Degradation of endothelial cell matrix collagen is correlated with induction of stromelysin by an activated ras oncogene

A conditional expression system was established whereby the human K-ras, v-src, and v-mos genes were cloned into a conditional expression vector downstream of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Rat-1 fibroblasts were transfected with these constructs and selected in medium containing G418. Cloned transfectants were isolated and characterized for absolute dependence on dexamethasone for expression of oncogene products and anchorage-independent growth in soft agar. Expression of activated p21^K-ras(val12) enabled the fibroblasts to degrade extracellular matrix collagen secreted by murine microvessel endothelial cells. Concurrent with p21^K-ras(val12) induction a proteinase with the characteristic size and substrate specificity of transin, the murine homologue of the human matrix metalloproteinase stromelysin, was expressed and secreted. Induction of v-mos and v-src oncogenes resulted in little or no detectable transin expression respectively coinciding with a relative or absolute failure to increase degradation of extracellular matrix collagen. This study suggests that in this system the expression of the ras oncogene can contribute to the in vitro invasive behavior of tumor cells by upregulating the production of a metalloproteinase capable of degrading collagen synthesized by vascular endothelial cells.     

Regression of v-src DNA-induced sarcomas is under host genetic control

Previous results have established that subcutaneous inoculation of chickens (line SC) with a v-src(+) subviral DNA fragment induces the formation of progressor sarcomas at the wing web site of inoculation. Because the sarcoma cells are incompetent for production of exogenous progeny virus, this system is a useful model of tumor expansion by sarcoma cell division, in the absence of infection-mediated recruitment of new tumor cells. The present study was undertaken to define conditions that modulate the pattern of growth (regression vs progression) of v-src DNA-induced sarcomas. These conditions were found to include the line of chicken or the presence on the subviral v-src(+) DNA fragment of a viral replication-specific sequence that includes env.     

Forsythia fructus inhibits the mast-cell-mediated allergic inflammatory reactions

Mast cells are key as effector cells in the early phase allergic inflammation and in diverse immunological and pathological processes. Forsythia fructus (F. fructus) has used as a traditional medicine for inflammatory diseases. In the present study, we determined the effect of F. fructus extracts on compound 48/80-induced paw oedema and vascular permeability in vivo. In addition, we investigated in vitro whether F. fructus has inhibitory effects on compound 48/80-induced histamine releases from rat peritoneal mast cells (RPMC), and on phorbol 12-myristate 13-acetate (PMA) plus A23187-induced tumor necrosis factor- (TNF-) releases from human mast cells (HMC-1). In mice orally administrered F. fructus (100 g/g) for 1 h, compound-48/80-induced oedema and vascular permeability were significantly reduced rather than those receiving intravenous injection of ketotifen, mast cell stabilizer. F. fructus dose-dependently inhibited the histamine release induced by compound 48/80 from RPMCs. Moreover, F. fructus had no cytotoxic effects on cell viability and had inhibitory effects on TNF- secretion from HMC-1. These results suggest that F. fructus is a potential herb medicine for treatment of inflammatory diseases through downmodulating mast cell activation.     

Src-Family Kinase-p53/56lyn Plays an Important Role in TNFα-Stimulated Production of O2 − by Human Neutrophils Adherent to Fibrinogen

Stimulation of neutrophil function by TNF is largely dependent on ₂ integrins. It has also been proposed that src-family kinases are involved in this process. However, the functions of src-like kinases in human neutrophils still remain to be determined. In the present study, we used the new src-family kinase specific inhibitor PP1 4-Amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine to investigate the role src-kinases play in TNF stimulation of neutrophil function. Our results demonstrated that, in neutrophils adherent to fibrinogen, PP1 inhibited TNF-stimulated superoxide production and protein tyrosine phosphorylation in a dose-dependent manner. In in vitro kinase assays, PP1 profoundly inhibited the activation of p53/56^lyn but not p59^hck or p72^syk. Only slight inhibition was found of p58^c-fgr. These data indicate that p53/56^lyn plays an important role in TNF-mediated stimulation of PMN function.     

