Biomedical subjects

J D Hsu

Publications and source records attributed to J D Hsu.

At least 19 recordsLinked to original sources

PubMed2005

Efficacy of albendazole-GM6001 co-therapy against Angiostrongylus cantonensis-induced meningitis in BALB/c mice.

Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole kills the nematode larvae staying in the brain. However, the dead larvae are capable of evoking a severe inflammatory response resulting in the brain damage. Matrix metalloproteinase 9 (MMP-9) is associated with the development of meningitis and with the immune inflammatory reaction. Presently, we studied the combination effects of albendazole and GM6001 (a MMP-9 inhibitor) against angiostrongyliasis in BALB/c mice. Co-administration of drugs produced marked effects; to kill the infecting larvae and to block MMP-9 activity. The combination treatment reduced MMP-9 activity by 89.2% in cerebrospinal fluid. The numbers of inflammatory cells increased significantly upon establishment of infection, but subsided upon co-treatment. Significantly fewer larvae were recovered from treated mice than from untreated, infected mice. The present results strongly suggest that co-therapy with albendazole and GM6001 may be an useful approach for the treatment of human angiostrongyliasis.

Albendazole↗

PubMed2004

The efficacy of therapy with albendazole in mice with parasitic meningitis caused by Angiostrongylus cantonensis.

Matrix metalloproteinase 9 (MMP-9) is involved in the pathogenesis of parasitic meningitis caused by the nematode Angiostrongylus cantonensis. The present study evaluated the efficacy of albendazole therapy in BALB/c mice infected with the third stage larvae of this nematode. Albendazole showed a pronounced larvicidal activity. Eosinophil numbers significantly increased in infected mice but decreased upon administration of albendazole. Densitometric scanning indicated that albendazole reduced gelatinolytic activity detected by gelatin-substrate zymography. In the cerebrospinal fluid, albendazole reduced the lytic area intensity of the 94 kDa MMP-9 band by 46.5% within 7 days, and by 51.5% by day 14. Examination of brain tissue revealed a similar pattern of decrease (48.6% by day 7, and 53.9% by day 14). Albendazole may thus be an effective compound for the treatment of angiostrongyliasis through its larvicidal activity and facilitation of an improved inflammatory response via the reduction of MMP-9 activity.

Albendazole↗

PubMed2004

Induced eosinophilia and proliferation in Angiostrongylus cantonensis-infected mouse brain are associated with the induction of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK signals.

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we show that A. cantonensis-induced eosinophilia and inflammation might lead to the induction of IAP/NF-kappaB, JAK/STAT1 and MEKK1/JNK signals. The phosphorylation levels of JAK and JNK, STAT1, IAP, NF-kappaB and MEKK1 protein products were significantly increased after 12 days or 15 days of A. cantonensis infection. However, no significant differences in MAPKs such as Raf, MEK-1, ERK1/2 and p38 expression were found between control and infected mice. The activation potency of JAK/STAT1, IAP/NF-kappaB and MEKK1/JNK started increasing on day 3, with significant induction on day 12 or day 15 after A. cantonensis infection. Consistent results were noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in the brain tissues of infected mice. These data suggest that the development of brain injury by eosinophilia of A. cantonensis infection is associated with activation of JAK/STAT1 signals by cytokines, and/or activation of MEKK1/JNK by oxidant stress, and/or activation of NF-kappaB by increasing IAP expression.

Angiostrongylus cantonensis↗

PubMed2004

Induction of matrix metalloproteinase-9 in murine eosinophilic meningitis caused by Angiostrongylus cantonensis.

