Biomedical subjects

J M Kim

Publications and source records attributed to J M Kim.

At least 145 records · Page 8Linked to original sources

PubMed1999

NF-kappa B is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria.

Human intestinal epithelial cells up-regulate the expression of an inflammatory gene program in response to infection with a spectrum of different strains of enteroinvasive bacteria. The conserved nature of this program suggested that diverse signals, which are activated by enteroinvasive bacteria, can be integrated into a common signaling pathway that activates a set of proinflammatory genes in infected host cells. Human intestinal epithelial cell lines, HT-29, Caco-2, and T84, were infected with invasive bacteria that use different strategies to induce their uptake and have different intracellular localizations (i.e., Salmonella dublin, enteroinvasive Escherichia coli, or Yersinia enterocolitica). Infection with each of these bacteria resulted in the activation of TNF receptor associated factors, two recently described serine kinases, I kappa B kinase (IKK) alpha and IKK beta, and increased NF-kappa B DNA binding activity. This was paralleled by partial degradation of I kappa B alpha and I kappa B epsilon in bacteria-infected Caco-2 cells. Mutant proteins that act as superrepressors of IKK beta and I kappa B alpha inhibited the up-regulated transcription and expression of downstream targets genes of NF-kappa B that are key components of the epithelial inflammatory gene program (i.e., IL-8, growth-related oncogene-alpha, monocyte chemoattractant protein-1, TNF-alpha, cyclooxygenase-2, nitric oxide synthase-2, ICAM-1) activated by those enteroinvasive bacteria. These studies position NF-kappa B as a central regulator of the epithelial cell innate immune response to infection with enteroinvasive bacteria.

Caco-2 Cells↗

PubMed1999

Phosphatidylinositol 3-kinase regulates differentiation of H9c2 cardiomyoblasts mainly through the protein kinase B/Akt-independent pathway.

Phosphatidylinositol 3-kinase (PI3-kinase) is known to be a crucial regulator of muscle differentiation. However, its downstream pathway for this function is quite obscure. In this experiment we demonstrated the regulatory mechanism of the differentiation of H9c2 cardiomyoblasts, focusing on PI3-kinase, protein kinase B/Akt (PKB/Akt) and p42/44 mitogen-activated protein kinase (p42/44 MAPK). When H9c2 cells stably transfected with a constitutively active p110 (H9c2-p110*), a constitutively active PKB/Akt (H9c2-Akt), and an empty vector (H9c2-con) were induced to differentiate, H9c2-p110* cells differentiated fastest, followed by H9c2-Akt cells. H9c2-con cells differentiated at the slowest rate. Consistent with this result, LY294002 completely blocked differentiation of all these transfected cell lines, whereas PD098059 had no effect on their differentiation. When H9c2-p110* cells were transiently transfected with a dominant negative form of PKB/Akt, differentiation was not affected. Taken together, we concluded that PI3-kinase, but not p42/44 MAPK, regulates differentiation of H9c2 cardiomyoblasts mainly through the PKB/Akt-independent pathway.

Animals↗

PubMed1999

Identification of a full-size hobo element and deletion-derivatives in Korean populations of Drosophila melanogaster.

We have isolated and characterized several members of the hobo transposable element family from Korean populations of Drosophila melanogaster. All of the Korean lines tested appeared to have 3.0 kb hobo elements and a high copy number of smaller derivatives of the element. To determine whether a 3.0 kb hobo element of these populations is consistent with the role of an autonomous hobo element, we cloned and sequenced this hobo element. Based on the result of the entire DNA sequence, a cloned 3.0 kb element called HKN96, it was found to be the same as a fully-functional 2959 bp HFL1-type sequence. Each small element appeared to have arisen from the HFL1 element by a different internal deletion. A specific 1.7 kb Kh hobo element, which is the most abundant in the Korean lines tested, seems to have originated from the HFL1 hobo element by an internal deletion of 1253 bp by the removal of nucleotides between positions 939 and 2191. The sequences of the Th1 and Th2 elements appeared to be identical to that of the HFL1 with the exception of internal deletions of 1442 bp and 1455 bp removing nucleotides 940-2381 and 923-2377, respectively. Based on the number of TPE repeats, all of the members of the hobo element family in Korean lines tested have three perfect S repeats. The widespread presence of identical copies of the Kh deletion derivative suggests that it might have a role in the regulation of hobo-induced hybrid dysgenesis.

