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Biomedical subjects

K M Chang

Publications and source records attributed to K M Chang.

At least 37 records · Page 2Linked to original sources

Immunopathology of hepatitis C.

Hepatitis C virus (HCV) infection becomes persistent in the majority of instances in the face of a humoral and cellular immune response, and persistent HCV infection is associated with chronic hepatitis. In particular, cytotoxic T lymphocytes (CTL), crucial in the eradication of virus-infected cells, have been observed in the liver and the peripheral blood of chronically infected patients, suggesting that CTL cannot completely eliminate the virus, and may contribute to chronic liver injury. In this review, the potential host and the viral factors involved in the pathogenesis of chronic HCV infection will be discussed with emphasis on the HLA-A2 restricted peripheral blood CTL response and its relationship to liver disease and viral load.

Amino Acid Sequence↗

Diagnosis of an advanced endodontic/periodontic lesion: report of a case.

Diagnosis of endodontic/periodontic lesions is often a challenge for clinicians. Treatment will not be successful without correct diagnosis. This article presents an advanced case of an endodontic/periodontic lesion in a patient who was referred to a periodontist. After careful examination of the patient, as well as consultation with an endodontist, an endodontic diagnosis was made and the patient treated accordingly. Success was attained without periodontal intervention.

Alveolar Bone Loss↗

The route of seminal vesicle involvement in adenocarcinoma of prostate: lymphaticovascular or local extension?

BACKGROUND: Adenocarcinoma of the prostate with seminal vesicle involvement indicates a rather poor prognosis. The aim of this study is to evaluate the route of seminal vesicle involvement via lymphaticovascular or local extension, as a possible way which may determine the extent of disease as systemic or local. METHODS: In a retrospective study of 32 patients who underwent radical prostatectomy for localized cancer of the prostate, medical records and imaging studies were reviewed, and the histopathological slides of the resected specimens were rechecked. RESULTS: Of 32 patients, 12 (37.5%) had seminal vesicle involvement. Seven patients had involvement of bilateral seminal vesicles and five had unilateral involvement. Tumor cells invaded the muscle portion of seminal vesicle from the adjacent prostatic tissues in all 12 patients. Four of the seven patients with involvement of bilateral seminal vesicles developed bony metastasis 7 to 12 months after operation. No patient with unilateral involvement of seminal vesicle was found to have disease progression to bony metastasis during follow-up for as long as 39 months. CONCLUSIONS: The route of seminal vesicle involvement in prostate cancer was through local extension in all of our patients. Involvement of bilateral seminal vesicles may have more chances to develop bony metastasis than unilateral involvement. Further study with a large number of patients is necessary to clarify the issue regarding the route of seminal vesicle involvement in adenocarcinoma of prostate.

Adenocarcinoma↗

Quantitative analysis of the peripheral blood cytotoxic T lymphocyte response in patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) are present in the peripheral blood and liver of chronically infected patients. The current study was performed to study the relationship between the strength of the CTL response, liver disease severity, and viral load. The results may be summarized as follows: first, using CTL precursor frequency (CTLpf) analysis to quantitate the peripheral blood CTL response, chronically infected patients were less strongly sensitized to a panel of well-defined HCV epitopes than they were to an epitope within the influenza matrix protein. Second, HCV-specific CTLpf did not correlate with disease activity or viral load in the majority of patients on a cross-sectional basis, although it did increase in three patients concomitant with sharp increases in liver disease. Finally, interferon therapy did not enhance the CTLpf against the HCV epitopes studied in these patients, indicating that its antiviral effect is independent of the CTL response. Since the HCV-specific CTLpf in the blood is actually quite low, the CTL may contribute to ongoing liver disease in these patients while being quantitatively inadequate to destroy all of the infected hepatocytes, thereby facilitating HCV persistence and contributing to chronic liver disease.

Adult↗

Epidermal growth factor in gingival crevicular fluid and its binding capacity in inflamed and non-inflamed human gingiva.

