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1.
J Hosp Infect ; 148: 129-137, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38621513

ABSTRACT

BACKGROUND: A well-established antimicrobial resistance (AMR) laboratory-based surveillance (LBS) is of utmost importance in a country like Zambia which bears a significant proportion of the world's communicable disease burden. This study assessed the capacity of laboratories in selected hospitals to conduct AMR surveillance in Zambia. METHODS: This cross-sectional exploratory study was conducted among eight purposively selected hospitals in Zambia between August 2023 and December 2023. Data were collected using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. FINDINGS: Of the assessed facilities, none had full capacity to conduct AMR surveillance with varying capacities ranging from moderate (63% (5/8)) to low (38% (3/8)). Some of the barriers of AMR-LBS were the lack of an electronic laboratory information system (63% (5/8)) and the lack of locally generated antibiograms (75% (6/8)). Quality control for antimicrobial susceptibility testing (AST), pathogen identification and media preparation had the lowest overall score among all of the facilities with a score of 14%, 20% and 44%, respectively. The highest overall scores were in specimen processing (79%), data management (78%), specimen collection, transport and management (71%), and safety (70%). Most facilities had standard operating procedures in place but lacked specimen-specific standard operating procedures. CONCLUSION: The absence of laboratories with full capacity to conduct AMR surveillance hinders efforts to combat AMR and further complicates the treatment outcomes of infectious diseases. Establishing and strengthening LBS systems are essential in quantifying the burden of AMR and supporting the development of local antibiograms and treatment guidelines.


Subject(s)
Hospitals , Zambia , Cross-Sectional Studies , Humans , Drug Resistance, Bacterial , Epidemiological Monitoring , Microbial Sensitivity Tests/standards , Anti-Bacterial Agents/pharmacology
2.
Transbound Emerg Dis ; 64(6): 1965-1969, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27888587

ABSTRACT

Mycobacterium orygis, commonly known as the oryx bacillus and a newly proposed Mycobacterium tuberculosis complex subspecies, was isolated from 18 cattle in a dairy farm and two captured rhesus monkeys in a zoo in Bangladesh. All the infected animals had tuberculosis lesions in their lungs, suggesting transmission and infection with M. orygis by an airborne route. The 20 isolates were analysed using a range of conventional and molecular typing methods, and RD-deletion typing and sequencing of selected genes confirmed the isolates as M. orygis. Multiple-locus variable-number tandem repeat analysis (MLVA) allowed the isolates to be divided into three clusters based on the relatedness of their MLVA profiles. The two monkey isolates shared the same MLVA pattern with 15 of the cattle isolates, whereas the remaining three cattle isolates had different patterns, even though the latter animals had been kept in the same dairy farm. The diversity observed among isolates may suggest the bacteria have been established in this area for a long period. This study along with other recent findings that report the detection of M. orygis from animals as well as humans originating from South Asia potentially indicate endemic distribution of M. orygis in South Asia.


Subject(s)
Macaca mulatta , Monkey Diseases/microbiology , Mycobacterium/isolation & purification , Tuberculosis/veterinary , Animals , Bangladesh , Cattle , Dairying , Female , Molecular Typing/veterinary , Mycobacterium/classification , Mycobacterium/genetics , Phylogeny , Tuberculosis/microbiology , Tuberculosis, Bovine/microbiology
3.
Transbound Emerg Dis ; 64(3): 929-937, 2017 Jun.
Article in English | MEDLINE | ID: mdl-26671520

