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Biomedical subjects

C H Chiang

Publications and source records attributed to C H Chiang.

At least 73 records · Page 4Linked to original sources

Pneumocephalus in a case of nasopharyngeal carcinoma.

An extensive mass involving the skull base was found in a 49-year-old male patient with nasopharyngeal carcinoma. Deteriorating neurologic status developed 2 weeks after radiation to the nasopharynx with the initial dosage of 5480 cGy and boosted dosage of 3520 cGy. Computerized tomography revealed multiple foci of air occupying the subarachnoid space, and an air-fluid level was found in the lateral ventricle. Antibiotics and conservative treatments were administered to the patient and consciousness returned gradually. Unfortunately, he died of hypovolemic shock owing to massive bleeding from the nasopharynx 7 days later.

Humans↗

Respiratory distress and selective muscle involvement in central core disease: report of a case.

A 10-year-old girl who had suffered life-threatening respiratory distress in late infancy and mild muscle weakness in the extremities was found to have central core disease (CCD). Her developmental milestones were markedly delayed and she became ambulant at the age of 6 years. On physical examination, she had a high-arched palate, nasal tone vocalization, a positive Gowers' sign, waddling gait, and decreased deep tendon reflexes. On magnetic resonance imaging (MRI) examination, the thigh, calf, arm, and paravertebral muscles were selectively involved, especially in the paravertebral, biceps brachii, gluteus maximus and medius, vastus lateralis and medialis, sartorius, adductor magnus, tibialis anterior, soleus, lateral head of gastrocnemius, and peroneus longus muscles. Two biopsy specimens from the left biceps brachii and rectus femoris muscles showed the common histochemical findings of CCD, including type 1 fiber atrophy and predominance, and core structures. Proliferation of adipose tissue was only present in the biceps brachii muscle. The patient improved clinically in muscle strength after three year follow-up. Muscle MRI may provide a non-invasive evaluation of gross muscle involvement in CCD.

Arm↗

Ocular hypotensive effects of L-arginine and its derivatives and their actions on ocular blood flow.

Effects of L-arginine and some related compounds on the intraocular pressure recovery (IOPR) and ocular blood flow in rabbits had been studied. It was found that L-arginine (RVC-579) and N alpha-benzoyl-L-arginine ethyl ester (RVC-578) delayed the IOPR markedly: The IOPR of the contralateral non-treated eye was delayed to the same extent as the treated eye. The effects of closely related congeners L-(+)-canavanine (RVC-581) and L-homoarginine (RVC-580) on the IOPR were qualitatively similar to RVC-579 and RVC-578 but less effective. RVC-578 was found to increase the blood flow significantly in ciliary body, retina and choroid. On the other hand, NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reduced the blood flow in choroid at 60 and 120 min after drug administration and did not increase the blood flow in iris, ciliary body and retina. These results indicate that L-arginine and its derivative are capable of lowering the IOP possibly through the formation of nitric oxide to relax the blood vessel and to reduce the IOP as a result.

Animals↗

Effects of cromakalim and nicorandil on intraocular pressure after topical administration in rabbit eyes.

In the study two potassium channel activators, cromakalim and nicorandil, were investigated in rabbits using three different levels of intraocular pressures (IOPs), including alpha-chymotrypsin-induced ocular hypertension, hypotension (IOP recovery method) and normal tension. Cromakalim significantly increased IOP during the initial period in normotensive and hypotensive rabbits, but in the later time, reduced IOP in the alpha-chymotrypsin-induced model. Nicorandil had a similar but less potent effect. In addition, cromakalim also affected ocular blood flows, which had a trend to reduce blood flow about 2-3 hr later, after topical administration of the eyedrop. Two possible mechanisms for increasing IOP effect of potassium channel activators were: (a) enhancing the formation of aqueous humor; (b) relaxing the trabecular meshwork to reduce the outflow of aqueous humor.

