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Biomedical subjects

Y J Yang

Publications and source records attributed to Y J Yang.

At least 19 recordsLinked to original sources

Ultrastructure of the development of a species of Encephalitozoon cultured from the eye of an AIDS patient.

Human fibroblast cell cultures inoculated with microsporidia-infected corneal scrapings from an AIDS patient were fixed in situ and examined by scanning and transmission electron microscopy. The parasite grew prolifically and all developmental stages were observed. Meronts underwent binary fission and the daughter cells transformed into elongate, chain-like sporonts that eventually separated into sporoblasts. The formation of components of the mature spores is described. The parasite, a species of Encephalitozoon, underwent development both in the cytoplasm and within a parasitophorous vacuole, distinguishing it from the morphologically similar species E. cuniculi and E. hellem, both of which have been described from lesions in the human eye and have been reported to develop exclusively within a parasitophorous vacuole.

Acquired Immunodeficiency Syndrome

Dose-response relationship between lymph insulin and glucose uptake reveals enhanced insulin sensitivity of peripheral tissues.

To examine the role of transcapillary insulin transport to peripheral insulin sensitivity in vivo, we performed dose-response experiments in which both plasma and thoracic duct lymph insulin and glucose utilization (Rd) were measured in conscious dogs. Euglycemic clamps (n = 22) consisted of a 3-h activation period in which insulin was infused (rates: "physiological" 3.6, 5.4, 7.2 pmol.min-1.kg-1; "pharmacological" 108 pmol.min-1.kg-1), followed by a 3-h deactivation period. [14C]inulin was also infused as a diffusionary marker. Insulin sensitivity was estimated as the ED50. When based on plasma insulin, ED50 was 480 pM. However, when calculated from lymph (i.e., interstitial) insulin measurements, ED50 was 240 pM. Thus, interstitial insulin measurements reveal that insulin sensitivity of peripheral tissues is approximately twice that estimated from plasma insulin and is similar to sensitivity reported for suppression of hepatic glucose production. Furthermore, although [14C]inulin achieved equilibrium between plasma and lymph within 180 min, within the physiological range, steady state plasma insulin was higher than insulin in lymph (306 +/- 18, 474 +/- 42, and 780 +/- 60 pM vs. 180 +/- 18, 318 +/- 12, and 504 +/- 36 pM; P less than 0.0001); plasma insulin achieved steady state faster than lymph insulin (6 +/- 1, 6 +/- 2, and 11 +/- 3 min vs. 29 +/- 4, 16 +/- 6, and 44 +/- 8 min; P less than 0.01) and disappeared faster (5 +/- 2, 7 +/- 2, and 15 +/- 6 min vs. 37 +/- 8, 32 +/- 4, and 43 +/- 9 min; P less than 0.01). The time course of lymph insulin at each dose was similar to that of Rd, and at each dose, unlike plasma insulin, lymph insulin was strongly correlated with Rd (r = 0.93 or better). At pharmacological hyperinsulinemia (plasma 35232 +/- 5250 pM, lymph 27366 +/- 4380 pM), Rd rose faster than lymph insulin and disappeared more slowly than insulin. Thus, lymph insulin data indicate that the periphery is more sensitive to insulin than previously realized from estimates based solely on plasma hormone. Furthermore, lymph insulin is proportional to Rd within the physiological but not pharmacological range of insulin, indicating that transcapillary insulin transport is rate limiting for insulin action in this range. Finally, based on in vivo lymph (i.e., interstitial) insulin measurements, peripheral tissue is almost twice as sensitive to insulin than previously realized.

Animals

Blood levels of platelet-activating factor in endotoxin-sensitive and endotoxin-resistant mice during endotoxemia.

