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Biomedical subjects

S Sell

Publications and source records attributed to S Sell.

At least 19 recordsLinked to original sources
PubMed1995

Multiple superinfections fail to activate defective human immunodeficiency virus-1 (HIV-1) infection of rabbits.

Superinfection of human immunodeficiency virus (HIV)-1-infected rabbits with Treponema pallidum, Mycobacterium avium, herpes simplex, Candida albicans, Mycoplama incognitus, and malignant catarrhal fever virus, as well as irradiation or cortisone treatment, fails to activate production of infectious virus. For up to 6 months after infection of rabbits with HIV-infected cells or free virus, there are neither clinical symptoms nor positive laboratory tests for detection of HIV. However, after superinfection with other agents, HIV sequences may be transiently found in peripheral blood mononuclear cells by polymerase chain reaction (PCR), and multiple antibodies to HIV antigens may be detected by Western blotting. Both the PCR positivity and Western blot reactivity become negative with time after superinfection. Other than delayed healing of the skin lesions produced by T. pallidum and vaccinia in HIV-infected rabbits, there is no evidence of any immune abnormality. After death, gag sequences are detectable in the splenocytes of essentially every HIV-infected rabbit, and the splenocytes of eight of 25 infected rabbits responded by proliferation to HIV peptides. In addition, gag sequences are detectable in rabbits that are injected with lymphoid cells from HIV-infected rabbits. However, after multiple testing of both peripheral blood of living rabbits and organs of rabbits that died or were killed (spleen, brain, lymph nodes, liver, and gastrointestinal tract), no viable virus has ever been convincingly detected by in vitro cultivation with indicator cells. In contrast to some other published reports, these data indicate that HIV-1 infection of rabbits does not provide a model for AIDS pathogenesis therapy or prevention, but it may be useful as a model to study the relative resistance of a small fraction of the human population to development of AIDS after HIV infection.

Animals↗
PubMed1995

Characterization of a murine p53ser246 mutant equivalent to the human p53ser249 associated with hepatocellular carcinoma and aflatoxin exposure.

A mutation in the tumor suppressor p53 gene resulting in an Arg-->Ser substitution in position 249 is found frequently in human hepatocellular carcinomas associated with hepatitis B infection and with aflatoxin exposure. To determine the significance of this mutation in an in vivo experimental model using transgenic mice, we introduced a two-nucleotide change in the mouse p53 gene at amino-acid position 246, which is equivalent to position 249 in human p53, by the recombinant polymerase chain reaction mismatched primer method. This p53 mutation resulted in the same change, an Arg-->Ser substitution, as in the human p53 gene at position 249. We now report that the protein product of this mutant mouse p53ser246 had properties similar to those of the wild-type protein when tested by binding to (i) monoclonal antibodies PAb246 and PAb240, ii) simian virus 40 large T antigen, and (iii) heat-shock protein. However, it had mutant-type transforming properties when tested for colony formation with an osteosarcoma cell line. It was not active, as is wild-type p53, in transcription activation of the muscle creatine kinase promoter. These properties are the same as those found in the p53trp248 product of the p53 mutation associated with the Li-Fraumeni syndrome. Although less is known about the human p53ser249 product associated with hepatocellular carcinoma, the mutant murine p53ser246 protein shares the known properties of the human gene product.

Aflatoxin B1↗
PubMed1995

Developmental control of transcription of the CAT reporter gene by a truncated mouse alphafetoprotein gene regulatory region in transgenic mice.

A truncated mouse alphafetoprotein (AFP) gene promoter/enhancer region was tested for its ability to regulate the expression of the Escherichia coli chloramphenicol acetyltransferase (CAT) reporter gene in the livers of transgenic mice. The AFP regulatory region lacked any AFP gene structural DNA, included one enhancer sequence together with the proximal promoter sequence, and an element believed to be responsible for the postnatal repression of AFP gene transcription. The neonatal livers of AFP/CAT transgenic mice showed a high level of CAT enzyme expression, which was dramatically reduced between 7 and 14 days after birth. The staining of liver sections with anti-CAT antibodies showed that this expression was limited to hepatocytes. In one lineage, reexpression of CAT in the adult liver could be achieved by restitutive proliferation of hepatocytes following partial hepatectomy or CCl4-induced necrosis; reexpression in young animals (3-4 weeks of age) was even greater. These studies show that a truncated AFP promoter/enhancer region functions in a tissue-specific and developmental stage-specific fashion, and may be used to control the expression of other genes in the livers of transgenic mice.