Animals↗

PubMed1999

Sequences downstream of the RNA initiation site of the HTLV type I long terminal repeat are sufficient for trans-activation by human cytomegalovirus immediate-early proteins.

Human T cell leukemia virus type I infection is associated with a low incidence of morbidity in the form of adult T cell leukemia and neurologic disease, suggesting that there are other factors determining the pathogenic outcome of infection. We found that HCMV could infect various human cell lines known to be susceptible to HTLV-I infection, including T cell lines already harboring HTLV-I, and that HCMV infection could highly activate gene expression from the HTLV-I LTR. In addition, the coexpression of IE1 and IE2 genes of HCMV increased transcription from the HTLV-I LTR. The deletion analysis indicated that the entire U3 region is not required, but that the 216-bp region from +101 to +316 is sufficient for activation of the LTR by IE1 and IE2. These results suggest that HCMV IE proteins may affect the level of HTLV-I gene expression in coinfected individuals by interacting with HTLV-I LTR sequences.

Antigens, Viral↗

PubMed1999

Retroactive DNA analysis for sex determination and dystrophin gene by polymerase chain reaction with archived cytogenetic slides.

We describe a rapid and efficient diagnostic method for sex determination and the dystrophin gene by the polymerase chain reaction (PCR) using archived cytogenetic slides. Archived cytogenetic slides stored for about 4 years at room temperature were used. To confirm whether DNA analysis is possible using the archived cytogenetic slides, we extracted the DNA from the slides and amplified the Y centromeric region (DYZ3), the X centromeric region (DXZ1) and the exon 46 of the dystrophin gene. Of the 50 cases, 24 were peripheral bloods, 13 were amniotic fluid cells, 5 were chorionic villus samplings and 8 were cord bloods. The PCR related sex determination in 22 females and 28 males, showed 100% concordance with the results of chromosome analysis, and all cases showed positive band for the exon 46 of the dystrophin gene. Of the 50 cases of the archived cytogenetic slides, we were fortunate enough to obtain the fresh blood sample from one fetus whose karyotype showed 45,X[34]/46,X,+mar[145] to compare the results of the gDNA with that from archived cytogenetic slide. To confirm whether the marker chromosome was derived from Y chromosome, we studied the six loci (PABY, SRY, RPS4Y (SY16, 17), ZFY, DYS14) on the short arm, one locus (DYZ3) on the centromere and one locus (DYZ1) on the long arm. Of the 8 loci studies, all PCR related Y chromosome showed positive band from both gDNA obtained from cord blood and archived cytogenetic slides. We could conclude from the above results that the marker chromosome was derived from the Y chromosome. We believe our experiment is rapid and efficient for studies of over 10 independent loci from a single slide which has been kept in storage for up to 4 years and that archival Giemsa-stained cytogenetic slide repositories represent valuable DNA resources for clinical and forensic studies.

DNA↗

PubMed1999

c-Fos basal immunoreactivity decreases in rat spinal cord during normal ageing.

The pattern of distribution in rat spinal cord and changing pattern during normal ageing of c-Fos expression were investigated by immunohistochemical staining in male Sprague-Dawley rats at the age of 1 week, 5 months and 2 years. c-Fos immunoreactivity was observed diffusely in gray matters in neonatal rats, preferentially located in deep dorsal horn and around central canal. Compared with those of neonatal rats, these cells decreased prominently in adult rats. In aged rats, immunoreactive cells were not seen in any segments. c-Fos immunoreactivity in spinal cord may be related to stress response, functional differentiation, and in part, neuronal death with target dependence. In conclusion, we demonstrated for the first time that c-Fos expression patterns change during normal ageing.

Aging↗

PubMed1999

Permeability of a capsaicin derivative, [14C]DA-5018 to blood-brain barrier corrected with HPLC method.