Platelet-activating factor (PAF) is a phosphoglyceride secreted by a variety of cells and has been implicated in endotoxin toxicities. To further confirm its role in endotoxin-induced tissue injuries and death, we conducted an experiment on endotoxin-resistant (C3H/HeJ strain) and endotoxin-sensitive (C3H/HeN strain) mice. The experiment consisted of three parts: 1) the LD50 of endotoxin from E. coli 0127:B8 cells was quantitated in C3H/HeN mice; 2) the lethality of PAF in C3H/HeJ mice at a dose lethal to C3H/HeN mice was determined; and 3) the blood levels of PAF in C3H/HeJ and C3H/HeN mice were measured after a dose of endotoxin lethal to the C3H/HeN strain was injected. PAF contained in the blood samples was extracted by a solid phase procedure and assayed by a radioimmunoassay method. The results showed that endotoxin-resistant and endotoxin-sensitive mice were equally susceptible to death induced by the same lethal dose of PAF. After injection with endotoxin, the blood PAF levels in C3H/HeN mice increased significantly (p < 0.01) at 60 minutes and 90 minutes, with a peak level three times that of the control group. The blood PAF levels in C3H/HeJ mice, however, remained unelevated throughout the experiment. The timing of the occurrence of the peak blood PAF level in the C3H/HeN mice corresponded with the emergence of their illness from the endotoxin injection. These findings shed new light on our understanding of the resistant mechanisms of C3H/HeJ mice to bacterial endotoxin and affirm the possible role of PAF in mediating endotoxin toxicities.

Animals

Mycotic aneurysm rupture: report of four cases.

"Mycotic" aneurysm was originally described by Osler in 1885. It occurs in a normal or atherosclerotic artery from septic emboli in patients with infective endocarditis. However, now the term "mycotic" aneurysm is applied to all cases of aneurysms caused by any organisms. From September 1988 to November 1990, four cases of ruptured mycotic aneurysm were diagnosed at our institute. Three were males and one was a female; they were elderly with atherosclerosis of the aorta. The diagnosis was established by computed tomography (CT) scan, bacteriology or operative findings. Two of the patients underwent emergency operation; only one survived. In general, the diagnosis of mycotic aneurysm is based on the classical features of fever, abdominal or chest pain, positive blood culture and a pulsatile mass. Because the clinical manifestations are often variable, a patient may present with chronic sepsis (esp. Salmonella sp) of unknown origin with deterioration to a fatal outcome from the aneurysmal rupture, which is a rare cause of retroperitoneal abscess or pericardial effusion. The principles of management, including high clinical suspicion, an accurate diagnosis by imaging studies (arteriography or CT scan), prolonged effective antibiotic therapy, arterial ligation or wide excision of the infected lesion, intraoperative Gram's stain and culture, extra-anatomic bypass grafting through clean tissue planes, and prolonged postoperative follow-up, are indispensable to reduce morbidity and mortality.

Aged

[Anthraquinones isolated from Morinda officinalis and Damnacanthus indicus].

From chloroform extract of the root of Morinda officinalis, eight anthraquinones were isolated whose structures were deduced to be rubiadin (I), rubiadin-1-methyl ether (II), 1-hydroxyanthraquinone (III), 1-hydroxy-2-methylanthraquinone (IV), 1,6-dihydroxy-2,4-dimethoxyanthraquinone (V), 1,6-dihydroxy-2-methoxyanthraquinone (VI), 1-hydroxy-2-methoxyanthraquinone (VII) and physcion (VIII). Except for compound I and compound II, the other compounds, 1-hydroxy-2-hydroxymethylanthraquinone (IX), 1,3-dihydroxy-2-methoxy-anthraquinone (X), 1,4-dihydroxy-2-methylanthraquinone (XI), 1-methoxy-2-hydroxyanthraquinone (XII) and 1,4-dimethoxy-2-hydroxyanthraquinone (XIII), were isolated from chloroform extract of root of Damnacanthus indicus. Compound V, VI and XIII are new compounds.

Anthraquinones

Vertebrobasilar insufficiency related to cervical spondylosis. A case report and review of the literature.

