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Biomedical subjects

Y Huang

Publications and source records attributed to Y Huang.

At least 847 records · Page 47Linked to original sources
PubMed1996

Antenatal screening and fetal diagnosis of beta-thalassemia in a Chinese population: prevalence of the beta-thalassemia trait in the Guangzhou area of China.

In this paper beta-globin gene mutations were detected in 452 beta-thalassemia carriers from 13462 unselected individuals (6731 pregnant women and their husbands) who were screened for the beta-thalassemia trait in the Guangzhou area of China. The incidence of beta-thalassemia was calculated as 3.36%. This is higher than found in previous studies performed in southern China. Using reverse dot blot analysis, we found 11 types of mutations and identified the mutations in 446 (98.7%) of the 452 cases. Direct sequencing was carried out on the 6 unknown alleles, and a novel amber mutation in a beta 0-thalassemia gene (beta 37TGG --> TAG) was found in one of them. Thus, the prevalence and spectrum of beta-thalassemia mutations were obtained for this region. Twelve couples were detected at risk for thalassemia, and prenatal diagnosis was carried out in 11 of them. This is the largest number of Chinese subjects studied by DNA analysis to date and is the first report on the prospective diagnostic trial for beta-thalassemia in a Chinese population. In addition, we have performed 80 prenatal diagnoses based on screening for beta-thalassemia retrospectively.

Amino Acid Sequence↗
PubMed1996

Differential expression of the EF-hand calcium-binding protein calsensin in the central nervous system of hirudinid leeches.

By immunocytochemistry the distribution and developmental expression of the small EF-hand calcium-binding protein calsensin in the peripheral (PNS) and central nervous system (CNS) of the three hirudinid leech species Haemopis, Hirudo, and Macrobdella was compared. Labeling with calsensin-specific antibodies demonstrated that there was a pronounced difference in the distribution of calsensin immunoreactivity in the CNS of these leeches. In Haemopis more than 70 neurons were labeled, whereas the number in Hirudo was 51 and in Macrobdella only 8. Furthermore, the expression of calsensin in identified cells common to all three leech species also differed. Immunoblot analysis indicated that this variability was not likely to be due to multiple proteins or isoforms being recognized by the calsensin antibody. Labeling of embryos in various stages of development shows that the ontogeny of calsensin expression in the CNS is a gradual process with some neurons expressing calsensin immediately after completion of neurogenesis, about one-third of the way through embryogenesis, and others expressing calsensin only postembryonically. In contrast to the variability in the pattern and temporal expression by CNS neurons, the early embryonic calsensin expression in a small subgroup of sensillar PNS neurons was a shared feature by all three leech species. These findings suggest that calsensin may have different functional properties in CNS and PNS neurons.

Animals↗
PubMed1996

High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport.

The incidence of coronary heart disease (CHD) was assessed via the Prospective Cardiovascular Münster (PROCAM) study in 19,698 volunteer subjects aged between 16 and 65 years. An adequate incidence of atherosclerotic CHD was only found in male subjects greater than 40 years of age. The analysis and subsequent 6 year follow-up period was, therefore, confined to 4559 male participants aged 40-64 years. In the follow-up period, 186 study participants developed atherosclerotic CHD (134 definite non-fatal myocardial infarctions (MIs) and 52 definite atherosclerotic CHD deaths including 21 sudden cardiac deaths and 31 fatal MIs). Univariate analysis revealed a significant association between the incidence of atherosclerotic CHD and high-density lipoprotein cholesterol (P < 0.001), which remained after adjustment for other risk factors.

Adolescent↗
PubMed1996

Modulation of the baroreceptor reflex by stimulation of the hypothalamic defense and vigilance areas.

Electrical stimulation of the hypothalamic defense area (HDA) elicits a pressor/tachycardia response that is believed to prepare an animal for fight or flight. In contrast, electrical stimulation of the hypothalamic vigilance area (HVA) evokes a pressor/bradycardia response that is associated with the inhibition of movement. The differences in the behavioral components of these two affective response patterns suggest differential modulation of the baroreceptor reflex. The present study tested this idea by assessing the effects of electrical stimulation of the HDA and the HVA upon the bradycardia/depressor response elicited by stimulation of the aortic nerve (AN) in rabbits. Concurrent HDA and AN stimulation was observed to attenuate the AN-elicited bradycardia but enhanced the depressor response elicited by AN stimulation. In contrast, concurrent stimulation of the HVA and AN enhanced the bradycardia elicited by AN stimulation but reduced the magnitude of the AN-elicited depressor response. These results provide evidence for differential modulation of the baroreceptor reflex during the defense and vigilance reactions.