In the present work, the transport mechanism of a capsaicin derivative, DA-5018, through blood-brain barrier (BBB) has been investigated to evaluate the feasibility of potential drug development. The result of pharmacokinetic parameters obtained from the intravenous injection of plasma volume marker, [3H]RSA and [14C]DA-5018, indicated that both AUC, area under the plasma concentration curve and VD, volume of distribution in brain of [3H]RSA agreed with those reported (1620 +/- 10 percentage injected dose minute per milliliter (%IDmin/ml) and 12.0 +/- 0.1 microliters/g, respectively). Elimination half-life and AUC of [14C]DA-5018 is corrected by the HPLC analysis, 19.6 +/- 1.2 min and 7.69 +/- 0.85% IDmin/ml, respectively. The metabolic rate of [14C] DA-5018 was very rapid. The blood-brain barrier permeability surface area (PS) product of [14C]DA-5018 was calculated to be 0.24 +/- 0.05 microliter/min/g. The result of internal carotid artery perfusion and capillary depletion suggested that [14C]DA-5018 pass through BBB with the time increasingly. Investigation of transport mechanism of [14C]DA-5018 using agonist and antagonist suggested that vanilloid (capsaicin) receptor did not exist in the BBB, and nutrient carrier system in the BBB has no effect on the transport of DA-5018. In conclusion, despite the fact that penetration of DA-5018 through BBB is significant, the intact drug found in the brain tissue is small because of a rapid metabolism. Therefore, for the central analgesic effect of DA-5018, the method to increase the metabolic stability in plasma and the brain permeability should be considered.

Analgesics, Non-Narcotic↗

PubMed1999

Symptomatic sacral extradural arachnoid cyst associated with lumbar intradural arachnoid cyst.

A case of sacral extradural arachnoid cyst associated with lumbar intradural arachnoid cyst in a 35-year-old male is reported. The patient presented with a history of severe sacrococcygeal pain, constipation, and dysuria for several months. Computed tomographic (CT) myelograms and magnetic resonance imaging (MRI) scans showed a huge sacral cyst without neural components. A favorable outcome could be achieved by decompression of the cyst, obliteration of the fistulous channel between the cyst and the thecal sac, and fenestration of the arachnoid cyst into the subarachnoid space. The relevant literatures are also reviewed.

Adult↗

PubMed1999

Sustained suppression of Fas ligand expression in cisplatin-resistant human ovarian surface epithelial cancer cells.

Although cisplatin derivatives are first line chemotherapeutic agents for the treatment of ovarian epithelial cancer, chemoresistance is a major therapeutic problem. Although the cytotoxic effect of these agents are believed to be mediated through the induction of apoptosis, the role of the Fas/FasL system in chemoresistance in human ovarian epithelial cancer is not fully understood. In the present study, we have used cultures of established cell lines of cisplatin-sensitive human ovarian epithelial tumours (OV2008 and A2780-s) and their resistant variants (C13* adn A2780-cp, respectively) to asses the role of Fas/FasL system in the chemo-responsiveness of ovarian cancer cell to cisplatin. Cisplatin was effective in inducing the expression of cell-associated Fas and FasL, soluble FasL and apoptosis in concentration and time-dependent fashion in both cisplatin-sensitive cell lines (OV2008 and A2780-s). In contrast, while cisplatin was effective in increasing cell-associated Fas protein content in C13*, it failed to up-regulate FasL (cell-associated and soluble forms) and induce apoptosis, irrespective of concentration and duration of cisplatin treatment. Concentrated spent media for OV208 cultures after cisplatin treatment were effective in inducing apoptosis in C13* cells which was partly inhibited by the antagonistic Fas monoclonal antibody (mAb) suggesting that the soluble FasL present in the spent media was biologically active. In the resistant A2780-cp cells, neither Fas nor FasL upregulation were evident in the presence of the chemotherapeutic agent and apoptosis remained low compared to its sensitive counterpart. Activation of the Fas signalling pathway, by addition to the cultures an agonistic Fas mAb, was equally effective in inducing apoptosis in the cisplatin-sensitive (OV2008) and -resistant variant C13*, although these responses were of lower magnitude compared to that observed with cisplatin in the chemosensitive cells. A significant interaction between cisplatin and agonistic Fas mAb was observed in the apoptotic response in OV2008 and C13* when cultured in the presence of both agents. Immunohistochemistry of human ovarian epithelial carcinomas reveals the presence of Fas in low abundance in proliferatively active cells but in high levels in quiescent ones. Although the expression pattern of FasL in the tumour was similar to tha tof Fas, the protein content was considerably lower. Taken together, these data suggest that the dysregulation of the Fas/FasL system may be an important determinant in cisplatin-resistance in ovarian epithelial cancer cells. Our results are also supportive of the notion that combined immuno- and chemo-therapy (i.e., agonistic Fas mAb plus cisplatin) may provide added benefits in the treatment of both chemo-sensitive and -resistant ovarian tumours.