A 64-year-old man suffered from symptoms of vertebrobasilar insufficiency (VBI) while turning his head to the left. Roentgenograms of the cervical spines showed severe spondylosis. Cerebral angiography demonstrated compression of the left vertebral artery by osteophytes of the cervical spine when the patient turned his head to the left. He was treated surgically by fixation of the vertebral bodies with good relief of symptoms during one year of follow-up. VBI induced by spondylotic compression of the vertebral artery is uncommon. We therefore reviewed the literature and suggested a more simple method of operation.

Cervical Vertebrae

Bi-affinity alpha 1-adrenoceptor binding in normal rat brain in vivo.

The specific binding in rat brain in vivo of [125I]HEAT ([125I]iodo-2-[beta-(4-hydroxyphenyl)ethylamino methyl), a selective alpha 1-adrenoceptor ligand, was analyzed by a method designed to distinguish sites with different affinities. The data indicate at least two sites with different affinities for the alpha 1-adrenoreceptor in normal rat brain in vivo: a high-affinity site with Kd (half-saturation constant) of 3.6 +/- 0.7 nM (AV +/- SD), and a low-affinity site with Kd of 668 +/- 552 nM. The density (Bmax) of the high-affinity site in nine brain regions--auditory, visual, sensorimotor (four layers) and frontal cortex and lateral thalamic and medial geniculate nuclei--varied from 2.2 +/- 0.8 to 14.6 +/- 0.6 pmole/g, while the low-affinity range was 149 +/- 44 to 577 +/- 30 pmole/g. The results also revealed a very dynamic relationship between the two sites regulated by the concentration of the ligand ranging from 80% preponderance of the high-affinity sites at low ligand concentrations to more than 95% preponderance of the low-affinity sites at high ligand concentrations.

Animals

A new model of global postischemic reperfusion in rabbit.

An ideal model of global ischemia in rabbits has not yet been developed. The present study describes a new model of global postischemic reperfusion (GPIR) in the rabbit, characterized by lack of systemic hypotension. The experimental procedure involves reversible occlusion of the bilateral internal carotid arteries (ICA) and bilateral external carotid arteries (ECA) for 60 min combined with permanent ligation of bilateral vertebral arteries (VA). This grouping is called 6-artery occlusion (6AO). Sixty minutes after the occlusion, bilateral ICA and bilateral ECA were released for 120 min at which time the experiment was terminated. The results revealed severely depressed EEG activity; Water content of brain tissue increased to 80.33 +/- 1.20% (control 78.28 +/- 0.59%, p less than 0.01); K, Mg, and Zn decreased (p less than 0.05 or p less than 0.01), and were negatively correlated with tissue water content. Na increased (p less than 0.05) and correlated with water content of brain. No significant changes were observed in lipid peroxide (LPO) levels, but the activity of superoxide dismutase (SOD) of brain tissue decreased (p less than 0.01), and was negatively correlated with water content (r = -0.5808, p less than 0.05). These results were compared with those obtained with the model of 4-artery (bilateral common carotid arteries (CCA) and VA) occlusion (4AO) and suggested that the brain damage be more severe with 6AO than with 4AO.

Animals

Protection of immature myocardium by the addition of mannitol to crystalloid cardioplegic solution.

The current method of myocardial protection for the immature heart with crystalloid cardioplegic solution remains unsatisfactory. In pursuit of a better method, mannitol, mixed into the St. Thomas' Hospital cardioplegic solution, was investigated for its effect on myocardial protection. The experiment consisted of three groups of young dogs, six in each group. Animals were maintained under ischemia for 60 minutes followed by reperfusion for 30 minutes. Those perfused with the St. Thomas' Hospital cardioplegic solution alone (group A) had poorer results, namely, a lower recovery rate (80% only) of peak left ventricular systolic pressure (LVSP), decline in left ventricular compliance, a lower preservation level (70%) of the myocardial ATP content and moderate ultrastructural damage. By contrast, in animals perfused with the cardioplegic solution containing mannitol (20mmol/L of mannitol in group B; 50 mmol/L in group C), not only the recovery of peak LVSP was higher, 130% in group B and 109% in group C, but the preservation of myocardial ATP content was also higher, 94% and 82%, respectively. The ultrastructure was well-preserved in group B, but mildly distorted in group C. Slight elevation of LVEDP was also noted in group C. These results suggest that the myocardial protective effect of the St. Thomas Hospital cardioplegic solution for immature hearts can be improved with the addition of mannitol. However, the dose dependent effects of mannitol, not revealed in this study, warrant further research.

