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Biomedical subjects

Y M Chen

Publications and source records attributed to Y M Chen.

At least 19 recordsLinked to original sources

Atrial natriuretic peptide degradation by CPA47 cells: evidence for a divalent cation-independent cell-surface proteolytic activity.

Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial-derived cell line, CPA47. CPA47 cells degraded 88% of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41% of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I-ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity.

Atrial Natriuretic Factor

Lymph node tuberculosis: 7-year experience in Veterans General Hospital, Taipei, Taiwan.

We retrospectively studied 71 cases of lymph node tuberculosis confirmed by culture or pathology from 1983 to 1989. Young adults were most frequently involved and the female to male ratio was 3:2. of 71 patients, three-quarters presented with palpable masses and two-thirds were asymptomatic. The cervical nodes were most frequently involved. Roentgenographic evidence of pulmonary tuberculosis was detected in 42% of patients and sputum culture-positive tuberculosis occurred in 7%. Tuberculin skin testing is less useful in our country due to routine BCG vaccination during infancy and early childhood. Selective excisional biopsy in addition to clinical information was necessary for differential diagnosis. 48 patients received regular treatment and were followed up for at least 1 year. Fresh nodes or enlargement of existing nodes developed in 10% of patients during treatment. Residual nodes were present in 10% of patients at the end of 9-month treatment with rifampicin, isoniazid and ethambutol, including prolonged or modified regimens in some individuals. In conclusion, in areas with a high frequency of tuberculous strains presenting a primary resistance to isoniazid, a 9-month regimen of rifampicin, isoniazid and ethambutol is recommended for lymph node tuberculosis.

Adult

HTLV among Israeli intravenous drug abusers.

Since human T lymphotropic virus (HTLV) infection was recently described in Israel and other Middle Eastern countries, we have investigated the presence of HTLV type 1 and type 2 in a group of 299 intravenous (IV) drug abusers who were seen at a large methadone clinic in the Tel Aviv area in 1986-1987. We found that 1.3% were seropositive to HTLV. Further testing revealed that HTLV1 was the only HTLV serotype. In addition, no coinfection HIV1/HTLV1 and no HIV2 infection were detected. Since all HTLV seropositives were born in Middle Eastern countries, did not travel outside Israel and were not infected by HIV1 or by HTLV type 2, it is possible that the source of HTLV1 infection in that group was in an endemic reservoir of HTLV1 in Israel. The detection of HTLV1 among IV drug abusers and among other groups in Israel necessitates more extensive HTLV testing in at-risk populations.

Adult

Human T lymphotropic virus types I- and II-specific antibody-dependent cellular cytotoxicity: strain specificity and epitope mapping.

Antibody-dependent cellular cytotoxicity (ADCC) against human T lymphotropic virus (HTLV) types I and II was investigated using sera obtained from infected individuals or from rabbits immunized with HTLV-I or -II envelope peptides. Target cells included an HTLV-I-transformed cell line (C91/PL), an HTLV-II-transformed cell line (729pH6neo), and Epstein Barr virus (EBV)-transformed B lymphocytes expressing HTLV-I or -II env or gag gene products after infection with vaccinia/HTLV recombinants. ADCC activity was directed at HTLV-I and -II envelope glycoproteins but not against core (gag) components. In contrast to the human immunodeficiency virus system, significant cross-reactivity between HTLV-I- and -II-directed ADCC activity was observed. Epitope mapping studies using sera from rabbits that had been immunized with HTLV-I or -II envelope peptides suggested that the critical epitopes for ADCC activity are located primarily in hydrophilic regions of the exterior (gp46) part of the envelope glycoprotein.

Animals

[Small cell lung cancer and long-term survival: our experience in VGH-Taipei from 1971 to 1985].