Epidermal growth factor (EGF) is a pro-inflammatory small peptide (6000 Da) with a variety of biological activities including stimulation of cell differentiation and mediation of proteolysis by binding to its specific receptor on the cell surface. The purpose of this study was to determine the levels of EGF in gingival crevicular fluid (GCF) and the EGF-binding capacity to its receptor in gingival tissue. The GCF samples were collected from six patients by inserting paper strips into shallow (< 5 mm) and deep pockets (> or = 5 mm) for 30 s. The strips were soaked in 0.2 M acetate for extraction and the EGF in the supernatants was analysed by radioimmunoassay. To determine the binding capacity of EGF to its receptor, inflamed gingival tissues (pocket depth > or = 5 mm, Gingival Index = 1, 2 or 3) were collected during periodontal flap surgery and non-inflamed gingival tissues (pocket depth < 5 mm, Gingival Index = 0) were collected during surgical "crown lengthening' for aesthetic purposes. The tissues were pooled by group, homogenized for membrane preparation and the supernatants obtained after centrifugation were used in a 125IEGF binding assay. To determine the effect of inflammation on gingival EGF receptor, inflamed and non-inflamed gingival tissues were collected from six patients and prepared similarly to the binding assay. Gingival preparations were then electrophoresed for Western blot analysis with EGF receptor antiserum. The EGF level in GCF was significantly lower (P < 0.05) in the samples collected from pockets > or = 5 mm (0.9 +/- 0.6 ng/ml) than in those from pockets < 5 mm (2.4 +/- 2.1 ng/ml). The average Gingival Index was higher (2.6 +/- 0.6) in pockets > or = 5 mm than in pockets < 5 mm (1.4 +/- 1.0). Specific binding of 125I-EGF to its receptor in inflamed gingiva was 2.7-fold higher than in non-inflamed gingiva (14.4 +/- 4.9 vs 5.4 +/- 1.8 fmol/g wet tissue). Western blot analysis showed two major immunoreactive bands (180 and 120 kDa), which represent EGF receptor and its degradation products, in inflamed gingiva. The findings show that inflammation activates EGF binding capacity in gingiva and that the up-regulation of EGF receptor in inflamed gingiva might be associated with a lowered concentration of EGF in GCF produced adjacent to inflamed gingiva. This up-regulation of EGF receptor during inflammation might be an important mechanism in the pathogenesis of periodontal disease.

Blotting, Western↗

Detection of epidermal growth factor receptor in inflammatory periapical lesions.

Epithelial cell proliferation is often observed in periapical lesions of endodontic origin. The mechanisms which stimulate the epithelial cell rests of Malassez to proliferate are not understood fully. Fifteen inflammatory periapical lesions (10 granulomas and five cysts) obtained from periapical surgery and six additional periapical lesions (four granulomas and two cysts) collected from extracted teeth were examined using immunohistochemical staining and 125I-EGF (epidermal growth factor) binding assay to detect the presence of epidermal growth factor receptor. The results indicated that the periapical lesions without epithelial cell proliferation had a weak immunoperoxidase staining or low specific binding of 125I-EGF. In contrast, the periapical lesions with epithelial cell proliferation and cyst formation exhibited a strong immunoperoxidase staining in the epithelial cells or high specific binding of 125I-EGF.

Epidermal Growth Factor↗

Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients.

Cytotoxic T lymphocytes (CTL) are thought to control hepatitis B virus (HBV) infection, since they are readily detectable in patients who clear the virus whereas they are hard to detect during chronic HBV infection. In chronic hepatitis C virus (HCV) infection, however, the virus persists in the face of a CTL response. Indeed, most infected patients respond to one or more HCV-1 (genotype 1a)-derived CTL epitopes in the core, NS3, and NS4 proteins, and the CTL response is equally strong in patients infected by different HCV genotypes, suggesting broad cross-reactivity. To examine the effect of the HCV-specific CTL response in patients with chronic hepatitis C on viral load and disease activity, we quantitated the strength of the multispecific CTL response against 10 independent epitopes within the HCV polyprotein. We could not detect a linear correlation between the CTL response and viral load or disease activity in these patients. However, the CTL response was stronger in the subgroup of patients whose HCV RNA was below the detection threshold of the HCV branched- chain DNA assay than in branched-chain-DNA-positive patients. These results suggest that the HCV-specific CTL response may be able to control viral load to some extent in chronically infected patients, and they indicate that prospective studies in acutely infected patients who successfully clear HCV should be performed to more precisely define the relationship between CTL responsiveness, viral clearance, and disease severity in this infection.

