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Results for “Serial Passage”

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PubMed2000

[Primary study of HCV replication in HepG2 cells inoculated by anti-HCV positive and HCVRNA RT-PCR positive serum].

OBJECTIVE: To study HCV replication in HepG2 cell line and to establish a stable HepG2 cell line infected with HCV. METHODS: Continuous inoculation of anti-HVC positive and HCVRNA RT-PCR positive sera was used to infect HepG2 cells. The plus and minus strains of HCVRNA were detected by reverse transcription polymerase chain reaction in the HepG2 cells. Virus particles were observed in postinoculated HepG2 cells by transmission electron microscope. Immunohistochemical staining was used respectively to detect HCV antigen, HCVNS5 and HVC capsid in postinoculated HepG2 cells. RESULTS: HCV RNAs (both plus and minus strains) were found from the first passage to the third passage of postinoculation HepG2 cells, and HCV viruslike particles were detected in the third passage of the infected HepG2 cells, those particles mostly occurred within cytoplasm, their diameters were between 30-60 nm, and gathering silver particles were found in immunogold silver staining of HCV NS5/capsid protein in infected HepG2 cells. Gathering gold particles were found mostly within vesicles in cytoplasm by immuno gold electron microscopy. CONCLUSION: HepG2 cell line infected by HCV is established by continuous inoculation of anti-HCV positive and HCVRNA positive sera. HCV can replicate and produce virus-like particles in HepG2 cells, which may occur in the serial passages of post-infected HepG2 cells.

Antibodies, Viral↗

PubMed1999

Nonrandom X inactivation and selection of fragile X full mutation in fetal fibroblasts.

In the fragile X female carriers the degree of cognitive impairment appears to be correlated with activation status of the X chromosome bearing the expanded trinucleotide repeat in the promoter of the FMR1 gene. In this study we asked if the deviations from the primarily random pattern of X inactivation are related to the selection which is thought to occur against cells carrying the fragile X full mutation (FM) on the active X chromosome. A fibroblast culture derived from a 20-week FM female fetus was serially passaged. The activation ratio (AR) of the culture increased from 0.68 to 0.92 between passages 2 and 9. All higher passage cells (up to 34 passages) display an AR of 1.0, indicating complete absence of cells in which the normal X chromosome would be inactivated. Of 29 clones established from the fetal culture with AR of 0.8, 28 had no visible 5.2-kb band on Southern blots indicating that these 28 clones consisted entirely of cells with FM on their inactive X chromosome. Only a single clone carried the FM on its active X chromosome. The figure of 1 of 29 is much lower than our expectation based on the AR of mass culture. Therefore cloning and serial cultivation indicate the possibility of selection depending on the activation status of the expanded X chromosome in fetal FM female fibroblasts.

Cells, Cultured↗

PubMed1978

Isolation and serial cultivation of rabbit skin epithelial cells.

A method to isolate and to serially cultivate rabbit skin epithelial cells from adult trunk skin has been developed. Using a collagen gel as substrate and trypsin and EDTA to dissociate cells, nonproliferative primary cultures of rabbit cells may be converted to proliferative populations, and at least 3 serial passages achieved. In the presence of large concentrations of methotrexate (up to 1000 microgram/ml), epithelial cells in primary culture show no decrease in their ability to attach, spread, or keratinize. Following conversion to proliferative populations by trypsin and EDTA low concentrations of methotrexate (1 microgram/ml) are strongly cytotoxic. When the incorporation of 32PO4(3-) and 3H-thymidine into DNA of proliferative and nonproliferative cells is compared, the incorporation of 32PO4(3-), but not that of 3H-thymidine, correlates with changes in cell number and DNA content. In both primary and serially cultivated cells, L-serine is required for optimal growth.

Animals↗

PubMed1979

Characteristics of Pseudomonas aeruginosa in relation to laboratory-induced resistance to gentamicin.

Pseudomonas aeruginosa strain C2 was habituated to gentamicin by serial passage in broth containing increasing concentrations of the antibiotic and up to 250 microgram/ml. The resistant progenies differed from the parent strain in antibiotic susceptibility to two other aminoglycosides, colonial morphology, lytic phage patterns, phage adsorption, and agglutination with the seven Fisher's antisera. All the progenies failed to grow at 42 degrees C and oxidised glucose in O/F tubes after incubation at 37 degrees C for three days but were catalase- and oxidase-positive. Reversion to the original properties of the parent strain was demonstrated in all cases after 10 serial subcultures in antibiotic-free broth.

