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Biomedical subjects

S Y Chang

Publications and source records attributed to S Y Chang.

At least 19 recordsLinked to original sources

In vitro metabolism of a potent HIV-protease inhibitor (141W94) using rat, monkey and human liver S9.

Compound 141W94 (Vertex VX478) (3S)-tetrahydro-3-furyl N-[((S,2R)-3-(4-amino-N-isobutylbenzenesulfonamido)-1-benzyl- 2-hydroxypropyl] carbamate, is a potent HIV-protease inhibitor and is currently undergoing clinical trials. The purpose of this study was the rapid identification of the phase I and II in vitro metabolite of 141W94 using mass spectrometry. Four different sources of liver S9 fractions were used for studying comparative in vitro metabolism of 141W94. They were obtained from Arochlor-induced rat, normal (untreated) rat, cynomolgus monkey and human livers. Selected incubations were supplemented with uridine diphosphate glucuronic acid and the reduced form of glutathione. The predominant species seen in the incubation mixture was the parent compound 141W94. Metabolites arising from ring opening to form the diol and carboxylic acid and oxidation of the tetrahydrofurran ring (formation of dihydrofuran) were identified. In addition, of the two monohydroxylated products identified, one resulted from hydroxylation on the aniline ring and the other from hydroxylation at the benzylic position. Two different glucuronides were also observed. Comparing the three species, very little metabolism was seen in the normal (non-induced) rat. The metabolic profile and extent of metabolism with induced rat, monkey and human S9 was similar. Induced rat S9 incubation showed the formation of two unique metabolites that were not seen in non-induced rat, monkey and human S9 fractions. They were the monohydroxylated glucuronide and a carbamate cleavage product. The metabolites were identified using mass spectrometry based on their molecular masses and fragmentation patterns.

Animals

The impact of the total motile sperm count on the success of intrauterine insemination with husband's spermatozoa.

PURPOSE: The purpose of this study was to evaluate the relationship between the total motile sperm count and the success of IUI treatment cycles with postwashed husband spermatozoa in couples with infertility in a large patient population. PATIENTS: When 939 couples underwent 1375 cycles of IUI with varying etiologies of infertility which included male factor, endometriosis, tubal factor, ovulatory dysfunction, uterine factor, cervical factor, and unexplained infertility, the results were 207 pregnancies. RESULTS: The overall pregnancy rate per cycle was 15.1% (207/1375). The total motile sperm count were significantly increased in the pregnant group than the nonpregnant group (38.7 x 10(6) versus 28.6 x 10(6); P < 0.001). There was a trend toward an increased success rate with increased total motile sperm count. Significance was reached when the total motile sperm count exceeded 5 x 10(6). Life table analysis was performed and the curve representing a cumulative chance of pregnancy calculated from our data reached 72%. CONCLUSIONS: Our findings suggest that a final postwashed total motile sperm count used for IUI may be considered predictive of the success for pregnancy and allow couples to be informed of the chances of success.

Female

Modal behavior of the mu 1 Na+ channel and effects of coexpression of the beta 1-subunit.

The adult rat skeletal muscle Na+ channel alpha-subunit (mu 1) appears to gate modally with two kinetic schemes when the channel is expressed in Xenopus oocytes. In the fast mode mu 1 single channels open only once or twice per depolarizing pulse, but in the slow mode the channels demonstrate bursting behavior. Slow-mode gating was favored by hyperpolarized holding potentials and slow depolarizing rates, whereas fast-mode gating was favored by depolarized holding potentials and rapid depolarizations. Single-channel studies showed that coexpression of beta 1 reduces slow-mode gating, so that channels gate almost exclusively in the fast mode. Analysis of open-time histograms showed that mu 1 and mu 1 + beta 1 both have two open-time populations with the same mean open times (MOTs). The difference lies in the relative sizes of the long and short MOT components. When beta 1 was coexpressed with mu 1 in oocytes, the long MOT fraction was greatly reduced. It appears that although mu 1 and mu 1 + beta 1 share the same two open states, the beta 1-subunit favors the mode with the shorter open state. Examination of first latencies showed that it is likely that the rate of activation is increased upon coexpression with beta 1. Experiments also showed that the rate of activation for the fast mode of mu 1 is identical to that for mu 1 + beta 1 and is thus more rapid than the rate of activation for the slow mode. It can be concluded that beta 1 restores native-like kinetics in mu 1 by favoring the fast-gating mode.