ABSTRACT

A study was undertaken to isolate and characterize Mycobacterium species from black wildebeest suspected of being infected with tuberculosis in South Africa. This led to the discovery of a new Mycobacterium avium complex species, provisionally referred to as the Gnou isolate from black wildebeest (Connochaetes gnou). Sixteen samples from nine black wildebeest were processed for Mycobacterium isolation. Following decontamination, samples were incubated in an ordinary incubator at 37°C on Löwenstein-Jensen slants and in liquid medium tubes using the BACTEC™ MGIT™ 960 system, respectively. Identification of the isolate was carried out by standard biochemical tests and using the line probe assay from the GenoType® CM/AS kit (Hain Lifescience GmbH, Nehren, Germany). The DNA extract was also analysed using gene sequencing. Partial gene sequencing and analysis of 16S rRNA gene, and 16S-23S rRNA (ITS), rpoB and hsp65 and phylogenetic analyses by searching GenBank using the BLAST algorithm were conducted. Phylogenetic trees were constructed using four methods, namely Bayesian inference, maximum likelihood, maximum parsimony and neighbour-joining methods. The isolate was identified as Mycobacterium intracellulare using the GenoType® CM/AS kit and as Mycobacterium avium complex (MAC) by gene sequencing. The gene sequence targeting all the genes, ITS, 16S rRNA, rpoB and hsp65 and phylogenetic analyses indicated that this isolate presented a nucleotide sequence different from all currently published sequences, and its position was far enough from other MAC species to suggest that it might be a new species.


Subject(s)
Antelopes , Mycobacterium avium Complex/genetics , Tuberculosis/veterinary , Animals , DNA, Bacterial/genetics , Mycobacterium avium Complex/classification , Phylogeny , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , South Africa/epidemiology , Tuberculosis/epidemiology , Tuberculosis/microbiology
4.
Int J Microbiol ; 2016: 5275724, 2016.
Article in English | MEDLINE | ID: mdl-27190518

ABSTRACT

The frequent administering of antibiotics in the treatment of poultry diseases may contribute to emergence of antimicrobial-resistant strains. The objective of this study was to detect the presence of extended-spectrum ß-lactamase- (ESBL-) producing Escherichia coli in poultry in Zambia. A total of 384 poultry samples were collected and analyzed for ESBL-producing Escherichia coli. The cultured E. coli isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction for detection of bla CTX-M, bla SHV, and bla TEM genes. Overall 20.1%, 77/384, (95% CI; 43.2-65.5%) of total samples analyzed contained ESBL-producing Escherichia coli. The antimicrobial sensitivity test revealed that 85.7% (66/77; CI: 75.7-92) of ESBL-producing E. coli isolates conferred resistance to beta-lactam and other antimicrobial agents. These results indicate that poultry is a potential reservoir for ESBL-producing Escherichia coli. The presence of ESBL-producing Escherichia coli in poultry destined for human consumption requires strengthening of the antibiotic administering policy. This is important as antibiotic administration in food animals is gaining momentum for improved animal productivity in developing countries such as Zambia.

5.
Sci Rep ; 5: 10711, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-26030090

ABSTRACT

We have studied the formation of Pd42.5Cu30Ni7.5P20 metallic glass droplets and wires in the gas atomization process. We demonstrate that the sizes of droplets and wires can be distinguished by the Ohnesorge number (Oh), which is the proportion of the spinnability to the capillary instability, and the diameter distributions follow a log-normal distribution function, implying cascade fragmentation. For droplets, the number significantly increases at Oh < 1 but the diameter gradually decreases. For wires, the number greatly increases at Oh > 1 while the diameter steadies below 400 nm. Further, the wire diameter is quadrupled at Oh = 16 due to the high viscosity which suppresses both capillary breakup and ligament elongation.

6.
Case Rep Oncol ; 7(1): 144-8, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24748865

ABSTRACT

A 59-year-old male patient presented with left chest discomfort on admission. His medical history included encephalitis in childhood and his smoking history was 20 cigarettes per day for 40 years. A physical examination showed an anemic and edematous face with weak respiratory sounds in the left lung. The patient had elevated calcium levels and decreased hemoglobin and potassium. His parathyroid hormone-related protein level was elevated. Thoracic radiography showed cardiomegaly and computed tomography revealed a left lung mass with invasion of the heart and pleural effusion. Magnetic resonance imaging showed endocardial invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in the region surrounding the heart. No diagnoses were possible upon frequent cytology of his sputum and pleural effusion. The patient died from congestive heart failure with anoxia 38 days after admission. An autopsy revealed tumoral mass occlusion in the left main bronchus and tumoral invasion of the left atrium, left ventricle, and aorta.

