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Biomedical subjects

S Sell

Publications and source records attributed to S Sell.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1992

[The spine--a problem area in high performance artistic gymnastics. A retrospective analysis of 24 former artistic gymnasts of the German A team].

24 former female artistic gymnasts of the German national team were examined for spinal deformities after the end of their athletic career. In 3 cases we found osseous lesions of the spine without neurological complications. However, emphasis was on spinal changes due to stress. During their athletic career 15 gymnasts complained of low back pain which persisted in 7 of them after finishing their athletic activities. The lumbar radiographs revealed bilateral spondylolysis at L5 in 6, unilateral spondylolysis in 1, spondylolisthesis at L5/S1 in 3, degenerative changes of the intervertebral joints in 5, retrolisthesis at L5/S1 in 2, and scoliosis in 6 cases.

Adult↗
PubMed1991

Synergy between hepatitis B virus expression and chemical hepatocarcinogens in transgenic mice.

Exposure of female hepatitis B virus transgenic mice of lineage 50-4, which display liver injury secondary to overexpression of the gene for the large envelope polypeptide of hepatitis B virus, to the hepatocarcinogens aflatoxin and diethylnitrosamine produced more rapid and extensive evidence of nodule formation and oval cell proliferation, as well as the development of adenomas and primary hepatocellular carcinomas, than was seen in transgenic mice not exposed to carcinogens. Adult mice are known to be resistant to the effects of aflatoxin or diethylnitrosamine, and the livers of carcinogen-treated nontransgenic littermate controls were essentially normal. By the time of sacrifice (15 mo), 20 adenomas and 2 primary hepatocellular carcinomas were found in 26 transgenic mice given aflatoxin and 8 adenomas and 2 primary hepatocellular carcinomas were seen in the 8 mice exposed to diethylnitrosamine, but no adenomas or carcinomas were identified in the 10 transgenic mice not exposed to carcinogens. These results suggest that the chronic liver damage and repair caused by overexpression of the hepatitis B virus large envelope polypeptide in the hepatocytes of the transgenic lineage 50-4 act synergistically with chemical hepatocarcinogens to produce neoplasia of the liver.

Adenoma↗
PubMed1991

[Nuclear magnetic resonance tomography and ultrasound imaging of anatomic structures of the shoulder joint].

The possibilities of MRI and ultrasound in visualizing the structures of the shoulder joint are compared. Both methods have a good accuracy in detecting changes of the soft tissue of the shoulder. Changes of the cartilage and the bony structures are better seen in the MRI. The MRI gives a static and clear view of the shoulder joint, meanwhile the ultrasound depends on the dynamic examination. Ultrasound and MRI are both reproducible and non-invasive methods, who seem to complete one another at the examination of the shoulder.

Acromioclavicular Joint↗
PubMed1991

Protracted Treponema pallidum-induced cutaneous chancres in rabbits infected with human T-cell leukemia virus type I.

In a preliminary study, two of four rabbits infected with human T-cell leukemia virus type I (HTLV-I) demonstrated prolonged primary chancres following superinfection with Treponema pallidum, the causative agent of syphilis. Two rabbits inoculated with 1 x 10(7) HTLV-I-infected human MT-2 cells and two with infected rabbit cells from a line established in this laboratory (RLT-P), developed latent HTLV-I infection as detected by seroconversion 10 weeks after infection and by detection of HTLV-I sequences in the DNA of peripheral blood lymphocytes after amplification by polymerase chair reaction (PCR) 15 weeks after infection. The rabbits remained clinically normal and had normal blood counts. Six months after infection, the four HTLV-infected rabbits and two noninfected controls were challenged by the intradermal inoculation of 1 x 10(6) Treponema pallidum into eight sites on the shaved back. The lesions of two of the HTLV-I-infected rabbits had a time course similar to non-HTLV-I-infected controls and were completely healed by 4 weeks. The lesions of one of the other two rabbits with progressive disease began to heal about 7 weeks after T. pallidum challenge. The cutaneous lesions in the other rabbit remained dark-field positive and became a confluent eschar at 8 weeks; healing only after treatment with penicillin. Four months after the primary challenge none of the six rabbits previously challenged with T. pallidum had developed lesions after rechallenge and thus expressed chancre immunity. These results demonstrate that rabbits with latent HTLV-I infections may have defective cell-mediated immunity.

