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H H Chang

Publications and source records attributed to H H Chang.

At least 37 records · Page 2Linked to original sources

The association between postmenopausal osteoporosis and kidney-vacuity syndrome in traditional Chinese medicine.

The aim of this study was to evaluate the association between postmenopausal osteoporosis and kidney-vacuity syndrome. Eighty-one postmenopausal women were enrolled; their age were between 40 to 65 years old. The mean ages of the non-osteoporosis group and osteoporosis group were 54.0 +/- 4.8 and 58.9 +/- 5.9 years old, respectively. Bone density examination was performed by DEXA technique and the diagnosis of osteoporosis was made by finding 2.5 standard deviations below the bone density of healthy youths. Kidney-vacuity syndrome was deduced according to the diagnostic criteria developed in the National Congress on Chinese Medicine and Sino-Western Combined Geriatric Medicine held in the People's Republic of China in 1986. The results showed that patients with kidney-qi-vacuity and kidney-yin-vacuity were more likely to have osteoporosis than those who were not. No significant difference in the rates of osteoporosis between the kidney-yang-vacuity group and non-kidney-yang-vacuity group was found. The kidney-qi-yin-vacuity group had a higher probability of developing osteoporosis than the kidney-qi-vacuity or kidney-yin-vacuity group. By logistic regression analysis, patients with kidney-qi-vacuity or kidney-yin-vacuity were more likely to develop osteoporosis than those who were not. In conclusion, a marked association between kidney-vacuity syndrome and postmenopausal osteoporosis was observed. Patients with kidney-qi-yin-vacuity syndrome were more likely to get osteoporosis than those with kidney-qi-vacuity syndrome or kidney-yin-vacuity syndrome.

Adult↗

Nitric oxide of neuronal origin mediates NMDA-induced cerebral hyperemia in rats.

The goal of this study was to determine whether neuronally derived nitric oxide mediates responses of cerebral blood flow (CBF) to N-methyl-D-aspartate (NMDA). In anesthetized Sprague-Dawley rats, regional CBF of the parietal cortex was monitored by laser-Doppler flowmetry. Topical application of either NMDA or acetylcholine produced concentration-related increases in CBF. Responses of CBF to NMDA (10(-5) M) but not to acetylcholine were inhibited (0+/-3% vs 21+/-5%, p < 0.05) by 7-nitroindazole (50 mg/kg, i.p.). MK-801 (0.5 mg/kg, i.v.) and tetrodotoxin (10(-6) M, topical application) also inhibited NMDA-induced responses. These results suggest that nitric oxide of neuronal origin mediates NMDA-induced increases in CBF.

Acetylcholine↗

Full-spreading platelets induced by the recombinant rhodostomin are via binding to integrins and correlated with FAK phosphorylation.

We have previously reported that non-activated platelets can be induced by morphological changes from the recombinant fusion protein of GST-rhodostomin [GST-RHO(RGD)], a member of disintegrin with an arginine-glycine-aspartic acid (RGD) motif. In this study, we further characterized the factors involved in platelet shape changes induced by rhodostomin. From less to full-spreading, four cell spreading indexes, p1, p2, s1 and s2, were designated to the platelet shape based on the scanning electron micrographs. Results of peptide competition and antibody blocking confirmed that interaction between the RGD of rhodostomin and the alpha(IIb)beta3 integrins of platelets was required for induction of a higher percentage of s2 cells. When platelets were pretreated with calphostin C, herbimycin A and cytochalasin B, respectively, the percentage of p1 and p2 cells on rhodostomin-coated plates was increased and, concomitantly, the percentage of s1 and s2 cells was decreased. Biochemical analyses indicated that the focal adhesion kinase (FAK or pp125FAK) in platelets that adhered to GST-RHO(RGD) was phosphorylated in contrast to little or no phosphorylation of FAK in cells adhered to fibrinogen or non-activated cells. Furthermore, the degree of FAK phosphorylation was consistently correlated with morphological changes in platelets treated with various drugs. Taking all the results together, we suggested that rhodostomin could directly bind to integrins of platelets and then trigger signal transduction leading to FAK phosphorylation and actin polymerization and finally resulting in platelet full-spreading.