Adenosine Triphosphate

Pure sensory stroke confirmed by CT scan.

Five cases of pure sensory stroke, including two cases of cheiro oral syndrome, are reported. Of the 5 cases, 2 presented thalamic lacunar infarcts, 2 basal ganglia hemorrhages, and 1 dorsal midbrain hemorrhage on computed tomography scan.

Aged

Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates.

Reexamination of Serratia marcescens isolates obtained in 1982 revealed two organisms that were resistant to the penem FCE 22101 (MIC, 512 micrograms/ml) and imipenem (MIC, 16 micrograms/ml) and that had slightly reduced susceptibilities to meropenem (MIC, 0.12 micrograms/ml). MICs of these agents for typical S. marcescens isolates were 1 to 8, 0.25 to 0.5, and 0.03 micrograms/ml, respectively. The two isolates were fully susceptible to broad-spectrum cephalosporins, and only one was highly resistant to ampicillin and carbenicillin (MICs, greater than 1,024 micrograms/ml). Both isolates had beta-lactamases that focused at pIs 8.2 and 9.7. The penicillin-resistant isolate additionally produced the TEM-1 enzyme. The enzymes with pIs of 8.2 and 9.7 were separated by cation-exchange chromatography. The pI 8.2 beta-lactamase was a class I enzyme of the type found in most S. marcescens isolates. It was almost inactive against carbapenems and penems, as was the class I enzyme from another S. marcescens strain. The pI 9.7 enzyme hydrolyzed penems and carbapenems rapidly: kcat (turnover number) values for FCE 22101, imipenem, and meropenem were 3.4, 26, and 1% of the kcat value for cephaloridine, respectively; kcat/Km values were 140, 915, and 150% of the kcat/Km value for cephaloridine, respectively. Otherwise, the pI 9.7 enzyme had predominantly penicillinase activity. It was inhibited more readily by clavulanate than by tazobactam and was inactivated by the chelating agents EDTA and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Expression of the pI 9.7 enzyme was not associated with any plasmid, and production was not transferred to Escherichia coli K-12 recipients, even after the mobilizing plasmid pUZ8 was inserted into the S. marcecens donor strains.

Carbapenems

Cloning and sequencing of a gene encoding a glutamate and aspartate carrier of Escherichia coli K-12.

A gene encoding a carrier protein for glutamate and aspartate was cloned into Escherichia coli K-12 strain BK9MDG by using the high-copy-number plasmid pBR322. The gene (designated gltP) is probably identical to a gene recently cloned from E. coli B (Y. Deguchi, I. Yamato, and Y. Anraku, J. Bacteriol. 171:1314-1319). A 1.6-kilobase DNA fragment containing gltP was subcloned into the expression plasmids pT7-5 and pT7-6, and its product was identified by a phage T7 RNA polymerase-T7 promoter coupled system (S. Tabor and C. C. Richardson, Proc. Natl. Acad. Sci. USA 82:1074-1078) as a polypeptide with an apparent mass of 38 kilodaltons. A portion of the gltP polypeptide was associated with the cytoplasmic membrane. The nucleotide sequence of the 1.6-kilobase fragment was determined. It contained an open reading frame capable of encoding a highly hydrophobic polypeptide of 395 amino acids, containing four possible transmembrane segments. Uptake of glutamate and aspartate was increased 5.5- and 4.5-fold, respectively, in strains containing gltP plasmids. Glutamate uptake was insensitive to the concentration of Na+ and was inhibited by L-cysteate and beta-hydroxyaspartate. These results suggest that gltP is a structural gene for a carrier protein of the Na(+)-independent, binding-protein-independent glutamate-aspartate transport system.