7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 78(4 Pt 1): 041132, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18999404

ABSTRACT

We study the phase transition of a nonequilibrium statistical-mechanical model, in which two degrees of freedom with different time scales separated from each other touch their own heat bath. A general condition for finding anomalous negative latent heat recently discovered is derived from a thermodynamic argument. As a specific example, the phase diagram of a spin-lattice-gas model is studied based on a mean-field analysis with the replica method. While configurational variables are spin and particle in this model, it is found that the negative latent heat appears in a parameter region of the model, irrespective of the order of their time scale. Qualitative differences in the phase diagram are also discussed.

8.
J Appl Microbiol ; 105(6): 2104-14, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19120656

ABSTRACT

AIMS: To investigate the prevalence of culturable and nonculturable Legionella species in hot water systems of public buildings in Japan and assess the risk factors associated with Legionella contamination in hot water systems. METHODS AND RESULTS: Legionella species were detected by conventional culture and molecular methods in 130 water samples collected from 40 buildings. A total of 26 (20.0%) water samples from 17 (42.5%) buildings were positive by culture, qualitative PCR or both methods: Legionella pneumophila and Leg. anisa were detected in four samples by a culture method, whereas 23 samples were positive by qualitative PCR, with the presence of various Legionella species confirmed by sequencing. Of these 23 samples, bacterial counts were quantifiable in 21 by real-time PCR (from 1.7 x 10(5) to 2.6 x 10(11) cells per litre). Phylogenetic analysis of amplified partial 16S rRNA gene showed close relations to various species of Legionella, including Leg. anisa and Leg. micdadei, all of which have been associated with respiratory diseases or increased antibody titres in human sera. Assessment of risk factors showed that turbidity, free chlorine concentration, iron concentration and heterotrophic plate count (HPC) were significantly associated with Legionella contamination (P < 0.05). CONCLUSIONS: Contamination of hot water systems of public buildings with culturable and nonculturable Legionella species may be a potential risk factor for Legionella infection in Japan. Adequate levels of chlorine, low levels of iron and HPC are important maintenance measures in the reduction of Legionella contamination in hot water systems. SIGNIFICANCE AND IMPACT OF THE STUDY: More than 40% of hot water systems in the Japanese public buildings examined were contaminated by not only culturable Leg. pneumophila and Leg. anisa but also by nonculturable pathogenic species. To our knowledge, this is the first report of both culturable and nonculturable Legionella contamination in hot water systems of public buildings in Japan.


Subject(s)
Fresh Water/microbiology , Hot Temperature , Legionella/isolation & purification , Water Pollution , Water Supply , Colony Count, Microbial , DNA, Bacterial/analysis , Japan , Legionella/classification , Legionella/genetics , Public Facilities/standards , RNA, Ribosomal, 16S , Risk Factors
9.
J Immunol ; 167(12): 6877-83, 2001 Dec 15.
Article in English | MEDLINE | ID: mdl-11739505

ABSTRACT

IL-12 was recently shown to induce CCR5 on TCR-triggered mouse T cells. Considering that STAT4 is the most critical of IL-12 signaling molecules, this study investigated the role for STAT4 in the induction of CCR5 expression. IL-12R was induced by stimulation with anti-CD3 plus anti-CD28 mAb similarly on T cells from wild-type (WT) and STAT4-deficient (STAT4(-/-)) mice, but the levels of IL-12R induced on IFN-gamma-deficient (IFN-gamma(-/-)) T cells were lower compared with WT T cells. Exposure of TCR-triggered WT T cells to IL-12 induced CCR5 expression. In contrast, TCR-triggered STAT4(-/-) T cells failed to express CCR5 in response to IL-12. IL-12 stimulation induced detectable albeit reduced levels of CCR5 expression on IFN-gamma(-/-) T cells. Addition of rIFN-gamma to cultures of IFN-gamma(-/-) T cells, particularly to cultures during TCR triggering resulted in restoration of CCR5 expression. However, CCR5 expression was not induced in STAT4(-/-) T cells by supplementation of rIFN-gamma. These results indicate that for the induction of CCR5 on T cells, 1) STAT4 plays an indispensable role; 2) such a role is not substituted by simply supplementing rIFN-gamma; and 3) IFN-gamma amplifies CCR5 induction depending on the presence of STAT4.