Blood Platelets↗

Analysis of interdigital spaces during mouse limb development at intervals following amniotic sac puncture.

A spectrum of limb abnormalities ranging from adactyly, syndactyly, acrosyndactyly to nail hypoplasia was encountered in mouse embryos subjected to amniotic sac puncture at the corresponding gestational stage when human chorionic villus sampling (cvs) would normally be performed clinically. Previous skeletal studies revealed that, apart from the occasional incidence of fusion of 2 distal phalanges, syndactyly usually only affected the soft tissues within the interdigital spaces. A similar situation was also observed in cases of adactyly; while the skeletal elements of the digits were present, the soft tissues in the interdigital spaces failed to separate. A transient period of bradycardia is induced, possibly secondary to compression of the embryo by the extraembryonic membranes and uterine muscles following amniotic sac puncture. These factors, we believe, produce temporary hypoxia/ischaemia of the distal extremities, and may lead to the modification of the interdigital mesenchymal tissues within the autopods. In order to investigate the mechanism(s) underlying soft tissue syndactyly, limbs recovered at 0.5, 4, 8, 12, 24, or 36 h following amniotic sac puncture (ASP) were examined histologically. Vascular disruption in the form of localised areas of haemorrhage, vascular dilatation and congestion and the presence of fluid-filled cavities occurred in relation to the marginal vein and vascular plexus in the interdigital spaces. It is hypothesised that this interfered with the normal equilibrium of the preset programs of mitosis/cell death and apoptosis within the mesenchymal cells of the interdigital spaces. Apoptosis in these areas was inhibited in the majority of the experimental limbs analysed 4 h after ASP. Instead of undergoing necrosis/apoptosis, increased mitotic activity was usually observed from 8 h following ASP at the sites where apoptosis would normally be expected to be seen. The aberrant fate of the interdigital mesenchyme following ASP and the underlying mechanism(s) involved are discussed, as is the critical importance of an adequate vascular supply to the interdigital spaces during the morphogenesis of the autopod. We believe that this report contributes to understanding the mechanism(s) which lead to syndactyly following ASP, and the limb defects occasionally seen following cvs when this is undertaken during early gestation.

Animals↗

Influence of anaesthetic agent on limb abnormalities observed following amniotic sac puncture.

In all of our previous studies into the effect of amniotic sac puncture (ASP) carried out on day 13 of pregnancy in mice, we have used intraperitoneal Avertin (tribromoethanol) as the general anaesthetic. In the present study, we used an inhalational anaesthetic (a mixture of halothane, oxygen and nitrous oxide in a ratio of 2:3:3). The principal difference between these two regimens is that even under optimal post-operative conditions when Avertin is used it can take between 45 and 90 min before complete recovery is achieved; when the inhalational anaesthetic is used, complete recovery is usually achieved within about 3-5 min. Because the experimental conditions were otherwise identical, this allowed the influence of the anaesthetic employed during ASP and the incidence of abnormalities induced on survival rate to day 19 of pregnancy to be studied. The survival rate was slightly higher when the inhalational anaesthetic was used, as was the incidence of limb abnormalities, although the overall incidence of gross abnormalities involving the palate, limbs and tail was not significantly different. The most marked difference, however, was in the incidence of syndactyly, which was significantly lower when the inhalational compared to the intraperitoneal anaesthetic was used: 26.6% v. 70.2% of the abnormal limbs analysed. A possible hypothesis is presented to explain this difference.

Amnion↗

Genomic structure and sequence analysis of human HOXA-9.