Adult↗

Screening for periodontal disease: radiographs vs. PSR.

This study compares the evaluation of periodontal health using bone levels measured on periapical and bitewing radiographs with clinical parameters, such as periodontal screening and recording, gingival indexes, probing depths and attachment levels. The authors found that bitewing radiographs taken within six months of the clinical examination correlated better with the clinical data than older radiographs. However, they concluded that, overall, radiographs are not highly reflective of periodontal status. PSR scores, by contrast, showed significant associations with probing depths and attachment levels. The results support use of PSR as a screening tool for periodontal diseases.

Adolescent↗

Local and systemic factors in periodontal disease increase matrix-degrading enzyme activities in rat gingiva: effect of micocycline therapy.

We previously reported that both local and systemic factors relevant to the pathogenesis of periodontal disease can increase gingival collagenase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdown requires multiple enzyme interactions, the current study was carried out to determine the effects of bacterial endotoxin (LPS) (a local factor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) in the gingiva of rats. In addition, the effects of therapy with a semisynthetic tetracycline (minocycline) were investigated. Ten male, Sprague-Dawley rats were made diabetic by IV injection of streptozotocin. Four of the ten rats then received minocycline (10 mg/day) by oral gavage on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 microliters of E. coli LPS (10 mg/ml) by injection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with saline into the gingiva. At the end of the 3 week experimental period, gingival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased the four matrix-degrading enzyme activities in both gingiva and skin. In contrast, local LPS injection increased these enzyme activities in the gingiva alone. Systemic therapy with minocycline completely ameliorated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containing skin extract from diabetic rats also inhibited collagenase and gelatinase activities, but no inhibition was observed for elastase and beta-glucuronidase activities, indicating that the MMPs and other enzymes were inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.

Alveolar Bone Loss↗

Malakoplakia of the prostate forming a fistulous tract to rectum: a case report.

Malakoplakia is a rare lesion of granulomatous inflammation which mainly affects urinary bladder but may involve other parts of the body. Differentiation from neoplastic process is often difficult due to its tumorous gross appearance and similarity to carcinoma microscopically. Malakoplakia of the prostate is even rare. We present a case of prostatic malakoplakia masquerading as a rectal tumor due to formation of a fistulous tract to the rectal muscular layers accompanied with ulceration of the rectal mucosa. Its clinical course is different from those of most reported cases, while the outcome is as satisfactory as in usual cases.

Diagnosis, Differential↗

Assessment of periodontal status with PSR and traditional clinical periodontal examination.

The system of peridontal screening and recording was developed by the American Dental Association and the American Academy of Periodontology to simplify early detection of periodontal pathology. The authors evaluated the results of PSR against those of a conventional periodontal examination in 24 subjects, each of whom had a minimum of 18 natural teeth. The results of this study suggest that the PSR examination, while a useful screening tool, could be improved to further enhance its identification of patients with peridontal diseases.

Adolescent↗

Inhibitory activity of cigarette-smoke condensate on the mutagenicity of heterocyclic amines.