Animals↗
PubMed1995

Participation of small intraportal stem cells in the restitutive response of the liver to periportal necrosis induced by allyl alcohol.

To determine the involvement of different hepatocyte populations in response to periportal injury, the restitutive response to allyl alcohol (AA) injury was examined. Adult female Sprague-Dawley rats were injected intraperitoneally (IP) with 0.62 mmol/kg AA, killed at 6, 9, 12, 33, 57, 81, and 153 hours after injection, and the livers were examined for injury and for restitutive proliferation by histology, autoradiography, and immunohistochemistry to detect alpha-fetoprotein (AFP), glutathione-s-transferase-p (GST-p), desmin, leukocyte common antigen, albumin, and monoclonal antibodies to liver cells: OV-6, H-4, and T-6. AA produces variable periportal liver necrosis predominantly at 6 to 12 hours. Proliferation of hepatocytes throughout the hepatic cord is seen early after injury in nonnecrotic areas: predominantly in zone II, but also in zones I and III, including some cells adjacent to the central vein. Within 2 to 3 days the necrotic zones are filled with small cells and by 1 week the liver architecture is essentially restored. During the active restitutive reaction from the immediate periportal rim the following cell phenotypes are seen: null cells: -->(AFP+, OV-6-, GST-p-) cells-->(AFP-, OV-6+, GST-p+) cells-->large (AFP-, OV-6-, GST-p-, H-4+) liver cells. Albumin staining was negative. We conclude that restitutive proliferation of periportal necrosis induced by AA appears to be accomplished by proliferation of intraportal (?stem) cells whose progeny differentiate and eventually repopulate the necrotic zone.

1-Propanol↗
PubMed1994

Isokinetic force-velocity curves in patients following implantation of an individual total hip prosthesis.

There are only a few studies which could support conclusions concerning the strength of the muscles surrounding the hip joint and especially concerning the strength relationships following implantation of endoprostheses. The aim of this study was to examine the post-operative course of strength deficits in this musculature compared to clinical parameters. Fifty-eight patients between 30 and 67 years of age, in whom individual total hip prostheses were implanted, were clinically examined prior, 9 weeks and 6 months after surgery. Moreover, the maximum isometric strengths of abductors, flexors, and rotator muscles as well as maximum isokinetic strengths of the extensors and flexor musculature at 60 degrees/s and 120 degrees/s were measured. The flexor and extensor musculature already showed a clear increase in maximum strength after 9 weeks and 6 months. By contrast, the isometric strengths of the rotators increased only slightly, the abductor strength decreased after 9 weeks to below the preoperative baseline level and attained this level again only after 6 months. The clinical parameters Trendelenburg sign, limping, and walking capacity were clearly improved after 6 months, but no correlation to the abductor strength could be demonstrated. It is concluded that limp-free gait can be attained even without maximum strength increase in the abductors, which are important for fluid gait, at least for short distances. The importance of regular training of the rotator and abductor musculature in coxarthrosis is emphasized to delay limitation of movement and decreased strength in the sense of a capsule pattern.

Adult↗
PubMed1994

[The problem of radiation exposure during radiography of the entire spine].

The stimulus for this investigation concerning radiation exposure during radiography of the spine, particularly in children with scoliosis, is the fact that there are no data in the literature. In 16 series of measurements we studied the effect of grids, kilovoltage, focus-film distance and film-screen systems using dosimeters. The use of grids led to a 5-7 times increase in radiation dose compared with exposures without grids. For this reason grids are not recommended for serial examinations in cases of scoliosis. It is easier to evaluate the spine on a single large film than on several small films and radiation dose is also halved. Therefore, the use of large single films is recommended, particularly for children and adolescents.