Distinct and opposite roles for SH2 and SH3 domains of <Emphasis Type="Italic">v-src</Emphasis> in embryo survival and hemangiosarcoma formation

The cellular proto-oncogene c-src is thought to be involved in formation, progression, and metastasis of a variety of tumor cell types, although its exact role during tumor cell genesis is not well defined. v-src, the viral oncogene counterpart of c-src, causes metastatic sarcomas, hemorrhagic disease, and hemangiosarcomas in chicken embryos and, thus, can be used as a constitutively activated form of src for experimentally-induced tumorigenesis. Here, we used retroviral vectors to express wild-type v-src or SH2 or SH3 domain-deleted forms (ΔSH2 or ΔSH3) to determine if different pathogenic effects resulted. Vectors were injected into early chick embryo midbrain ventricles and embryos were sacrificed at various ages up to embryonic day (E) 18. Retroviral expression of all forms of v-src resulted in transformation of pial connective tissue cells into large, rounded abnormal-appearing cells. Surprisingly, all forms of v-src were lethal. The v-src retrovirus was lethal and killed most embryos by E15 with the development of hemangiosarcomas over the injection site between E10–E12. The ΔSH3 retrovirus was the most deadly, killing most embryos by E12, however, it never resulted in hemangiosarcoma formation. The ΔSH2 retrovirus injected embryos survived longer than v-src or ΔSH3 embryos, and some of these embryos also developed large hemangiosarcomas over the injection site between E13 and E18. These results demonstrate that the src SH2 domain is required to be fully lethal, whereas the presence of the SH3 domain attenuated lethality. Furthermore, the formation of hemangiosarcomas absolutely required the presence of the src SH3 domain and to some extent required the SH2 domain. This implicates distinct and opposite roles for SH2 and SH3 domains of src and their cellular binding partners in tumorigenesis and hemorrhagic disease.     

Cyclic AMP decreases chemotaxis,invasiveness and lung colonization of H-ras transformed mouse fibroblasts

We transfected mouse 10T1/2 fibroblasts with the H-ras oncogene and isolated lines expressing H-ras. One of the lines exhibited a highly malignant phenotype with the ability to produce large tumors and to colonize the lung after tail vein injection. In addition, the cells of this line showed increased collagenase IV production, directed migration and invasiveness, properties associated with the ability of tumor cells to metastasize. Since cyclic adenosine 3,5-monophosphate (cAMP) is known to down-regulate ras expression, we exposed the malignant cells (Cl-1) to either N⁶, 2,0-dibutyryl cAMP (DB-cAMP) or 8-bromo cAMP (8-Br-cAMP), either with or without a phosphodiesterase inhibitor. We found that these treatments reduced the expression of ras, chemotaxis, invasiveness, and lung colonization of the ras-transformed cells. We therefore postulate that the malignancy of some cells may be regulated by alterations in the intracellular cAMP levels by suppressing ras expression and/or by reducing other activities required for the dissemination of tumor cells.     

Structural and nonstructural proteins of strain Colburn cytomegalovirus

The growth of most Rous sarcoma viruses (RSV) is severely restricted on MSB-1 cells (a line of chicken T lymphoblasts) in comparison to growth on chicken embryo fibroblast (CEF). Nonconditional transformation defective mutants of RSV from which the complete src region has been deleted (td RSV) are not subject to growth restriction. We examined the formation and integration of RSV and td RSV in MSB-1 cells following high multiplicity infection. Nearly equivalent quantities of the linear form of unintegrated RSV and td RSV DNA were formed in these cells during the first 10 hr after infection. Linear RSV DNA from MSB-1 cells could not be distinguished from linear RSV from CEF by restriction endonuclease analysis and by previously described transfection assays (P. E. Neiman, C. McMillin-Helsel, and G. M. Cooper, 1978, Virology 89,360–371). Beyond 10 hr after infection, and with progressive cell growth in the MSB-1 cultures, the level of RSV linear DNA rapidly decreased. Presumptive circular RSV DNA was detected only transiently, and at very low levels, about 15 hr after infection. Association of RSV DNA with high-molecular-weight chromosomal DNA, i.e., integration, was not detected in this study. In contrast, nearly constant levels of td RSV unintegrated linear DNA and, after 20 hr, circular DNA persisted in MSB-1 cells for at least 7 days after infection. Integration of td RSV proviral DNA was inefficient, occurring in only about 5% of MSB-1 cells (even at very high multiplicities of infection) in the first round of infection, and in 25–40% of cells by 3 days after infection. Almost all MSB-1 cells containing td RSV DNA produced virus. Analysis of eight nonconditional transformation defective mutants of RSV which retain the src region to different extents showed that all of these mutants replicated to the same normal titer on MSB-1 cells as on CEF without further deletion of the src region. Two temperature sensitive src mutants that thermal inactivation of the scr gene on MSB-1 cells at both 35° and 41°, indicating that thermal inactivation of the src gene product could not abrogate the replication block. These studies clearly demonstrate that the presence of the src region in RSV impedes the formation and/or integration of provirus in some types of host cells.     