We diagnosed 627 cases of SCLC from 1971 to 1985 in VGH-Taipei. Sixty-nine cases received no treatment, while 558 cases received treatment including chemotherapy, radiotherapy, surgical intervention or combined modality. The median survival time of the treated group and untreated group was 6 and 1 months respectively (p less than 0.001). Female sex was a positive prognostic factor (p less than 0.05) and median survival time of female and male were 7 and 5 months respectively. Age (older or younger than 65 y/o) was not a significant prognostic factor in our series (p = 0.13). Thirteen cases (2.33%) of patients in the treated group survived longer than 5 years. Among them, 11 cases were limited disease and 2 cases were extensive disease. The characteristics of these 13 patients were analysed to find them in relatively good performance status, less body weight loss, less biochemical abnormality and more limited disease. In them, no secondary tumor was noted during the follow-up period.

Aged

[Changes of subtypes of alpha 1-adrenoceptor in blood vessels of spontaneously hypertensive rats].

The two subtypes of alpha 1-adrenoceptors in blood vessels were compared between stroke prone spontaneously hypertensive rats (SHRSP) and WKY rats in vitro and in vivo. Pretreatment with 50 mumol/L chlorethylclonidine (CEC) for 30 min decreased the maximal contractions induced by norepinephrine (NE) to 31.4 +/- 8.3% and 35.2 +/- 2.9% (aortae); 68.4 +/- 8.2% and 80.1 +/- 7.2% (renal arteries); 68.4 +/- 6.3% and 5.4 +/- 7.0% (mesenteric arteries) of the controls in the SHRSP and the WKY rats, respectively. All the differences between the SHRSP and WKY rats were not statistically significant. In contrast, the blocking effects of nifedipine were much stronger in the SHRSP rats than those in the WKY rats. In the presence of 10 mumol/L nifedipine the maximal contractions induced by NE were decreased to 3.1 +/- 1.5% and 56.5 +/- 4.8% (P < 0.01, aortae); 9.0 +/- 4.1% and 23.6 +/- 3.5% (P < 0.05, renal arteries); 5.9 +/- 2.5% and 28.0 +/- 0.8% (P < 0.01, mesenteric arteries) of the controls in the SHRSP and the WKY rats, respectively. The experiment in vivo also showed that the effects of nifedipine on decreasing basal blood pressure and on antagonizing phenylephrine were increased in the SHRSP rats, as compared to the WKY rats. Analyses of two components of the contractions induced by 10 mumol/L NE in aortae demonstrated that both phasic and tonic contractions were mainly caused by activations of the alpha 1B subtype. There were no significant differences of blocking effects of nifedipine on the phasic contractions between the SHRSP and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Alpha adrenoceptor subtypes in smooth muscles of rat pulmonary artery].

The contributions of subtypes of alpha-adrenoceptor to contraction induced by agonists were studied in smooth muscles of isolated rat pulmonary arteries. The results showed that the antagonizing effects of prazosin on the contraction induced by norepinephrine (NE) or phenylephrine (Phe) were more potent than those of yohimbine. The effect of prazosin against Phe was more potent than against NE, and yohimbine was just the reverse. Preincubation of preparations with chlorethylclonidine (CEC) 50 mumol.L-1, after which only alpha 1A adrenoceptors were left, reduced the vascular contraction induced by NE to 36% of the control (P < 0.01). While in the presence of nifedipine 10 mumol.L-1, during which only the responses of alpha 1B adrenoceptors were left, the contraction was weakened to 70% (P < 0.05). The pKA values of alpha 1A subtype (3.37 +/- 0.34) were smaller than those of alpha 1B (6.64 +/- 0.40, P < 0.01). But the values of KA/EC50 were much higher in alpha 1A than those in alpha 1B. The results suggest that in smooth muscle of rat pulmonary artery both alpha 1 and alpha 2 adrenoceptors exist, but alpha 1 is superior functionally. Both subtypes of alpha 1 adrenoceptor are involved in the contraction induced by NE. Compared with alpha 1B subtype, alpha 1A subtype has a lower affinity but a more reserve and a higher efficacy for NE.

Animals

Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.

Adult

[Blood pressure and metabolic response to converting enzyme inhibitor in hypertensive patients: comparison between delapril and captopril].