Subject(s)
DNA-Binding Proteins/physiology , Interleukin-12/pharmacology , Receptors, CCR5/biosynthesis , T-Lymphocytes/immunology , Trans-Activators/physiology , Animals , Cells, Cultured , DNA-Binding Proteins/genetics , Flow Cytometry , Humans , Interferon-gamma/genetics , Interferon-gamma/pharmacology , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Mice, Knockout , RNA, Messenger/biosynthesis , Receptors, Antigen, T-Cell/metabolism , Receptors, CCR5/genetics , Receptors, Interleukin/biosynthesis , Receptors, Interleukin/genetics , Receptors, Interleukin-12 , STAT4 Transcription Factor , Signal Transduction , T-Lymphocytes/drug effects , Trans-Activators/genetics
10.
Int Immunol ; 13(12): 1471-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11717188

ABSTRACT

Contact hypersensitivity (CHS) is a T cell-mediated cellular immune response caused by epicutaneous exposure to contact allergens. In this reaction, after the first epicutaneous allergen sensitization, Langerhans cells (LC) catch allergens and migrate from the skin to draining lymph nodes (LN) and activate naive T cells. Although IL-1 is suggested to be involved in these processes, the mechanisms have not been elucidated completely. In this report, to elucidate roles of IL-1alpha and IL-1beta in CHS, we analyzed ear swelling in 2,4,6-trinitrochlorobenzene (TNCB)-induced CHS using gene-targeted mice. We found that ear swelling was suppressed in IL-1alpha-deficient (IL-1alpha(-/-)) mice but not in IL-1beta(-/-) mice. LC migration from the skin into LN was delayed in both IL-1alpha(-/-) and IL-1beta(-/-) mice, suggesting that this defect was not the direct cause for the reduced CHS in these mice. However, we found that the proliferative response of trinitrophenyl (TNP)-specific T cells after sensitization with TNCB was specifically reduced in IL-1alpha(-/-) mice. Furthermore, adoptive transfer of TNP-conjugated IL-1-deficient epidermal cells (EC) into wild-type mice indicated that only IL-1alpha, but not IL-1beta, produced by antigen-presenting cells in EC could prime allergen-specific T cells. These observations indicate that IL-1alpha, but not IL-1beta, plays a crucial role in TNCB-induced CHS by sensitizing TNP-specific T cells.


Subject(s)
Allergens/immunology , Dermatitis, Contact/immunology , Epitopes, T-Lymphocyte/immunology , Interleukin-1/physiology , Lymphocyte Activation , Picryl Chloride/immunology , T-Lymphocytes/immunology , Administration, Cutaneous , Adoptive Transfer , Allergens/administration & dosage , Animals , Antibody Formation/genetics , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Movement/genetics , Cell Movement/immunology , Dermatitis, Contact/genetics , Dose-Response Relationship, Immunologic , Epidermal Cells , Epidermis/transplantation , Immunization , Interleukin-1/biosynthesis , Interleukin-1/deficiency , Interleukin-1/genetics , Langerhans Cells/cytology , Langerhans Cells/immunology , Lymph Nodes/immunology , Lymph Nodes/pathology , Lymphocyte Activation/genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Picrates/immunology , Picryl Chloride/administration & dosage
11.
Eur J Immunol ; 31(8): 2411-20, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11500825

ABSTRACT

Despite increasing evidence for the role of the chemokine system in leukocyte trafficking, the mechanism underlying the induction of chemokine receptors is poorly understood. Here, we investigated how CCR5, a chemokine receptor implicated in T cell migration to inflammatory sites, is induced in the T cell. CCR5 mRNA was hardly detected in resting T cells and marginally induced following T cell receptor (TCR) stimulation. However, TCR-triggered T cells expressed IL-12 receptor, and stimulation with recombinant IL-12 resulted in high levels of CCR5 expression on both CD4(+) and CD8(+) T cells. In contrast, IL-2 failed to up-regulate CCR5 expression. The effect of IL-12 was selective to CCR5 because IL-12 did not up-regulate CXCR3 expression. Surface expression of CCR5 was shown by staining with anti-CCR5 monoclonal antibody. Stimulation of these CCR5-positive T cells with the relevant chemokine MIP-1 alpha elicited Ca(2+) influx, showing that IL-12-induced CCR5 is functional. These results indicate a critical role for IL-12 in the induction of CCR5 on TCR-triggered T cells.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Interleukin-12/immunology , Receptors, Antigen, T-Cell/immunology , Receptors, CCR5/metabolism , Animals , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , Calcium/metabolism , Calcium Signaling/drug effects , Cells, Cultured , Chemokine CCL4 , Fluorescent Antibody Technique , Interferon-gamma/immunology , Macrophage Inflammatory Proteins/pharmacology , Mice , Mice, Inbred BALB C , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, CCR5/genetics , Up-Regulation
12.
Mech Dev ; 102(1-2): 95-105, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11287184

