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Biomedical subjects

C M Lee

Publications and source records attributed to C M Lee.

At least 217 records · Page 12Linked to original sources

Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins.

Escherichia coli heat-labile enterotoxins (LT) are responsible in part for "traveler's diarrhea" and related diarrheal illnesses. The family of LTs comprises two serogroups termed LT-I and LT-II; each serogroup includes two or more antigenic variants. The effects of LTs result from ADP ribosylation of Gs alpha, a stimulatory component of adenylyl cyclase; the mechanism of action is identical to that of cholera toxin (CT). The ADP-ribosyltransferase activity of CT is enhanced by 20-kD guanine nucleotide-binding proteins, known as ADP-ribosylation factors or ARFs. These proteins directly activate the CTA1 catalytic unit and stimulate its ADP ribosylation of Gs alpha, other proteins, and simple guanidino compounds (e.g., agmatine). Because of the similarities between CT and LTs, we investigated the effects of purified bovine brain ARF and a recombinant form of bovine ARF synthesized in Escherichia coli on LT activity. ARF enhanced the LT-I-, LT-IIa-, and LT-IIb-catalyzed ADP ribosylation of agmatine, as well as the auto-ADP ribosylation of the toxin catalytic unit. Stimulation of ADP-ribosylagmatine formation by LTs and CT in the presence of ARF was GTP dependent and enhanced by sodium dodecyl sulfate. With agmatine as substrate, LT-IIa and LT-IIb exhibited less than 1% the activity of CT and LT-Ih. CT and LTs catalyzed ADP-ribosyl-Gs alpha formation in a reaction dependent on ARF, GTP, and dimyristoyl phosphatidylcholine/cholate. With Gs alpha as substrate, the ADP-ribosyltransferase activities of the toxins were similar, although CT and LT-Ih appeared to be slightly more active than LT-IIa and LT-IIb. Thus, LT-IIa and LT-IIb appear to differ somewhat from CT and LT-Ih in substrate specificity. Responsiveness to stimulation by ARF, GTP, and phospholipid/detergent as well as the specificity of ADP-ribosyltransferase activity are functions of LTs from serogroups LT-I and LT-II that are shared with CT.

ADP-Ribosylation Factors↗

Heterotopic heart transplantation--a life-saving procedure with a size-mismatched donor.

A 32-year-old B-type male weighing 60 kg suffered from end-stage dilated cardiomyopathy. Although aggressive medical treatment with dobutamine 21 micrograms/kg/min, dopamine 17 micrograms/kg/min, digoxin 0.25 mg i.v. once daily, furosemide 40 mg i.v. every 6 h, and bumetanide 0.5 mg i.v. every 6 h were given, he was finally ventilator dependent for the last 3 weeks until a B-type donor weighing 42.5 kg was found. Because of the 29.2% weight mismatch, a heterotopic heart transplantation was performed. Posterior plication mitral annuloplasty was also performed to correct the severe mitral regurgitation of the recipient heart. Postoperatively the patient remained respirator dependent for 17 days and was finally discharged in good condition on the 46th postoperative day.

ABO Blood-Group System↗

Conversion of 5(10)-oestrene-3 beta,17 beta-diol to 19-nor-4-ene-3-ketosteroids by luteal cells in vitro: possible involvement of the 3 beta-hydroxysteroid dehydrogenase/isomerase.