Adolescent↗
PubMed1994

Defective infection of rabbit peripheral blood monocyte cultures with human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) produces abortive infections of primary cultures of rabbit peripheral blood mononuclear cells (PMBCs). Mitogen activation of rabbit PBMCs or the addition of exogenous cytokines to the cultures does not change the level of release of the early HIV core protein, p24, into the culture medium. The amount of p24 increases steadily and reaches peak levels about 7 days after infection. HIV-1-specific DNA env sequences are also detected in infected PBMCs. However, reverse transcription of RNA of samples from activated infected cultures to cDNA, followed by amplification by the polymerase chain reaction, revealed transcription of gag, but not env, regions, suggesting that HIV-1 infection of rabbit PBMC does not lead to the replication and maturation of complete HIV-1 virions. In addition, neither CPE nor lytic infection was observed in HIV-1-infected rabbit cells and infectivity could not be transferred from rabbit cells infected with HIV for up to 2 weeks to MT-2 or H9 indicator cell lines. In addition, no CPE was seen in long-term cultures of the HTLV-I-transformed rabbit cell line PLT-1441, after inoculation with HIV. It is concluded that primary rabbit PBMCs may be infectable by HIV-1 but are not permissive for production of infectious virus. This conclusion is consistent with the apparent long-term latent infection seen after inoculation of rabbits with HIV-1 or HIV-1-infected cells.

Animals↗
PubMed1994

Dietary cadmium may enhance the progression of hepatocellular tumors in hepatitis B transgenic mice.

The effect of high cadmium levels in the diet on development of primary hepatocellular carcinomas (PHC) in transgenic mice expressing hepatitis B surface antigen (high expressing lineage 50-4) was determined to test the hypothesis that the incidence of PHC in areas of the world with endemic hepatitis B infections is related to the amount of cadmium in the diet. Groups of transgenic 50-4 mice and non-transgenic litter-mates consumed a diet containing high (5 micrograms/g) or low (< 0.05 micrograms/g) cadmium concentrations ad libitum for up to 20 months. Grossly visible and microscopic changes in the livers were examined at different time points after initiation of the cadmium feeding (3, 6, 9, 14-15 and 18-20 months). Although there was no difference in the incidence of tumors in 50-4 male or female mice fed high or low cadmium diets, male mice fed with high cadmium had more poorly differentiated liver tumors than did low-cadmium fed male mice. These observations suggest that dietary cadmium levels do not affect the number of tumors, but may affect progression of the carcinogenic process leading to development of more poorly differentiated tumors. In addition, after uniform liver dysplasia at 6-13 months in all 50-4 mice, 'remodeling' of large areas of the liver with formation of normal appearing liver cords, admixed with dysplastic and nodular areas, was noted in both male and female aged 50-4 transgenic mice.

Animals↗
PubMed1994

Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers.

Analysis of the cellular origin of carcinomas of different organs indicates that there is in each instance, a determined stem cell required for tissue renewal that is the cell of origin for carcinomas. The normal tissue-determined stem cells are the result of differentiation in the embryo and are little changed, if at all, from the embryonic cells. Malignant stem cells are derived from these normal stem cells of adult tissues. The resultant tumors are caricatures of the normal process of tissue renewal with many stem cells and imperfect differentiation (14). This imparts an undifferentiated appearance to the tumors, not a dedifferentiated one. Study of the regulation of normal stem cells in the embryo should lead to rational therapies for malignant ones, and conversely, study of secretions and regulation of malignant stem cells will provide insights into normal regulation. The cancer-derived differentiated cells are benign (12, 74) if not normal (39, 53) leading to the conclusion that attempts to direct normal differentiation of malignant stem cells might serve as an alternative to cytotoxic therapy. Attempts to develop such therapies are currently underway (208). The degree of differentiation of a carcinoma depends on the proportion of undifferentiated tumor stem cells, the stage of maturation arrest of the majority of cells in the tumor, and on the ability of some cells to escape arrest and to differentiate (Fig. 1). These concepts of the stem cell contribution to tumors originated largely from studies of teratocarcinoma (209) and were not widely accepted because many considered the lessons learned were unique to teratocarcinomas and would not apply to other tissues. On the basis of the concepts covered in this review, it is clear that teratocarcinomas are unique only in the potential of their stem cells. Other stem cells have more limited potential. The balance of expression of the differentiated histiotype of the tumor cell lineage and the undifferentiated phenotype of the tumor stem cells determine the morphology of the tumor. Normal tissue renewal of epithelial organs is also from stem cells or their differentiating progeny. The cellular events during liver development and regeneration and the changes that precede the development of liver cancer during hepatocarcinogenesis are similar to the cellular response in pancreas, prostate, breast, lung, and gut. In liver, as in the leukopoietic system, the primitive tissue-specific stem cell is not primarily involved in renewal because that would be too slow a process; individuals would die before generation of sufficient replacement cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Activation of distinct multidrug-resistance (P-glycoprotein) genes during rat liver regeneration and hepatocarcinogenesis.