Maintenance and copy number control of ARS1 plasmids in Saccharomyces cerevisiae

Summary Following mating of a and isogenic haploids we observe that the frequency of plasmid bearing cells, during selective growth, increases three fold. By examining the mitotic stability, the frequency of plasmid bearing cells during the cell cycle and the copy number of ARS1 plasmids in isogenic haploid and diploid cells, we show that the apparent stability of circular ARS1 plasmids in a/ cells is largely due to a diminished copy number in these cells. This observation is fully comprehensible with the model for plasmid segregation as presented by Murray and Szostak (1983). In order to account for the differences in copy numbers, a and a/a isogenic strains were compared. Likewise a number of mating type nonspecific sterile mutants were compared with the parental Ste⁺ strain. It seems that a diminished copy number is established when the MATa1/MAT2 regulatory system (Klar et al. 1981) is switched on, since the effect is observed in Sir^– strains only.     

Karyotype analysis of the acute fibrosarcoma from chickens infected with subgroup J avian leukosis virus associated with v-src oncogene

To understand the cytogenetic characteristics of acute fibrosarcoma in chickens infected with the subgroup J avian leukosis virus associated with the v-src oncogene, we performed a karyotype analysis of fibrosarcoma cell cultures. Twenty-nine of 50 qualified cell culture spreads demonstrated polyploidy of some macrochromosomes, 21 of which were trisomic for chromosome 7, and others were trisomic for chromosomes 3, 4, 5 (sex chromosome w), and 10. In addition, one of them was trisomic for both chromosome 7 and the sex chromosome 5 (w). In contrast, no aneuploidy was found for 10 macrochromosomes of 12 spreads of normal chicken embryo fibroblast cells, although aneuploidy for some microchromosomes was demonstrated in five of the 12 spreads. The cytogenetic mosaicism or polymorphism of the aneuploidy in the acute fibrosarcoma described in this study suggests that the analysed cells are polyclonal.     

FLP recombinase induction of the breakage-fusion-bridge cycle and gene conversion in Saccharomyces cerevisiae

Summary A YEp chimaeric plasmid containing URA3 and SMR1 [sulfometuron methyl resistant (SM^R) allele of ILV2] as selectable markers, and the 2 m site-specific recombination FLP recognition target (FRT), was integrated at the ilv2-1 site in chromosome XIII in a cir°] haploid. Southern analysis defined two integrant structures. Structure I had URA3 distal and SMR1 proximal to FRT whereas in structure II both markers were distal to FRT. Selectable markers were stably inherited in [cir°] haploids and [cir°] diploids heterozygous for the integrant and ILV2. Approximately 14% of heterozygous [cir ⁺] diploid cells exhibited homozygotization for the distal (500 kb) ade4 marker in trans. In [cir ⁺] diploids FLP-FRT recombination resulted in the simultaneous loss of both structure II markers, whereas the structure I distal URA3 marker loss always preceded the variable loss of the proximal SMR1 marker. URA^– cells continued to segregate for loss of SMR1 until stable URA^– SM^R or URA^–SM^S cells were produced. Gene conversion was identified in stable URA^–SM^R cells that were homozygous SMR1/SMR1 but contained wild type ILV2 restriction endonuclease sites. These observations support a model based on concerted FLP-FRT action resulting from the secondary integration of native 2 m DNA followed by unequal sister chromatid exchange (USCE) within inverted FRTs. The resultant chromatid bridge resulted in a double-stand break. Fusion of the broken ends of sister chromatids generated a breakage-fusion-bridge cycle (BFBC). Repeated rounds of the BFBC resulted in proximal marker loss and the generation of additional double-strand breaks. Recombinogenic properties of the double-strand break initiated events leading to homozygotization and gene conversion.     