Aggression↗
PubMed1996

Amylin mobilizes [Ca2+]i and stimulates the release of pancreatic digestive enzymes from rat acinar AR42J cells: evidence for an exclusive receptor system of amylin.

Amylin dose-dependently stimulated the secretion of amylase and cholesterol esterase from rat pancreatic acinar AR42J cells. The biochemical basis of this action was investigated using fura-2-loaded AR42J cells. Amylin increased intracellular free calcium. [Ca2+]i, in a dose-dependent manner. The Ca2+ signal persisted even in Ca(2+)-free medium, suggesting mobilization from intracellular stores rather than influx. Consistently, thapsigargin abolished amylin-induced responses, suggesting that Ca2+ is released from an inositol 1,4,5-triphosphate (IP3)-sensitive pool. This was confirmed by the finding that amylin elevated IP3 levels. AR42J cells pretreated with amylin did not respond to amylin, suggesting that the receptors mediating this response undergo homologous desensitization. However, pretreatment with related peptides, calcitonin gene-related peptide (CGRP) and salmon calcitonin, did not diminish [Ca2+]i mobilization by amylin. CGRP and calcitonin also failed to mobilize [Ca2+]i even at 10 microM. These results suggests that the stimulatory effects of amylin on pancreatic digestive enzyme secretion from AR42J cells are mediated by a G-protein-linked membrane receptor coupled to IP3-dependent calcium pools.

Amylases↗
PubMed1996

Anti-inflammatory and analgesic activities of 3-imino-1-oxoisoindolines in CF1 mice.

A series of 3-imino-1-oxoisoindolines were shown to be potent anti-inflammatory and analgesic agents at 8 mg/kg, intraperitoneally in mice. The compounds were also able to protect against lipopolysaccharide induced endotoxic shock and death better than the current clinical agents. These agents appear to function by blocking the release of TNF alpha and IL-1 from macrophages as well as competition with their respective high affinity receptors on target tissue, eg. fibroblasts, and macrophages. In addition lysosomal hydrolytic enzymes were inhibited as well as leukotriene synthesis in macrophages by the agents.

Animals↗
PubMed1996

The oxygen-binding intermediates of human hemoglobin: evaluation of their contributions to cooperativity using zinc-containing hybrids.

Hemoglobin tetramers [Zn/FeO(2)] containing oxygenated subunits (FeO(2)), in combination with unligated subunits containing zinc-substituted hemes (Zn), were analyzed to determine their contributions to the cooperativity of oxygen binding at the Fe sites. Energetic consequences of possible perturbation by zinc substitution were evaluated in all combinations of unligated Zn/Fe hybrid tetramers. A general thermodynamic strategy that corrects for the energetic effects of substituting a second metal for Fe showed the perturbations of Zn substitution to be negligible. This permitted cooperativity parameters of the native Fe/FeO(2) intermediates to be calculated from data on the corresponding Zn/FeO(2) molecules. These parameters, determined explicitly for all eight oxygen-binding intermediates (Fe/FeO(2)), were found to be identical to those predicted earlier from analyzing the O(2) binding data of normal hemoglobin according to the "molecular code" of hemoglobin allostery. The cooperativity parameters determined for this system showed the same distribution pattern found previously for five other oxygen analog systems (Fe/FeCN, FE/Mn(3+), Co/FECO, Co/FeCN, and Fe/FeCO).

Dimerization↗
PubMed1996

Heterotropic effects of chloride on the ligation microstates of hemoglobin at constant water activity.

