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Biomedical subjects

H L Yang

Publications and source records attributed to H L Yang.

At least 37 records · Page 2Linked to original sources

Humic acid reduces protein-C-activating cofactor activity of thrombomodulin of human umbilical vein endothelial cells.

Humic acid in the drinking water of blackfoot disease endemic areas in Taiwan has been implicated as one of the aetiological factors of the disease. For this report we examined the effects of humic acid on the expression of thrombomodulin (TM) cofactor activity by cultured human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with humic acid (HA) isolated from the drinking water, as a synthetic humic acid polymer (SHA) or with commercial HA, resulted in a dose-dependent reduction of cell surface thrombomodulin activity. Characterization of the mechanism by which humic acid reduced the protein C activation indicated that inhibition was not caused by production or release of a protein C inhibitor. Kinetic analysis showed that binding affinities of TM to thrombin and of TM-thrombin complex to protein C was unchanged upon humic acid treatment. However, the cell surface TM activity was reduced by humic acid, which functions as an irreversible noncompetitive inhibitor of thrombin binding. Down-regulation of TM was inhibited by non-selective protein kinase C inhibitors and a selective inhibitor. These results suggest that protein kinase C is intricately involved in HA-induced TM down-regulation. Down-regulation of TM was also inhibited by free radical scavengers. All these changes occurred in the absence of significant cytotoxic effect. In conclusion, our results suggest that HA induces down-regulation of TM by directly increasing permeability of the cell membrane, thus causing elevation in [Ca2+]i. This species functions as a second messenger to activate protein kinase C, and/or Ca-dependent enzymes eventually inducing down-regulation of TM. Attenuation of vascular endothelial cell TM cofactor activity by humic acid may play a role in the humic acid-induced thrombotic vascular disorders of blackfoot disease.

Cell Membrane Permeability↗

Status of trace elements in patients with idiopathic dilated cardiomyopathy in central Taiwan.

BACKGROUND: Sporadic cases of dilated cardiomyopathy (DCM) are often seen in central Taiwan. Though trace elements may play a role in the pathogenesis of idiopathic DCM, there are no reports concerning study of Taiwan's population in relation to trace elements in patients with DCM. METHODS: Serum selenium, zinc, copper and iron concentrations and blood glutathione peroxidase (GPX) activity were measured in 32 patients with DCM (24 males, 8 females; mean age, 44 +/- 14 years) and 31 age-matched normal volunteers (16 males, 15 females; mean age, 38 +/- 12 years). RESULTS: The average serum selenium concentration of 27.6 +/- 8.4 micrograms/l found in the DCM group was significantly lower than the average concentration of 47.2 +/- 14.7 micrograms/l in the normal group. Blood GPX activity was also significantly lower in the DCM group than in the normal group. Serum selenium concentration correlated well with blood GPX activity in the studied subjects. Serum copper and iron concentrations were significantly higher in the DCM group than in the normal group. There was no difference in serum zinc concentration between the two groups. CONCLUSIONS: Deficiency of serum selenium in association with a low blood GPX activity, and high serum copper and iron concentrations, are found in patients with idiopathic DCM in central Taiwan.

Adult↗

Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction.

OCI-5/Glypican 3, a member of the glypican family of proteoglycans, is the defective gene in the Simpson-Golabi-Behmel overgrowth syndrome. OCI-5 expression is developmentally regulated in the intestinal epithelium, and the mechanism of its regulation was studied in the rat intestinal epithelial cell line IEC-18. A large induction of OCI-5 transcript and protein was observed at high cell density. Among other glypican family members, kappa-glypican also exhibited a confluence-dependent induction in select cell types. Nuclear run-on analysis indicated that cell-density regulation of OCI-5 occurs at the level of transcription. The rat and mouse OCI-5 promoters were cloned and found to be highly conserved, located within CpG islands and contain regions of alternating purine and pyrimidine residues. No TATA-box or recognizable INR element was observed. Consensus binding sites for AP-2, SP-1, zeste and NF-1/CTF are conserved across human, mouse and rat promoters. 5' deletion mapping of the rat promoter identified regions which enhance and repress promoter activity, with no apparent confluence-dependence or tissue-specificity. Nuclear run-on analysis probing different regions of the gene suggests that elongation control plays a role in the induction of OCI-5 by confluence.

