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Biomedical subjects

P Chang

Publications and source records attributed to P Chang.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and structure-activity relationships of 7-diazabicycloalkylquinolones, including danofloxacin, a new quinolone antibacterial agent for veterinary medicine.

A series of novel 6-fluoro-7-diazabicycloalkylquinolonecarboxylic acids substituted with various C8 (H, F, Cl, N) and N1 (ethyl, cyclopropyl, vinyl, 2-fluoroethyl, 4-fluorophenyl, 2,4-difluorophenyl) substituents, as well as, 9-fluoro-10-diazabicycloalkylpyridobenzoxazinecarboxylic acids, were prepared and evaluated for antibacterial activity against a range of important veterinary pathogenic bacteria. The diazabicycloalkyl side chains investigated at the 7-position (benzoxazine 10-position) include (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (2), (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (3), (1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptane (4), 8-methyl-3,8-diazabicyclo[3.2.1]octane (5), 9-methyl-3,9-diazabicyclo[4.2.1]nonane (6), 1,4-diazabicyclo[3.2.2]nonane (7), 1,4-diazabicyclo[3.3.1]nonane (8), and 9-methyl-3,9-diazabicyclo[3.3.1]nonane (9). Among these side chains, in vitro potency was not highly variable; other properties therefore proved more critical to the selection of possible development candidates. However, the relative potencies observed for several of these compounds in mouse, swine, and cattle infection models correlated well with those seen in vitro. A combination of the N1 cyclopropyl group and the C7 (1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl appendage conferred the best overall antibacterial, physiochemical, and pharmacodynamic properties. Hence, danofloxacin (Advocin, 2c) (originally CP-76,136, 1-cyclopropyl-6-fluoro-7-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1] hept-2-yl]-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid) was selected as a candidate for development as a therapeutic antibacterial agent for veterinary medicine.

Actinobacillus Infections↗
PubMed1992

Distribution of type A and type B EBV in normal individuals and patients with head and neck carcinomas in Taiwan.

The subtypes of Epstein-Barr virus (EBV) according to the EBNA 2 gene were investigated in Taiwan by the polymerase chain reaction (PCR) and by Southern blot hybridization. The materials included 53 nasopharyngeal carcinoma (NPC) biopsies, 49 other head and neck cancers and 32 throat washings of normal individuals. EBV DNA was found in all NPC biopsies, 27 of 49 other head and neck carcinomas and 81% of normal individuals. Type A EBV was the predominant type of EBV in both normal individuals and patients with head and neck carcinomas in Taiwan. Type B EBV or coexistence of the A and B types comprised a small number of samples in this study.

Base Sequence↗
PubMed1992

Study of elasto-gel pads used as surface bolus material in high energy photon and electron therapy.

Bolus materials are occasionally used during the high energy photon and electron radiation treatments of head, neck, breast, and chest wall areas in order to deliver the full prescribed dose to the skin surface and underlining tissue. Where skin surface curvatures make uniform contact between the bolus material and skin surface difficult, we have studied a new bolus material called Elasto-gel. Elasto-gel, packed in a sterilized envelope, is routinely used in the treatment of superficial burns and wounds. The adhesive nature of Elasto-gel bolus material provides excellent skin contact without air gaps. The Elasto-gel is made of non-toxic material and is transparent. High dose irradiation has no effect on the appearance and property of the Elasto-gel pad. We are presenting in this note the radiation attenuation and build up effects of the Elasto-gel pads of photon energies of 6 and 18 MV and of electron energies of 6 MeV and 20 MeV. There is little difference between Elasto-gel and Polystyrene in radiation dosimetry.

Electrons↗
PubMed1992

Cardiovascular responses in the normotensive rat produced by intravenous injection of gambirine isolated from Uncaria callophylla B1. ex Korth.

Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.

Alkaloids↗
PubMed1992

Acquired perforating disease associated with chronic renal failure.

