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Biomedical subjects

M H Fan

Publications and source records attributed to M H Fan.

7 recordsLinked to original sources

Protegrin-1 enhances bacterial killing in thermally injured skin.

OBJECTIVE: Septic complications and the emergence of drug-resistant microbes represent serious risks to patients. Recently, naturally occurring peptides have been discovered that possess potent and broad-spectrum antimicrobial activity. Protegrin-1 is particularly attractive for clinical use in human wounds because, unlike defensins, protegrin-1 retains broad antimicrobial and antifungal activity at physiologic salt concentration and in the presence of serum. The objective of this study was to examine the efficacy of protegrin-1 in killing multiple drug-resistant microbes isolated from human burn patients. DESIGN: For thein vitroexperiment, bilayer radial diffusion was performed comparing standard antibiotics with protegrin-1 on multiple-drug-resistant microbial organisms isolated from infected burn wounds. In vivo, rats received a 20% total body surface area partial-thickness burn by immersion in 60 degrees C water for 20 secs followed by wound seeding with 106 colony forming units of Silvadene-resistant Pseudomonas aeruginosa. SETTING: University of Michigan research laboratory. SUBJECTS: Adult, male Sprague-Dawley rats. INTERVENTIONS: Rats were randomized into three groups: those receiving synthetic protegrin-1, acetic acid (carrier), or gentamicin (positive control). Protegrin-1 was administered by topical application or intradermal injection. Wound tissues were harvested aseptically at different time points for quantitative bacterial counts. MEASUREMENTS AND MAIN RESULTS: In vivo and in vitro experiments revealed rapid and significant decreases in bacterial counts for protegrin-1-treated groups compared with controls. CONCLUSIONS: This study shows that protegrin-1 potentially may be used as an alternative or adjunct therapy to standard agents used to treat wound infections.

Administration, Topical↗

Potent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1.

A mutant of Bacillus subtilis IMR-NK1, which is used for the production of domestic "natto" in Taiwan, produced high fibrinolytic enzyme activity by solid-state fermentation using wheat bran as medium. In addition, a strong fibrinolytic enzyme was purified from the cultivation media. The purified enzyme was almost homogeneous, as examined by SDS-PAGE and capillary electrophoresis. The enzyme had an optimal pH of 7.8, an optimal temperature of 55 degrees C, and a K(m) of 0.15% for fibrin hydrolysis. The molecular mass estimated by gel filtration was 31.5 kDa, and the isoelectric point estimated by isoelectric focusing electrophoresis was 8.3. The enzyme also showed activity for hydrolysis of fibrinogen, casein, and several synthetic substrates. Among the synthetic substrates, the most sensitive substrate was N-succinyl-Ala-Ala-Pro-Phe-pNA. PMSF and NBS almost completely inhibited the activity of the enzyme. These results indicate that the enzyme is a subtilisin-like serine protease, similar to nattokinase from Bacillus natto.

Bacillus subtilis↗

Infection with GB virus C and hepatitis C virus in hemodialysis patients and blood donors in Beijing.

RNAs of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought by reverse-transcription polymerase chain reaction with nested primers deduced from the 5' untranslated region: 79 patients on maintenance hemodialysis, 205 commercial blood donors, and 205 voluntary donors in Beijing were studied. GBV-C RNA was detected in 43 (54%) patients and 17 (8%) commercial donors, and HCV RNA in 43 (54%) patients and 13 (6%) commercial donors, respectively. By contrast, GBV-C RNA was detected only in 2 (1%) and HCV RNA in none among 205 volunteer blood donors serving as controls. Thus both patients and commercial blood donors were at higher risk for infection with GBV-C (P < 0.001) than controls. HCV RNA was detected more often in patients with GBV-C RNA than without (29/43 or 67%, vs. 14/36 or 39%, P < 0.05) as well as in commercial donors with GBV-C RNA than without (5/17 or 29% vs. 8/188 or 4%, P < 0.01). A phylogenetic tree constructed on a sequence of 100 base pairs in the helicase region indicated that GBV-C isolates from Beijing are more similar to Japanese isolates than to isolates from the United States and Africa. Sequences from certain hemodialysis patients and those from some commercial donors were similar, suggesting nosocomial infection and spread among restricted groups.

Adult↗

Transmembrane residues of the parathyroid hormone (PTH)/PTH-related peptide receptor that specifically affect binding and signaling by agonist ligands.

Polar residues within the transmembrane domains (TMs) of G protein-coupled receptors have been implicated to be important determinants of receptor function. We have identified mutations at two polar sites in the TM regions of the rat parathyroid hormone (PTH)/PTH-related peptide receptor, Arg-233 in TM 2 and Gln-451 in TM 7, that caused 17-200-fold reductions in the binding affinity of the agonist peptide PTH-(1-34) without affecting the binding affinity of the antagonist/partial agonist PTH-(3-34). When mutations at the TM 2 and TM 7 sites were combined, binding affinity for PTH-(1-34) was restored to nearly that of the wild type receptor. The double mutant receptors, however, were completely defective in signaling cAMP or inositol phosphate production in response to PTH-(1-34) agonist ligand. The results demonstrate that Arg-233 and Gln-451 have important roles in determining agonist binding affinity and transmembrane signaling. Furthermore, the finding that residues in TM 2 and TM 7 are functionally linked suggests that the TM domain topology of the PTH/PTH-related peptide receptor may resemble that of receptors in the rhodopsin/beta-adrenergic receptor family, for which structural and mutagenesis data suggest interactions between TMs 2 and 7.

Amino Acid Sequence↗

[The experiment research of OB glue used in tracheoanastomosis].

Resect a segment of canine cervical trachea. The length of resected trachea is from 1-4cm and 5-8cm. In the first group, one dog was used for each length and two dogs were used for each length in the second group, therefore twelve were used in the experiment. The upper and lower ends were matched and seved by three stitches, and OB glue was used to coat in the anastomosis crevice, and at last the cre-vice was wrapped with a sheet of loose tracheal sheath. After the operation, irritating cough, barking, swallowing and free movement of neck didn't cause fistula. Nakedeyes and tissue examination showed that the healing of the anastomostic orifice was well and no stenosis was found. The glue membrane was absorbed completely within 1-2 months. Outside body anti-pulling force experiment (for 8 cases) showed that the anastomostic line can hold 100cm H2O stress and 2kg pulling strength if only OB glue was used to connect the resected ends. Hence, this experiment shows that the usage of OB glue for tracheal anastomosis is a safety, simple and convenient method.

Anastomosis, Surgical↗

The long-term effects of recombinant human erythropoietin on the cardiovascular system.

Fifty-five hemodialysis patients (pts) received rHuEpo for 3-5 years (51 +/- 11 months, hematocrit 32.5 +/- 3.7). BP medication was required in 42% of pts prior to rHuEpo (Hct 20.8 +/- 3.5) and 69% (38 patients) now require such therapy. BP was controlled with single therapy in 16 pts and only 8 required 3 or more different BP drugs. Vascular access clotting episodes were rare in pts with autologous fistula (17 of 24 pts had no clotting), whereas access clotting episodes were 10 times more common in pts with AV grafts, yet 20% had no clotting after 3-5 years of rHuEpo. Heart size decreased in most who initially had cardiomegaly. Cardiovascular related and other deaths were decreased in this selected group when compared to other dialysis pts matched for age, race and type of renal disease.

Anemia↗