The antihypertensive and metabolic responses to delapril and captopril in hypertensive patients were studied. Forty-six hypertensive patients entered the study and were divided into two groups. The delapril group included 21 essential hypertensive and five renoparenchymal hypertensive patients; while the captopril group included 11 essential hypertensive and nine renoparenchymal hypertensive patients. The patients in the delapril group took delapril 7.5 mg twice a day for 2 weeks. If the antihypertensive effect was inadequate, the dose was increased to 15mg twice a day, and then to 30mg twice a day. The period of delapril treatment was 12 weeks. The patients in the captopril group took captopril 25 mg twice a day or three times a day for 12 weeks. After delapril treatment, there were significant decreases in the systolic (from 163 +/- 17 to 141 +/- 15 mmHg) and diastolic blood pressure (from 105 +/- 13 to 91 +/- 10 mmHg). There were also significant decreases in the systolic (from 161 +/- 18 to 141 +/- 24 mmHg) and diastolic blood pressure (from 100 +/- 10 to 90 +/- 12 mmHg) after captopril treatment (p < 0.001). The pulse rates in both groups showed no significant changes after treatment. The laboratory data in both groups showed few changes after treatment. Plasma renin activity increased after delapril treatment. A cough was the side effect most commonly seen. We conclude that hypertensive patients have the same blood pressure and metabolic responses to delapril as captopril.

Adult

Unusual pattern of antibodies to human T-cell leukemia virus type-I in family members of adult T-cell leukemia patients.

Detection methods for the human T-cell leukemia virus type-I (HTLV-I) for blood screening and diagnosis generally rely on antibody tests that use the structural proteins of HTLV-I as antigen. We have found an unusual pattern of antibody reactivity among people who are at high risk of HTLV infection due to being a family member of an adult T-cell leukemia (ATL) patient: a specific antibody reaction exclusively directed to the HTLV regulatory protein tax, and not to the HTLV-I structural proteins. Sera from 7 of 82 (8.5%) structural antibody-undetectable family members of ATL patients had the anti-tax reactivity. Two seroconverters were observed. One seroconverter a healthy resident of Miyazaki, tested negative for structural antibody, but positive for tax antibody. Two years later she tested positive for both. The other seroconverter, an Israeli hemophiliac, tested negative for both antibodies, but converted to tax antibody-positive/structural antibody-negative. The HTLV-I tax-only antibody profile was also observed in sera sets from two other populations at risk for HTLV infection, human immunodeficiency virus-1-infected patients at the Bronx-Lebanon Hospital in New York and Israeli hemophiliacs. DNA samples from lymphocytes of four individuals with antibody reactivity only to HTLV-I tax were tested in polymerase chain reaction experiments; no HTLV-I or -II DNA was detected.

Animals

Delineation of type-specific regions on the envelope glycoproteins of human T cell leukemia viruses.

Two different approaches were used to map the type-specific regions on human T cell leukemia virus (HTLV) envelope glycoproteins. 1) Antibody reactivities of polymerase chain reaction-confirmed HTLV-I or HTLV-II carriers' sera were analyzed by Western blot assay with seven recombinant proteins containing different regions of HTLV-I or HTLV-II envelope proteins. 2) Rabbit antibodies elicited by nine HTLV-I Env synthetic peptides were used to react with the native HTLV envelope glycoproteins in an antibody-dependent cellular cytotoxicity (ADCC) assay. The results of the Western blot analysis showed that RP-B2, which contains amino acid residues 166 to 213 from HTLV-II exterior glycoprotein, was specifically reactive with 90.6% (48 of 53) of the HTLV-II carriers' sera but not with any of the HTLV-I carriers' serum (0 of 71). In contrast, RP-B, which contains amino acid residues 166 to 229 from HTLV-I exterior glycoprotein, was reactive with 85.1% (114 of 134) of the HTLV-I carriers' sera but not with any HTLV-II carrier serum (0 of 62). Furthermore, anti-HTLV-I Env synthetic peptide antibody-mediated ADCC identified several distinguishing HTLV-I ADCC epitopes in the middle region (amino acid residues 177 to 257) of the HTLV-I exterior glycoprotein. Therefore, HTLV type-specific epitopes reside mainly in a 69-amino acid sequence bounded by two cysteine residues (amino acids 157 and 225 for HTLV-I and 153 and 221 for HTLV-II), in the middle region of the exterior envelope glycoproteins.