Bacteriophage Typing↗

PubMed1975

Eimeria tenella in chickens: development of resistance to quinolone anticoccidial drugs.

The development of drug resistance by the present Houghton strain of Eimeria tenella to the quinolones, methyl benzoquate and buquinolate, was found to take place after a single experimental passage. The development of resistance was independent of drug selection pressure and showed cross resistance to other quinolones, but not to amprolium and robenidine. When the Weybridge, Beltsville and Elberfeld strains of E. tenella were compared under similar laboratory conditions, the Weybridge and Elberfeld strains developed resistance to methyl benzoquate after 6 passages and the Beltsville after 5. Studies on the response of the Houghton strain to methyl benzoquate and buquinolate revealed that the drugs did not completely control the infection as measured by weight gain and that oocyst production was not suppressed. These observations indicate that the strain had already acquired some resistance to these drugs. This was confirmed by examining the resistance to methyl benzoquate of a culture of the Houghton strain of E. tenella which had been stored frozen in liquid nitrogen since 1969. This showed full sensitivity to the drug and developed resistance after 8 passages. This suggests that drug tolerance has been acquired by the Houghton strain since 1969. Oocyst lines were established from the Houghton strain by infecting single birds with approximately 10 oocysts. Eleven of these lines were found to be sensitive to methyl benzoquate, and nine to give rise to resistant parasites. It is concluded that the Houghton strain is contaminated by a small number of resistant oocysts which can be eliminated from a culture by dilution of the challenge inoculum. One of these Houghton oocyst lines, sensitive to methyl benzoquate, developed resistance after 8 serial passages.

Animals↗

PubMed2006

Development of the osteoblast phenotype of serial cell subcultures from human bone marrow.

Bone marrow cells have been used for testing biocompatibility of bone substitute materials that would be applied in maxillofacial and orthopedic surgeries. However, it remains unclear whether cells in serial subcultures retain the ability to differentiate into osteoblasts. The purpose of this study was to compare the development of osteoblast phenotype of serially passaged cells from human bone marrow. Cells from first to third passage were cultured (2 x 10(4) cells/well) in supplemented culture medium. Cells were incubated at 37 degrees C in a humidified atmosphere of 5% CO2 and 95% air. Cell attachment was assessed at 4 and 24 h. At 7, 14 and 21 days, cell proliferation, cell viability, total protein content and alkaline phosphatase (ALP) activity were evaluated. Bone-like formation was evaluated at 14 and 21 days. Data were compared by two-way ANOVA and Duncan's multiple range test. Cell attachment, cell viability and total protein content were not affected by serial subcultures. However, serial subcultures did interfered negatively with osteoblast differentiation as shown by osteoblast parameters observed in second and third subcultures, such as continuous cell proliferation, lower ALP activity and bone-like formation in comparison to first subculture. Therefore, it is important to evaluate cell ability to growth and differentiate before selecting the cell population for studies that investigate the biocompatibility of materials to replace bone tissue.

Adolescent↗

PubMed1997

Serial in vivo passage of HIV-1 infection in Macaca nemestrina.

In an earlier study we found that pigtailed macaques (Macaca nemestrina) that were experimentally infected with human immunodeficiency virus type 1 (HIV-1) initially became viremic and seroconverted, but HIV-1 replication diminished markedly over time. In an attempt to develop a longer term pathogenic model, blood from HIV-1-infected macaques was serially transfused into three groups of naive macaques. Transfer was successful through two transfusions as shown by repeated virus isolations and confirmed by the development of cell-free plasma viremia and by seroconversion. Three to five weeks after transfusion, plasma levels of HIV-1 RNA from several macaques in the first two groups exceeded those of the initially inoculated macaques. However, animals in the third group had diminished RNA levels, were virus culture negative, and did not seroconvert. Sequence analyses of env-region clones from infected animals revealed only minimal changes over the course of the passages. These results confirm HIV-1 replication in M. nemestrina during the acute phase of infection. However, adaptation of HIV-1 to a macaque-pathogenic variant did not occur during serial passage, possibly because the animals were able to restrict HIV-1 replication below a level required for a pathogenic variant to emerge. Whether such containment is a function of the host's immune response or a virus cell incompatibility remains to be determined.