ABSTRACT

Eph receptors have been implicated in cell-to-cell interaction during embryogenesis. We generated EphA2 mutant mice using a gene trap method. Homozygous mutant mice developed short and kinky tails. In situ hybridization using a Brachyury probe found the notochord to be abnormally bifurcated at the caudal end between 11.5 and 12.5 days post coitum. EphA2 was expressed at the tip of the tail notochord, while one of its ligands, ephrinA1, was at the tail bud in normal mice. In contrast, EphA2-deficient notochordal cells were spread broadly into the tail bud. These observations suggest that EphA2 and its ligands are involved in the positioning of the tail notochord through repulsive signals between cells expressing these molecules on the surface.


Subject(s)
Fetal Proteins , Notochord/metabolism , Proteins/metabolism , Receptor Protein-Tyrosine Kinases/physiology , Tail/physiology , Trans-Activators , Animals , Base Sequence , Blotting, Northern , Blotting, Southern , Cell Communication , DNA, Complementary/metabolism , Ephrin-A1 , Female , Galactosides/metabolism , Genetic Vectors/metabolism , Hedgehog Proteins , Homozygote , In Situ Hybridization , Indoles/metabolism , Ligands , Male , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Mice, Transgenic , Models, Genetic , Molecular Sequence Data , Notochord/chemistry , Phenotype , Protein Binding , Protein Biosynthesis , Receptor, EphA2 , Signal Transduction , T-Box Domain Proteins/biosynthesis , Time Factors , Tretinoin/pharmacology
13.
Cancer Res ; 61(8): 3399-405, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11309299

ABSTRACT

IFN-gamma-deficient (IFN-gamma-/-) mice induce potent in vitro immune responses such as anti-allo mixed lymphocyte reaction and CTL responses, whereas they often fail to exhibit in vivo immunity. Here, we investigated whether there exists a defect in tumor rejection responses and if so, which process of responses is impaired. IFN-gamma-/- and wild-type (WT) BALB/c mice were immunized with attenuated syngeneic CSA1M tumor cells. The capacity of T cells to mediate tumor protection was examined in Winn assays to assess the growth of tumor cells admixed with tumor-sensitized T cells. Splenic T cells from both groups of mice exhibited comparable levels of tumor-neutralizing activity. When portions of immunized mice were directly challenged with viable tumor cells, tumor rejection was induced only in WT mice. CD4(+) and CD8(+) T-cell infiltration were observed at the site of tumor challenge in WT mice, whereas such a T-cell infiltration did not occur in IFN-gamma-/- mice. Similarly, splenic T cells from interleukin 12-treated CSA1M-bearing IFN-gamma-/- and WT mice neutralized tumor cells at comparable efficacies in Winn assays. However, the migration of these T cells to tumor masses and the resultant interleukin 12-induced tumor regression took place in WT mice, but neither intratumoral T-cell infiltration nor tumor regression occurred in IFN-gamma-/- mice. These results indicate a critical requirement for IFN-gamma in the process of inducing T-cell migration to tumor sites rather than of generating antitumor protective T cells.