Matrix metalloproteinases (MMP) have been implicated in the pathogenesis of various inflammatory diseases of the central nervous system. In the present study, a gelatinase was found to be induced in parasitic meningitis caused, in mice, by Angiostrongylus cantonensis. The enzyme had a molecular weight of about 94 kDa, showed maximal activity between pH 6 and pH 8, and was clearly inhibited by EDTA and 1,10-phenanthroline but not by leupeptin or phenylmethanesulphonyl fluoride. When samples of cerebrospinal fluid from the mice with meningitis were blotted with specific antiserum against gelatinase B (MMP-9), a 94-kDa immunopositive band was observed, indicating that the induced gelatinase was MMP-9. In the A. cantonensis-infected mice, immuno-histochemistry demonstrated MMP-9 within the endothelial cells lining the vascular spaces of the brain and in the leucocytes that were found, in aggregates, in the subarachnoid space. Leucocytes may play an important role in the pathogenesis of inflammatory disorders of the central nervous system.

Angiostrongylus cantonensis↗

PubMed2001

Increased expression of iNOS and c-fos via regulation of protein tyrosine phosphorylation and MEK1/ERK2 proteins in terminal bronchiole lesions in the lungs of rats exposed to cigarette smoke.

Epidemiological evidence suggests that smoking is a major cause of human lung cancer. However, the mechanism by which cigarette smoke induces the cancer remains unestablished. To evaluate the effects of cigarette smoke on the expression of inducible nitric oxide synthase (iNOS), nuclear protooncogenes and related mitogen-activated protein kinases (MAPKs) in rat lung tissue, a histopathological study of the effects of gas-phase cigarette smoke on rat lung tissue were carried out. The terminal bronchioles were found to be infiltrated predominantly by lymphocytes in the peribronchiolar region and a mild to moderate degree of emphysema was noted in the alveolar spaces. The terminal bronchioles also showed marked lipid peroxidation, dilatation, and peribronchiolar fibrosis. Immunohistochemical evaluation showed that the expression of iNOS, NF-kappa B, MAPKs (MEK1, ERK2), phosphotyrosine protein and c-fos was increased in the terminal bronchioles but protein kinase C (PKC), MEKK-1, c-jun, p38 and c-myc showed no change. These results provide evidence to suggest that exposure to cigarette smoke results in oxidant stress which leads to the stimulation of iNOS and c-fos together with the induction of protein tyrosine phosphorylation and MEK1/ERK2 which in turn may promote lung pathogenesis.

Animals↗

PubMed2001

Tumor-promoting effect of GGN-MRP extract from the Maillard reaction products of glucose and glycine in the presence of sodium nitrite in C3H10T1/2 cells.

GGN-MRP is an extract from the Maillard reaction products of nitrite with glucose and glycine in the Maillard browning system. No genotoxicity of GGN-MRP in culture hepatocyte was found. A two-stage transformation protocol was used to transform chemically mouse embryo fibroblast C3H10T1/2 cells. To initiate transformation, the cells were treated with benzo[a]pyrene [B(a)P; 0.1 microg/mL], and GGN-MRP (0.01, 0.1, and 1.0 mg/mL) was employed to subsequently complete the transformation process. Malignant transformed foci were formed in B(a)P-initiated and GGN-MRP-promoted C3H10T1/2 cells after 8 weeks. Cells treated with GGN-MRP alone failed to induce transformation. However, cells initiated with B(a)P and promoted by GGN-MRP demonstrated oncogenic properties. Transformed colonies derived from GGN-MRP-treated cells exhibited enhanced growth rate, anchorage independence, and tumorgenicity in animals relative to parent cells. These results indicated that GGN-MRP contains a tumor promoter and may induce tumor promotion by two-stage oncogenesis.

Animals↗

PubMed2000

Suppressive effect of penta-acetyl geniposide on the development of gamma-glutamyl transpeptidase foci-induced by aflatoxin B(1) in rats.