In order to understand the regulatory mechanisms establishing and maintaining HOXA-9 gene expression, structural information about the gene is a prerequisite. Therefore, we sequenced the 7.2-kb region of the human HOXA-9 gene and mapped the positions of two partial cDNAs consisting of one of two 5' exons, AB (358 bp) or CD (568 bp), and a common 3' exon (exon II), which are separated by 5.4- and 1.0-kb introns, respectively. When the amino acid sequence homologies were compared with those of other Hox genes belonging to the same paralogous group, exon CD exhibited the strongest homology: 73% of 91 aa residues exactly matched those of chicken Hoxa-9. An intermediate exon (90 bp) was detected within exon CD. It was surrounded by a splice acceptor and a donor at both the 5' and 3' ends, and one branchpoint site was found near the splice-acceptor site. Nucleotide sequence analysis along this region revealed two TATA boxes, one CAAT box, one GC box, and one each of the following binding sites--engrailed, eve-stripe2-hb3, and Krox20--just upstream of exon CD. A CpG island and two RARE repeats were detected within intron I. Northern blot analysis showed that at least four main transcripts were generated along this region: all fetal tissues tested (brain, lung, liver, and kidney) produced a 1.8-kb homeobox-containing transcript (HA-9A); a 2.2- and a 3.3-kb transcript were generated from exon CD and exon II (HA-9B), especially in fetal and adult kidneys as well as in adult skeletal muscle; the 1.0-kb transcript was likely to be generated by the intermediate exon in all adult and fetal tissues. Several weak bands without tissue specificity were likely to be contributed by the hybrid transcripts between HOXA-9 and the other HOXA gene(s). Together, these results may account for the unique degree of conservation of the HOX cluster in general.

Adult↗

The correlation between skin electrical conductance and the score of qi vacuity.

In traditional Chinese medicine, the syndrome of qi vacuity means that the patient's body has a low level of energy to react to stress. Recently, we used a score, the QV score, by scaling the severity of symptoms and signs of qi vacuity in patients with tiredness. The aim of this study was to investigate the relationship between QV score and skin electrical conductance in patients with tiredness. One hundred and forty-three healthy controls and 103 patients with tiredness were involved. Each subject received a weak electrical stimulation with constant voltage (1.75 volt), and conductance was measured between two different limbs. The mean value of skin conductance among four limbs was calculated and expressed by a special unit, namely Chin. The correlation between the skin conductance and QV score was analyzed by a linear regression analysis. The results showed that skin electrical conductance of healthy controls was negatively correlated with age (r-coefficient = -0.51, P = 0.000). The skin conductance of patients with tiredness was significantly lower than that of healthy controls with matching age (P = 0.000 by Student's t-test). Moreover, there was a positive correlation between the decrease of skin conductance and the QV score in patients with tiredness (r-coefficient = +0.68, P = 0.000). These results suggest that a decrease in skin electrical conductance may be closely related to the severity of qi vacuity. The skin conductance test is a simple, reliable, and quantitative method for detection of syndrome of qi vacuity.

Adult↗

Effects of gamma-radiation on ovarian follicles.

In order to observe the morphological and endocrinological changes of the rat and mouse ovarian follicles by gamma-radiation, rats were whole-body irradiated with doses of 3.2 Gy and 8.0 Gy and mice with 2.9 Gy and 7.2 Gy. Sections of ovaria were examined by light microscopy. Concentrations of progesterone, testosterone, and estradiol in ovarian homogenate were determined by radioimmunoassay techniques. Gamma-radiation resulted in the increased percentage of atretic follicles in the groups killed on day 0, day 4, and day 8 after irradiation. The decrease in granulosa cell viability was found in animals killed on day 4 after irradiation. The finding of the high ratio of testosterone to estradiol compared to that of progesterone to testosterone suggests that aromatase activity--steroid biosynthesis from testosterone to estradiol--in granulosa cell could be affected by gamma-radiation.

Animals↗

Glutathione S-transferase-rhodostomin fusion protein inhibits platelet aggregation and induces platelet shape change.