Journal Article↗

PubMed1999

Phenytoin penetration into brain after administration of phenytoin or fosphenytoin.

PURPOSE: This study was designed to measure the brain penetration of phenytoin (PHT) after intravenous (i.v.) administration of either standard PHT or fosphenytoin (FPHT), a PHT prodrug. The study was formulated to answer the question whether the time required for FPHT to be converted to PHT in the bloodstream would delay the accumulation of PHT in brain. METHODS: Four rats were sampled at various times after intravenous infusion of 30 mg/kg PHT i.v. or 30 mg/kg PHT equivalents of FPHT i.v. PHT was measured in serum, protein-free ultrafiltrate, and in brain, by using high-performance liquid chromatography. RESULTS: Although the initial PHT-free fraction was significantly higher for FPHT-treated rats than it was for PHT-treated rats, brain PHT levels were significantly reduced after infusion of FPHT. CONCLUSIONS: When FPHT is used for treatment of generalized status epilepticus, it should be anticipated that lower initial brain PHT levels will be achieved than are typically found with standard PHT.

Animals↗

PubMed1999

Precise detection and tracing of Trichoderma hamatum 382 in compost-amended potting mixes by using molecular markers.

Randomly amplified polymorphic DNA (RAPD) analysis and the PCR assay were used in combination with dilution plating on a semiselective medium to detect and enumerate propagules of Trichoderma hamatum 382, a biocontrol agent utilized in compost-amended mixes. Distinct and reproducible fingerprints were obtained upon amplification of purified genomic DNA of T. hamatum 382 with the random primers OPE-16, OPH-19, and OPH-20. Three amplified DNA fragments of 0.35 (OPE-16(0.35)), 0.6 (OPH-19(0.6)), and 0.65 (OPH-20(0.65)) kb were diagnostic for T. hamatum 382, clearly distinguishing it from 53 isolates of four other Trichoderma spp. tested. Some isolates of T. hamatum shared these low-molecular-weight fragments with T. hamatum 382. However, RAPD analysis of isolates of T. hamatum with all three random primers used in consecutive PCR tests distinguished T. hamatum 382 from other isolates of T. hamatum. These three RAPD amplicons were cloned and sequenced, and pairs of oligonucleotide primers for each cloned fragment were designed. Use of the primers in the PCR assay resulted in the amplification of DNA fragments of the same size as the cloned RAPD fragments from genomic DNA of T. hamatum 382. A combination of dilution plating on a semiselective medium for Trichoderma spp. and PCR, with the RAPD primers OPH-19, OPE-16, and OPH-20 or the three sequence-characterized primers, was used successfully to verify the presence of T. hamatum 382 propagules in nine different soil, compost, and potting mix samples. All 23 Trichoderma isolates recovered on semiselective medium from commercial potting mixes fortified with T. hamatum 382 were identified as T. hamatum 382, whereas 274 Trichoderma isolates recovered from the other nine samples were negative in the PCR assay. Thus, this highly specific combination of techniques allowed detection and enumeration of propagules of T. hamatum 382 in fortified compost-amended potting mixes. Sequence-characterized amplified region markers also facilitated the development of a very simple procedure to amplify DNA of T. hamatum 382 directly from fortified compost-amended potting mixes.

Base Sequence↗

PubMed1999

Involvement of the Fas/Fas ligand system in p53-mediated granulosa cell apoptosis during follicular development and atresia.