The suppressive effects of penta-acetyl geniposide, (Ac)(5)-GP, on the hepatotoxic lesions-induced by aflatoxin B(1) (AFB(1)) were investigated in male Wistar rats. Rats were divided into six groups: groups I and II served as normal and solvent control, respectively; group III was given AFB(1) (2 mg/kg body weight) alone; group IV was given (Ac)(5)-GP (2 mg/kg) alone; and groups V and VI received both AFB(1) (2 mg/kg body weight) and (Ac)(5)-GP (1 mg and 2 mg/kg body weight, respectively). Rats received treatments for 8 weeks, then were maintained on basal diet for 32 weeks. At the end of the experiment (week 40), the liver lesions (e.g. fatty change, eosinophilic and bile duct dilation) and preneoplastic changes in rats of groups V and VI were reduced when they were compared with group III. There were no liver lesions and preneoplastic changes in rats treated with (Ac)(5)-GP alone. Although no differences in the total number of gamma-glutamyl transpeptidase (GGT)-positive foci was observed between the groups treated with AFB(1) along with or without (Ac)(5)-GP, the treatment of (Ac)(5)-GP significantly reduced the number of AFB(1)-induced GGT positive foci (with diameter larger than 0.3 mm). These results indicated that the protective effect of (Ac)(5)-GP on early hepatocarcinogenesis-induced by AFB(1) was associated with the inhibition of GGT foci development.

Aflatoxin B1↗

PubMed2000

Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver.

The antitumor effect of green tea polyphenols has been well characterized in numerous papers. However, the mechanism of their action is still poorly defined. In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea extract, was studied for its effect on the expression of glutathione S-transferases (GSTs) in rat liver to examine the mechanism of action. Liver samples were collected from Sprague-Dawley rats treated with EGCG in H(2)O by portal vein perfusion and examined for total GST activity and GST expression. The results showed that the induction of GST activity by EGCG was dose- and time-dependent. GST activity was increased about 28-fold at 12 hr after treatment. Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 mg/kg weight). Only GSTM2 revealed a significant time-dependent increase, with a maximal induction of approximately 2.0-fold. The differential effect of EGCG on GST subunit expression was also verified by immunocytochemical examination and showed strong induction of the GSTM2 (but not the GSTA1/2 and GSTM1) level in liver section. This induction occurred as early as 3 hr after treatment and extended gradually outward from the hepatic veins as treatment time increased. The change in the GSTM2 protein level was accompanied by a corresponding alteration in mRNA quantity ( approximately 2.0-fold of control). Our report is the first to demonstrate a specific induction of the GSTM2 subunit by a chemopreventor and suggests a primary influence of EGCG on GSTM2 gene expression.

Animals↗

PubMed2000

Tumor promotion of N-nitroso-N-(3-keto-1, 2-butanediol)-3'-nitrotyramine derived from nitrosation of Maillard reaction product in CD-1 mice.

N-Nitroso-N-(3-keto-1,2-butanediol)-3'-nitrotyramine (NO-NTA) is a product of a model browning system generated in the presence of sodium nitrite. Our previous study showed that NO-NTA had genotoxicity and proved to be an initiator and promoter on mouse C3H10T1/2 cells. In this study, a two-stage skin carcinogenesis protocol was used to promote CD-1 mouse skin carcinogenesis using NO-NTA. Twice weekly, for 38 weeks, topical application of NO-NTA at the concentration of 250 nmol to mice previously initiated with benzo(a)pyrene (BaP) caused 90% tumor incidence. However, no tumors were observed in mice treated with BaP or treated with NO-NTA alone. The NO-NTA-promoted tumors that were observed histologically in mice showed well-differentiated squamous cell carcinoma with invasion into the subcutaneous region. Application of the same amount of NO-NTA not only caused significant induction of hyperplasia but also epidermal ornithine decarboxylase (ODC) activity. Treatment of mouse skin (1 cm(2)) with various amounts of NO-NTA (10, 50, or 250 nmol) caused production of hydrogen peroxide by 1.63-, 1.91-, and 2. 38-fold, respectively, and marked induction of myeloperoxidase (MPO) by 21-, 39-, and 61-fold. These results indicate that NO-NTA is a new tumor promoter and may induce tumor promotion by oxidant stress in CD-1 mouse skin.