Rhodostomin (RHO) from Agkistrodon rhodostoma venom, consisting of 68 amino acids with an arginine-glycine-aspartic acid (RGD) sequence and 12 cysteine residues, is a potent inhibitor of platelet aggregation. We previously demonstrated that cell culture plates coated with the bacterially produced fusion protein of glutathione S-transferase-RHO [GST-RHO(RGD)] can facilitate human hepatoma cell attachment via intergrin interaction within 15 min. In this study, we further characterized the effect of RHO fusion protein on platelet cells by creating two other related fusion proteins, GST-RHO(RGE) and GST-(PS)RHO. The former was a single amino acid-substituted mutant, in which the aspartic acid residue of RGD was replaced by glutamic acid, and the latter was an insertion mutant, in which a pentapeptide of protein kinase A phosphorylation site was inserted between GST and RHO. These two mutant proteins together with a wild-type of GST-RHO(RGD) and native form of RHO were used to study effects on the inhibition of ADP-induced platelet aggregation. Results indicated that GST-RHO(RGD) inhibited platelet aggregation as potently as the native RHO, while the two other mutants were inactive. Furthermore, when unactivated platelet cells attached on the GST-RHO(RGD)-coated plate, they became a flattened pancake shape. From the results of facilitation of cell attachment on fusion protein-coated plates, we concluded that: (1) the GST-RHO(RGD) fusion protein is equally functional in inhibition of platelet aggregation and facilitation of cell attachment, which is through the interaction of RGD and integrins on the cell membrane; (2) the GST-RHO(RGE) mutant protein is unable to bind with integrins and results in loss of function; (3) the insertion mutant of GST-(PS)RHO may disrupt a proper conformation of RHO and also results in loss of function; (4) the bacterially produced fusion protein GST-RHO(RGD) can be properly used as an antithrombotic agent and an extracellular matrix.

Animals↗

Transient bradycardia in a mouse model for the oromandibulofacial limb hypogenesis syndrome following chorionic villus sampling.

Amniotic sac puncture carried out on day 13 mouse embryos induces a high incidence of craniofacial and limb abnormalities that resemble the anomalies seen in the oromandibulofacial limb hypogenesis syndrome occasionally encountered following chorionic villus sampling carried out during early human pregnancy. It has been hypothesized that this syndrome probably has a vascular basis, possibly due to hypotension and hypoperfusion of tissues secondary to placental trauma, though no detailed aetiology has so far been described. We have determined embryonic heart rates in control embryos, in embryos at intervals following anaesthesia, and following amniotic sac puncture. An increased duration of bradycardia is seen following this procedure which is not observed in anaesthetic-only controls and in embryos in the contralateral (non-operated) uterine horns. We discuss why the incidence of oromandibulofacial limb hypogenesis syndrome is low following chorionic villus sampling, and propose a possible aetiology for the limb abnormalities seen in this condition.

Abnormalities, Multiple↗

Sequence and functional analysis of an upstream regulatory region of human HOXA7 gene.

The Hox genes have been known to be involved in pattern formation during vertebrate development through differential expression along the anteroposterior body axis. Human homologue of position-specific regulatory region of murine Hoxa-7 was cloned from human genomic library. The restriction map of the 18-kb insert was determined, of which a 3.9-kb region was sequenced. Homology plot between the murine and the corresponding human sequence showed high sequence conservation over 70% in several regions. The homologous region has been reduced to about 1.1 kb (HCR: human control region), which contained several putative factor binding sites. The function of HCR was analyzed in transgenic mice and turned out to be a position-specific regulatory element of human, setting the precise anterior boundary of expression in transgenic embryos; at day 12.5 post-coitum a distinct anterior limit of expression was noted at the level of C5 in neural tube and spinal ganglia in transgenic embryos. These results indicate that the regulatory sequences as well as the molecular mechanism for Hox gene expression are highly conserved among vertebrates.

Animals↗

Limb and other postcranial skeletal defects induced by amniotic sac puncture in the mouse.

A mouse model for studying the teratogenic effects of amniotic sac puncture has recently been established (MacIntyre et al. 1995), and the anomalies encountered included cleft palate, limb and tail abnormalities, and postural deformities. In order to investigate the underlying mechanism(s) involved, mouse embryos subjected to amniotic sac puncture on day 13 of gestation were examined externally on day 19, then 'cleared' and bulk stained with alizarin red S and Alcian blue to reveal, respectively, their bony and cartilaginous elements. This procedure allowed a comparison to be made between the incidence of soft tissue anomalies of the distal parts of the limbs and the appearance of the underlying skeletal elements. Despite a high incidence of soft tissue (principally digital) anomalies, relatively few skeletal anomalies were encountered. Measurements of intact long bones, and regions of ossification, were made in the major long bones of 'nonexperimental' and 'internal' controls and 'experimental' fetuses that displayed external morphological malformations to establish whether the experimental procedure had a greater effect on the proximal or distal components of the limb skeleton. No significant difference was observed when the ratios of proximal: distal length were compared with those obtained from the control series. The degree of severity of 'clubhand' and 'clubfoot' deformity was determined, and a comparison made between the severity observed on the right and left sides. This analysis revealed that for 'clubhand', the left forelimb was more severely affected than the right forelimb. The incidence of 'clubfoot' deformity was similar between the 2 sides. A possible explanation for this asymmetric effect is provided. An unexpected finding was the abnormal pattern of ossification seen in the sternum of two thirds of the 'experimental' fetuses that displayed external morphological malformations. This abnormal pattern was seen in none of the controls nor in fetuses in the 'experimental' series that displayed no external morphological malformations.