Administration, Topical↗

Ethanol and acetaldehyde metabolism in chinese with different aldehyde dehydrogenase-2 genotypes.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. Both enzymes exhibit genetic polymorphisms among racial populations. About half of the Chinese population lack mitochondrial ALDH2 activity and such a deficiency has been believed to be a negative risk factor for the development of alcoholism. To assess ethanol and acetaldehyde metabolism in Chinese with different ALDH2 genotypes, we genotyped 273 male adults at the ADH2, ADH3, and ALDH2 loci by using polymerase chain reaction-directed mutagenesis and restriction fragment length polymorphisms. Of the 143 individuals homozygous for both the ADH2*2 and the ADH3*1 alleles, 80, 55, and 8 were identified as ALDH2*1/*1, ALDH2*1/*2, and ALDH2*/*2, respectively. Five each from the above three ALDH2 genotypic subjects underwent alcohol elimination testing. Blood ethanol and acetaldehyde levels were determined at various times up to 130 min after intaking a low dose of ethanol (0.2 g/kg body weight) by using head-space gas chromatography and high-performance liquid chromatography with fluorescence detection, respectively. The mutant homozygotes of ALDH2*2/*2 and the heterozygotes exhibited significantly higher peak acetaldehyde concentrations and also greater areas under the blood concentrations-time curve (AUC) than did the normal homozygotes of ALDH2*1/*1, with the mutant homozygotes both being the largest. The mutant homozygotes displayed significantly higher peak ethanol levels and AUC compared to the normal homozygotes. Of the 17 subjective feeling items tested, palpitation, facial warming, effects of alcohol, and dizziness were found to be most pronounced among the mutant homozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Changes in phrenic, hypoglossal and recurrent laryngeal nerve activities after intravenous infusions of aminophylline in cats.

Aminophylline is known to have respiratory stimulant properties, and it has been suggested that it may also be effective in sleep apnoea. However, its role in this disorder remains uncertain. Theoretically, increasing upper airway motoneural activity in order to maintain airway patency might alleviate obstructive sleep apnoea. On the other hand, increasing the respiratory drive may also prove beneficial in treating central sleep apnoea. In these studies, we attempted to determine the effect of aminophylline on neural activities of the upper airway and diaphragm. We administered intravenously either a low dose (4 mg.kg-1) or a high dose (16 mg.kg-1) of aminophylline to decerebrated, vagotomized and paralysed cats, and continuously recorded the phrenic hypoglossal and recurrent laryngeal nerve activities for 3 h. Results showed that a high dose of aminophylline induced a marked increase in phrenic nerve activity, but not hypoglossal or recurrent laryngeal nerve activity. In a group treated with a low dosage of aminophylline, a significant increase of activity was found in all three nerves. Furthermore, phrenic nerve activity increased more with a high dose than with a low dose. We confirmed that aminophylline has dose-dependent and selective effects on respiratory neural activity. A low dose acts on the upper airway and diaphragm, but a high dose induces a marked increase in central respiratory drive. According to our results, low dose aminophylline might be beneficial in obstructive sleep apnoea, whereas, a high or low dose might improve some cases of central sleep apnoea.

Aminophylline↗

Studies of topical carbonic anhydrase inhibitors: ocular hypotensive effect of thiadiazole derivatives.

A series of thiadiazole derivatives were topically applied in gels or suspensions to rabbits to determine their ocular hypotensive effect. As a result, the compounds with higher corneal permeabilities showed stronger effect in lowering IOP. In addition, gels also caused stronger effect than suspensions. Different concentrations of gel preparations produced diverse ocular hypotensive effects. A linear relationship between the integrated IOP response and logarithm concentration of inhibitor was found. It is proposed that the ocular hypotensive effect was attributed to the level of inhibitor in ciliary body.

Administration, Topical↗

Studies of carbonic anhydrase inhibitors: physicochemical properties and bioactivities of new thiadiazole derivatives.

A series of thiadiazole derivatives of carbonic anhydrase inhibitors were prepared and their physicochemical properties and pharmacological activities such as corneal permeabilities, inhibition of carbonic anhydrase activities were evaluated. The solubilities and pKa values were determined in varied pH of phosphate buffers at 35 degrees C after equilibrium. Intrinsic solubility and pKa value were calculated from the plot of solubility versus the reciprocal of hydrogen ion concentration. The distribution coefficient was determined in the system of octanol/pH 7.65 phosphate buffer. As a result, the sigma (Hammett constant) and pi (hydrophobic substituent constant) values of substituents were found to be correlated to the logarithm of Ka and partition coefficient. Corneal permeabilities of the analogue were determined in a specially designed diffusion cell using excised rabbit cornea, which ranged from 1.32 x 10(-5) (compound II) to 3.48 x 10(-7) cm/sec (compound VI). Compound with high permeability might be expected to be absorbed well after topical administration into the eye. The methodology of pH-stat was used to determine the inhibition of the carbonic anhydrase activity of the analogue. The IC50 values of the analogue around 10(-8) M as determined were less than that of acetazolamide. The results suggest that the analogue had good pharmacological activity. Finally, an equation for quantitative structure-activity relationship was established for the analogue, which is as follows: [formula: see text]

Absorption↗

Duchenne muscular dystrophy: MR grading system with functional correlation.