Animals↗

PubMed2000

Development of brain injury in mice by Angiostrongylus cantonensis infection is associated with the induction of transcription factor NF-kappaB, nuclear protooncogenes, and protein tyrosine phosphorylation.

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we showed that A. cantonensis-caused eosinoplia and inflammation might lead to the induction of NF-kappaB and protooncogene expression via activation of the tyrosine phosphorylation signal pathway. After mice were infected daily with 30 third-stage larvae of A. cantonensis by oral adminstration for 6 weeks, no significant differences PKC-alpha, MEK-1, ERK-2, JNK, and p38 protein expression were found between the control and infected mice. However, the protein tyrosine phosphorylation levels, NF-kappaB, and iNOS protein products were significantly increased by 3.5-, 3.3-, and 6.3-fold, respectively, after 3 weeks of A. cantonensis infection. The same pattern was found for c-Myc, c-Jun, and c-Fos proteins, which were elevated by 3.2-, 2.3-, and 3.4-fold, respectively, compared to control animals after 3 weeks. The expression potency of these proteins started increasing in week 1, reaching maximal induction in week 3, and then declining in week 5 after A. cantonensis infection. Another consistent result was noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in brain tissues of infected mice. These data suggest that the development of brain injury by eosinophlia of A. cantonensis infection is associated with NF-kappaB and/or nuclear protooncogenes expression, which is activated by the tyrosine phosphorylation pathway.

Angiostrongylus cantonensis↗

PubMed2000

Rancho Los Amigos Medical Center. A unique orthopaedic resource and teaching institution.

Rancho Los Amigos Medical Center, initially a poor farm in the County of Los Angeles, CA became a world renown medical institution because of the polio epidemics in the 1950s. Responding to the need for day to day inpatient care were an overflow of victims of polio who had spine and extremity weakness and were dependent on respirators. Team care, developed at the institution, was used by Vernon L. Nickel, chief orthopaedic surgeon so that maximum use of the limited staff's efforts would be to take care of patients. This need spawned many innovative developments through clinical observations and trials, basic research, and engineering innovations that resulted in the patient's functional improvement and helped return many victims of polio to independence and to their communities. Subsequently, orthopaedic surgeons, Jacquelin Perry, and Alice Garrett joined the full-time staff as the workload increased. Stabilizing the spine using fascial supports, spinal fusion, spinal instrumentation, orthoses, and seating systems allowed those patients who were not totally dependent on respirators to be upright and mobilized. When polio was eradicated, newer programs were established for physically disabled persons with musculoskeletal disorders affecting the spine and extremities and for those patients with congenital, acquired, neurologic, and neuromuscular disorders. In formal graduate residency affiliations, fellowships, and continuing medical education programs orthopaedic surgeons from around the world have been taught the basic principles of "categorical care" for physically disabled people for 50 years. Orthopaedic care given through these programs formed the basis of a new orthopaedic subspecialty, Orthopaedic Rehabilitation.

Education, Medical, Graduate↗

PubMed1998

Tumor promoting effect of N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (a nitrosated Maillard reaction product) in benzo(a)pyrene-initiated mouse skin carcinogenesis.

N-nitroso-N-(2-hexanonyl)-3'-nitrotyramine (NO-HNTA) is a product generated in a model browning system in the presence of sodium nitrite. The chemical structure of this compound has been confirmed by UV, mass, nuclear magnetic resonance and infrared spectroscopy in our study. Twenty weeks, twice weekly, topical application of NO-HNTA at the concentration of 10, 50 and 250 mumol to mice previously initiated with benzo(a)pyrene (B[a]P) increased their tumor formation by 3.2-, 4.6- and 5.8-fold respectively. Application of the same amount of NO-HNTA not only caused significant induction of hyperplasia but also the activity of epidermal ornithine decarboxylase (ODC). Treatment of mouse skin with various amounts of NO-HNTA (10, 50 and 250 mumol) caused production of hydrogen peroxide by 1.38-, 1.95- and 3.26-fold respectively, and induction myeloperoxidase (MPO) by 24-, 63- and 102-fold. These results indicate that the formation of NO-HNTA or its derivatives derived from the reaction of tyrosine and glucose in the presence of sodium nitrite has the potential as a tumor promoter.