Amino Acid Sequence

Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody.

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.

Agglutination Tests

Pathodynamics of intoxication in rats and mice by enterotoxin of Clostridium perfringens type A.

The pathodynamics of lethal intoxication in rats and mice by i.v. administration of enterotoxin of Clostridium perfringens type A was studied using whole animals and isolated organs. A lethal i.v. dose (50 micrograms/kg) of enterotoxin killed anesthetized rats and mice within 4-15 min. Rapid changes of ECG pattern suggestive of hyperpotassemia, rapid fall of blood pressure and transient hyperpnea followed by respiratory depression were observed. Analysis of plasma levels of cations revealed hyperpotassemia in both animal species. On the other hand, enterotoxin (up to 100 micrograms) showed little direct cardiotoxicity on the isolated heart. ECG changes produced by i.v. injection of KCl (0.5 ml of 50 mM) mimicked the ECG changes observed in the intoxicated rats injected with a lethal dose of enterotoxin. Perfusion of rat isolated organs showed that potassium concentration in the eluent from the liver (but not lungs or lower extremities) increased markedly within 1-2 min after the administration of enterotoxin. The amount of potassium liberated from a rat liver was about 133 mumoles, which is sufficient to increase the plasma level of potassium to more than 10 mM. In addition to potassium, cytoplasmic enzymes, such as glutamate oxalacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase, were also liberated from the intoxicated liver, indicating that potassium was liberated from hepatocytes by the change in membrane permeability produced by enterotoxin. It is concluded that hyperpotassemia elicited by the cytotoxic action of enterotoxin on hepatocytes caused cardiac failure leading to the death of the intoxicated animals.

Animals

Radiation-protective and platelet aggregation inhibitory effects of five traditional Chinese drugs and acetylsalicylic acid following high-dose gamma-irradiation.

High doses of 60Co radiation (4.0-8.0 Gy) in mice, rats and rabbits caused increases in rate of platelet aggregation during the first 5 days after irradiation. The inhibitory effects of the extracts of five Chinese drug plants and acetylsalicylic acid on rate of platelet aggregation were observed in both in vitro and in vivo tests, averaging 23-53% in vitro and 46-69% in vivo. Antiradiation tests on mice vs. 7.5-8.0 Gy of gamma-radiation, using the plant extracts and acetylsalicylic acid as protective agents, increased survival rates by 8-50% for the plant extracts and 35% for acetylsalicylic acid.

Animals

Identification of a recombinant HTLV-II envelope protein for serological detection of HTLV-II carriers.

To understand the pathogenic potential and the true extent of human T-cell leukemia virus type II (HTLV-II) infection, it is important to develop a specific HTLV-II antigen-based serological test. Plasmid pIIB was constructed and induced in Escherichia coli to express a recombinant protein (RP) containing 140 amino acids (amino acid residues 96 to 235) from the middle region of the HTLV-II exterior envelope glycoprotein gp52. Serum samples from polymerase chain reaction-confirmed HTLV-II-infected people, HTLV-I carriers, and adult T-cell leukemia (ATL) patients were tested for antibody reactivity to RP-IIB by Western blot assay. The results showed all 27 HTLV-II carriers, 10 of 20 HTLV-I carriers, and 4 of 17 (23.5%) ATL patients had antibody reactivities to RP-IIB. The difference in rates of seropositivity to RP-IIB between HTLV-II carriers (100%) and HTLV-I-infected people (carriers plus ATL patients) (37.8%) is statistically significant (Fisher's exact test, p = 4.30E-08).

Carrier State