Animals↗

Evaluation of multiple antibodies to Epstein-Barr virus as markers for detecting patients with nasopharyngeal carcinoma.

Five serological tests were assessed for their sensitivity for screening and early detection of nasopharyngeal carcinoma (NPC). The tests included the detection of antibodies to various gene products of EBV: viral capsid antigen (VCA) using an indirect immunofluorescence assay (FA), DNase using an activity neutralisation test (NT), Dnase using an enzyme-linked immunosorbent assay (ELISA), DNA polymerase (DP) using NT, and major DNA binding protein (MDBP) by ELISA. Sera from 100 NPC outpatients and 20 NPC patients, who were detected in a prospective study, were examined. The results showed that levels of antibody to DNase detected by ELISA and to DP detected by NT and the positivity rate for VCA by FA increased with NPC stage. More species of EBV antibody became detectable as NPC progressed. The detection of anti-MDBP antibody by ELISA was suitable for screening for NPC. Anti-DP antibody detected by NT was a valuable marker both for early detection and prognosis of NPC. Detection of anti-DNase antibody by ELISA was the most sensitive method for detection of NPC. No single test was sufficient to detect all the NPC patients and a combination of anti-DNase by ELISA with other tests are recommended to identify NPC patients.

Antibodies, Viral↗

In vitro sensitivity of Plasmodium falciparum to eight antimalarials in China-Myanmar and China-Lao PDR border areas.

In 1991-1995 by using the Rieckmann in vitro micro-method, susceptibilities of Plasmodium falciparum to eight antimalarials in the China-Lao PDR and China-Myanmar border areas were tested. The resistant rates of P. falciparum to chloroquinine were 95.0%-100%; IC50 114-240nmol/l. P. falciparum resistant rates to amodiaquine resistance accounted for 83.5%-100%, IC50 52-72nmol/l. All cases were sensitive to quinine, IC50 470-608nmol/l. P. falciparum isolates from the Lao PDR frontier were highly sensitive to artesunate, dihydroartemisinin, and arteether. Resistant rates from other areas were 0-11%. P. falciparum from China-Myanmar and Lao PDR border areas were also sensitive to mefloquine, IC50 68-88nmol/l. A longitudinal survey of the sensitivity of P. falciparum in vivo on the China-Lao PDR border showed that the average defervescent time of falciparum malaria was treated by pyronaridine increased from 32.7 +/- 16.0 hours during 1984-85 to 56.2 +/- 27.4 hours in 1995; the recrudescence rate rose up from 15.2% to 37.5%. The results monitored in vitro showed that all cases assessed in 1988 for response to pyronaridine were sensitive, but 36.4% of cases had emerging resistance, IC50 increased from 13nmol/l to 40 nmol/l. The above results suggested that P. falciparum in these areas has expressed resistance to chloroquine and amodiaquine. However, the parasites are still sensitive to artemisinin, pyronaridine, mefloquine, quinine, but with a declining sensitivities.

Amodiaquine↗

Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells.

We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10-200 micrograms/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 micrograms/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease.

Arterial Occlusive Diseases↗

Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts.