Animals

Epidermoid cysts of the testis: diagnosis by ultrasonography and magnetic resonance imaging resulting in organ-preserving surgery.

OBJECTIVE: To present experience in the diagnosis and management of patients with an epidermoid cyst of the testes and to confirm the role of conservative surgery. PATIENTS AND METHODS: The records from the last 26.5 years of patients diagnosed as having a testicular tumour were reviewed retrospectively. Those patients with a confirmed epidermoid cyst were evaluated for age, clinical assessment, methods of diagnosis, treatment and follow-up. RESULTS: Amongst a total of 131 testicular tumours, 11 patients (8.4%; mean age 25.7 years, range 21-35) were diagnosed pathologically as having an epidermoid cyst. Pre-operative suspicion of the benign nature of the lesions was supported by testicular ultrasonography in six patients and supplemented with magnetic resonance imaging (MRI) in one. An operation sparing the testicles was performed in eight patients after the diagnosis of epidermoid cyst was confirmed from frozen sections. Three patients were treated by radical orchidectomy. There were no relapses after a median follow-up of 47.3 months (range 2-82). CONCLUSION: In this series, the relative incidence of epidermoid cyst was higher than that reported in the literature (1-2%). Ultrasonography and MRI of the testes may allow the diagnosis to be made preoperatively. The absence of relapse in these patients further supports the use of organ-sparing surgery in these young men.

Adult

T cell recognition and cytokine production elicited by common and type-specific glycoproteins of herpes simplex virus type 1 and type 2.

T cell recognition of common and type-specific herpes simplex virus (HSV) glycoproteins was measured in 72 subjects. T cells were stimulated with whole HSV-2 antigen and glycoproteins gB2, gD2, and gG2. T cell proliferation in response to HSV-2 antigen and gG2 was significantly higher in subjects with HSV-2 infection than in those with HSV-1 infection only; responses to gB2 and gD2 were the same. T helper (Th) type 1 and Th2 cytokine production in response to whole HSV-2 antigen, gB2, and gD2 was evaluated in 33 subjects. Interleukin (IL)-2 and interferon-gamma responses to most antigens were significantly higher among HSV-2-seropositive subjects than among seronegative subjects. IL-4 synthesis was negligible; IL-10 was produced in seronegative and seropositive persons, but HSV-2 antigen responses were significantly higher in HSV-2-seropositive persons. Naturally acquired immunity to HSV involves T cell recognition of common and type-specific glycoproteins, prominent Th1 responses, and discordant Th2 responses with little IL-4 but substantial IL-10 production.

Antigens, Viral

The relationship between ultrasonic volume and actual weight of pathologic uterus.

Our purpose was to assess the correlation between the estimated volume based on ultrasonic measurement in vivo and the actual weight of the diseased uterus after hysterectomy, and then retrospectively tried to establish a simple equation to convert the volume into the weight in grams. A total of 105 women with nonmalignant diseased uteri which were prepared to undergo laparoscopy-assisted vaginal hysterectomy had had preoperative ultrasound scanning to estimate the uterine size by measuring three dimensions including the length (L), width (W) and anteroposterior (AP) diameter. The uterine volume was calculated by the use of a prolate ellipsoid formula (4/3 x pi x L/2 x W/2 x AP/2). Actual uterine weight was immediately taken after extirpation of the uterus. Linear regression analysis revealed uterine weight (g) = 50.0 + 0.71 x volume (cm3), with correlation coefficient = 0.93 and SE = 49.6 g. There was a close, positive correlation between the estimated uterine volume and actual uterine weight. With utilization of this equation, the uterine size in vivo can thus be expressed as a concrete, objective value in weight instead of "weeks' size' by comparison with pregnant uterus, which has been commonly used in traditional gynecologic practice.