Adaptation, Physiological↗

PubMed1989

Rat pituitary tumor cells in serum-free culture. I. Selection of thyroid hormone-responsive and autonomous cells.

The growth of GH4C1, GH3, GH1, and GH3C15 rat pituitary tumor cell lines was studied in a serum-free medium (designated TRM-1) formulated with 1:1 (vol/vol) mixture of Ham's F12 nutrient mixture and Dulbecco's modified Eagle's medium (F12-DME) containing 15 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 50 micrograms/ml gentamicin supplemented with 10 micrograms/ml bovine insulin, 10 micrograms/ml human transferrin (Tf), 10 ng/ml selenous acid, 10 nM 3,5,3'-triiodothyronine (T3), 50 microM ethanolamine (Etn), and 500 micrograms/ml bovine serum albumin. Of the lines evaluated, only the GH1 failed to grow in TRM-1. Passage of the GH4C1 and GH3 lines from serum-containing medium into TRM-1 caused an initial selection resulting in cells that grew progressively at higher rates and finally were maintained indefinitely in TRM-1. These populations showed a requirement for supraphysiologic concentrations of T3 (1.0 to 10 nM). After adaptation of the GH4C1 line in TRM-1 for greater than or equal to 20 generations, removal of components gave a less complex mixture containing 15 mM HEPES, 50 micrograms/ml gentamicin, 10 micrograms/ml Tf, 10 nM T3, and 50 microM Etn (designated TRM-2) that supported serial passage of the cells. Under these conditions, thyroid hormone dependence was lost progressively. When T3 was removed from TRM-2 adapted cells, a third population was selected that no longer required thyroid hormones and was only slightly stimulated by T3. These studies demonstrated that the combination of serum-containing and serum-free conditions can be used to select pituitary cell populations that a) required both serum-factor(s) and T3 for optimum growth, b) required supraphysiologic concentrations of T3 without serum proteins other than Tf and albumin, and c) were completely autonomous in that they proliferated in medium supplemented only with Tf and nutrients without necessity of other serum factor(s) or T3.

Animals↗

PubMed1980

Alterations in virus protein synthesis and capsid production in infection with DI particles of herpesvirus.

High multiplicity, undiluted passage of equine herpesvirus type 1 (EHV-1) in L-M cells resulted in the rapid production of virus particles whose genome was genetically less complex, contained more reiterated DNA sequences and exhibited a greater buoyant density (rho = 1.724 g/ml) than the DNA (rho = 1.716 g/ml) of standard virus. These data and the finding that these particles inhibited the replication of standard virus in interference assays confirmed that these were defective interfering (DI) particles (Henry et al. 1979). Additional evidence for this has been obtained from the pattern of cyclic fluctuation in infectious virus titre through 17 serial passages as well as from the pronounced variation in the particle to plaque ratio for each passage. Total particle production was markedly reduced in cells infected with virus preparations containing DI particles and quantification of major cell-associated EHV-1 capsid species by electron microscopy and analysis in Renografin density gradients indicated that this reduction occurred at the level of capsid assembly. Although total capsid production was reduced in cells infected with DI particle preparations, the synthesis of I (immature) capsids increased relative to that of L (empty) capsids and these alterations in the assembly of capsid species could be related to changes in the synthesis of capsid proteins. In cells infected with EHV-1 preparations rich in DI particles, the synthesis of major capsid protein 150000 was greatly reduced, whereas core protein 46000, a major component of I capsids, was overproduced as compared to standard virus infection. Capsids produced in cells infected with virus preparations rich in DI particles were identical in polypeptide composition to those made in standard virus infection.

Animals↗

PubMed1985

Morphological response of cultured cells to Naegleria amoeba cytopathogenic material.