The pelvic girdle, thigh, and calf muscles of 29 patients with Duchenne muscular dystrophy (DMD) were evaluated with magnetic resonance (MR) imaging. The muscles that were most resistant to disease were the gracilis, followed by the sartorius, semitendinous, and semimembranous. Sixteen patients had asymmetric involvement in part of the muscle bundles of thigh. An MR grading system was developed to assess the number of preserved pelvic and thigh muscles, the severity of fatty infiltration of the calf, and the increase of subcutaneous fat. Statistically significant correlations were obtained between MR grade and clinical functional grade (P < .01), MR grade and disease duration (P < .01), and MR grade and patient age (P < .01). An inverse correlation was observed between the creatine kinase values and the MR grade (P < .05). The MR grading system helped identify disease severity in patients with low clinical functional grades. Twenty-four follow-up studies were performed in 22 patients. In 13 of the 24 cases, the MR grade progressed while the clinical functional grade remained unchanged. Both the MR and clinical functional grades progressed in six cases. The results suggest that MR imaging may be useful in prebiopsy mapping and may help accurately monitor the progression of DMD.

Adolescent↗

Protamine-induced acute lung injury and the protective effect of agents that increase cAMP.

Polycations, such as protamine sulfate and polylysine, have been implicated in acute lung injury. We studied the vascular effect of protamine sulfate and the protective effect of agents that increase cAMP in isolated rat lungs perfused with a cell- and plasma-free solution. Protamine sulfate (3 mg) markedly increased pulmonary artery pressure (PAP) from 15.6 +/- 0.5 to 30.8 +/- 1.2 mmHg (P < 0.01) and lung weight gain (LWG) by 7.8 +/- 1.5 g within 30 min (P < 0.001). The protective effects of pharmacological agents that increase intracellular cAMP were investigated. These agents included dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, a cAMP analogue), aminophylline and pentoxifylline (both are phosphodiesterase inhibitors). Pretreatment with these agents 5 min before protamine administration largely attenuated the increases in PAP and LWG. Because DBcAMP, aminophylline and pentoxifylline all share the effects of increasing intracellular cAMP and were effective on the protamine-induced lung changes, the intracellular level of cAMP could be a major determinant of lung injury. Since there is no blood in the perfusate, the mechanism of cAMP on cellular components in the blood such as neutrophils, can be ruled out. The endothelial cells are likely to be the target cells because charge interaction is believed to occur on the endothelial surface. This result will be very important in the elucidation of the protective effect of cAMP in acute lung injury.

Aminophylline↗

The mucoceles or pyoceles of the paranasal sinuses.

Fifty-five mucopyoceles in 53 patients were diagnosed during the 10-year period from 1982 to 1992 in our department. These included 8 from the frontal sinus, 25 from the maxillary sinus, 10 from the ethmoidal sinus, 1 from the maxillary and ethmoidal sinuses, 7 from the frontoethmoidal sinuses and 4 from the sphenoethmoidal sinuses. The patients ranged in age from 8 to 78 years (mean 47.1 years). The ratio of males to females was 31 to 22. The rhinologic symptoms occurred most often in maxillary mucopyoceles and were rare in the other groups whereas ophthalmic symptoms were noticed in most of the cases. All of the cases received surgery and postoperatively most of the initial symptoms subsided except that two patients still had occasional diplopia and one did not recover at all from complete blindness. Two cases had a recurrence and one suffered from subarachnoid hemorrhage shortly after discharge. Surgery is the only treatment modality for mucopyoceles and the building of a new patent communication between the lesion and nasal cavity is important for the success of this surgery.

Adolescent↗

Distribution of ganglion neurons in the trachea of the rat.