We have previously suggested that in porcine granulosa cells, a putative intermediate, 5(10)-oestrene-3,17-dione is involved in 4-oestrene-3,17-dione (19-norandrostenedione; 19-norA) and 4-oestren-17 beta-ol-3-one (19-nortestosterone: 19-norT) formation from C19 aromatizable androgens. In this study, luteal cells prepared from porcine, bovine and rat corpora lutea by centrifugal elutriation were used as a source of 3 beta-hydroxysteroid dehydrogenase/isomerase in order to investigate the role of this enzyme in the biosynthesis of 19-norsteroids. Small porcine luteal cells made mainly 19-norT and large porcine luteal cells 19-norA from 5(10)-oestrene-3 beta,17 beta-diol, the reduced product of the putative intermediate 5(10)-oestrene-3,17-dione. However, neither small nor large cells metabolized androstenedione to 19-norsteroids. Serum and serum plus LH significantly stimulated formation of both 19-norA and 19-norT from 5(10)-oestrene-3 beta,17 beta-diol, compared with controls. Inhibitors of the 3 beta-hydroxysteroid dehydrogenase/isomerase (trilostane and cyanoketone) significantly reduced formation of 19-norT in small porcine luteal cells and 19-norA in large porcine luteal cells, although they were effective at different concentrations in each cell type. In parallel incubations, formation of [4-14C]androstenedione from added [4-14C]dehydroepiandrosterone was also inhibited by cyanoketone in both small and large porcine luteal cells in a dose-dependent manner; however, trilostane (up to 100 mumol/l) did not inhibit androstenedione formation in large porcine luteal cells. In addition, the decrease in progesterone synthesis induced by trilostane and cyanoketone (100 mumol/l each) was accompanied by a parallel accumulation of pregnenolone in both cell types. These results suggest that 3 beta-hydroxysteroid dehydrogenase/isomerase, or a closely related enzyme, present in small and large porcine luteal cells can convert added 5(10)-3 beta-hydroxysteroids into 19-nor-4(5)-3-ketosteroids in vitro. In the porcine ovarian follicle, therefore, formation of 19-norA from androstenedione can be envisaged as a two-step enzymatic process: 19-demethylation of androstenedione to produce the putative intermediate 5(10)-oestrene-3,17-dione, and subsequent isomerization to 19-norA. In contrast to granulosa cells, porcine luteal cells synthesized 19-norA or 19-norT only when provided with the appropriate substrate. Unfractionated rat luteal cells also metabolized 5(10)-oestrene-3 beta,17 beta-diol to a mixture of 19-norA and 19-norT; conversion was inhibited by trilostane. In addition, small bovine luteal cells synthesized mainly 19-norT and formation was also inhibited by trilostane and cyanoketone.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Polymorphonuclear neutrophil function in Kartagener's syndrome--report of two cases.

The clinical triad of Kartagener's syndrome (KS) includes situs inversus, sinusitis and bronchiectasis or at least chronic bronchitis. Immotile cilia with various ultrastructural defects have been seen in KS. Because the enhanced susceptibility to infections seen in KS it had been suspected due to significant abnormality of neutrophil function in addition to a defect of ciliary function. In this report, neutrophil functions such as PMN phagocytosis, PMN chemotaxis, Migration inhibition test and PMN bacterial killing test were studied in two cases of KS at a time when they were free of infection. The defects observed by us were only slight. We conclude that although neutrophil motility of patients is normal, the bactericidal activity is depressed in the early stage. Whether this abnormality enhances patient susceptibility to bacterial infections is not yet clear. The significance and actural mechanism for his delayed killing are now under investigation.

Adult↗

The clinical characteristics of acute myocardial infarction in aged patients.

Age is one of the important prognostic factors for acute myocardial infarction. This study was performed to clarify the clinical characteristics and outcome of acute myocardial infarction in Chinese geriatric patients. The study subjects included 742 patients, divided by age into 2 groups: Group A greater than or equal to 65 years, 321 cases; and Group B less than 65 years, 421 cases. The following characteristics were compared between these 2 groups: sex composition; presence of chest pain, heart failure or shock at presentation; cardiac functional status; occurrence of various complications, and follow-up data. Males were less prominent in the older group: 229 patients (71.3%) in Group A, and 371 patients (88.1%) in Group B. At onset, the older patients presented with less chest pain (72% vs 86.5%) and more heart failure (35.2% vs 20.2%), but the occurrence of shock was similar (5.9% vs 4.5%, for Groups A and B, respectively). During hospitalization, more patients in Group A showed impaired cardiac function, as evidenced by a higher percentage of patients identified as in Killip class III or IV (35.4% vs 21.1%). Concerning complications, the older group showed a higher incidence of hypotension, low cardiac output, lung edema, frequent premature ventricular beats, atrial flutter and/or fibrillation, complete heart block and intraventricular conduction defects, but ventricular septal defects, ventricular tachycardia and ventricular fibrillation did not show any difference in occurrence. Life table analysis showed that the survival rate was significantly lower for Group A during the follow-up period of 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Mammography of breast carcinoma: experience of 108 cases.