Animals↗

PubMed1998

Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse skin.

Hibiscus protocatechuic acid (PCA), a phenolic acid isolated from Hibiscus sabdariffa L., was evaluated for its ability to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion in skin tumors of female CD-1 mice. Topical application of PCA (5, 10 or 20 micromol) 5 min prior to TPA (15 nmol) treatment twice weekly for 20 weeks to mice which were initiated with benzo[a]pyrene (B[a]P) inhibited the incidence of tumors in mice to 81.3, 62.5 and 56.3%, respectively, while all mice in the TPA-treated group developed tumors. The average number of tumors in mice pretreated with PCA was 2-4 and that of mice treated only with TPA was 6.6. The protection effects of PCA were also presented by its significant suppression on the TPA-induced hyperplasia in the skin and edema of mouse ears by 65 and 73% at doses of 10 and 20 micromol, respectively. When it was applied to the dorsal surface of CD-1 mice before TPA application, PCA (5, 10 or 20 micromol) inhibited the induction of epidermal ornithine decarboxylase (ODC) activity by 5 nmol TPA and myeloperoxidase (MPO) activity by 6.5 nmol TPA. The same doses of PCA also reduced the formation of hydrogen peroxide in the mouse skin to an inhibition of 61, 84 and 89%, respectively, when compared with that of the TPA-treated group. These results indicate that PCA possesses potential as a cancer chemopreventive agent against tumor promotion.

Animals↗

PubMed1997

Potential effect of sodium nitrite on the expression of nuclear proto-oncogenes during 2-acetyl aminofluorene-induced hepatocarcinogenesis in rats.

2-acetyl aminofluorene (AAF) reacts in acidic conditions with nitrous fume yielding N-nitroso-AAF (N-NO-AAF), as previously described, that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodium nitrite (NaNO2) on the tumorigenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control; group II were treated with NaNO2 (0.3%); group III was given 0.02% AAF alone; groups IV and V received both AAF and NaNO2 (0.2 and 0.3% respectively) in their diet for 12 weeks. At the end of the experiment, all rats in groups III, IV and V developed early stage phenomena of hepatocellular carcinoma, including hepatomegaly with variable-sized foci and neoplastic nodules. Severe damage was observed in the rats treated with AAF and NaNO2. Feeding of AAF (0.02%) for 3 months elevated the levels of c-Fos, c-Jun and c-Myc proteins in the rat livers. The AAF-induced c-Jun, c-Fos and c-Myc expressions were significantly magnified (P < 0.001) by NaNO2. These data confirmed that the strengthening of AAF-induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced increases in the expressions of c-Jun, c-Fos and c-Myc.

2-Acetylaminofluorene↗

PubMed1996

Hepatotoxicity of 1,3,5-trinitro-2-acetyl pyrrole derived from nitrosation of Maillard reaction product in BALB/C mouse.

1,3,5-Trinitro-2-acetyl pyrrole (TNAP) is a product derived from the reaction of 2-acetyl pyrrole with nitrite in the model of Maillard browning systems. This compound is moderately mutagenic to the Salmonella strains TA98 and TA100 and is markedly cytotoxic to mouse C3H10T1/2 cells. Experiments are performed to investigate the effects of TNAP on the hepatic toxicity in mouse. Male BALB/C mice were subjected to a dose of 7.2 mg/kg body weight twice a week by i.p. injection for 24 weeks, then followed by a feeding diet for 21 weeks. TNAP-treated mice showed an increase in mortality and time-dependent appearance of lesions in the liver. TNAP is hepatotoxic as demonstrated by a marked increase in the activities of serum alanine transaminase (ALT) and aspartic transaminase (AST). TNAP-related lesions observed histologically in mice, included hapatic atrophy, mild fatty metamorphosis with multilocular cysts in the liver. In conclusion, TNAP was considered to be a toxic compound in mice as evidenced by increased incidences of mortality, and lesions of liver.