Adult

Relationship of uterine perfusion to outcome of intrauterine insemination.

This prospective study was undertaken to evaluate the prognostic value of uterine perfusion on the day of human chorionic gonadotropin administration in patients who were undergoing intrauterine insemination. Uterine perfusion was evaluated by measuring the pulsatility index of the ascending branch of the uterine arteries on the day of administration of human chorionic gonadotropin. No pregnancy occurred when the pulsatility index of the ascending branch of the uterine arteries was more than 3. The fecundity rate was 18% when the pulsatility index was less than 2 and was 19.8% when the pulsatility index was between 2 and 3 (not significant). The continuing pregnancy rate was 18% when the pulsatility index was less than 2, compared with 12.1% when the pulsatility index was between 2 and 3 (P < 0.05). Our data suggest that the measurement of uterine perfusion on the day of human chorionic gonadotropin administration may have predictive value regarding fecundity and the continuation of pregnancy in intrauterine insemination.

Adult

Coexpression of beta 1 with cardiac sodium channel alpha subunits in oocytes decreases lidocaine block.

Coexpression of the rat beta 1 subunit with rat brain and skeletal muscle sodium channel alpha subunits in Xenopus oocytes normalizes currents by accelerating sodium current decay kinetics, shifting steady state availability relationships, and accelerating recovery from inactivation. Unlike brain and skeletal muscle, the heart alpha subunit expressed without beta 1 has native-like decay kinetics in oocytes. Messenger RNA for beta 1 has been found in heart, but whether and how it affects cardiac sodium channel function are unclear. We studied coexpression of human heart alpha subunit with beta 1 in Xenopus oocytes using two microelectrode voltage-clamp and macropatch techniques. Coexpression with beta 1 caused a significant positive shift of 3-7 mV in the midpoint of the steady state inactivation relationship but did not affect single-channel conductance, activation, current decay, or recovery from inactivation. Sensitivity to lidocaine block, however, was decreased for both resting state block (Kd = 0.5-1.3 mM) and phasic block in response to pulse trains, but inactivated state block was not affected (Kd = approximately 10 microM). Coexpression with beta 1 increased the rate of recovery from lidocaine block, which accounted for the major part of the observed differences in tonic and phasic block. A beta 1 construct with the cytoplasmic tail removed also produced these effects, demonstrating that the beta 1 cytoplasmic tail was not involved in altering lidocaine block. We conclude that the beta 1 subunit is capable of affecting function of the cardiac sodium channel in oocytes by decreasing tonic and phasic lidocaine block with small effects on gating.

Animals

Early discontinuation of gonadotropin-releasing hormone agonist in controlled ovarian hyperstimulation: a preliminary report.

The purpose of this study was to evaluate the applicability of continuing daily injectable GnRHa, after pituitary desensitization, for the first 4 or 5 days of ovarian stimulation. We proposed a new calculation and estimated that it took as early as 6 to 7 days for pituitary and gonadotropin release to return after cessation of daily administered leuprolide acetate. A modified regimen based on this new calculation, i.e. Daily administered GnRHa continued for the first 4 or 5 days with ovarian stimulation after pituitary desensitization had been achieved was applied to patients undergoing assisted reproductive technology (ART). Thirty-five patients prospectively assigned to use this early discontinuation regimen were analyzed with respect to age, indications, duration of ovarian stimulation, dose of exogenous gonadotropin required, ovarian response and oocytes obtained, rate of fertilization, and rates of pregnancy. There was no spontaneous LH surge occurred. Premature luteinization occurred in one patient. We concluded that, after pituitary desensitization, there was no spontaneous LH surge when daily administered GnRHa continued for 4 or 5 days only with ovarian stimulation. Impacts on the ART outcome required further evaluation in a prospectively randomized study. Based on theoretical estimation, cessation of GnRHa at the beginning of ovarian stimulation might eliminate most, but not all, spontaneous LH surges.