Mammography is the radiographic imaging of the breast and includes screen-film mammography and xeromammography. From September 1987 to March 1990, 108 patients with breast carcinoma received mammographic examinations at Chang Gung Memorial Hospital. The spectrum of mammographic appearance included mass abnormalities (50.9%), calcifications (10.2%), a combination of mass abnormalities and calcifications (25%), asymmetrical increased density (4.6%), and parenchymal distortion (1.9%). The remaining 7.4% of the lesions lacked any radiologic sign of malignancy and primarily appeared as dense breast on the mammogram. In this series, mammography had a sensitivity of 86.1%, a specificity of 77.3% and a positive predictive value of 67.4%. Recognition of these mammographic appearances is beneficial in detecting breast carcinoma and in establishing a correct diagnosis. In addition, knowing the abilities, as well as limitations, of mammography will optimize the efficacy of this examining modality.

Adult↗

Comparative histochemical studies of rats infected with a pathogenic and nonpathogenic trypanosome.

Histochemical variations in tissues from rats inoculated with Trypanosoma lewisi and Trypanosoma rhodesiense were investigated. During peak parasitemia, the liver of rats inoculated with T lewisi showed increased glycogen distribution. However, glycogen depletion was noted in the liver and spleen of animals inoculated with living cells of T rhodesiense. Depletion was very apparent from day 4 to day 10. Throughout the period of observation, only a small amount of lipid infiltration occurred in tissues from animals inoculated with both organisms. Protein tests revealed a normal distribution of protein in tissues. Sections of the liver from rats inoculated with T lewisi showed strong alkaline phosphatase activity on days 7, 10, and 13. Alkaline phosphatase activity for T rhodesiense-infected animals was positive for days 4, 7, and 10. Strong positive reactions for acid phosphatase were observed on days 10 and 13 for some tissues (liver, spleen, and kidney) from rats inoculated with T lewisi. On days 4, 7, and 10, intense staining reactions also were observed for livers and spleens of animals inoculated with T rhodesiense. Regardless of tissues observed, histochemical variations were not observed in animals inoculated with the derivatives (ie, metabolic products and homogenates) of T lewisi and T rhodesiense.

Acid Phosphatase↗

Biodynamic simulations of the effect of a neck-mounted air bag on the head/neck response during high G acceleration.

New helmet-mounted devices (such as night-vision goggles, laser eye protection, etc.) have created new safety hazards for pilots during ejection or high G maneuvering. In order to prevent the resulting head/neck injuries, this study extends the air-bag protection system developed for ground vehicles to a neck mounted system for aircrew personnel. Results, carried out by computer biodynamic simulations using the Articulated Total Body Model (ATB), showed that: 1) helmet weight had little effect on head/neck torque, contact force and flexion angle; 2) initial head/neck position and center of gravity offsets of the helmet-mounted devices had significant effects on head-neck torques, contact forces, and neck flexion angles; and 3) the neck mounted air bag significantly reduced neck torques, contact forces, and neck flexion angles. We conclude that the neck-mounted air bag system could significantly reduce the severity of head/neck injuries to pilots during ejection or high G maneuvering.

Acceleration↗

Molecular cloning and characterization of an isolate of hepatitis delta virus from Taiwan.

The genomic RNA of an Asian isolate of hepatitis delta virus was cloned from a Chinese patient from Taiwan, using the polymerase chain reaction to amplify cDNA for cloning and sequencing. The sequence of this hepatitis delta virus isolate shares an 86% to 88% similarity with the three published hepatitis delta virus RNA sequences, suggesting heterogeneity of hepatitis delta viruses from different geographical areas. Four highly conserved, long stretches of sequence were found. These four regions corresponded to the sequences required for the autocatalytic cleavage activities of the genomic and antigenomic RNAs and the middle and the carboxyl terminal parts of the open reading frame for the delta antigen on the antigenomic strand. The conservation of nucleotide sequence in these four regions was further confirmed by sequencing additional hepatitis delta virus RNAs obtained from three patients with chronic delta hepatitis who lived in Los Angeles. These findings suggest that the conserved sequences are critical for viral replication. These conserved regions offer ideal sites for primer selection to carry out polymerase chain reactions to detect hepatitis delta virus RNA in patients with hepatitis delta virus infection.