A 48-year-old man, in a chronic hemodialysis program, had numerous skin lesions develop that consisted of follicular papules and small hyperkeratotic nodules, located on the trunk, hips, and upper and lower extremities (where the lesions were more numerous). The nodules measured 3 to 5 mm and had a dark discoloration (Figs 1 and 2). Four months previously, the patient noticed the appearance of disseminated papular and pruritic lesions. The lesions did not improve with the prescribed local nonspecific treatment. The patient had chronic renal failure during the previous 10 years, secondary to renal vein thrombosis. As a result, he has had periodic hemodialysis for 18 months. The clinical diagnosis of the skin lesion was Kyrle disease, and a skin biopsy was performed on a nodular lesion from the thigh. The histologic sections showed skin with hyperkeratosis, an invagination of the epithelium filled with keratin and amorphous material. In some sections, the invagination appeared to be a cyst, which in serial sections, showed partial rupture of the lateral wall. No evidence of hair was found inside the invagination.

Darier Disease↗
PubMed1992

The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum.

Virulent Treponema pallidum reacts poorly with the specific antibodies present in human and rabbit syphilitic sera, a phenomenon often attributed to an outer coat of host serum proteins. Here we present additional evidence that the limited antigenicity of virulent organisms actually is due to a paucity of proteins in the outer membrane. Initially, we used electron microscopy to demonstrate that the outer membrane is highly susceptible to damage from physical manipulation (i.e., centrifugation and resuspension) and nonionic detergents. Organisms with disrupted outer membranes were markedly more antigenic than intact treponemes as determined by immunoelectron microscopy (IEM) with rabbit syphilitic and antiendoflagellar antisera. Data obtained with a new radioimmunoassay, designated the T. pallidum surface-specific radioimmunoassay, corroborated these IEM findings by demonstrating that the major T. pallidum immunogens are not surface exposed; the assay also was unable to detect serum proteins, including fibronectin, on the surfaces of intact organisms. Furthermore, IEM of T. pallidum on ultrathin cryosections with monospecific anti-47-kDa-immunogen antiserum confirmed the intracellular location of the 47-kDa immunogen. On the basis of these and previous findings, we proposed a new model for T. pallidum ultrastructure in which the outer membrane contains a small number of transmembrane proteins and the major membrane immunogens are anchored by lipids to the periplasmic leaflet of the cytoplasmic membrane. This unique ultrastructure explains the remarkable ability of virulent organisms to evade the humoral immune response of the T. pallidum-infected host.

Animals↗
PubMed1992

Platelet-dependent thrombin generation after in vitro fibrinolytic treatment.

BACKGROUND: Fibrinolytic therapy is associated with frequent rethrombosis. There is evidence of both increased coagulation and platelet activation. METHODS AND RESULTS: Platelet-rich plasma (PRP) or washed platelets were incubated with the fibrinolytic agents urokinase, recombinant tissue-type plasminogen activator (rt-PA), or plasmin at concentrations consistent with those in the plasma of patients treated for myocardial infarction. All of the fibrinolytic agents induced a more rapid generation of thrombin and decreased the clotting times of non-contact-activated PRP than in untreated PRP. This effect was not blocked by the inclusion of thrombin inhibitors during the fibrinolytic treatment. Washed platelets derived from rt-PA-treated PRP induced more rapid thrombin generation when resuspended in untreated plasma or treated plasma. Washed platelets were treated with plasmin, rt-PA, and urokinase and added to platelet-poor plasma. Platelets treated with either plasmin or rt-PA increased the ability of washed platelets to support thrombin generation, but urokinase was without significant effect. CONCLUSIONS: These results indicate not only that plasmin can cause increased platelet support of prothrombin activation but also that rt-PA in the absence of plasminogen can have a direct effect on the platelet, which increases thrombin generation.

Blood Platelets↗
PubMed1992

Pulmonary status of habitual cocaine smokers.