Naegleria amoebae contain cytopathogenic material (NACM). The morphological response of cultured cells to this material follows a number of characteristics in common with those resulting from infectious agents. The cytopathologic changes varied depending on the strain of the cultured cells. Among those from 17 different vertebrate sources, both primary and continuous cell lines, some were destroyed completely by dilutions of NACM up to 10(-8) while others appeared unaffected by NACM at any concentration. The response had no apparent relationship to species, organ source, or passage level of the cells. The reaction was typified by a long latent period (4-10 days) during which the number of cells in the culture increased up to 10-fold, followed abruptly by a short period (less than 24 h) during which all of the cells were destroyed. The latent period was prolonged when the culture conditions were adverse, or when the amount of NACM in the inoculum was minimal. A high multiplicity of NACM in the inoculum lysed the entire culture, while dilutions near the end-point caused generalized or only focal changes of rounded cytopathic cells. The cytopathic effect could be maintained in cultured cells by serial passage, such that the total activity greatly exceeded what could be attributed to the original inoculum. These findings are consistent with the concept that NACM has properties of an infectious agent and that its quantity is enhanced and spread through the culture by cell-to-cell contact and by cell division.

Amoeba↗

PubMed1983

Alterations in the equine herpesvirus 1 genome after in vitro and in vivo virus passage.

The effect of in vitro and in vivo serial virus passage on the genetic stability of equine herpesvirus 1 (EHV-1) was investigated by restriction endonuclease analysis of the viral DNA. DNAs of EHV-1 isolates at different passage levels in cultured cells or in Syrian hamsters were compared by electrophoresis of the DNA cleavage fragments produced by restriction endonuclease digestion. No changes were observed in the restriction profile of the DNAs of EHV-1 strains after 100 sequential passages in cultured equine cells. However, serial passage of the virus in hamsters or in cells of non-equine origin quickly gave rise to alterations in the viral DNA. These changes occurring in the restriction endonuclease profiles of EHV-1 DNA during serial virus passage in non-equine cells or animals hosts could be explained by sequence additions or deletions to preexisting restriction fragments resulting in variation in their electrophoretic mobilities.

Animals↗

PubMed1985

Actin content and organization of microfilaments in primary cultures of mouse embryonic fibroblasts (in vitro ageing).

Actin distribution in serially passaged embryonic mouse fibroblasts has been visualized by the anti-actin-PAP method; the organization of the microfilaments has been observed by electron microscopy (SEM and TEM). Four successive actin patterns have been identified: early (few well-organized bundles of microfilaments), middle-aged (many well-organized bundles and patches around the nucleus), late (numerous ill-organized filamentous structures and diffuse perinuclear-actin) and "senescent" (heavy packs of short microfilaments around the nucleus). All the observed actin-positive filaments were disrupted by cytochalasin B treatment. The cytoplasmic actin complex was cell-age and not cell-size-dependent; it behaved differently from the cytoplasmic microtubular complex to serially subcultivated fibroblasts. Measurements of the cell-protein content (Lowry's method) and SDS-polyacrylamide gel electrophoresis (Laemmli's method) have been performed in the successive population doubling levels (PDL) of the primary cultures. Triton-insoluble actin increased in parallel with total protein and reached about 4% of the total proteins in all the PDLs. Triton-soluble actin also increase at the beginning of the middle-aged period (generally 6 PDL) and another in declining cultures (generally 10 PDL). Total actin amounted to about 8% of the total proteins in early fibroblasts, to about 16% at the beginning of the middle-aged period and to about 20% in the declining terminal cultures. Taking into account all the known characteristics of subcultivated primary cultures, we tentatively consider the evolution of the fibroblasts as an in vitro differentiation followed by true in vitro senescence in the declining cultures. Regarding the cytoplasmic actin-complex, senescence would be characterized by a sharp increase in soluble actin, an unbalanced ratio between soluble and insoluble actin and an impairment of the ability of the microfilaments to form well-organized bundles.

Actin Cytoskeleton↗

PubMed1998

Persistent infection with an influenza C virus variant is dominantly established in the presence of the parental wild-type virus.

Two influenza C viruses were used for double-infection experiments to investigate the dominance of their phenotypes. The wild-type virus (C/AA-wt) had been characterized by its short-lived productive cycle, whereas a distinct variant derived from it (C/AA-pi) was demonstrated to persist in long-term passages of infected MDCK cultures. Here we show that the persistent virus C/AA-pi is capable of replicating in the presence of abundant amounts of wild-type virus: the persistent virus could be diluted to 10(-9) within wild-type inoculum, still developing a stable form of persistence. This behaviour was reflected by permanent virus release and by continuous enzymatic activity of the viral HEF glycoprotein in infected cells. All long-term cultures tested remained positive for viral NS protein and vRNA. On the vRNA level, it was shown that viral segments originated from the persistent-type genome, while wild-type vRNAs were not maintained after double-infection. Thus, the genotype of the persistent variant was dominantly selected in serial passages. These results indicate a specific intracellular advantage of persistent influenza C virus over the parental wild-type.