Amnion↗

Treatment of obsessive-compulsive symptoms in schizophrenic patients with clomipramine.

Recent studies show that obsessive-compulsive symptoms may occur in many patients with schizophrenia and may predict a poor prognosis. Pilot studies have shown that some schizophrenic patients may improve if a serotonin reuptake blocker is added to their neuroleptic. We have performed a pilot, double-blind, crossover study of clomipramine (CMI) or placebo, added to maintenance psychotropic medication. Six schizophrenic patients with obsessive-compulsive symptoms were studied in a double-blind CMI versus placebo crossover protocol. The patients met DSM-III-R criteria for chronic schizophrenia, experienced obsessive-compulsive symptoms, and had been previously stabilized on their psychiatric medication. The patients were rated at baseline and longitudinally through the study with the Positive and Negative Symptom Scale for Schizophrenia (PANSS) and the Yale Brown Obsessive-Compulsive Scale (YBOCS). An analysis of covariance was used to compare the drug versus placebo effect at the final visit with the baseline rating as a covariate. Ratings on both the YBOCS and the PANSS showed that patients improved significantly more on CMI than on placebo. No patients experienced an exacerbation of psychotic symptoms. Preliminary findings from this double-blind, crossover, pilot study of CMI and placebo, designed to assess the effect of CMI in the treatment of schizophrenic patients with obsessive symptoms, suggest that CMI is superior to placebo in the treatment of obsessions and compulsions and improves overall schizophrenic symptoms. Further studies with larger samples and longer follow-up period are necessary to confirm these preliminary findings.

Adult↗

Elevated ras p21 expression in oral premalignant lesions and squamous cell carcinoma in Taiwan.

Expression of ras p21 oncoproteins was examined in histological sections of oral squamous cell carcinoma (SCC), epithelial dysplasia, epithelial hyperkeratosis and normal oral mucosa using antibodies to ras p21 with an immunoperoxidase technique. Ras p21-positive staining was found in 47 of 51 (92.2%) cases of oral SCC, 4 of 4 (100%) cases of epithelial dysplasia, 7 of 7 (100%) cases of epithelial hyperkeratosis, and 1 of 6 (16.7%) cases of normal oral mucosa. The positive staining rate of ras p21 in oral SCC, epithelial dysplasia or epithelial hyperkeratosis was significantly higher than that in normal oral mucosa (P < 0.05). No correlation was found between ras p21 expression and patient age, tumour location, tumour size, clinical staging or histological differentiation of SCC. However, a significant positive correlation was found between ras p21 expression and patients' sex (P < 0.05) or regional lymph node status (P < 0.05). A significant positive correlation was also discovered between ras p21 expression and patients' smoking habits (P < 0.01), as well as daily or total betel quid (BQ) consumption (P < 0.05). Of the 47 immunostain-positive SCC patients, specimens from 6 patients were also obtained after chemotherapy, when ras p21 expression was found to be reduced. These results indicate that ras p21 overexpression may play an important role in the initiation and progression of oral SCCs in patients who are smokers and BQ chewers.

Adult↗

Estimating the costs of substance abuse to the Medicaid hospital care program.