We determined the prevalence of respiratory symptoms and lung dysfunction in a large sample of habitual smokers of freebase cocaine ("crack") alone and in combination with tobacco and/or marijuana. In addition, we compared these findings with those in an age- and race-matched sample of nonusers of crack who did or did not smoke tobacco and/or marijuana. A detailed respiratory and drug use questionnaire and a battery of lung function tests were administered to (1) a convenience sample of 202 habitual smokers of cocaine (cases) who denied intravenous drug abuse and (2) a reference sample of 99 nonusers of cocaine (control subjects). The cocaine smokers (85% black) included the following: 68 never-smokers of marijuana, of whom 43 currently smoked tobacco and 25 did not, and 134 ever-smokers of marijuana (42 current and 92 former), of whom 92 currently smoked tobacco and 42 did not. The control subjects (96% black) included the following: 69 never-smokers of marijuana, of whom 26 currently smoked tobacco and 43 did not, and 30 ever-smokers of marijuana (18 current and 12 former), of whom 21 currently smoked tobacco and 9 did not. Cases smoked an average of 6.5 g cocaine per week for a mean of 53 months. The median time of the most recent use of crack prior to study was 19 days (range less than 1 to 180 days). After controlling for the use of other smoked substances, frequent crack use was associated with: (1) a high prevalence of at least occasional occurrences of acute cardiorespiratory symptoms within 1 to 12 h after smoking cocaine (cough productive of black sputum [43.7%], hemoptysis [5.7%], chest pain [38.5%], usually worse with deep breathing, and cardiac palpitations [52.6%]) and (2) a mild but significant impairment in the diffusing capacity of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Polarity of the ascidian egg cortex before fertilization.

The unfertilized ascidian egg displays a visible polar organization along its animal-vegetal axis. In particular, the myoplasm, a mitochondria-rich subcortical domain inherited by the blastomeres that differentiate into muscle cells, is mainly situated in the vegetal hemisphere. We show that, in the unfertilized egg, this vegetal domain is enriched in actin and microfilaments and excludes microtubules. This polar distribution of microfilaments and microtubules persists in isolated cortices prepared by shearing eggs attached to a polylysine-coated surface. The isolated cortex is further characterized by an elaborate network of tubules and sheets of endoplasmic reticulum (ER). This cortical ER network is tethered to the plasma membrane at discrete sites, is covered with ribosomes and contains a calsequestrin-like protein. Interestingly, this ER network is distributed in a polar fashion along the animal-vegetal axis of the egg: regions with a dense network consisting mainly of sheets or tightly knit tubes are present in the vegetal hemisphere only, whereas areas characterized by a sparse tubular ER network are uniquely found in the animal hemisphere region. The stability of the polar organization of the cortex was studied by perturbing the distribution of organelles in the egg and depolymerizing microfilaments and microtubules. The polar organization of the cortical ER network persists after treatment of eggs with nocodazole, but is disrupted by treatment with cytochalasin B. In addition, we show that centrifugal forces that displace the cytoplasmic organelles do not alter the appearance and polar organization of the isolated egg cortex. These findings taken together with our previous work suggest that the intrinsic polar distribution of cortical membranous and cytoskeletal components along the animal-vegetal axis of the egg are important for the spatial organization of calcium-dependent events and their developmental consequences.

Actin Cytoskeleton↗
PubMed1992

Respiratory effects of cocaine freebasing among habitual cocaine users.