Amino Acid Sequence

Role of transesophageal echocardiography in detecting left atrial thrombus and spontaneous echo contrast in patients with mitral valve disease or non-rheumatic atrial fibrillation.

Instances of left atrial (LA) thrombus and spontaneous echo contrast were evaluated by both transthoracic echocardiography (TTE) and subsequent transesophageal echocardiography (TEE) in 50 patients with rheumatic mitral stenosis (Group I) and 52 patients with non-rheumatic atrial fibrillation (Group II). Among these 102 patients, TEE detected LA thrombi in 16 patients (15.7%) and spontaneous echo contrast in 35 (34.3%). In contrast, TTE revealed LA thrombi in only 8 patients (7.8%) and spontaneous echo contrast in only 2 patients (2.0%). All of the LA thrombi and spontaneous echoes detected by TTE were also found by TEE. When TEE was applied, patients with spontaneous echo contrast had a significantly higher incidence of LA thrombus than did those without this echo (42.8% vs 1.5%, p less than 0.01). Spontaneous echo contrast was coexistent in all but one of the patients with LA thrombi (15 of 16, 93.7%). In Group I, the incidence of spontaneous echo contrast for patients with isolated or predominant mitral stenosis was high (68.3%) when TEE was applied, but this echo was not observed in any patient who had more than a moderate degree of mitral regurgitation. In Group II, 7 patients (13.5%) were also found to have spontaneous echo contrast, which could only be detected by TEE. Of these 7 patients, LA thrombus was noted in 4 by TEE, but only in 1 by TTE. Thus, it can be concluded that: (1) TEE is superior to TTE for detecting LA thrombus and spontaneous echo contrast; (2) spontaneous echo contrast in LA is not only frequently encountered in mitral stenosis without significant mitral regurgitation, but is also found in some patients with non-rheumatic atrial fibrillation; and (3) the presence of spontaneous echo contrast is associated with a higher incidence of LA thrombus and may be considered as a warning sign for further formation of LA thrombus.

Adult

The role of the transcapillary insulin transport in the efficiency of insulin action: studies with glucose clamps and the minimal model.

Insulin action to augment glucose utilization (Rd) and suppress endogenous glucose production is not directly determined by changing plasma insulin, but rather by that insulin which traverses the capillary endothelial boundary to enter the interstitial space bathing insulin-sensitive cells. We have examined the importance of transcapillary insulin transport to the efficiency of insulin action by sampling insulin in thoracic duct lymph, believed to represent interstitial fluid, during euglycemic glucose clamps or intravenous glucose tolerance tests (IVGTTs) in conscious dogs. During clamps (insulin infusion: 0.6 mU/min per kg), we observed a 3:2 gradient between plasma and lymph insulin both at basal and at hyperinsulinemic steady state, which was reestablished after termination of infusion. No such gradient was observed for inulin, a non-metabolizable diffusionary marker infused along with insulin. Furthermore, lymph insulin was proportional to Rd during clamps, and these two independently measured variables were strongly correlated (r = 0.96). These results indicate that transcapillary insulin transport is rate-limiting for insulin action during clamps. Compartmental analysis of insulin and inulin data was consistent with receptor-mediated transport of insulin across capillary endothelium from plasma to interstitium. Glucose tolerance tests were subjected to minimal model analysis, which yields the insulin sensitivity index (SI) and X(t), the rate of net glucose disposition during the intravenous test. Preliminary data reveal a striking similarity between the time courses of X and measured lymph insulin during IVGTTs, evidence that interstitial insulin is virtually at equilibrium with the rate of glucose uptake. Thus, even in the non-steady state, transendothelial insulin transport is the rate determining step for insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

In-vitro activity of tigemonam, an oral monobactam, against gram-negative rods, including variants in beta-lactamase-production.