Adult

Child malnutrition in China--present status and changing trend.

Halving the malnutrition of under five of years has been set as one of the goals to be achieved by the year of 2000 by Chinese government. So it is important to know the present status of child malnutrition and its trend of changing, in order to predict the possible outcome of the achievement of the goal. According to the Child Survey carried out by the State Statistic Bureau (SSB) in 26 provinces and autonomous regions and 3 municipalities in 1992, the prevalence of malnutrition of under five was: moderate and severe underweight, stunting and wasting were 17.9%, 34.7% and 4.7% respectively. But there are significant differences among urban and rural children and between different provinces. The highest prevalence rate usually occurred in the second year of life of the children, and this may be the result of inadequate weaning food provided to the children. As compared with the data collected in 1987 by SSB in 9 provinces and autonomous regions, an impressive improvement in underweight has occurred within these 5 years. The average declined prevalence was 20.5%. It is specially true for urban children. To stunting, there was also improvement for urban children but not in the rural, resulting and over all increasing of prevalence by 5.9%. To wasting, the prevalence for urban children was low and remained at the same level while there was some what increase in the rural. So, according to these results, with constant economic development and more attempt made in areas and groups at risk, the goal to decrease malnutrition in half in terms of underweight could be reached by the year of 2000.

Body Height

Autogenous fat intracordal injection as treatment for unilateral vocal palsy.

BACKGROUND: Intracordal injection, which is less time-consuming and avoids neck incision, remains an important method to correct glottic insufficiency induced by unilateral vocal palsy. Among the various new materials proposed for intracordal injection, autogenous fat draws our attention for its availability without cost and high bio-compatibility. This article reports our preliminary experiences of intracordal injection using autogenous fat to treat glottic insufficiency induced by unilateral vocal palsy. METHODS: Autogenous fat is collected under local anesthesia by syringe aspiration from femoral or lower abdomen. Precautions to reduce resorption are taken while collecting and processing the fat. Under the guidance of flexible laryngovideostroboscopy, Bruning syringe with a bended needle is inserted transorally to make the intracordal injection. Serial pre-operation and postoperation evaluations by flexible laryngovideostroboscopy, the patient's selfassessment on the voice, the speech pathologist's perceptual ratings on the breathiness and roughness of the patient's voice, maximum phonation time, and mean airflow rate are made. RESULTS: A total of 19 cases were recruited for the treatment, and 17 of them completed the procedure. The clinical applicability was 89.5%. The fat injection had no obvious effect on the posterior glottic gap correction. The postoperative glottic gap estimated by the videostroboscopy, was improved in 15 of the 16 cases two weeks after operation, and in five of the seven cases who has been followed up for three months. Twelve of the 16 cases felt improved voice in two postoperative weeks, and six of the seven cases still felt the improvement three months after operation. The rate and amount of resorption varied greatly among individuals. None of the injected cords showed untoward morphological or vibratory changes up to three months after injection. CONCLUSIONS: Intracordal injection of autogenous fat to treat unilateral vocal palsy by the method we propose is relatively simple with high clinical applicability and no extra-cost. None of the injected cords showed unfavorable changes. Most of the patients were improved after injection, at least for a short period of time. The long-term effectiveness remains to be observed. Repetition of the injection is also simple, if the voice results deteriorate due to resorption of the injected fat.

Adolescent

The effects of Vero cell co-culture on human zygotes resulting from in vitro fertilization and oocytes following subzonal insemination.