Dimer-tetramer assembly reactions of the 10 CN-met ligation microstates of hemoglobin (Hb) were analyzed as a function of NaCl concentration while maintaining constant water activity by the addition of compensating sucrose. The assembly free energy for fully ligated cyanomet Hb and for fully oxygenated Hb becomes less favorable by 1.8 kcal when [NaCl] is increased from 0.08 to 0.7 M, whereas that of unligated Hb is practically insensitive to changes in [NaCl]. Values of 1.6 and 0.3 mol chloride release were found for the assembly of fully ligated and deoxy Hb, respectively; i.e., a net release of 1.3 mol chloride is coupled to the ligation of tetramers for both oxygen and cyanomet ligation. The ligation-linked salt component at constant water activity was evaluated to be 1.0 mol for the full oxygenation of the Hb tetramer in agreement with the overall value previously reported. When the detailed salt linkages accompanying all 16 stepwise cyanomet ligation reactions were experimentally resolved, only two "chloride" effects were found. The first chloride effect correlates with the ligation steps, which create tertiary constraint, and the second effect is coupled to the six switchpoints of quaternary T-->R transition. The distribution of these chloride effects agrees closely with predictions of the "symmetry rule mechanism." The total chloride release for CN-met ligation is in good agreement with that for oxygenation. Free energy contributions to assembly and cooperativity arising from the osmotic effects of chloride were found to be small for all ligation species.

Allosteric Regulation↗
PubMed1996

Behavioral characteristics of defense and vigilance reactions elicited by electrical stimulation of the hypothalamus in rabbits.

An automated tracking system was used to assess the behavioral changes elicited by electrical stimulation of the hypothalamic sites that yield the cardiorespiratory components of defense reaction and vigilance reaction in rabbits. Electrical stimulation of the hypothalamic defense area (HDA) at intensities near threshold led to cessation of body movements coupled with head movements suggesting increased attention to the environment. HDA stimulation at higher intensities evoked agitated running and hindlimb thumping; the amount of running was proportional to stimulus intensity. Electrical stimulation of the hypothalamic vigilance area (HVA) at intensities near threshold elicited orienting behaviors that were similar to those elicited by stimulating the HDA at low suprathreshold current intensities. Stimulation of the hypothalamic vigilance area (HVA) at higher intensities elicited phasic immobility, increased extensor muscle tension, and head tremor. The behavioral changes elicited by HDA and HVA stimulation were accompanied by pupil dilation and exophthalmos.

Aggression↗
PubMed1996

Synthesis, structure, and antagonistic properties of des-Asn29[D-Trp28,32]NPY(27-36).

We have previously reported that [D-Trp32]NPY and its centrally truncated analogues such as des-AA7-24[D-Trp5,32,Aoc6]NPY can competitively antagonize NPY effects on rat hypothalamus and Y1 (SK-N-MC AND HEL) cells, respectively. In continuation of this work, we performed structure-activity studies with C-terminal decapeptide sequence keeping D-Trp at position 32 to develop lower molecular weight Y1-selective antagonists. This study led to the development of des-Asn29[D-Trp28,32]NPY(27-36), which bound to both Y1 (SK-N-MC, Ki > or = 10 microM) and Y2 (SK-N-BE2, Ki = 1.01 +/- 0.03 microM) receptors. This peptide did not exhibit any agonist activity at Y1 receptors, and exhibited comparable potencies in antagonizing the effects of NPY on the synthesis of cAMP and mobilization of [Ca2+]i in HEL cells. However, in SK-N-MC cells, it was more potent in antagonizing the mobilization of [Ca2+]i than inhibition of cAMP synthesis. Substitution of Nva for Gln34 to increase the hydrophobicity without altering the carbon skeleton substantially increased Y1 affinity (Ki = 0.33 +/- 0.15 microM) and imparted Y1 selectivity (Ki for Y2 affinity = 3.16 +/- 0.50). Moreover, this peptide exhibited good antagonistic potency in HEL cells. 2D NMR studies of des-Asn29[D-Trp28,32]NPY(27-36) revealed the existence of a fairly stable loop-like structure between residues 27 and 32 and a less stable one between residues 32 and 36. The increased Y1 affinity of des-Asn29[D-Trp28,32,Nva34]NPY(27-36) may be due to the stabilization of the 32-36 loop by Nva34. It appears therefore that stabilization of the loop structures in these peptides should result in the development of more potent Y1 receptor antagonists. Our investigations also suggest that HEL cells express a homogeneous population of NPY Y1 receptors whereas SK-N-MC cells express high- and low-affinity Y1 receptors coupled to Ca2+ and cAMP, respectively.

Animals↗
PubMed1996

Aggressive versus conventional strategies in the treatment of rectal adenocarcinoma.