Cigarette-smoke condensate (CSC) is a complex mixture containing over 3800 identified chemicals including nicotine, water, mutagens, antimutagens, cytotoxins and inert chemicals. Although CSC is mutagenic in the Ames test, its effect on the activity of other mutagens has not been characterized. Using the Ames Salmonella bacterial mutagenesis assay, we found CSC exerts a significant inhibitory effect on mutagens requiring bioactivation. Those studied included heterocyclic amines (Glu-P-1, Glu-P-2, IQ, MeIQ, Trp-P-1 and Trp-P-2), benzo[a]pyrene (B[a]P) and aflatoxin B1. However, CSC had no effect on the activity of direct-acting mutagens (2-nitrofluorene, sodium azide, 4-nitro-1,2-phenylenediamine, 4-nitroquinoline N-oxide and methyl methanesulfonate). With indirect-acting mutagens, the reduced number of revertants observed in the presence of CSC was not attributable to cytotoxicity. CSC exhibited a potent inhibitory effect on the cytochrome P-450 dependent monooxygenases, ethoxyresorufin O-deethylase and B[a]P hydroxylase. This suggests inhibition of the cytochrome P-450 isozymes as one possible mechanism for the antimutagenicity of CSC. Fractionation studies of CSC revealed that the neutral, weakly acidic (phenolic) and basic fractions are all effective as antimutagens against Glu-P-1, a representative heterocyclic amine. This indicates that several classes of chemicals contribute to the inhibitory effect of CSC on the mutagenicity of the heterocyclic amines.

Aflatoxin B1↗

Tetracyclines inhibit Porphyromonas gingivalis-induced alveolar bone loss in rats by a non-antimicrobial mechanism.

Tetracyclines have been widely used as adjuncts in periodontal therapy due to the antimicrobial efficacy of these drugs. Recently, their ability to inhibit host-derived matrix metalloproteinases (collagenase and gelatinase) and bone resorption in organ culture has also been invoked as a therapeutic rationale. The current study was undertaken to determine whether tetracyclines can inhibit alveolar bone loss in vivo due to a non-antimicrobial action of these drugs. Experimental periodontitis was induced by inoculating adult, male Sprague-Dawley rats with P. gingivalis (strain 381) following kanamycin/ampicillin pretreatment. Doxycycline, non-antimicrobial chemically-modified tetracycline (CMT-1) and vehicle alone were administered daily to 3 infected groups of rats (n = 6 rats per group; each group housed in a sterilized inflatable isolator) beginning 10 days after P. gingivalis inoculation. The control group (n = 6; non-infected rats) received only vehicle. After 5 weeks of daily drug administration by gastric intubation, the experiment was terminated and blood samples were taken from each animal to determine antibody levels against P. gingivalis. Plaque samples were collected from each group of animals before and after P. gingivalis inoculation and at the end of the experiment for microbiological examination. The jaws were removed from each rat, defleshed and then analyzed morphometrically and radiographically to assess bone loss. Serum antibody levels against P. gingivalis were significantly elevated in the 3 infected groups compared to the non-infected controls. This, together with the microbiologic findings, indicated that these groups of rats were infected with P. gingivalis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗

Chemically-modified tetracycline normalizes collagen metabolism in diabetic rats: a dose-response study.

An earlier study indicated that a chemically-modified non-antimicrobial tetracycline (4-de-dimethylaminotetracycline; CMT-1) can inhibit excess collagenase activity in the connective tissues of diabetic rats, however, the optimum oral dose and resulting serum concentration were not determined. In the current study, adult male Sprague-Dawley rats (body weight approx. 350 g) were made diabetic by streptozotocin injection and administered by oral gavage either 0, 1, 2, 5, or 10 mg CMT-1 per day. After 3 weeks of drug therapy, the rats were killed and gingiva, skin, and serum collected. The tissues were 1) extracted, partially purified and analyzed for collagenase activity using [3H-methyl] collagen as substrate and SDS-PAGE/fluorography; 2) extracted in neutral salt and dilute acid solutions (4 degrees C) to assess collagen solubility; and 3) analyzed for hydroxyproline to determine tissue (skin) collagen mass. Serum was analyzed for glucose and CMT-1 concentration, the latter by HPLC. Inducing diabetes dramatically increased both gingival and skin collagenase activity and reduced skin collagen mass by 69.8%. Increasing the oral dose of CMT-1 progressively increased the serum concentration of the drug from 0.6-6.5 micrograms/ml and progressively decreased the excessive collagenase activity in gingiva and skin (p < 0.01 vs untreated diabetics). Although skin collagen mass tended to be increased at all oral doses of CMT-1, only the 5 mg dose effect was statistically significant (p < 0.01). The diabetes-induced reduction in collagen solubility, a classic abnormality (reflecting excessive collagen crosslinking) of this disease, was also normalized by CMT-1 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