Smoking of alkaloidal cocaine ("crack") has become increasingly prevalent in our society. Recent evidence suggests that crack smoking can cause acute respiratory symptoms, abnormalities in lung function and, in some instances, severe, life-threatening acute lung injury. To evaluate further the relationship between frequent cocaine smoking and respiratory symptoms and lung dysfunction, we studied a sample of 177 heavy, habitual smokers of freebase cocaine (mean 6.6 gm/wk for an average of 27 months) with or without concomitant smoking of tobacco and/or marijuana. Results in this sample were compared with those in a control sample of 75 age-, sex- and race-matched nonsmokers of cocaine who did or did not also smoke tobacco and/or marijuana. After controlling for the use of other smoked substances, heavy, habitual cocaine smoking was associated with the following: (1) a high frequency of acute respiratory symptoms (cough, black sputum, chest pain) in temporal association with freebase use; (2) an obstructive ventilatory abnormality involving the large airways; and (3) a mild but significant impairment in the diffusing capacity of the lung. These findings suggest that heavy, habitual crack smoking produces (1) respiratory tract injury manifested by acute respiratory symptoms and evidence of chronic airflow obstruction in large airways, and (2) an abnormality in diffusion of gas at the alveolar-capillary level. The mechanism of the diffusion defect is unknown but could reflect damage to the alveolar-capillary membrane. Further study of the magnitude, persistence, reversibility, mechanism and clinical significance of the abnormality in diffusing capacity is needed.

Adult↗
PubMed1992

Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia.

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Interaction properties of doubly phosphorylated beta-casein, a major component of the human milk caseins.

Doubly phosphorylated beta-casein constitutes nearly 30% of the total human beta-caseins and is thus one of the major components of that fraction. The properties and mode of association of doubly phosphorylated beta-casein are therefore important determinants of the structure and function of the human casein micelle. Doubly phosphorylated beta-casein has an absorbency of 6.2 and a partial specific volume of .74. The protein precipitated at room temperature when 10 mM Ca2+ was added but produced a clear solution in 1 M NaCl. Equilibrium dialysis produced an average of 2.06 major Ca(2+)-binding sites at 37 degrees C with a dissociation constant of 12.1 x 10(-4) M. The monomer at 20 degrees C was calculated to have a solvation of 2.1 g of H2O/g of protein and an axial ratio of 6.8, suggesting a prolate ellipsoid of about 11 by 2 nm. At high ionic strength, evidence exists for a spherical structure with a molecular weight of 2.25 x 10(6). This structure would represent a polymer of about 90 monomers with a radius of 14.8 nm and a solvation of 1.93 g of H2O/g of protein. This association behavior is similar to that of other phosphorylated human beta-caseins but differs from the nonphosphorylated form. It changes when both Ca2+ and inorganic orthophosphate are present.

Calcium↗
PubMed1992

Relationship between cardiovascular functions and ionic hypocalcemia induced by citrate infusion in anhepatic swines: CaCl2 therapy in severe ionic hypocalcemia.

Baseline and serial values of serum [Ca++], [K+], [Na+], arterial blood gas tensions, acid-base status, temperature and hemodynamic functions were measured during infusion of citrate-phosphate-dextrose (CPD) solution (0.35 ml.kg-1 x min-1) in anhepatic pigs of three randomized groups. Thirteen pigs (group I) continued to receive intravenous infusion of CPD solution until cardiac arrest. When mean arterial pressure (MAP) decreased to about 50 mmHg (group II, n = 7), or 40 mmHg (group III, n = 7) infusion of CPD solution was discontinued, and pigs received CaCl2 (20 mg/kg) intravenously. Serial (1, 4, 8, and 12 min after CaCl2 administration) values of all the above variables and serum citrate at baseline and lowest [Ca++] were measured. After hepatectomy and venovenous bypass, cardiac output (CO) decreased 30%. When ionic hypocalcemia was above 0.7 mM, there was no significant change of cardiovascular functions. When [Ca++] was between 0.34-0.7 mM, there were linear relationships between [Ca++] and CO, systemic vascular resistance (SVR) and MAP, respectively. When [Ca++] was below 0.34 mM, cardiovascular functions decreased abruptly, and the pigs died at [Ca++] of 0.26 +/- 0.06 mM. When [Ca++] decreased to 0.36 +/- 0.06 mM and MAP to 50 +/- 4 mmHg, most hemodynamic functions could be reversed by calcium therapy. However, when [Ca++] decreased to 0.33 +/- 0.05 mM and MAP to 40 +/- 2 mmHg, hemodynamic functions could not be reversed by calcium therapy alone.

Animals↗