Animals↗

PubMed1994

Experimental model of liver metastases: adhesion and growth of cells on contact with endothelial or hepatocyte cell monolayer cultures.

In a rat colon carcinoma model (DHD/K 12-PROb), two varieties of cells were selected after in vivo passaging: PROb h2, representing a liver-specific variant and PROb Mp1, representing a lung metastatic variant and producing liver and lung metastases after intracecal injection (one out of four). The study of the adhesion and the growth of cells in vitro for contact hepatocytes and/or endothelial cells gave the following results: (1) except for PROb Mp1, tumor cell growth was independent of the cell support; (2) adhesion of PROb Mp1 to endothelial cells was lower between 30 and 120 min, whereas adhesion of PROb h2 to hepatocytes was greater and durable after 60 min (P < or = 0.05). These results suggest that the formation of liver metastases in a dynamic process and that tumor cells have a great ability to adhere to hepatocytes. Improved by serial passaging in vivo, our intracecal model might be useful for studying many aspects of the pathogenesis of colon cancer metastasis, while concurrent in vitro studies of the adhesion and growth ability of cells might be a useful indicator for assessing the in vivo behavior.

Animals↗

PubMed1996

Structure, growth and cell proliferation of human osteosarcoma and malignant fibrous histiocytoma xenografts in serial transplantation in nude mice.

Tumour specimens from one patient with osteosarcoma and one with malignant fibrous histiocytoma were transplanted in serial passages in nude mice. Structure, growth and cell kinetics of the xenografts were studied in order to assess the validity of the two tumour models. Cell proliferation was analysed using in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd) and the IdUrd labelling index (LI) was determined by immunohistochemistry. The DNA index (DI) was examined by flow cytometry. The c-myc oncoprotein expression was studied by immunohistochemistry. More intense proliferation was observed in the peripheral parts of the tumours. There was no correlation between tumour growth and cell proliferation in the two tumour groups. Stability of the tumour models was indicated by low intrapassage and interpassage variations of DI, LI, and volume doubling time, and also by retained histopathological characteristics and c-myc staining patterns of donor patients' tumours during serial transplantation.

Aged↗

PubMed1987

Antagonism of wild-type and resistant Escherichia coli and its DNA gyrase by the tricyclic 4-quinolone analogs ofloxacin and S-25930 stereoisomers.

The mechanism of action of the quinolone analogs ofloxacin and S-25930, which are unusual because of the presence of a third ring with an asymmetric carbon, was studied. Drug-resistant strains of Escherichia coli were selected by serial passage in the presence of ofloxacin, and a mutation was mapped near the gyrA gene of DNA gyrase. DNA gyrase containing the A subunit purified from this strain as compared with the isogenic wild-type strain exhibited increased resistance to ofloxacin, proving that the mutation was located in the gyrA gene. For S-25930, the S stereoisomer was more potent than the R isomer in inhibiting wild-type E. coli and DNA gyrase containing an A subunit isolated from this strain. Both isomers had decreased potency against the isogenic ofloxacin-resistant (gyrA) strain and its purified enzyme, but the S isomer remained more potent than the R isomer. These studies, using a combined genetic and biochemical approach, demonstrate (i) that DNA gyrase is a target of the tricyclics ofloxacin and S-25930, (ii) that serial exposure to ofloxacin can select resistance to tricyclic quinolone agents by mutation in the gyrA gene, and (iii) that the more potent antibacterial activity of S relative to R S-25930 correlates with increased activity against DNA gyrase for both wild-type and ofloxacin-resistant (gyrA) isogenic strains.

Anti-Bacterial Agents↗

PubMed1993

Human CD4+ T cells proliferate to HLA-DR+ allogeneic vascular endothelium. Identification of accessory interactions.