Animals↗
PubMed1991

Contribution of rabbit leukocyte defensins to the host response in experimental syphilis.

In the companion paper (L. A. Borenstein, M. E. Selsted, R. I. Lehrer, and J. N. Miller, Infect. Immun. 59:1359-1367, 1991), we report that rabbit alveolar macrophage and neutrophil derived defensins possess antimicrobial activity against Treponema pallidum subsp. pallidum, the etiologic agent of syphilis. In this study, antisera specific for NP-1 and NP-2 (defensins present in certain macrophages and polymorphonuclear leukocytes) and NP-5 (a defensin produced only in neutrophils) were used to detect these peptides by immunoperoxidase staining in testicular lesions from infected rabbits. Profound amounts of cell-free and cell-associated defensins were detected in the tunica albuginea and interstitial spaces during the first 24 h of infection. The presence of defensins was transient and almost undetectable by day 4. Interstitial defensins were detected again at day 10 and increased through day 16, at which time lesion healing was evident by hematoxylin and eosin staining. The appearance and increase in detectable defensins between days 10 and 16 of infection correlated with a reduction in numbers and disappearance of T. pallidum, as demonstrated by using silver staining. The extent and pattern of immunostaining for NP-1 and NP-2 corresponded with immunostaining for NP-5 and identified neutrophils as the cellular source of the defensins. These findings indicate that defensins may contribute to the control of local T. pallidum infection and suggest a role for acute inflammatory processes in the resolution of early experimental syphilis.

Animals↗
PubMed1991

Syphilis superinfection activates expression of human immunodeficiency virus I in latently infected rabbits.

Superinfection of latently human immunodeficiency virus (HIV)-infected rabbits with either Treponema pallidum or Shope fibroma virus (SFV) activates HIV expression. In addition, HIV-infected rabbits demonstrate prolonged cutaneous lesions (chancres) after intracutaneous challenge with T. pallidum, the causative agent of syphilis. Rabbits were infected by intravenous inoculation of 3 x 10(7) human T-cell lymphotrophic virus type III (HTLV-III)/B10 (HIV-1)-infected H9 (human) cells. Five weeks after initial infection, integrated HIV-1-specific DNA sequences were detected in the DNA of the peripheral blood lymphocytes of only one of eight rabbits using polymerase chain reactions (PCR); human DNA could not be detected at this time. Furthermore HIV infection could not be demonstrated by either seroconversion or PCR during the next 6 months. All HIV-infected rabbits remained clinically healthy and had normal white blood cell counts. Six months after HIV infection, four HIV-infected and two noninfected controls were superinfected with 10(6) T. pallidum in eight skin sites in the shaved skin of the back, and four infected and two control animals were challenged with an intradermal injection with SFV. After infection with either syphilis or SFV, the DNA from the white blood cells of all eight HIV-infected rabbits contained HIV sequences, and HIV sequences were demonstrated in dermal mononuclear cells of the syphilitic lesions by in situ hybridization. The SFV-induced tumors were rejected normally in the HIV-infected rabbits, but four of the four rabbits challenged with T. pallidum had delayed development of cutaneous lesions and three of four demonstrated larger and more prolonged lesions. White blood counts, mitogen responses, and interleukin-2 production remained within normal limits, and seroconversion for HIV was not detected. Three of four rabbits in a second group, challenged with T. pallidum 4 months after HIV-inoculation, also had delayed healing of syphilitic lesions. These results indicate that latent HIV-infection of rabbits may be activated by immunostimulation and that latently HIV-infected rabbits have impaired delayed hypersensitivity reactions. It is hypothesized that true latent HIV-infection in the rabbits is in monocytes and postulated that further immunostimulation may produce infection of lymphocytes and activation of disease.

Animals↗