A variety of co-culture systems have been devised to enhance the human embryo development in vitro. Vero cells were selected because they can be highly controlled and are easy to handle. To evaluate the embryotrophic effects of Vero cell monolayers, when they were co-cultured with human in vitro fertilized zygotes or subzonal inseminated oocytes. Total 1695 two-pronuclear embryos resulting from in vitro fertilization were cultured with Vero cells or medium alone for 24 hours. Similarly, sixty-six two-pronuclear embryos resulted from subzonal insertion of sperm (SUZI) with co-culture starting immediately following SUZI were compared with fifty-two two-pronuclear embryos resulted from SUZI, without co-culture. The numbers of blastomere and morphology of embryos were compared between the co-culture group and control group using student's t-test. Cell numbers in each embryo were greater in the IVF/co-culture group than in the control group (4.01 +/- 1.32 vs. 3.86 +/- 1.45, p < 0.05). The rates of poor quality embryo with major fragmentation were lower in the co-culture group than in the control group(11.5% vs. 19.9%, p < 0.001, for IVF embryos; 9% vs. 27%, p < 0.005, for SUZI oocytes). Co-culture SUZI oocytes on Vero cells prior to fertilization did not positively influence embryo cleavage, but improved embryo quality. We conclude that Vero cells can enhance human embryo development; however, the period for one-day or two-day co-culture is too short to provide a maximal support. Short term co-culture did not increase implantation rates. Immediate co-culture following SUZI might somewhat rescue the microinseminated oocytes. However, a longer duration of co-culture is necessary to exert the maximal effects on embryo development and implantation.

Adult

Multivariate analyses of the relationship between umbilical cord length and obstetric outcome.

To investigate the clinical significance of umbilical cord length in human pregnancies, 1087 deliveries at Kaohsiung Chang Gung Memorial Hospital from May 1995 to August 1995 were studied. Our data showed that male fetuses had longer cord length than female and vertex presentation had longer cord length than breech presentation. The cord length and placental weight were significantly related to the birth weight. We found that: 1) only intrauterine growth retardation was associated with the increased risk of fetal distress; 2) secondary arrest of labor and advanced gestational age were correlated with meconium stain; and 3) birth weight and presence of meconium stain were correlated with the secondary arrest (p < 0.05). However, there was no significant correlation between umbilical cord length and fetal well-being. As a result of multivariate analyses, we conclude that the umbilical cord length does not significantly correlate with either maternal age, gestational age (> or = 28 weeks), parity fetal outcome or intrauterine fetal well-being. Birth weight is the only characteristic that is correlated with cord length.

Adult

Second trimester diagnosis of thanatophoric dysplasia.

Thanatophoric dysplasia is one of the most common skeletal dysplasia, with an incidence from 1:6,400 to 1:100,000 births. While the etiology is unknown, either autosomal recessive or polygenic transmission with 0.2% recurrence risk had been suggested. It is a lethal disorder characterized by extremely short ribs, tubular bones and macrocephaly. Death is often secondary to pulmonary hypoplasia caused by the small thoracic cavity. We present a fetus with shortening of four limbs, typical thanatophoric dwarfism, diagnosed by sonography at the 25th week of gestation. The second trimester diagnosis by ultrasound was crucial, because it gave an alternative option of pregnancy termination when the affected fetus was discovered.

Adult

Improved sperm recovery rate with Percoll gradient method in intrauterine insemination.

The purpose of this study was to compare the different sperm manipulation methods on the recovery rate of motile sperm that was collected to use in the intrauterine insemination. Three hundred and thirty-five IUI (intrauterine insemination) cycle from a total of 963 treatment cycles was performed for non-peritoneal factor infertility couples. The sperm separation methods were swim-up, swim-down and Percoll gradient (since Mar. 1992). We compared the different sperm preparation methods in normal and abnormal semen analysis group. Our results show that in the abnormal semen samples (oligospermic approximately, asthenospermic approximately), the Percoll gradient method is superior to the swim-up and swim-down methods on the recovery of a higher number of total, motile and active motile spermatozoa (p < 0.05), even though the sperm quality before preparation was rather poorer than the samples prepared by the other two methods. The pregnancy rate in both groups are not statistically significant. We conclude that the Percoll gradient is an improved method for semen manipulation as it allows greater recovery of sperm with higher motility in intrauterine insemination.