Serially passaged human endothelial cell (EC) cultures will stimulate highly purified peripheral blood CD4+ T cells to proliferate if and only if the EC cultures are pretreated with IFN-gamma to induce de novo expression of MHC class II molecules, principally HLA-DR. HLA-DR-expressing EC alone appear sufficient to stimulate purified CD4+ T cell proliferation without the involvement of other leukocyte populations, as indicated by the following observations: (1) we find no contaminating leukocytes in our EC cultures by FACS analysis or fluorescence microscopy; specifically, there are no detectable CD45 or HLA-DR expressing cells; (2) neither the EC cultures nor the purified CD4+ T cells contain HLA-DR expressing cells detectable by polymerase chain reaction (PCR) of reverse-transcribed mRNA; (3) the stimulatory capacity of the EC cultures is maintained through serial subculture and through low-density replating, indicating that the stimulatory cell type must proliferate in culture as well as EC; and (4) in contrast to MLRs, the response to EC cultures is not inhibited by pretreatment of the stimulator cells and/or responding T cells with the monocyte toxin L-leucine-O-methyl ester. We have used mAb to investigate the role of various EC and T cell surface molecules in the T cell response. mAb to HLA-DR and CD4 inhibit proliferative responses of CD4+ T cells to EC cultures, as would be expected if T cells recognize and proliferate to IFN-gamma-induced allogeneic class II MHC molecules; whereas, also as expected, mAb to class I MHC molecules were without effect. Proliferation is also inhibited by mAbs to T cell CD2 and LFA-1 beta chain (CD18) and by mAbs to LFA-3 (CD58) and CD44, which are expressed by T cells and EC. mAb to ICAM-1 (CD54, a ligand for LFA-1) provides inconsistent inhibition, and mAb to ICAM-2, used with or without anti-ICAM-1, is not inhibitory. Because both of these mAb block adhesion of LFA-1 expressing T cells to EC, our data suggest that additional ligands for LFA-1 must be important for allogeneic proliferation. mAb to VLA-4 alpha or beta chains (CD49d, CD29) enhance proliferation, presumably through direct costimulation of the T cells by these antibodies. However, a mAb to VCAM-1, an EC ligand for VLA-4, is partially inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

PubMed1951

Passage of Coxsackie virus (Connecticut-5 strain) in adult mice with production of pancreatic disease.

1. With Conn.-5 strain of Coxsackie virus, pancreatic disease can be regularly produced in adult mice. 2. The lesions consist of widespread necrosis, followed by repair; there occurs more or less complete loss of glandular acini, with fatty or fibrous replacement. The islands of Langerhans and pancreatic ducts persist. 3. Injection of virus suspensions by the intraperitoneal, subcutaneous, intramuscular, or intracerebral route is followed by selective necrosis of the pancreas. 4. The liver, in the earlier stages of the disease, is the seat of fat infiltration. There may be necrosis of individual hepatic cells, but the diffuse hepatitis described in suckling mice does not occur. In the later stages of the disease, the liver is not significantly altered. 5. Localized areas of fat necrosis, scattered through intra-abdominal adipose tissue, are usually present in the acute phase of the disease. These undergo fibrosis without calcification. 6. No lesions have been found in the skeletal muscle, even at the site of intramuscular injection. Central nervous system, heart, lungs, and peripheral fat lobules show no lesions comparable to those described in suckling mice. 7. Multiplication of virus takes place in the pancreas. Serial passage in adult mice, by injection of pancreas suspensions prepared from organs removed on the 4th day after infection, is readily accomplished. Five consecutive passages in adult mice have thus far been carried out. Pancreas suspension from 4th passage material produced typical disease in suckling mice when diluted 10(-6). No virus could be demonstrated in pancreas obtained 25 days after inoculation. 8. Complete protection against the pancreatic disease is obtained when the virus is neutralized, before injection, with Conn.-5 antiserum. Normal mouse serum and antiserum against the Ohio-R strain of Coxsackie virus have no protective effect. 9. Mice surviving the initial necrotizing effect of the virus, develop chronic pancreatic insufficiency. This is manifested by extreme weight loss-in some cases, 40 per cent or more of the body weight-and by hypoproteinemia, sometimes leading to anasarca. 10. The substitution of fox-chow which has been predigested with hog pancreas brings about a restoration of weight. 11. The possibility is considered that similar lesions of the pancreas in human beings may be due to virus infection.

Animals↗