Tigemonam was compared in vitro with other orally active beta-lactams, aztreonam and ciprofloxacin against a selection of Gram-negative clinical isolates and laboratory-derived beta-lactamase-producing variants. Of the orally active beta-lactams, tigemonam was the most potent, with a spectrum of activity similar to that of aztreonam. This included stability to plasmid-mediated beta-lactamases and poor induction of chromosomal beta-lactamases. The susceptibility to Class I enzymes was only clinically significant for derepressed Enterobacter cloacae mutants. Tigemonam may have a valuable role in the management of infection caused by enterobacteria, particularly if bioavailability following oral administration is confirmed in human subjects.

Anti-Bacterial Agents

Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance mechanisms.

Four major mechanisms cause resistance to beta-lactams in Pseudomonas aeruginosa: (i) cell wall impermeability gives broad-spectrum intrinsic resistance to all beta-lactams except imipenem, (i) loss of D-group outer membrane proteins correlates with narrow spectrum imipenem resistance, (iii) plasmid mediated beta-lactamases compromise antipseudomonal penicillins, cefoperazone and cefsulodin, and (iv) chromosomal beta-lactamase hyper-production compromises most beta-lactams except carbenicillin and imipenem. Meropenem was tested in vitro against P. aeruginosa isolates, mutants and transconjugants with these mechanisms. Meropenem had impaired activity (MIC 1-2 mg/l compared to 0.25 mg/l for sensitive isolates) for organisms with broad-spectrum intrinsic resistance. MICs of meropenem also were elevated (to 1-2 mg/l) for mutants with D2-protein-deficiency-associated imipenem resistance. Most plasmids encoding TEM, OXA or PSE beta-lactamases did not increase the MIC (0.12 mg/l) of meropenem for P. aeruginosa PU21. Decreased susceptibility (MIC 4 mg/l), however, was observed when plasmids coding the uncommon NPS-1, PSE-2 and OXA-3 enzymes were present in this strain. MICs of meropenem remained identical for chromosomal beta-lactamase-inducible P. aeruginosa strains and their enzyme-derepressed and basal mutants, indicating that the chromosomal beta-lactamase could not protect against the new carbapenem, regardless of its mode of expression.

Bacterial Outer Membrane Proteins

Interactions of meropenem with class I chromosomal beta-lactamases.

Most newer penicillins and cephalosporins are labile to the Class I beta-lactamases that are inducible in Pseudomonas aeruginosa. Enterobacter spp., Citrobacter spp., Serratia spp. and indole-positive Proteeae, but fail to induce enzyme synthesis below the MIC. They remain active against the inducible strains but not against mutants (termed 'stably depressed') that manufacture beta-lactamase copiously without induction. Such mutants are segregated at high frequency and may be selected during therapy, sometimes causing clinical failure. Meropenem induced Class I enzymes weakly below the MIC in Ps. aeruginosa, Ent. cloacae, C. freundii, Ser. marcescens, Morganella morganii and Pr. vulgaris. Nonetheless it remained equally active against inducible strains and their derepressed mutants, and was no more active against laboratory-derived beta-lactamase basal mutants. It did not select derepressed mutants from beta-lactamase-inducible populations. These data suggested great stability to Class I beta-lactamases, and this deduction was confirmed by direct assays with purified beta-lactamases. Initial hydrolysis rates ranged from 0.9-10.0 drug molecules hydrolysed/enzyme molecule/minute but these values declined by 80-90% before 5% of the antibiotic had been hydrolysed, indicating that the carbapenem could deactivate the enzymes. Deactivation was reversible, full activity being restored once the meropenem was removed. These results suggest that meropenem, like imipenem and various experimental penems, may overcome the resistance problems presented by Class I beta-lactamases.

Bacteria