Adult

Comparison between short-term and long-term post-operative evaluation of sleep apnoea after uvulopalatopharyngoplasty.

For a long time uvulopalatopharyngoplasty (UPPP) has been used to treat the obstructive sleep apnoea syndrome (OSAS). The diverse surgical effects, the inadequate understanding of operation effect consistency, the possibility of disease progression, and the few reported papers for long-term evaluation after UPPP aroused our interest in designing this study. Fifteen OSAS patients who had undergone UPPP with pre-operative, initial post-operative and long-term post-operative polysomnographic studies were included in this study. Long-term post-operative polysomnography was undertaken more than five years after surgery. The polysomnographic evaluations included respiratory disturbance index (RDI), duration of saturation SaO2 < 85 per cent (DOS), and the lowest O2 saturation (LOS). Amongst them, 10 patients with initial post-operative RDI reduction > 50 per cent were considered responders. In these responders, the long-term follow-up results of all three parameters showed improvement compared to the pre-operative data. In a comparison between the initial and long-term post-operative sleep study results, LOS and DOS showed no significant difference. However, the long-term post-operative RDI result became significantly worse. More than 80 per cent of all cases had subjective symptomatic improvement in the long-term post-operative evaluation. The subjective improvement after operation is not adequately correlated to the polysomnographic result. We suggest that long-term follow-up for patients after UPPP is necessary.

Adult

Founding mutations and Alu-mediated recombination in hereditary colon cancer.

By screening members of Finnish families displaying hereditary nonpolyposis colorectal cancer (HNPCC) for predisposing germline mutations in MSH2 and MLH1, we show that two mutations in MLH1 together account for 63% (19/30) of kindreds meeting international diagnostic criteria. Mutation 1, originally detected as a 165-base pair deletion in MLH1 cDNA comprising exon 16, was shown to consist of a 3.5-kilobase genomic deletion most likely resulting from Alu-mediated recombination. Mutation 2 destroys the splice acceptor site of exon 6. A simple diagnostic test based on polymerase chain reaction was designed for both mutations. Our results show that these two ancestral founding mutations account for a majority of Finnish HNPCC kindreds and represent the first report of Alu-mediated recombination causing a prevalent, dominantly inherited predisposition to cancer.

Base Sequence

Neurotoxin quinolinic acid is selectively elevated in spinal cords of rats with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is an autoimmune, animal model of multiple sclerosis (MS) in which demyelination and paralysis are evident. Quinolinic acid (QUIN) is a neurotoxin and endogenous N-methyl-D-aspartate receptor agonist formed from tryptophan. The role of neurotoxins in general and QUIN in particular in EAE or MS is unknown. Lewis rats inoculated with myelin basic protein developed signs of EAE by day 12, were killed, and their tissues assayed for QUIN by gas chromatography with mass spectrometry. QUIN levels were significantly elevated in the more caudal regions of the spinal cords of animals with EAE. Brain, serum, and liver levels of QUIN were not altered. In a similar manner, QUIN in mylin basic protein-injected, asymptomatic animals was not different from control animals. The time course for QUIN was similar to the neurological signs of the disorder; however, the initial elevation in QUIN occurred before the appearance of behavioral signs. Last, treatment with the glucocorticoid dexamethasone prevented both the signs of EAE and the elevation in spinal cord QUIN. It is not known whether QUIN contributes to the paralysis in EAE. However, if QUIN is pathogenic in EAE this finding could have therapeutic implications for MS.

Animals