The multidrug transporter P-glycoproteins are encoded by three multidrug-resistance (mdr) genes in rodents, designated mdr1a (mdr3), mdr1b (mdr1), and mdr2. Only the first two genes are functionally related to multidrug resistance. Activation of rodent mdr genes during liver regeneration and hepatocarcinogenesis has been reported. In mice, mdr1a is activated in hepatocellular carcinomas (HCCs) produced by various carcinogenic protocols, whereas both mdr1a and mdr2 are activated during liver regeneration. In this communication, we report isolating three gene-specific probes for the rat mdr homologues, which were used as probes in an RNase protection assay to demonstrate that mdr1b mRNA was expressed in HCCs induced by two different protocols. Furthermore, high levels of hepatic mdr1b mRNA but only moderate levels of mdr1a and mdr2 mRNA were seen in preneoplastic lesions in rats treated with 2-acetylaminofluorene. Likewise, highly elevated levels of hepatic mdr1b mRNA but only moderately increased levels of mdr1a and mdr2 mRNA were seen after partial hepatectomy. Nevertheless, the general patterns of tissue-specific expression of these three mdr genes were similar in rats and mice. These results reveal a complex hepatic gene expression pattern during hepatocarcinogenesis and hepatic proliferation for this conserved gene family in rodents.

2-Acetylaminofluorene↗
PubMed1993

Delayed hypersensitivity, immune deviation, antigen processing and T-cell subset selection in syphilis pathogenesis and vaccine design.

T-cell mediated delayed-type hypersensitivity (DTH) is the predominant immune mechanism for clearing tissues of infecting organisms in the primary lesion of syphilis. Here, Stewart Sell and Pei-Ling Hsu propose a strategy for vaccination against syphilis in which selective induction of DTH may be accomplished by using BCG vectored vaccines containing selected DNA sequences for T. pallidum antigens.

Animals↗
PubMed1993

[Ultrasound in inflammatory rheumatic joint diseases].

Inflammatory changes of the shoulder joint could be detected at a very early stage, when the clinical and radiological examinations were unremarkable. In 50% of the cases a rupture of the rotator cuff could be demonstrated. Only 10% of the shoulder joints had normal sonographic findings, whereas 50% were normal on clinical or radiological examination. Synovitis and effusion of the hand can be diagnosed very well by clinical examination, and can be documented in ultrasound. The sonographic diagnostic accuracy in tendon ruptures of the hand is lower than accuracy of the clinical examination. New technical developments may yield better results. Inflammatory changes of the hip joint are very difficult to diagnose by clinical examination. Synovitis, effusion and changes of the capsule can be better detected by ultrasound. Sonography of the hip joint has become part of our routine diagnostic programme, especially because early changes of the joint do not present clear symptoms.

Arthritis, Rheumatoid↗
PubMed1993

Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?