To determine whether lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are involved in the induction of superoxide dismutase (SOD) in gingival tissue, we examined their effect on induction of SOD isozymes in cultured normal (NGF) and phenytoin-induced hyperplastic (PHF) gingival fibroblasts. Treatment of both NGFs and PHFs with 10 to 50 ng/mL TNF-alpha for 24 hours increased the level of manganese SOD (MnSOD) to as much as four times the level of untreated cultures. PHFs, but not NGFs, were shown to be responsive to TNF-alpha in eliciting a significant increase in copper-zinc SOD (Cu/ZnSOD), albeit in a lesser amount than MnSOD. Additionally, treatment of both types of cells with 5 to 50 mg/mL of LPS for 24 hours also elicited an increase in the levels of MnSOD. Again, an LPS-induced increase in Cu/ZnSOD levels could only be demonstrated in PHFs, but not in NGFs. These observations were further confirmed by comparing the achromatic bands associated with SOD isozymes exhibited in the electrophoretogram using a nondenaturing polyacrylamide electrophoresis technique. These results indicate that TNF-alpha and LPS were capable of inducing both MnSOD and Cu/ZnSOD simultaneously in PHF fibroblasts. PHFs may be inherently more capable than NGFs in combating oxidative stress.

Anticonvulsants↗

Characterization of Epstein-Barr virus DNase and its interaction with the major DNA binding protein.

Bacterially expressed Epstein-Barr virus (EBV) DNase was purified to 98% purity and used as the source for characterization of the enzyme activities. Complete digestion of DNA by EBV DNase yielded 5'-monophosphate nucleosides as the final products. During the logarithmic phase of the reaction, EBV DNase acted processively on dsDNA but distributively on ssDNA. Both 5' to 3' and 3' to 5' exonuclease activities were present, although the former was shown to be 10-fold stronger. No significant discrepancy was seen in the liberation of end-labeled nucleotides by DNase when substrates with 5'-protruding, blunt, or 3'-protruding ends were used. EBV DNase was demonstrated also to have an endonuclease activity using supercoiled plasmid DNA as substrate. Two preferential dsDNA cleavage sites were mapped on pBS-TR, a pBlueScript vector containing one copy of the EBV terminal repeat; both are in vector sequences. Finally, an N-terminally truncated EBV major DNA binding protein, but not EA-D, was shown to inhibit EBV DNase activity. This inhibitory effect may due to direct protein-protein interactions between EBV DNase and the major DNA binding protein. The biological significance of these characteristics is discussed.

Antigens, Viral↗

Molecular cloning of cDNA coding for the 68 kDa allergen of Penicillium notatum using MoAbs.

To characterize the 68 kDa allergen of Penicillium notatum (also known as P. chrysogenum), a molecular antibody (MoAb) (P40) was previously generated. For cDNA cloning, three more MoAbs (3F, 5A3, 5G2) were generated in the present study. A mixture of all the four MoAbs was used in cloning of the gene coding for the 68 kDa allergen from a lambda gt11 cDNA library of P. chrysogenum. A cDNA clone (A6) with DNA insert of about 0.5 kb which encodes for the 3'-terminal nucleotide sequence of the 68 kDa allergen was obtained. The cloned sequence contained two putative N-glycosylation sites. The reduction in molecular weight from 68 to 62 kDa in immunoblotting after treatment of the crude extract of P. notatum with N-glycosidase F indicates that the 68 kDa allergen is a glycoprotein. Nucleotide sequence determination showed that 188 (54%) of the 348 nucleotides of the cDNA sequence obtained were identical to the same region of the nucleotide sequence of the beta-N-acetylglucosaminidase gene of Candida albicans. Although the cDNA clone obtained did not encode the full-length gene of the 68 kDa allergen, polypeptide expressed from the A6 cDNA showed positive immunological reactivities to all four MoAbs used in the cloning experiment and to IgE antibodies in sera of asthmatic patients. There was a loss of immunoblotting activity to the 68 kDa component after absorption of MoAb P40-containing culture supernatant with filters blotted on plaque lawns of cDNA clone A6. Moreover, the immunoblotting activity remained when the MoAbs affinity-purified with filters containing polypeptides encoded by the cDNA insert of clone A6 were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Cloning and expression of an antigenic domain of glycoprotein gE of pseudorabies virus in Escherichia coli and its use as antigen in diagnostic assays.