OBJECTIVE: Comparison of an aggressive approach (including total mesorectal excision and combined modality adjuvant therapy) with a conventional approach in the treatment of primary rectal cancer. DESIGN: Retrospective study. SETTING: Memorial Sloan-Kettering Cancer Centre, New York (MSKCC) and University Hospital Leiden, the Netherlands (UHL). SUBJECTS: One hundred and sixty-nine patients treated at MSKCC and 96 patients treated at UHL. INTERVENTIONS: Total mesorectal excision (MSKCC) and conventional resection (UHL). MAIN OUTCOME MEASURES: Overall survival and local recurrence-free survival. RESULTS: Five-year overall survival was 73% for MSKCC patients and 52% for UHL patients (P < 0.001). Five-year local recurrence-free survival was 83% for MSKCC patients and 72% for UHL patients (P=0.001). Relative risk of dying or developing a local recurrence was 3.37 and 2.61, respectively, for patients treated at UHL compared to patients treated at MSKCC (P<0.001 and P=0.008, respectively). CONCLUSIONS: These data suggest that an aggressive approach including total mesorectal excision and combined modality adjuvant therapy improves survival and local control compared to a conventional approach.

Adenocarcinoma↗
PubMed1996

The role of a mutant CCR5 allele in HIV-1 transmission and disease progression.

A 32-nucleotide deletion (delta 32) within the beta-chemokine receptor 5 (CCR5) gene has been described in subjects who remain uninfected despite extensive exposure to HIV-1. This allele was found to be common in the Caucasian population with a frequency of 0.0808, but was not found in people of African or Asian ancestry. To determine its role in HIV-1 transmission and disease progression, we analyzed the CCRS genotype of 1252 homosexual men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS). No infected participant was found to be homozygous for the delta 32 allele, whereas 3.6% of at-risk but uninfected Caucasian participants were homozygous, showing the highly protective role of this genotype against sexual acquisition of HIV-1. No evidence was found to suggest that heterozygotes were protected against HIV-1 infection, but a limited protective role against disease progression was noted. The delta 32 allele of CCR5 is therefore an important host factor in HIV-1 transmission and pathogenesis.

Alleles↗
PubMed1996

Modulation of multidrug resistance gene (mdr-1) with antisense oligodeoxynucleotides.

1. Multidrug resistance is the major obstacle to successful cancer chemotherapy. Circumventing multidrug resistance therefore represents a high priority for clinical anti-cancer treatment. Among many reversal strategies, antisense oligodeoxynucleotides may offer a molecular targeting tool for overcoming cellular multidrug resistance. 2. Two 17-mer phosphorothioate antisense oligomers, complementary to the 5' end of the ATG initiator codon-containing region and loop-forming site (located at nucleotides 991-1007 from the first ATG codon) in mdr-1 cDNA sequence, were synthesized. The purpose was to study their effects on the function and expression of P-glycoprotein and mdr-1 gene. 3. The results showed that 10 mumol/l antisense oligomers could significantly inhibit the growth of multidrug resistant K562/Adm cells cultured in adriamycin-containing medium. No such effect was observed for parental (sensitive) K562/S cells. Intracellular daunorubicin accumulation increased greatly in the K562/Adm cells after they were treated with oligomers for 48 h and P-glycoprotein synthesis was strikingly reduced. 4. Further investigation with [alpha-32P]dCTP incorporation by the reverse transcriptase-polymerase chain reaction method revealed that antisense oligomers could result in a reduction in the level of mdr-1 mRNA, probably through hindering mdr-1 gene transcription. 5. The high reversal efficiency and specificity of antisense oligomers in regulating mdr-1 gene expression suggest a potential clinical application in gene therapy for drug resistant malignancies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Antineoplastic activities of 2,3,4-chloro-substituted beta-alkylaminopropiophenone derivatives in CF1 mice and in murine and human tumor cells.

A series of beta-alkylaminopropiophenone derivatives were demonstrated to be potent antineoplastic agents. Several compounds showed activity against Ehrlich ascites carcinoma growth in CF1 mice by demonstrating over 70% inhibition. Most of these agents proved to be potent cytotoxic agents in inhibiting the growth of a number of murine and human cancer cell lines grown in tissue culture. Their ED50 values were comparable to those of the selected standard anticancer drugs, such as 6-MP, ara-C, hydroxyurea, 5-FU, 6-aza-UMP, etoposide, antimycin A, actinomycin D and cycloheximide. In the mode of action studies in Tmolt3 cells, beta-(3",5"-dimethyl)piperidinopropiophenone was observed to reduce DNA and RNA synthesis significantly at 25 microM within 60 min incubation. The site of action of this agent appears to involve the reduction of the activities of Tmolt3 DNA polymerase alpha 1 dihydrofolate reductase, PRPP-amido transferase and ribonucleoside reductase.