The nerve plexuses and ganglionic nerve cells of rat trachea were studied quantitatively in whole-mount preparations stained for acetylcholinesterase. Two nerve plexuses were observed overlaying the smooth muscle layer of the membranous part or the rat trachea. On average, 70 ganglia (range 63-78, S.D. = 6) and 549 neurons (range 334-661, S.D. = 125) were found on the nerve plexuses. About 80% of ganglia are distributed in the thoracic part of the trachea. The ganglia are relatively small, 77% of the tracheal ganglia contain only 5 (or fewer) neurons. The profile area of neurons are about 474 microns2 (range 207 microns2-918 microns2). It appears that the uneven distribution of neurons is attributed to the increased volume of the thoracic tracheal smooth muscle. The ultrastructural features of the rat tracheal ganglia is similar to that of other species. A few regular processes of fibroblasts form the perineurium of the ganglia. Collagen fibrils, myelinated and unmyelinated nerve fibers and blood vessels are present inside the ganglia. The presence of muscular blood vessel within the tracheal ganglion has nerve been reported before. This may further support the possibility that the tracheal ganglion receives a separate blood supply.

Animals↗

Alteration of amino acid in plasma and cerebrospinal fluid of children with seizure disorders.

Amino acid levels in plasma were measured by amino acid autoanalyser in 130 convulsive children. The levels of taurine, serine and tryptophan were significantly lower in convulsive children as compared to normal control; in contrast, isoleucine, homocystine, GABA, histidine, arginine and ammonia were higher. The children with paroxysmal disorders (headache, dizziness and abdominal epilepsy) had the highest levels of isoleucine, histidine and arginine and the lowest levels of glutamate and cystein. Clinical seizure activity within 6 months prior to the test seemed to have no obvious effect on the plasma amino acid pattern, except for the levels of glycine and arginine tended to return to normal, and the level of GABA was significantly increased in patients with the seizure being controlled. The patients treated with carbamazepin as a single anticonvulsant had the highest GABA level compared to those with other anticonvulsants. Hyperglycinemia and hyperammonaemia were also noted in patients who took valproic acid. The levels of serine, isoleucine and phenylalanine in the CSF within 6 hours after convulsion were significantly lower than the normal control; while asparagine, tyrosine, lysine and arginine were significantly higher. The concentration of ammonia in the CSF was also elevated after convulsion as compared to the normal control. Amino acids play an important role in the generation of epilepsy and recently there has been an increasing number of studies to help determine their effects during an epileptic attack. However, there still is much debate and controversy on this topic. Therefore, further studies are needed and researchers should carefully consider factors that might affect the accurate assessment of the results.

Adolescent↗

Stability studies of topical carbonic anhydrase inhibitor 6-hydroxyethoxy-2-benzothiazole sulfonamide.

A new carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-hydroxyethyoxyzolamide), was studied to determine its stability in aqueous solution from pH 2.9 to 9.2 at a constant ionic strength of 0.15 M. This newly synthesized derivative of ethoxyzolamide has demonstrated clinical efficacy for use as an ophthalmic drug to lower intraocular pressure. Drug solution in sealed ampules was placed in a constant temperature over either at two temperatures (75 and 85 +/- 0.2 degrees C) or four temperatures (75, 80, 85, and 90 +/- 0.2 degrees C). Samples were analyzed by known HPLC methods. The results indicated that 6-hydroxyethoxyzolamide is most stable at pH 4 to 5.5. The aqueous drug solutions at pH 7.0 and 8.0 were, nevertheless, sufficiently stable, based on extrapolation of kinetic data at high temperatures using the experimentally determined Arrhenius equation. The degradation compound was identified by spectral analysis to have a hydroxyl group substituting for the original -SO2NH2 group.

Administration, Topical↗

Spinal muscular atrophy: MR evaluation.

The neurogenic myopathy of spinal muscular atrophy (SMA) is degeneration of anterior horn cells of the spinal cord and associated muscle weakness. In three patients with the severe type, according to Dubowitz's classification, magnetic resonance imaging (MRI) of the lower extremity showed severe atrophy of the entire muscle bundles of the thigh and the calf. Nine intermediate type patients had ragged atrophy of muscle bundles of the thigh and the calf with selective preservation of adductor longus muscle. Five patients with the mild type had fatty infiltration of muscle bundles and increased intermuscular fat planes. MRI was insufficient for the evaluation of cervical cord abnormalities. MRI of the lower extremity was a reliable complementary modality for the diagnosis and follow-up of SMA patients.