In the present study we have examined the presence of Fas, Fas ligand (FasL), and p53 in rat granulosa cells during follicular development and atresia, especially in relation to the granulosa cell cycle progression and the onset of granulosa cell apoptosis. Fas, FasL, and p53 proteins were immunolocalized, and their contents were determined by Western blotting. Granulosa cell apoptosis was assessed by DNA fragmentation analyses (DNA ladder) and in situ terminal deoxynucleotidyl transferase mediated deoxy-UTP-biotin nick end labeling (TUNEL) as well as by flow cytometry. Ovaries not exposed to gonadotropins (control) consisted predominantly of preantral and early (small) antral follicles, the latter of which were mostly atretic and demonstrated intense TUNEL staining in granulosa cells exhibiting positive immunoreactivities for FasL and Fas. Granulosa cells isolated from these follicles were apoptotic, as evident by clear ladder pattern of DNA fragmentation upon electrophoretic analysis and the high percentage (>10%) of the cell population in the A0 phase of the cell cycle. After gonadotropin treatment, these features completely disappeared during each of the 3 days of follicular growth to the medium to large antral stages. Cell cycle analysis showed significantly higher proportion of the cells in S and G2/M phases compared with controls, which was accompanied by marked decrease in immunoreactivities for Fas, FasL, and p53. By days 4 and 5, widespread atresia and extensive granulosa cell apoptosis were noted in large antral and preovulatory follicles and were coincidental to increased expression of p53 and Fas, but not of FasL, as well as an apparent arrest of granulosa cell G1/S progression, as evident by an increased cell population in G0/G1 and a decrease in the S and G2/M. Granulosa cells from equine CG-primed ovaries exhibited marked increases in p53 and Fas protein contents and apoptosis after adenoviral p53-sense complementary DNA infection in vitro and were more responsive to Fas activation by an agonistic Fas monoclonal antibody challenge. Taken together, these findings are consistent with the well accepted concept that gonadotropin plays a central role as a survival factor in the regulation of granulosa cell Fas/FasL and p53 expression during ovarian follicular development. In addition, the control of granulosa cell apoptosis may involve two consecutive cellular/molecular events: cell cycle arrest at G1/S and exit from G0 into A0 phase, via regulation of the p53 and Fas/FasL death pathways.

Animals↗

PubMed1999

Increased intracellular cAMP renders HL-60 cells resistant to cytotoxicity of taxol.

The treatment of advanced cancers with paclitaxel (taxol) is hindered by the development of drug resistance. Resistance to taxol is known to be associated with multidrug resistance (MDR) and a mutation affecting either the alpha- or beta-subunit of tubulin. In this study, we demonstrated that an intracellular cAMP level may also play an important role in resistance to taxol in HL-60, acute promyelocytic leukemia cells. Exposure of HL-60 cells to various doses of taxol for 18 hr resulted in cell death. However, pretreatment of the cells with cAMP analogs such as N6:O2-dibutyl cAMP (Db-cAMP), 8-(4-chlorophenylthio) cAMP (CPT-cAMP) and 8-bromo-cAMP (8-Br-cAMP) or an intracellular cAMP elevating agent such as forskolin apparently rendered HL-60 cells more resistant to taxol, but not with dimethyl sulfoxide (DMSO) or retinoic acid (RA), well known differentiating agents. To investigate whether protein kinase A (PKA) activated by an increase in intracellular cAMP level could be involved in increased taxol resistance of the cells, we examined the effects of PKA inhibitors, including H-89 and KT5720, on taxol resistance induced by Db-cAMP. The PKA inhibitors significantly abolished Db-cAMP-induced taxol resistance. These results suggest that cAMP analogs may render tumor cells more resistant to taxol via PKA activation.

Antineoplastic Agents, Phytogenic↗

PubMed1999

Experimental autoimmune myasthenia gravis and CD5+ B-lymphocyte expression.

Myasthenia gravis is one of the typical organ specific autoimmune disease and the CD5+ B-lymphocytes are known to be associated with the secretion of autoimmune antibodies. The authors performed the study to establish an animal model of experimental autoimmune myasthenia gravis (EAMG) by immunizing the nicotinic acetylcholine receptor (AChR) and to understand CD5+ B-lymphocyte changes in peripheral blood of EAMGs. Lewis rats weighing 150-200 g were injected subcutaneously three times with 50 microg AChR purified from the electric organ of Torpedo marmorata and Freund's adjuvant. The EAMG induction was assessed by evaluating clinical manifestations. The CD5+ B-lymphocyte was double stained using monoclonal PE conjugated anti-CD5+ and FITC conjugated anti-rat CD45R antibodies and calculated using a fluorescence-activated cell sorter (FACS). In three out of ten Lewis rats injected with purified AChR, the EAMG models were established. The animals showed definite clinical weakness responded to neostigmine; they had difficulty in climbing the slope, or easily fell down from a vertical cage. The range of CD5+ B-lymphocytes of peripheral blood in the EAMG models was 10.2%-17.5%, which was higher than in controls. In conclusion, the EAMG models were successfully established and the CD5+ B-lymphocyte expression in peripheral blood increased in EAMGs. This provided indirect evidence of the autoimmune pathomechanism of human myasthenia gravis.