Use of a combination of an effective gE gene-deleted pseudorabies virus (PRV) vaccine with a companion diagnostic kit for PRV glycoprotein gE has proven successful in several pseudorabies-eradication programs. To produce a large quantity of functional gE protein for development of a PRV-gE diagnostic kit, an Escherichia coli expression system containing the distal region of the PRV-gE gene of a PRV strain CF was constructed. The expressed protein contained 134 amino acids of gE protein (amino acids 77-210) fused to a 19-amino acids tag containing 6 histidine residues. After induction, a truncated PRV-gE polypeptide of 18-kd was expressed to about 20% of the total E coli proteins. Results of immunoblot analysis indicated that this E coli-produced PRV-gE protein reacted specifically with serum from PRV-hyperimmunized pigs and from field PRV-infected pigs, but not with serum samples from specific-pathogen-free pigs or pigs inoculated with gE-deleted PRV vaccine. These data indicate that, although the recombinant gE protein is produced in E coli, it still retains the antigenicity of the viral gE glycoprotein. Comparison between the recombinant gE protein, using immunoblot analysis with a commercial gE ELISA containing natural PRV-gE protein, revealed comparable test performance. This finding indicated that recombinant gE protein produced by E coli can be used for development of a companion serologic assay for a PRV-gE gene-deleted vaccine.

Animals↗

Synthesis of Hsp72 induced by exercise in high temperature.

An investigation was undertaken involving the physiological effects of exercise in high temperature and its effect on the induction of heat shock proteins synthesis in peripheral lymphocytes and gastrocnemius. Male Long-Evans rats were employed. Environmental temperature was designed as three conditions: room temperature (26-27 degrees C), middle temperature (30-31 degrees C), and high temperature (36-37 degrees C). Rats were divided into one of three groups and exercised passively in an automatic round treadmill. Body temperature, biochemical changes were determined and the synthesis of heat shock protein 72 were analyzed by SDS-PAGE and immunochemical stain with monoclonal anti-Hsp72 antibody. Those results indicated that the body temperature elevated faster and higher in rats of high-temperature exercise group than those of a house temperature significantly (p < 0.05). Hsp72 could be detected only in lymphocytes from rats exercising in high temperature more than 60 minutes whose body temperatures were elevated above 41 degrees C. The induced Hsp72 appeared in lymphocytes 2 hours after exercise and reached maximally at 16-24 hours and then disappeared gradually. In gastrocnemius, Hsp72 could be detected even before the passive exercise, and its amount changed as in lymphocytes did in all three groups. No difference was found in blood sugar, hematocrit and CK among the three groups of rats. On the basis of above results, we can conclude that Hsp72 is synthesized in the muscle of intact rats, and exercise is a sufficient inducer. For lymphocytes, the presence of Hsp72 can be viewed as a heat stress in exercise.

Animals↗

Plasma protein C activity is enhanced by arsenic but inhibited by fluorescent humic acid associated with blackfoot disease.

Blackfoot disease is a peripheral vascular disease causally related to the fluorescent humic acid found in the drinking water of endemic areas in Taiwan. We compared the effects of humic acid (HA) purified from the well water of Blackfoot disease endemic areas with the effects of commercial humic acid (Aldrich) as well as trivalent arsenic (As2O3) on protein C activity, which plays an important role in regulation of blood coagulation and fibrinolysis. Humic acid, either purified from drinking water or obtained commercially, dose-dependently inhibited both activated protein C activity and the activation of protein C induced by Protac, a snake venom-derived protein C activator. In contrast to humic acid, arsenic oxide dose-dependently enhanced both activated protein C activity and the Protac-stimulated activation of protein C. In the presence of humic acid the enhancement effect of arsenic oxide was completely abolished, resulting in concentration-dependent inhibition of protein C activity. Therefore, the results of this study indicate that humic acid is a potent protein C inhibitor even in the presence of arsenic, which enhances the protein C activity. Since protein C is a potent anticoagulant and profibrinolytic agent, acquired defects of protein C induced by humic acid might cause a thrombophilic or hypercoagulable state. Whether this is one of the possible mechanisms of humic acid-induced thrombotic disorders in Blackfoot disease needs to be further characterized.