OBJECTIVES: The purpose of this study was to develop a model, using the epidemiologic tool of attributable risk, for estimating the cost of substance abuse to Medicaid. METHODS: Based on prior substance-use and morbidity research, population attributable risks for substance abuse-related diseases were calculated. (These risks measure the proportion of total disease cases attributable to smoking, drinking, and drug use.) The risks for each disease were applied to Medicaid hospital discharges and days on the 1991 National Hospital Discharge Survey that had these diseases as primary diagnoses. The cost of these substance abuse-related days were added to Medicaid hospital costs for direct treatment of substance abuse. RESULTS: More than 60 medical conditions involving 1100 diagnoses were identified, at least in part, as attributable to substance abuse. Factoring these substance abuse-related conditions into hospital costs, 1 out of 5 Medicaid hospital days, or 4 million days, were spent on substance abuse-related care in 1991. In 1994, this would account for almost $8 billion in Medicaid expenditures. CONCLUSIONS: The use of tobacco, alcohol, and drugs contributes significantly to hospital costs. To address rising costs, substance abuse treatment and prevention should be an integral part of any health care reform effort.

Alcoholism↗

Teratogenic effects of amniotic sac puncture: a mouse model.

The possibility of an association between chorionic villus sampling (cvs) and limb abnormalities has prompted a review of the relevant experimental data. Although a vascular aetiology is favoured by many at present, the possibility exists that a proportion of cases may be caused by oligohydramnios secondary to inadvertent amniotic sac puncture. A mouse model of amniotic puncture syndrome has been developed to study the craniofacial and limb abnormalities produced by this procedure. Pregnant mice were anaesthetised and a laparotomy performed. One uterine horn was exteriorised, and the amniotic sacs punctured through the wall of the uterus with either a 21 gauge or a 25 gauge needle. The conceptuses in the contralateral uterine horn acted as controls. The mice were all killed on d 19 of pregnancy (day of finding a vaginal plug = d 1 of pregnancy) by cervical dislocation, and the morphological features of the embryos examined in detail. In a preliminary study, amniotic sac puncture was carried out on d 12, 13, 14, 15 or 16 of pregnancy, with either a 21 or a 25 gauge needle. Since the highest rates of palatal defects and limb deformities were observed following amniotic sac puncture using a 21 gauge needle, when this procedure was carried out on either d 13 or 14 of pregnancy, the main study was undertaken using a 21 gauge needle on these two days of pregnancy. Of 102 embryos in which amniotic sac puncture was carried out on d 13, 53% survived to d 19. Of the latter, 35% had a cleft palate, 61% had one or more morphologically abnormal limbs, and 43% had an abnormal tail. When amniotic sac puncture was carried out on d 14 of pregnancy, of 83 embryos subjected to this procedure, 81% survived to d 19. Of the latter, 27% had a cleft palate, 39% had one or more morphologically abnormal limbs, and 19% had an abnormal tail. In the controls, of 86 and 61 embryos isolated respectively from the d 13 and 14 mice, the survival rates were 97 and 90%, respectively. Palatal, limb and tail abnormalities were not observed in the control series. Tentative relationships are drawn between cvs and amniocentesis-associated abnormalities, the Robin sequence and their rodent phenocopies.

Amnion↗

Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice.

The Small eye (Sey) gene in the mouse is lethal in the homozygous state. It is located on chromosome 2, is a mutation in the Pax-6 gene, and is genetically homologous with the human aniridia 2 (AN2) gene mutation. Numerous studies over the last few years, using genetic and molecular biological approaches, have investigated both the location of the gene as well as its possible mode of action. In the homozygous state, the primary defect appears to be limited to the failure of differentiation of the presumptive lens and nasal placodes. Such mice therefore display a characteristic phenotype; they possess neither eyes nor any nasal derivatives. Their heterozygous (Sey/+) and normal (+/+) littermates may be distinguished before birth only by a detailed examination of their eyes. Few detailed morphological/histological studies have been undertaken to date in the Sey/Sey embryos and newborn, and in the present study we describe a variety of craniofacial abnormalities that have not previously been reported. We observed, with one exception, delayed closure of the palate, and the presence in 80% of mice of an abnormal complement of upper incisor teeth, so that 35% possessed 1 supernumerary tooth while 45% possessed 2 supernumerary teeth. In these mice, a total of either 3 or 4, rather than the normal complement of 2, upper incisor teeth were present. Possibly the most unexpected finding, however, was the presence of a median cartilaginous rod-like structure which protruded between the 2 maxillae to give the Alizarin red S and Alcian blue-stained 'cleared' skulls of the newborn mice a characteristic 'unicorn-like' appearance. While this structure appeared to be a rostral extension of the chondrocranium, its exact derivation is unclear.

Animals↗