Animals↗

PubMed1999

Spinocerebellar ataxia type 2 in seven Korean families: CAG trinucleotide expansion and clinical characteristics.

Studies on spinocerebellar ataxias (SCA) have been hampered by a lack of disease markers. Clinical and pathological heterogeneity also made the classification unreliable. Linkage studies established that there are multiple subtypes of SCA. Five types are found to have unstable CAG expansion; the diagnosis can be established by molecular genetic study. Therefore, we systemically screened degenerative ataxia patients for these five SCA types, and identified eight patients with SCA2 (seven from six families and one sporadic case). This paper presents the clinical information on the seven patients, whose clinical information was available in detail. CAG repeat expansion in the patients ranged from 38 to 47 (normal control, 19 to 27). The onset ages ranged from 16 to 41 with 27.1 years as the mean, which correlated inversely with repeat lengths. All patients presented dysarthria and gait ataxia. Upper limb dysmetria or dysdiadochokinesia appeared later but progressed, causing severe disability. Slow saccade (4 patients in 7) and decreased DTR (4 in 7) were common. MRIs showed severe atrophy of the brainstem and cerebellum in all patients. We conclude that SCA2 is the most frequent type in Korea and carries rather pure cerebellar syndrome, slow saccade, and hyporeflexia.

Adolescent↗

PubMed1999

Antibodies to human T-cell lymphotropic virus type I (HTLV-I) by particle agglutination (PA) test in Korean blood donors.

HTLV-I infection is a recently recognized disease entity that is common in some tropical and subtropical areas, including the southwestern district of Japan. Despite the geographical proximity and frequent cultural exchanges between Korea and Japan, it is understood that Korea is not an endemic area and HTLV-I-associated illnesses are very rare in Korea. This study was designed to evaluate the positive rate of anti-HTLV-I antibodies in Korean blood donors and its regional distribution. Sera were obtained from blood donors from various districts around Korea. Anti-HTLV-I antibodies were detected by using the microtiter particle agglutination test employing an indirect agglutination technique. A total of 9,281 donors were tested and 12 donors (0.13%) were positive for anti-HTLV-I antibodies, 10 (0.11%) out of 8,845 males and 2 (0.46%) out of 436 females, with relative female predominance. A relatively high incidence of anti-HTLV-I positive donors was observed in Cheju Island (0.80%), Kyungnam (0.31%), and Chonnam (0.15%). In conclusion, the positive rate of anti-HTLV-I antibodies seemed to be very low in Korea, but the highest positive rate of anti-HTLV-I antibodies was noticed on Cheju Island, warranting further research for confirmation.

Adolescent↗

PubMed1999

Establishment of BALB/c mice model infected with Helicobacter pylori.

OBJECTIVES: Considering the geographic differences in the prevalence of virulence factors such as CagA or VacA of H. pylori isolated from Korean adults compared with those from western countries, the establishment of a mouse model infected with H. pylori isolated from Korean adults is needed to investigate the pathogenesis and to develop vaccines against H. pylori infection in Korea. The aim of this study was to establish the BALB/c mouse model infected with H. pylori isolated from Korean. METHODS: Six-week-old BALB/c mice were inoculated intragastrically with 10(9) CFU of H. pylori. Loss of glandular architecture, erosions and infiltration of inflammatory cells within the lamina propria compared with normal gastric mucosa were scrutinized. Evidence for H. pylori infection was assessed by rapid urease test of gastric mucosa and by microscopic examination using the H & E stain and Warthin-Starry silver stain. RESULTS: Rapid urease test was positive in 55% of all inoculated mice. Definite histologic changes and the evidence of H. pylori colonization were observed in the H. pylori infected group. Significant infiltration of inflammatory cells was observed 6 weeks after the last inoculation and the level of serum IgG against H. pylori was increased from 2 weeks after the last inoculation. CONCLUSIONS: The H. pylori isolated freshly from Korean adults could colonize the stomach of BALB/c mice and induce pathologic alterations that mimics human gastric diseases. This model would facilitate the investigations for the pathogenetic mechanisms of H. pylori infection.

Adult↗

PubMed1998

Apoptosis of human intestinal epithelial cells after bacterial invasion.

Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers.

Antibodies↗