the incidence of large dense core vesicles in the plasma and projections of Schwann cells. Their diameter ranges between 150...200 nm. The character of these vesciles, which also correspond to Merkel granules, may be explained by ultrahistochemical examination. Oblique sections through the lamellae of Schwann cells could imitate the incidence of sympathetic nerve fibres between the lamellae of th inner core or in neighbourhood of the axon, as stated by Santini. Finally, in one section at the very beginning of the corpuscle, the authors observed in close neighbourhood of the central axon a formation whose structure resembled a vegetative nerve fibre. However, its existence was not found in further sections. Evaluation will be possible only after gathering more material.

Animals↗
PubMed1985

Urokinase binding to bovine corneal endothelial cells.

Previously, we showed that the clotting factor thrombin binds to bovine corneal endothelial cells forming a covalent complex with a protein released by these cells into the culture media. We report that the plasminogen activator, urokinase, an enzyme involved in dissolution of blood clots, binds specifically to bovine corneal endothelial cells. [125I]-urokinase is rapidly bound by corneal endothelial cells. The serine active site of urokinase is required for binding since [125I]-urokinase inactivated with diisoprophylfluorophosphate does not bind to the cells. Pre-incubation of corneal cells with unlabeled urokinase for 20 hr results in increased release of binding sites for [125I]-urokinase into the culture media and at least a 3.5-fold increase in binding by the cells. [125I]-urokinase forms a 73 300 dalton sodium dodecyl sulfate complex with a corneal endothelial cell protein. Although thrombin competes with urokinase for binding to corneal endothelial cells, urokinase has at least a 10-fold higher affinity for binding to the cells. Furthermore, these cells make a plasminogen activator identical in molecular weight to urokinase. Thus, under physiological conditions, urokinase rather than thrombin binds to corneal endothelial cells. Binding may serve to regulate endogenous urokinase activity in the anterior chamber of the eye by limiting its extracellular proteolytic activity.

Animals↗
PubMed2002

Developmental potential of hematopoietic and neural stem cells: unique or all the same?

Like many other animals, mammals develop from fertilized oocytes - the ultimate stem cells. As embryogenesis proceeds, most cells lose developmental potential and eventually become restricted to a specific cell lineage. The result is the formation of a complete and structured mature organism with complex organs composed of a great variety of mature, mostly mitotically quiescent effector cells. However, along the way, some exceptional cells, known as somatic stem cells (SSCs) are set aside and maintain a high proliferation and tissue-specific differentiation potential. SSCs, in contrast to embryonic stem (ES) cells, which are able to give rise to all cell types of the body, have been regarded as being more limited in their differentiation potential in the sense that they were thought to be committed exclusively to their tissue of origin. However, recent studies have demonstrated that somatic stem cells from a given tissue can also contribute to heterologous tissues and thus show a broad nontissue restricted differentiation potential. The question arises: how plastic are somatic stem cells? To provide a tentative answer, we describe and review here recent investigations into the developmental potentials of two somatic stem cell types, namely hematopoietic and neural stem cells.

Animals↗
PubMed1992

The interaction of Cryptococcus neoformans with primary rat lung cell cultures.

Conditions under which Cryptococcus neoformans adhered to and was internalized by primary lung epithelial cell cultures were studied. Adherence was affected by the yeast culture age, glucose concentration and growth temperature. Formalin or heat treatment did not affect yeast adherence. Trypsin treatment, however, inhibited adherence.

Animals↗