Child↗

Recombinant pseudorabies virus carrying a plasmodium gene: herpesvirus as a new live viral vector for inducing T- and B-cell immunity.

In Balb/c mice, the sterile protective immunity induced by immunization with radiation-attenuated Plasmodium yoelii sporozoites is eliminated by in vivo depletion of CD8+ T lymphocytes, suggesting that cytotoxic T lymphocytes (CTL) against malaria antigens expressed on infected hepatocytes are required for mediating this protective immunity. To produce a vaccine that would induce CTL against the P. yoelii circumsporozoite protein (CS), we constructed an attenuated pseudorabies virus (PRV) containing a gene encoding this protein. Balb/c mice that received three doses of 10(7) plaque-forming units (p.f.u.) of this vaccine intravenously at 3 week intervals developed high levels of antibodies to sporozoites (indirect fluorescent antibody titre = 4096) and CTL against a 16 amino acid epitope (SYVPSAEQILEFVKQI, amino acids 281-296) from the P. yoelii CS protein designated PYCTL1. The cytotoxic activity of the CTL was antigen-specific, MHC-restricted, and dependent on CD8+ T cells. Furthermore, these CTL eliminated P. yoelii-infected hepatocytes from in vitro culture, indicating that they recognize this peptide on the surface of infected hepatocytes. However, all nine mice that were challenged with 200 sporozoites developed a blood-stage malaria infection. We attribute this lack of protection to the great difficulty of inducing sterile immunity against this highly infectious parasite P. yoelii. We conclude that recombinant pseudorabies virus (PRV) worked successfully as a live vaccine vector to induce both antibodies and CTL, albeit non-protective in vivo, and the herpesviruses should be considered as subunit vaccines where T- and B-cell immunity is required.

Amino Acid Sequence↗

Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs.

BACKGROUND AND METHODS: The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (.OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 g/kg in saline) for 1.5 hrs, beginning 1 hr before an i.v. bolus injection of phorbol myristate acetate (17 micrograms/kg); six dogs received phorbol myristate acetate (17 micrograms/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage. RESULTS: As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p less than .01); protein concentrations in lung lavage fluid were lower (p less than .01); the decrease in PaO2 was significantly reduced (p less than .01); and there were significant reductions in the alveolar-arterial oxygen tension difference (P[A-a]O2) (p less than .01) and shunt (Qsp/Qt) (p less than .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment. CONCLUSIONS: These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate.

Acute Disease↗

Complete nucleotide sequence and genetic organization of papaya ringspot virus RNA.

The complete nucleotide sequence of the RNA genome of papaya ringspot virus (PRSV) was determined from four overlapping cDNA clones and by direct sequencing of viral RNA. The genomic RNA is 10326 nucleotides in length, excluding the poly(A) tract, and contains one large open reading frame that starts at nucleotide positions 86 to 88 and ends at positions 10118 to 10120, encoding a polyprotein of 3344 amino acids. The highly conserved sequence AAAUAAAANANCUCAACACAACAUA at the 5' end of the RNA of PRSV and those of the other five reported potyviruses shows 80% similarity, suggesting that this region may play a common important role for potyvirus replication. Two cleavage sites of the polyprotein were determined by amino acid sequencing of the N termini of helper component (HC-Pro, amorphous inclusion) and cylindrical inclusion (CI) proteins. Other cleavage sites were predicted by analogy with the other potyviruses. The genetic organization of PRSV is similar to that of the other potyviruses except that the first protein processed from the N terminus of the polyprotein (NT protein) has an M(r) of 63K, 18K to 34K larger than those of the other potyviruses. The cleavage site for liberating the N terminus of the HC-Pro protein was found at the same location down-stream from the consensus sequence FI(V)VRG as that reported for tobacco vein mottling virus. The NT protein of potyviruses is the most variable and may be considered important for identification of individual potyviruses. The most conserved protein of potyviruses appears to be the NIb protein, the putative polymerase for the replication of the potyviral RNA. The genetic organization of PRSV RNA is tentatively proposed to be VPg-5' leader-63K NT-52K HC-Pro-46K-72K CI-6K-48K NIa-59K NIb-35K coat protein-3' non-coding region-poly(A) tract.

Amino Acid Sequence↗