Arsenic↗

A modified hepatitis B virus surface antigen with the receptor-binding site for hepatocytes at its C terminus: expression, antigenicity and immunogenicity.

A modified hepatitis B virus (HBV) surface antigen, the SA-28 protein, was constructed and expressed by recombinant vaccinia virus in mammalian cells. This protein was composed of a PreS1 region-derived peptide (amino acids 21 to 47) that contained the hepatocyte receptor-binding site, joined to the C terminus of the major S protein at amino acid position 223. This modified surface antigen could be efficiently assembled into particles with a density of 1.23 g/ml and could be secreted from several mammalian cell lines. The results of immunoprecipitation revealed that the SA-28 protein was recognized by both the anti-S protein antibody and the anti-PreS1 antibody. A strong antibody response, against both the S protein and PreS1 epitopes, was induced in BALB/c mice immunized by the SA-28 particles indicating good immunogenicity. These results suggested that the HBV surface antigen consisting of the SA-28 protein could be a promising candidate as a new HBV vaccine with higher efficacy.

Animals↗

Humic acid induces expression of tissue factor by cultured endothelial cells: regulation by cytosolic calcium and protein kinase C.

Blackfoot disease is a thrombotic peripheral vascular disease causally related to the fluorescent humic acid (HA) found in the drinking water of wells in endemic areas in Taiwan. In this study we examined the effect of HA on tissue factor (TF) expression by vascular endothelial cells. Incubation of cultured human umbilical vein endothelial cells (HUVEC) with HA isolated from endemic area drinking water or with a synthetic humic acid polymer (SHA), resulted in enhanced cell surface expression of TF activity by HUVEC. The intracellular calcium level ([Ca2+]i) was measured using a calcium-specific fluorescent probe, fura 2. Changes in [Ca2+]i level were followed and quantitatively analyzed by spectrofluorometric microscopy, after incubation of the fura 2-loaded HUVEC with HA or SHA in a medium containing 1.8 mM CaCl2. Both HA and SHA increased [Ca2+]i in the presence of extracellular calcium ions, but not in their absence, indicating that influx of extracellular Ca2+ occurred during incubation of HUVEC with HA or SHA. Verapamil, a potent calcium channel blocker, did not abolish the enhancement of [Ca2+]i induced by HA or SHA, indicating that specific calcium channels may not be involved in the HA/SHA-induced elevation of [Ca2+]i. The elevated [Ca2+]i level induced by HA or SHA returned to basal level following removal of HA or SHA and incubation of the washed cells in medium containing 1.8 mM CaCl2. All these changes occurred in the absence of significant cytotoxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[Longitudinal surveillance of chloroquine resistance of Plasmodium falciparum after cessation of medication in south Yunnan].

The resistance of P. falciparum to chloroquine was assayed by in vitro microtest in 1981 and after cessation of medication in 1984, 1988-1990 and 1992 in south Yunnan Province of China. The resistance rates were 97.4% (38/39), 100% (25/25), 96.1% (73/76) and 93.7% (59/63), respectively; ID50 were 170, 132, 125 and 110 nmol/L; ID95 were 1,000, 740, 707 and 576 nmol/L; mean dosages for complete inhibition of schizont formation were 55.4, 46.7, 45.8 and 35.4 (pmol/well). A comparison of the results in 1981, 1984, 1988-1990 and 1992, the resistance rate showed no marked change, ID50 dropped 22.3% (P < 0.05), 26.4% (P < 0.05) and 35.3% (P < 0.01); ID95 declined 26.0% (P < 0.05), 29.3% (P < 0.05) and 42.2% (P < 0.01); mean dosage of inhibition dropped 15.7% (P > 0.05), 17.3% (P < 0.05) and 36.1% (P < 0.01). The results show that the extent of resistance in chloroquine-resistant P. falciparum to chloroquine in south Yunnan has been declined markedly, indicating that coresistance was variable and dropped along with the declining of drug pressure.