Given the fundamental principle that cancer must arise from a cell that has the potential to divide, two major nonexclusive hypotheses of the cellular origin of cancer are that malignancy arises a) from stem cells due to maturation arrest or b) from dedifferentiation of mature cells that retain the ability to proliferate. The role of stem cells in carcinogenesis is clearly demonstrated in teratocarcinomas. The malignant stem cells of teratocarcinomas are derived from normal multipotent stem cells and have the potential to differentiate into normal benign mature tissue. A widely studied model supporting dedifferentiation has been the putative origin of hepatocarcinomas from "premalignant" foci and nodules induced in the rat liver by chemicals. However, the dedifferentiation concept for hepatocarcinogenesis is challenged by more recent interpretations indicating that hepatocellular carcinoma arises from maturation arrest caused by aberrant differentiation of determined stem cells. Either hypothesis is supported by the cellular changes that occur in the rodent liver after different hepatocarcinogenic regimens. The formation of foci and nodules from altered hepatocytes supports dedifferentiation; the proliferation of small oval cells with the potential to differentiate into either biliary ducts or hepatocytes supports arrested maturation of determined stem cells. It is now postulated that foci and nodular change reflect adaptive changes to the toxic effects of carcinogens and not "preneoplastic" stages to cancer. The stem cell model predicts that genotoxic chemicals induce mutations in the determined stem cell which may be expressed in its progeny. Proliferation of initiated cells is induced by promoting events which also allow additional mutations to occur.

Animals↗
PubMed1993

Detection of cancer by tumor markers in the blood: a view to the future.

Markers for cancers in the blood include secreted glycoproteins of solid tissue tumors as well as cell surface markers, and chromosomal rearrangements or mutated genes in circulating blood cells. The most successful markers for the diagnosis of solid tissue cancers have been alphafetoprotein and prostate specific antigen. Other markers, such as CEA and a number of carbohydrate epitopes, e.g., CA 15.3, CA 19.9, CA 50, CA 242, and mucin epitopes, such as MCA, CA 125, and DU-PAN-2 are now being used to determine prognosis and to monitor the response to therapy of a variety of cancers. Cytologic markers in the blood include clusters of differentiation (CD) epitopes on blood cells and chromosomal changes, primarily translocations found in many human lymphomas. In the future more specific mutations in specific oncogenes or alterations in expression of oncogenes or suppressor genes, such as p53, may provide clinically useful markers.

Animals↗
PubMed1993

The role of determined stem-cells in the cellular lineage of hepatocellular carcinoma.

The concept that hepatocellular cancer (HCC) arises by dedifferentiation of mature hepatocytes is challenged by more recent interpretations indicating that HCC arises from arrested maturation of determined stem cells. Either hypothesis is supported by the cellular changes that occur in the rodent liver following different hepatocarcinogenic regimens. The formation of foci and nodules from altered hepatocytes supports dedifferentiation; the proliferation of small "oval" cells with the potential to differentiate into either biliary ducts or hepatocytes supports arrested maturation of determined stem cells. The stem cell model predicts that genotoxic chemicals induce in the determined stem cell mutations that may be expressed in its progeny. Promoting agents act by inducing cell proliferation and increasing the chances for the additional mutations needed for expression of the malignant phenotype in proliferating progeny of the stem cell. Events which increase hepatocyte proliferation, such as cirrhosis or hepatitis B infection, may allow the number of critical mutations to occur in the absence of exposure to an external carcinogen. Exposure to hepatocarcinogens, such as aflatoxin, or integration of virus DNA, such as in hepatitis B infection, may produce transforming mutations. However, these mutations are most likely not sufficient to cause cancer, but are potentiated by increased endogenous mutations that occur when proliferation is increased, leading to very high incidence of HCC in areas in which there is endemic hepatitis B and aflatoxin contamination of the diet.

Animals↗
PubMed1992

[Nuclear magnetic resonance tomography and sonography in diagnosis of lesions of the rotator cuff].

The diagnostic value of MRI and ultrasound in the examination of 37 patients with chronic shoulder pain is compared. All the results were controlled or by arthroscopy/arthrotomy or by arthrography. Ruptures and degenerative changes of the rotator cuff and degenerative lesions could be detected with a high sensibility. The ultrasound examination as a fast, reproducible diagnostic method has now become part of the routine diagnosis. The MRI produces exacter information about the extent of the lesions; but it will be reserved for special questions.

Arthroscopy↗