Alanine Transaminase↗

PubMed1996

Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet.

To examine the influence of hypercholesteremia on 1,2-dimethylhydrazine (DMH)-induced rat colon cancer, Sprague-Dawley rats received dietary cholesterol (CH, 0-2%) and cholic acid (CA, 0.25%) with or without DMH (20 mg/kg, s.c. injection) for 18 weeks. The rats receiving dietary cholesterol and cholic acid all significantly increased total serum cholesterol and lipids but only a high cholesterol diet (2% CH plus 0.25% CA) decreased the activity of glutathione peroxidase (GSH-Px) and increased the formation of peroxides in the colon (P < 0.01). The rats that received the combination of DMH and high cholesterol diet enhanced these effects. At the end of the experiment, the diet group administered DMH and high cholesterol (2% CH plus 0.25% CA) developed colon adenoma at 50% of incidence in pathological examination, but no colon adenoma formed in the rats treated with high cholesterol alone. It is supposed that a non-carcinogenic agent like cholesterol may potentiate the carcinogenicity of DMH in rats via an increase of lipid peroxidation and decrease in the activity of peroxidase in the target organ.

1,2-Dimethylhydrazine↗

PubMed1996

Regulatory effects of dietary n-3 and n-6 lipids on plasma and hepatic lipid levels, liver cell number and microsomal protein content in spontaneously hypertensive rats.

Weanling male spontaneously hypertensive rats were fed semipurified diets containing either corn or fish oil for 8 weeks. Rats fed on fish oil diet had significantly lower plasma triglyceride, total cholesterol and HDL-cholesterol levels than rats fed on corn oil diet (P < 0.05). Moreover, rats fed on fish oil diet had significantly lower liver total lipid and triglyceride concentrations than rats fed on corn oil diet (P < 0.05). Dietary lipids were reflected in plasma fatty acid composition. Rats fed on fish oil diet had significantly greater plasma eicosapentaenoate (EPA) and docosahexaenoate (DHA) (n-3 PUFAs) with an accompanying decrease in plasma linoleate (LA) and arachidonate (AA) (n-6 PUFAs), in comparison with the rats fed corn oil (P < 0.05). Those results would suggest that the n-3 PUFAs were incorporated into plasma lipids at the expense of the n-6 PUFAs. Rats fed on corn oil diet had significantly greater liver DNA content than rats fed on fish oil diet (P < 0.05), thereby implying that the n-3 PUFAs in fish oil had an inhibitory effect on liver cell proliferation. Furthermore, rats fed on fish oil diet had significantly greater hepatic microsomal protein content than rats fed on corn oil diet (P < 0.05), indicating that fish oil exerted a stimulatory effect on hepatic microsomal enzymes.

Animals↗

PubMed1995

A dumbbell spinal lipoma presenting as a neck mass: CT and MR demonstration.

A case of histologically confirmed spinal lipoma without associated spinal dysraphism is presented. This tumor appeared lobulated, extending through an enlarged neuroforamen to form a so-called dumbbell tumor. In a review of the literature, there were found to be only four case reports of a dumbbell spinal lipoma. Our case was unique in that it manifested as a neck mass without neurological deficits. The fatty nature of the tumor allowed easy detection by computed tomography (CT), as well as by magnetic resonance (MR) imaging. MR is judged to be superior to CT for preoperative planning by virtue of its superb intraspinal resolution and multiplanar capability, and should be the procedure of choice for evaluating spinal lipomas.

Child, Preschool↗