Adult↗

Synthesis of some C-8-modified 3-deoxy-beta-D-manno-2-octulosonic acid analogs as inhibitors of CMP-Kdo synthetase.

Selective C-8 modifications of 2,6-anhydro-3-deoxy-D-glycero-D-talo-octonic acid ("2,3-dideoxy-beta-D-manno-2-octulosonic acid", 1a) were effected via the protected 8-hydroxy derivatives 2d and 2e. Swern oxidation of 2d and 2e gave the aldehydes 3a and 3b, respectively. Compounds 3a and 3b were converted into the oxime 13b and the O-methyloxime 13c derivatives, respectively. Methodology was developed for selective cleavage of the protecting groups of 13b and 13c to give the deprotected oxime 12m and the deprotected O-methyloxime 12n, respectively. Side chain-extended products were prepared from the aldehyde 3a utilizing Wittig methodology. The branched chain allylic amine 12p was prepared from 3a in a sequence the keys steps of which were preparation of the methyl ketone 19a using LiCuMe2, followed by Swern oxidation, methylenation of 19a using CH2I2-Zn-TiCl4 to give the alkene 19b, followed by Wohl-Ziegler bromination of 19b to give the allylic bromide 19c, and conversion of the latter to the allylic azide 19d. A number of the analogs showed significant activities vs CMP-Kdo synthetase. The most active of these was the side-chain extended alkene 12d, which proved second in activity only to the 9-amino analog (1c).

Enzyme Inhibitors↗

Synergistic effect of phorbol myristate acetate on bacterial lipopolysaccharide induced rat splenocyte proliferation.

1. Bacterial lipopolysaccharide (LPS) stimulated [3H]TdR incorporation of rat splenocytes in a concentration dependent manner. 2. Phorbol 12-myristate 13-acetate (PMA) alone has little effect on rat splenocyte proliferation but it exerted a marked synergistic effect on LPS-induced [3H]TdR incorporation when added at the first few hours of incubation with LPS. Minimal synergistic effect of PMA was observed if it was added later than 4 hr after LPS application. 3. Both LPS-stimulated and PMA synergized incorporation of [3H]TdR in rat splenocytes were inhibited by H-7, a protein kinase C inhibitor. 4. The results support the notion that the activation of protein kinase C is a necessary but insufficient cellular signal in the initiation of proliferative response of rat splenocytes by LPS.

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

Pulmonary hypertension in lambs with congenital diaphragmatic hernia: vasodilator prostaglandins, isoprenaline, and tolazoline.

After antenatal induction of diaphragmatic hernias in fetal lambs, prostaglandins D2, E1, and I2 were compared to tolazoline, or isoprenaline, for the treatment of pulmonary hypertension. When rendered hypoxic, these, and normal lambs, showed an increase in pulmonary artery pressure, a decrease in systemic pressure, and a decrease in pulmonary blood flow. All of the drugs altered that response, but to different degrees. None of the drugs tested was consistently successful in reversing the adverse affects of hypoxia, but prostaglandin D2 came closest to the ideal vasodilator, decreasing the pulmonary artery pressure in all seven hypoxic lambs having a diaphragmatic hernia. There was a concomitant increase in pulmonary blood flow in six; in the remaining lamb the decrease in blood flow induced by the hypoxia was arrested. At the same time, there was an increase in systemic artery pressure in three, the decrease was arrested in two, but the decrease continued in the other two. Isoprenaline was a more effective drug than tolazoline, producing an increase in pulmonary blood flow in five of the seven lambs, with minor decreases in systemic pressure in five. Tolazoline improved blood flow in three of six lambs (not all lambs survived the full study), with a marked decrease in systemic pressure in four of them. Prostaglandin D2 seems to be a useful drug for the treatment of patients having diaphragmatic hernias and pulmonary hypertension, and warrants further study. Isoprenaline was the most effective of the readily available drugs tested in this animal model.