Animals↗

Stimulation of endothelin production in cultured human endothelial cells by fluorescent compounds associated with blackfoot disease.

The fluorescent compounds (FC) in humic substances isolated from the drinking water of endemic areas of blackfoot disease have been characterized as the causative factor of the disease. In this report we studied the effects of these fluorescent compounds on the synthesis and secretion of endothelin-1 by cultured human umbilical cord vein endothelial cells (HUVEC) in order to explore the possible pathological mechanism(s) of FC in the development of atherothrombotic vasculopathy in blackfoot disease. Incubation of confluent HUVEC with FC (100 micrograms/ml) enhanced endothelin mRNA expression. A sensitive ELISA method was developed to quantitate secreted endothelin antigen levels in conditioned medium. Incubation of confluent HUVEC cultures with different concentrations of FC (0-200 micrograms/ml) resulted in concentration-dependent enhanced production of endothelin. No significant changes in endothelin production were observed when subconfluent HUVEC cultures were incubated with FC. FC dose-dependently reduced the growth rate of subconfluent cultured HUVEC and exerted cytotoxic effects on the viability and integrity of confluent HUVEC monolayers. Since endothelin is one of the most potent vasoconstrictors affecting blood pressure and blood flow, and is mitogenic for smooth muscle cell proliferation, these results imply that the enhanced endothelin production and the reduced cell viability and growth rate induced by FC may contribute to the atherothrombotic vasculopathy observed in blackfoot disease.

Arterial Occlusive Diseases↗

Polypoid lesions of the gallbladder: diagnosis and indications for surgery.

One hundred and eighty-two patients with an ultrasonographic and/or pathological diagnosis of polypoid lesions of the gallbladder (PLG) were reviewed to determine the reliability of ultrasonography in the diagnosis of PLG and the indications for operation in this disease. Of the 182 patients operated on, PLG were demonstrated by the gross appearance of the resected gallbladder in 172. Histologically benign lesions were present in 159 gallbladders and malignant lesions in 13. Cholesterol polyps accounted for most benign PLG. The sensitivity of ultrasonography in detecting PLG was 90.1 per cent, significantly higher than that of oral cholecystography, computed tomography or endoscopic retrograde cholangiopancreatography (P less than 0.01). The specificity of ultrasonography in the diagnosis of PLG was 93.9 per cent. Therefore, ultrasonography is a highly sensitive method for investigating PLG, and the preoperative diagnosis of PLG in this unit has now become entirely dependent on this technique. The size and number of PLG, the presence of gallstones and the patient's age all correlate with the nature of PLG, and these features are helpful in differentiating malignant from benign lesions before operation. Surgical treatment is indicated when PLG exceed 1.0 cm in diameter, when PLG are single in number, when PLG are associated with gallstones, when patients with PLG are over the age of 50 years, or when clinical symptoms of PLG are apparent.

Adolescent↗

Primary structure and disulfide bridge location of arrowhead double-headed proteinase inhibitors.

Two arrowhead proteinase inhibitors (inhibitors A and B) were characterized and their primary structures were determined. Both inhibitors A and B are double-headed and multifunctional protease inhibitors. Inhibitor A inhibits an equimolar amount of trypsin and chymotrypsin simultaneously and weakly inhibits kallikrein. Inhibitor B inhibits two molecules of trypsin simultaneously and inhibits kallikrein more strongly than does inhibitor A. The amino acid sequences of inhibitors A and B were determined by sequencing the reduced and S-carboxamidomethylated proteins and their peptides produced by cyanogen bromide or proteolytic lysylendopeptidase or Staphylococcus aureus V8 protease cleavage. Inhibitors A and B consist of 150 amino acid residues with three disulfide bonds (Cys 43-Cys 89, Cys 110-Cys 119, and Cys 112-Cys 115) and share 90% sequence identity, with 13 different residues. Since the primary structures are totally different from those of all other serine protease inhibitors so far known, these inhibitors might be classified into a new protease inhibitor family.

Amino Acid Sequence↗