Restitution of fibroblast-transforming ability in src deletion mutants of avian sarcoma virus during animal passage.

The Schmidt-Ruppin strain of Rous sarcoma virus subgroup D (SR-D) gives rise to transformation defective (td) mutants which have lost either all or almost all of the src gene (standard td or std viruses) or have only a partial deletion of src. These partial deletion mutants, designated ptd viruses, contain genomic RNA slightly larger than std isolates, and heteroduplex analyses suggest that ptd viruses retain approximately 25% of src from the 5′ end of that gene [Lai et al. (1977) Proc. Natl. Acad. Sci. USA74, 4781–4785]. Several ptd isolates of SR-D were injected into newly hatched chickens and after prolonged latent periods caused sarcomas in about 30% of the birds. The tumors occurred in internal organs away from the site of injection. Infectious sarcoma viruses isolated from these growths show the envelope markers of subgroup D are nondefective for replication and induce a transformation in vitro which is morphologically distinct from that of SR-D. Electrophoresis of 35 S genomic RNA from these recovered sarcoma viruses shows it to be of the size characteristic for nondefective sarcoma viruses. Fingerprint analysis of ³²P-labeled RNA from one of the new sarcoma viruses detected all oligonucleotides present in ptd viruses, the src-specific oligonucleotides of SR-D, and one new oligonucleotide not present in SR-D. This new RNase T₁-resistant oligonucleotide and the src-specific oligonucleotides identical to those of SR-D map close to the 3′ end in the genome of the recovered sarcoma virus, which is the position expected for the src gene. These studies suggest that recovered avian sarcoma viruses have acquired cellular sequences which are closely related in structure and function to the viral src gene.     

Inverse expressions of the N-myc oncogene and β1 integrin in human neuroblastoma: relationships to disease progression in a nude mouse model system

A nude mouse model for human neuroblastoma has been developed to examine possible relationships between amplification/over-expression of the N-myc oncogene and altered regulation of expression of specific integrin subunits during tumor progression. Subcutaneous (ectopic) or intra-adrenal (orthotopic) injection of the neuroblastoma cell lines SK-N-SH or IMR-32 has generated a number of derivative tumor cell lines. Tumor cell lines derived from SK-N-SH cells (which do not express N-myc) or IMR-32 cells (which over-express N-myc) produce tumors at higher rates when re-injected into the subcutaneous space of nude mice. Moreover, cell lines derived from tumors initiated by IMR-32 cells exhibit shorter latent periods than do IMR-32 cells direct from tissue culture. With regard to integrin subunit expression, SK-N-SH and related cell lines express high levels of ₁ integrin, which is associated with the ₂ and ₃ integrin subunits (predominantly ₃). IMR-32 cells display reduced ₁ expression, and that which is produced is not associated with common a subunits. LaN1 cells, which express N-myc at even higher levels than do IMR-32 cells, express even less ₁. Interestingly, the tumor-derived cell lines (especially those from tumors initiated in adrenal glands) also exhibit reduced integrin expression compared with the parental cell lines; this reduction is associated with the enhanced tumor take rate observed when the cells are re-injected into nude mice. Our results raise the possibility of a relationship between over-expression of N-myc and down-regulation of ₁ integrin expression (possibly some a subunits also). In addition, the data suggest that human neuroblastoma-derived cell lines which exhibit reduced integrin expression display more aggressive tumor growth in nude mice.     

Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine

Skeletal muscle catabolism, low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection. In addition, a high glycolytic activity is commonly found in muscle tissue of cachectic cancer patients, suggesting insufficient mitochondrial energy metabolism. We therefore investigated (a) whether an anaerobic physical exercise program causes similar changes in plasma amino acid levels, and (b) whether low plasma glutamine or high glutamate levels are risk factors for loss of body cell mass (BCM) in healthy human subjects, i.e., in the absence of a tumor or virus infection. Longitudinal measurements from healthy subjects over longer periods suggest that the age-related loss of BCM occur mainly during episodes with high venous glutamate levels, indicative of decreased muscular transport activity for glutamate. A significant increase in venous glutamate levels from 25 to about 40 M was seen after a program of anaerobic physical exercise. This was associated with changes in T lymphocyte numbers. Under these conditions persons with low baseline levels of plasma glutamine, arginine, and cystine levels also showed a loss of BCM. This loss of BCM was correlated not only with the amino acid levels at baseline examination, but also with an increase in plasma glutamine, arginine, and cystine levels during the observation period, suggesting that a loss of BCM in healthy individuals terminates itself by adjusting these amino acids to higher levels that stabilize BCM. To test a possible regulatory role of cysteine in this context we determined the effect of N-acetyl-cysteine on BCM in a group of subjects with relatively low glutamine levels. The placebo group of this study showed a loss of BCM and an increase in body fat, suggesting that body protein had been converted into other forms of chemical energy. The decrease in mean BCM/body fat ratios was prevented by N-acetyl-cysteine, indicating that cysteine indeed plays a regulatory role in the physiological control of BCM.Abbreviations BCM Body cell mass - HIV Human immunodeficiency virus type 1 - NAC N-Acetyl-cysteine     

Localisation of CEA, β-HCG,SP1, and keratin in the tissue of lung carcinomas

Summary One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA and-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1. CEA and SP1 could be demonstrated in 80% of the studied cases, while-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.This study was supported by Deutsche Stiftung für Krebsforschung - Dr. Mildred Scheel-Stiftung     

Cell-free translation of purified avian sarcoma virus src mRNA

Avian sarcoma virus 21 S RNA, purified by hybridization from virus-infected cells, was translated in a cell-free system. The major product of translation was a protein of 60,000 daltons. This protein was the same as authentic pp60^src, the product of the ASV src gene, when compared by electrophoretic mobility in polyacrylamide gels, immunological reactivity and partial protease digestion. These findings confirm that the 21 S ASV RNA serves as mRNA for pp60^src. Furthermore, pp60^src is the only major product of translation of the src gene and is apparently synthesized without a cleavable signal sequence.     

Null cell adenoma of the human pituitary

Summary Among 343 surgically-removed pituitary adenomas, 56 tumors were unassociated clinically or biochemically with increased hormone secretion and contained no adenohypophysial hormones by the immunoperoxidase technique, except for 10 cases in which a few scattered cells showed positive immunostaining for -TSH or -FSH, -EH, prolactin and/or -subunit. These tumors were chromophobic adenomas with no PAS, lead hematoxylin or carmoisine positivity and electron microscopy failed to reveal their morphogenesis. The term null cell adenoma of the pituitary is proposed to designate this tumor type. This term recognizes the most obvious features of these tumors: the absence of markers which would permit the disclosure of their cellular origin. Null cells are also found in the nontumorous adeno-hypophysis, suggesting that null cell adenomas derive from preexisting nonneoplastic null cells. The question of whether pituitary null cells are hormonally inactive committed precursors, uncommitted stem cells or dedifferentiated cells remains to be elucidated.This work was supported in part by Grant MA-6349 of the Medical Research Council of Canada and Grant 1 R01 CA 21905-01 awarded by the National Cancer Institute, DHEW     

Direct observation of sexual competition inDrosophila melanogaster: The mutantWhite in competition with other genotypes

When two types ofDrosophila are in competition, the frequency dependence of mating success routinely is measured in our laboratory by direct observation of mating pairs in Elens-Wattiaux observation chambers. The present experiments concern white mutants (used here as a reference standard) in competition with three other genotypes: wild-type Canton S, giantgt w ^a , and giantgt ^13z /w ⁺ Y/C(1)Dx, y f. From the present observations, the frequency dependence of mating success seems a very common phenomenon: a rare-type sexual advantage exists for females and for males. Sexual activity of male and femalewhite mutants is significantly higher when food is present in the mating chamber. Males of the other strains also are more active in the presence of food. Homogamic matings are more frequent amonggt ^13z /w ⁺ Y/C(1)Dx, y f flies.     

Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens

We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small dimensions, the same technique was not applicable to vesicles. For these structures dot-blot analysis and immunoelectron microscopy (IEM) were employed. When applicable, both cell membranes and membrane vesicles were immunoprecipitated and the precipitate (IP) was analyzed by SDS-PAGE. Cells of both lines expressed HLA class I antigens, epithelial cytokeratins, 1 integrins, CEA and the glycoprotein detected by mAb 19.9, but only MCF-7 cells expressed Lewis Y, episialin and globo-H antigens and only 8701-BC cells expressed folate receptor. Membrane vesicles of both cell lines appeared to be rich in 1, 3 and 5 integrin chains, expressed HLA class I antigens and carried most of the plasma membrane antigens found in the cell membranes. Overall we have analyzed 17 antigens on the two cell lines and on their vesicles. The results obtained for cells (IF and IP) and those for vesicles (dot-blot and IP) were generally concordantly positive or concordantly negative. We obtained a total of 26 clearly concordant combinations on 34 analyses. In three cases we found discordant results, whereas in the remaining combinations we observed slight reactivity and we found difficulties in determining concordance. Discordant results concerned the expression of the following antigens: folate receptors, which were clearly expressed in 8701-BC cells but not detected by dot-blot analysis or IEM on their shed membrane vesicles; neu (c-erb-B2) receptor found in MCF-7 cell membranes but not in their vesicles; and the globo-H antigen recognized by mAb MBr1, detected at low levels on 8701-BC plasma membranes but undetectable on their membrane vesicles. Like vesicles shed in vitro by cultured cells, the vesicles shed in vivo by human breast carcinoma cells could be tagged with several antibodies against tumor-associated antigens. The vesicles shed in vivo were found in association with a fiber network. Some of the fibers had the characteristic fibrin periodicity. These data suggest that tumor markers detected in the circulation of carcinoma patients, at least in part, are carried by shed membrane vesicles. Moreover the observation that membrane vesicles carry both tumor-associated antigens and HLA class I molecules indicate that these structures could in principle present antigens to the immune system. Together with our previous demonstration that membrane vesicles shed by breast carcinoma cells contain TGF-, these results suggest an important role for vesicles in the immunological escape of these cells. The presence in membrane vesicles of integrins, together with the previous observation that they are rich in gelatinolytic activities, also points to a possible role of these structures in the metastatic behavior of tumor cells.     

Effects of the CDC2 gene on adaptive mutation in the yeast Saccharomyces cerevisiae

We have studied the influence of a temperature-sensitive cdc2-1 mutation in DNA polymerase on the selection-induced mutation occurring at the LYS-2 locus in the yeast Saccharomyces cerevisiae. It was found that in cells plated on synthetic complete medium lacking only lysine, the numbers of Lys⁺ revertant colonies accumulated in a time-dependent manner in the absence of any detectable increase in cell number. When cdc2-1 mutant cells, after selective plating, were incubated at the restrictive temperature of 37°C for 5 h daily for 7 days, the frequency of an adaptive reversion of lys ^- Lys⁺ was significantly higher than the frequency in cells incubated only at the permissive temperature, or in wild-type cells incubated either at 23°C or 37°C. Therefore, when the proof-reading activity of DNA polymerase is impaired under restrictive conditions, the frequency of adaptive mutations is markedly enhanced.     

An unusual presentation of <Emphasis Type="Italic">helicobacter pylori</Emphasis> infection: so-called “Russell body gastritis”

Helicobacter pylori (H. pylori) is a slow bacterial pathogen, which induces several gastroduodenal diseases. Varying degrees of inflammation can be present in the gastric mucosa of patients infected with H. pylori. The case presented here is a male patient suffering from dyspepsia and nausea. His upper gastrointestinal endoscopy revealed pan gastritis. Histological examination of multiple gastric biopsies taken from the body and antrum showed a rare morphological expression of H. pylori gastritis characterized by diffuse plasma cell infiltration with extensive Russell body formation. Diffuse infiltration of plasma cells with Russell bodies in gastric mucosa can cause difficulties in differentiation from neoplastic processes. However, immunohistochemically, the infiltrating cells in the gastric mucosa stained negatively with cytokeratins while they expressed both kappa and lambda light chains showing their polyclonal nature. The presence of diffuse plasma cells with Russell bodies in the gastric mucosa may represent a different presentation of H. pylori gastritis. There are only two case reports of similar presentation and both have been called Russell body gastritis.