Subject(s)
Cell Movement/immunology , Fibrosarcoma/immunology , Interferon-gamma/immunology , T-Lymphocytes/immunology , Animals , Interferon-gamma/deficiency , Interferon-gamma/genetics , Interleukin-12/immunology , Interleukin-12/pharmacology , Lymphocyte Activation/immunology , Male , Mice , Mice, Inbred BALB C , Spleen/cytology , Spleen/immunology
14.
Int Immunol ; 12(5): 701-9, 2000 May.
Article in English | MEDLINE | ID: mdl-10784616

ABSTRACT

While IL-12 administration induces tumor regression through stimulating T cells in tumor-bearing mice, this IL-12 effect is observed in some but not all tumor models. The present study aimed to compare IL-12 responsiveness of T cells from tumor-bearing mice in IL-12-responsive (CSA1M and OV-HM) and -unresponsive (Meth A) tumor models. Tumor regression in IL-12-responsive tumor models required the participation of T cells, but not of NK1.1(+) cells. Because a NK1.1(+) cell population was the major producer of IFN-gamma, comparable levels of IFN-gamma production were induced in IL-12-responsive and -unresponsive tumor-bearing mice. This indicates that the amount of IFN-gamma produced in tumor-bearing individuals does not correlate with the anti-tumor efficacy of IL-12. In contrast, IL-12 responsiveness of T cells differed between the responsive and unresponsive models: purified T cells from CSA1M/OV-HM-bearing or Meth A-bearing mice exhibited high or low IL-12 responsiveness respectively, when evaluated by the amounts of IFN-gamma produced in response to IL-12. T cells from CSA1M- or OV-HM-bearing but not from Meth A-bearing mice exhibited enhanced levels of mRNA for the IL-12 receptor (IL-12R). These results indicate that a fundamental difference exists in IL-12 responsiveness of T cells between IL-12-responsive and -unresponsive tumor models, and that such a difference is associated with the expression of IL-12R on T cells.


Subject(s)
Interleukin-12/therapeutic use , Killer Cells, Natural/immunology , Neoplasms, Experimental/drug therapy , T-Lymphocytes/immunology , Animals , Antigens/immunology , Antigens, Ly , Antigens, Surface , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Enzyme-Linked Immunosorbent Assay , Female , Interferon-gamma/analysis , Interferon-gamma/blood , Interleukin-12/immunology , Killer Cells, Natural/drug effects , Lectins, C-Type , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , NK Cell Lectin-Like Receptor Subfamily B , Neoplasms, Experimental/immunology , Proteins/immunology , RNA, Messenger/analysis , Receptors, Interleukin/analysis , Receptors, Interleukin/genetics , Receptors, Interleukin-12 , Spleen/immunology , T-Lymphocytes/drug effects , Time Factors , Tumor Cells, Cultured , Tumor Escape
15.
J Immunother ; 23(6): 643-53, 2000.
Article in English | MEDLINE | ID: mdl-11186152

ABSTRACT

Interleukin-12 (IL-12) treatment is effective in the CSA1M but not in the Meth A and CSA1M-variant tumor models. The authors investigated the cause by which IL-12 treatment fails to induce tumor regression in these two tumor models. T cells from CSA1M-bearing mice have high levels of IL-12 responsiveness, whereas cells from Meth A-bearing mice display marginal levels of responsiveness. Because IL-12 responsiveness in T cells is induced after T-cell receptor stimulation, the lack of IL-12 responsiveness suggests that T cells in Meth A-bearing mice are not sensitized to Meth A tumor antigen. Immunization of normal mice with attenuated Meth A tumor cells resulted in a protective immunity, as shown by the rejection of challenged viable Meth A cells. Such an immunization, when performed in Meth A-bearing mice, induced potent IL-12 responsiveness in T cells. Nevertheless, IL-12 treatment in these mice did not inhibit tumor growth. In another IL-12-incurable (CSA1M-variant) model, IL-12 responsiveness was observed before tumor cell immunization. However, IL-12 treatment was ineffective regardless of whether tumor cell immunization was performed. In these two models, the failure of IL-12 treatment to induce tumor regression was associated with the lack of T-cell migration to tumor sites. These results indicate that the sensitization of T cells to tumor antigens and generation of IL-12 responsiveness are insufficient to induce tumor regression when these sensitized T cells are not allowed to migrate to tumor sites.