Animals↗
PubMed1996

A histochemical and x-ray diffraction study of keratoconus epikeratoplasty. Report of two cases.

Two epikeratoplasty lenticules (Epi-L) with keratoconus host corneas (Epi-H) were removed by penetrating keratoplasty because of poor visual acuity although they were clinically clear. Light microscopy showed that the keratocytes were underpopulated and unevenly distributed in Epi-L. Transmission electron microscopy showed that abnormal sized proteoglycans (PGs) were unevenly accumulated in the stromas of both Epi-L and Epi-H. The low-angle x-ray diffraction results from case 1 showed lower collagen interfibrillar spacings, compared with those from one keratoconus cornea, seven cryolenticules, and four normal human corneas. The fibril diameters and the collagen axial periodicity D were similar in all tissues. Allowing selected samples to swell, the interfibrillar spacing increased by 30.6-45.5% in Epi-H and by 29.8% in the keratoconus control. However, it increased by only 7.6-9.7% in Epi-L and by 11.4% in a cryolenticule. The uneven distribution of PGs and the lower interfibrillar spacings in the swollen lenticules suggest that there is an uneven distribution of water in different parts of the Epi-L and Epi-H stromas. This may lead to a variation of the refractive index or optical properties in the stroma and the deterioration of the visual image, which may explain the poor visual results.

Adult↗
PubMed1996

Inhibitory effect of noradrenaline uptake inhibitors on contractions of rat aortic smooth muscle.

1 The effects of noradrenaline (NA) uptake inhibitors on contractions induced by NA, high K+, and 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat isolated aorta were investigated. 2 Protriptyline (0.3 microM) and amitriptyline (0.3 microM) produced an approximately parallel shift to the right in the dose-response curve to NA. Protriptyline (> 0.3 microM), amitriptyline (> 0.3 microM) and xylamine (0.01-1 microM) significantly reduced the maximal contractile response to NA. The IC50 values for inhibition of the contractile response to 3 microM NA were 1.58 microM for xylamine, 1.70 microM for amitriptyline and 2.57 microM for protriptyline. 3 Protriptyline and amitriptyline dose-dependently inhibited the high K+ (60 mM)-induced contraction (IC50 = 0.69 microM for protriptyline and IC50 = 3.15 microM for amitriptyline). In contrast, xylamine did not affect the high K(+)-induced contraction. 4 Protriptyline and amitriptyline dose-dependently inhibited TPA (1 microM)-induced contraction in calcium-free solution; xylamine (up to 30 microM) was without effect. Staurosporine (10 nM) completely inhibited the TPA- and NA-induced contraction. 5. Protriptyline (3 microM) and amitriptyline (3 microM) caused about 54% and 60% inhibition, respectively, of aortic contractions caused by endothelin-1 (10 nM) in the absence of endothelium. Xylamine (10 microM) was without effect. 6 Inhibitory effects of NA uptake inhibitors on contractions were independent of the presence of endothelium and were unaffected by the K+ channel blockers, tetraethylammonium ions (up to 3 mM) and glibenclamide (up to 30 microM). 7 These results indicate that tricyclic antidepressant drugs such as protriptyline and amitriptyline could act as both postsynaptic adrenoceptor antagonists and direct inhibitors of muscle contraction; whereas, xylamine, a structurally distinct NA uptake blocker might principally exert its action only at alpha-adrenoceptors on rat aortic smooth muscle.

Adrenergic Uptake Inhibitors↗
PubMed1996

A pilot evaluation of the EMBU Scale in Japan and the USA.

Cultural differences in parental attitudes and child-rearing practices among European countries have been demonstrated in previous studies using a scale for assessment of memories of upbringing (the EMBU). In this pilot study we evaluated the EMBU in two previously unstudied populations: a culturally homogeneous sample from Japan (n = 105) and a culturally mixed sample from Southern California (n = 73). The results suggest that, compared to European parents, Japanese parents are more emotionally distant from their children, while the Southern Californians as a group scored similarly to the Europeans. Further studies are needed in order to establish the EMBU as a transcultural tool for assessment of parental rearing behaviour.

Adolescent↗