Animals↗

Effect of chronic renal failure on high-density lipoprotein kinetics.

Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a significant increase in plasma VLDL-cholesterol (P less than 0.002) and a significant decrease (P less than 0.05) in plasma HDL-cholesterol concentration. The rate of removal of 125I-apoAI/HDL from plasma was slower (P less than 0.001) in the patients with CRF, resulting in an increase in the residence time of 125I-apoAI/HDL (P less than 0.001) and a decrease in the fractional catabolic rate (P less than 0.001). Since plasma apoAI concentration was lower in patients with CRF, total apoAI/HDL synthetic rate was also significantly (P less than 0.05) decreased. These data provide support for the view that low plasma HDL-cholesterol concentrations in patients with CRF are related to decreases in the synthetic rate of apoAI/HDL.

Adult↗

Chicken gastrin: a member of the gastrin/CCK family with novel structure-activity relationships.

The biological activity of natural chicken gastrins isolated from the "antrum"-like region of the chicken gut have been studied on gastric secretion in chickens, turkeys, and rats, pancreatic secretion in turkeys and rats, and gallbladder contraction in chickens and guinea pigs. Natural chicken gastrin was shown to be approximately 85% sulfated on the tyrosine that occurs at position 7 from the COOH-terminus. In both avian and mammalian systems, chicken gastrins were found to be potent stimulants of acid secretion but were virtually inactive as stimulants of pancreatic secretion and gallbladder contraction. Peptides with the COOH-terminal tetrapeptide amide of CCK and a sulfated tyrosine at position 7 from the COOH-terminus are usually potent stimulants of pancreas and gallbladder. However, although chicken gastrin has a CCK-like structure, it has a gastrin-like spectrum of biological actions. A proline immediately adjacent to the sulfated tyrosine may produce a steric effect that lowers the activity of chicken gastrin on pancreas and gallbladder. Evidently, then, the factors that determine specificity of action of CCK and gastrin are different in birds and mammals.

Amino Acid Sequence↗

[Solitary squamous papilloma of the bronchus: report of a case].

A 30-year-old man had a history of smoking 1-2 packs per week for 10 years. He had suffered from a productive cough with whitish mucoid sputum for two months. Left anterior chest pain, palpitation and shortness of breath developed about two weeks before his admission. Chest radiographs showed collapse of the left lower lobe. Bronchoscopy revealed a strawberry-like tumor on the left main bronchus with nearly complete obstruction. Pathology showed bronchial squamous papilloma with surface dysplasia, but no evidence of malignancy. The obstructed lumen was completely reopened by bronchoscopic Nd-YAG laser therapy. Unfortunately, the tumor recurred two months later. Therefore a sleeve resection of the tumor was performed six months after the laser photoresection. After two years of follow-up, no evidence of tumor recurrence has been found.

Adult↗

The coronary hemodynamics and left ventricular function in patients with compensated hypertension.

In this study, we tried to characterize the changes in left ventricular (LV) function and coronary hemodynamics in patients with compensated hypertension (HT) who were free from coronary artery disease. The study group consisted of 10 men with compensated essential HT at ages 48-65 years (mean = 58). The durations of HT history for the various patients ranged from 5 to 14 years. Mean arterial pressure (MAP) was 122 +/- 2 mmHg at the time of study. The control group was composed of 8 men with mild mitral valve prolapse. They were studied because of chest pain with no demonstratable pathological conditions. Their ages ranged from 39 to 65 years (mean = 57). The MAP for controls was 86 +/- 3 mmHg. All patients in both groups underwent routine cardiac catheterization, coronary arteriography, and measurements of the coronary sinus (CS) and great cardiac vein (GCV) blood flows. Left ventricular muscle mass (LVMM), coronary resistance and coronary reserve were also derived from the hemodynamic study. There was a significant difference in the LVMM index between the study patients (114.9 g/m2) and the control subjects (96.8 g/m2, p less than 0.001). The LV function of the patients in the study group was essentially normal, but the following parameters were significantly different from those of the control subjects: cardiac index, stroke volume index, and dp/dtmax. There was a good correlation between repeated measurements of both the CS and GCV blood flows (r = 0.97 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