Subject(s)
Cancer Vaccines/therapeutic use , Cell Division , Fibrosarcoma/immunology , Interleukin-12/therapeutic use , Lymphocytes, Tumor-Infiltrating/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , Antigens, Neoplasm/therapeutic use , Combined Modality Therapy , Fibrosarcoma/pathology , Histocompatibility Antigens/therapeutic use , Immunologic Factors/therapeutic use , Lymphocytes, Tumor-Infiltrating/drug effects , Male , Mice , Mice, Inbred BALB C , T-Lymphocytes, Cytotoxic/drug effects , Tumor Cells, Cultured
16.
J Am Soc Nephrol ; 10 Suppl 14: S408-11, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10541274

ABSTRACT

Prothrombin has remarkable affinity for calcium oxalate crystals. It is produced in renal tubular cells and is detected as a urinary form of prothrombin F1. The aim of this basic study was (1) to isolate prothrombin mRNA from normal human and rat kidneys; (2) to confirm expression level changes in stone-forming rat kidneys; and (3) to analyze the DNA sequence of renal prothrombin. The aim of the clinical investigation was to measure the serum levels of renal prothrombin in clinical cases of various urologic diseases. The expression of prothrombin mRNA in human kidneys and male Wistar rat kidneys was investigated using reverse transcription-PCR, with prothrombin (F1, F2, and thrombin) primers. Renal prothrombin levels were measured in the sera of patients with renal cell carcinoma, renal transplant donors, patients with chronic renal failure, and renal transplant recipients, using an enzyme-linked immunosorbent assay. Expression of cyclophilin as well as prothrombin mRNA could be detected. Prothrombin mRNA expression levels seemed to be increased in stone-forming rats. The DNA sequence of renal prothrombin differed from that of liver prothrombin at three points. Repeated measurements of renal prothrombin showed that values were high during the acute tubular necrosis period and tended to decrease with the recovery of renal function. Prothrombin mRNA expression could be confirmed in human and rat kidneys, as well as in stone-forming rat kidneys. Serum concentration measurements can be considered useful for assessment of recovery from acute tubular necrosis after renal transplantation and for diagnosis of acute rejection.


Subject(s)
Kidney/metabolism , Prothrombin/genetics , RNA, Messenger/analysis , Adult , Animals , Cadaver , Female , Graft Rejection , Humans , Kidney/chemistry , Kidney Transplantation , Male , Middle Aged , Prothrombin/analysis , Rats , Rats, Wistar
17.
Cancer Res ; 59(7): 1531-8, 1999 Apr 01.
Article in English | MEDLINE | ID: mdl-10197625

ABSTRACT

Interleukin (IL) 12 has been shown to elicit tumor regression when this cytokine induces the migration of T cells to tumor sites. The present study investigates the role of a peritumoral stromal reaction in IL-12-induced T-cell migration. In the CSA1M and OV-HM tumor models, IL-12 treatment induced tumor regression that is associated with T-cell migration. Neither T-cell migration nor tumor regression was observed in the Meth A and MCH-1-A1 models. Stromal tissue containing neovascular blood vessels developed at the peritumoral area of the former two IL-12-responsive tumors but not at the peritumoral area of the latter two IL-12-unresponsive tumors. The significance of stroma development was investigated using a pair of tumor models (CSA1M and a subline derived from CSA1M designated the CSA1M variant), both of which exhibit the same tumor immunogenicity. In contrast to the parental CSA1M cell line, the variant cell line was not responsive to IL-12, and neither stroma development nor T-cell migration was observed, even after IL-12 treatment. Histological analyses revealed that the parental cell line had peritumoral stroma with intrastromal vessels but only a few vessels in tumor parenchyma, whereas the variant cell line showed no stroma but had abundant vasculature in the tumor parenchyma. Most importantly, only stromal vessels in the parental tumors expressed detectable and enhanced levels of vascular cell adhesion molecule 1 (VCAM-1)/ intercellular adhesion molecule 1 (ICAM-1) before and after IL-12 treatment, respectively. In contrast, parenchymal vasculature in the variant cell line failed to express VCAM-1/ICAM-1 even after IL-12 treatment. When transferred into recipient tumor-bearing mice, IL-12-stimulated T cells from the parental CSA1M-bearing or the variant CSA1M-bearing mice migrated into the parental but not into the variant tumor mass. Together with our previous finding that T-cell migration depends on the VCAM-1/ICAM-1 adhesive interactions, the present results indicate a critical role for peritumoral stroma/stromal vasculature in the acceptance of tumor-infiltrating T cells that is a prerequisite for IL-12-induced tumor regression.


Subject(s)
Interleukin-12/therapeutic use , Neoplasms, Experimental/blood supply , T-Lymphocytes/physiology , Animals , Cell Movement , Female , Intercellular Adhesion Molecule-1/analysis , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Neoplasms, Experimental/immunology , Neoplasms, Experimental/therapy , Tumor Cells, Cultured , Vascular Cell Adhesion Molecule-1/analysis
18.
Gan To Kagaku Ryoho ; 26(4): 509-14, 1999 Mar.
Article in Japanese | MEDLINE | ID: mdl-10097748

ABSTRACT

We performed a study to compare the usefulness of double or single anticancer agents in the prophylactic treatment after the transurethral resection (TUR) of superficial bladder cancer. We experienced 127 superficial bladder cancer cases. Of these cases, 42 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 56 with ADR, PEP, epirubicin (epi-ADR) or pirarubicin (THP) only, and the remaining 29 with TUR only. Nonrecurrence rates were significantly higher in the intravesical treated cases than in the cases with TUR only, and also significantly higher in the cases treated with ADR and PEP than the other treated cases. We concluded that intravesical chemotherapy with combined agents was more effective than with a single agent.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Neoplasm Recurrence, Local/prevention & control , Peplomycin/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Administration, Intravesical , Aged , Drug Therapy, Combination , Female , Humans , Male
19.
J Vet Pharmacol Ther ; 21(4): 269-73, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9731948

ABSTRACT

Disposition of mirosamicin, a macrolide antibiotic, to honeybee adults, larvae, honey and royal jelly in the beehive after in-feed administration to adult bees was studied. Treatment was initiated at the end of July when the availability of natural pollen and nectar was poor. The drug was mixed with pollen-substitute paste and administered to honeybee colonies continuously for a week at a dosage of 200 mg/hive/week. High distributions in adult bees, jelly, larvae and a relatively low distribution in honey, of mirosamicin were observed. One day dosing of microsamin in sucrose syrup, a nectar substitute, resulted in a very high and long lasting residue in honey. Both royal and worker jelly, secreted from the jelly glands of adult bees, are acidic, so that a high distribution of a basic drug, such as mirosamicin, in jelly can be expected. This mechanism was considered to be responsible for a high concentration of mirosamicin in honeybee larvae, the host of Paenibacillus-larvae infection (American foulbrood), as primary larval food is jelly.


Subject(s)
Anti-Bacterial Agents/analysis , Bees/metabolism , Fatty Acids/analysis , Honey/analysis , Macrolides , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Drug Stability , Insect Hormones/analysis , Larva/metabolism
20.
Pediatr Surg Int ; 13(5-6): 341-5, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9639612

ABSTRACT

We examined the changes in pulmonary function values in 27 patients who underwent a lobectomy due to cystic lung disease and compared the results regarding such factors as disease type, age at operation, and preoperative infections. Percent vital capacity (%VC) decreased immediately after lobectomy, but recovered to normal values within 2 postoperative years and remained within or above the normal range. The ratio of residual volume to total lung capacity (RV/TLC) rose temporally with the increase in %VC, but then remained normal after 2 postoperative years. There was no difference in %VC and RV/TLC between diseases, while bronchial atresia showed a significantly lower correlation with percent of forced expiratory volume at 1 s. The older group operated upon at over 4 years of age and the group that had infections before operation showed relatively low %VC and high RV/TLC. Some patients demonstrated extremely low %VC along with funnel chest deformities. Our study suggests that overinflation of the remaining lung compensates VC in the early period after lobectomy while subsequently alveolar multiplication occurs. Factors affecting compensatory lung growth were considered to be operation later than 4 years of age, preoperative infection, and a thoracic deformity.


Subject(s)
Lung Diseases/physiopathology , Lung/physiopathology , Pneumonectomy , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Lung Diseases/surgery , Male , Postoperative Period , Respiratory Function Tests , Treatment Outcome
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