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Biomedical subjects

H M Wu

Publications and source records attributed to H M Wu.

At least 37 records · Page 2Linked to original sources

Early recognition of cerebral hyperperfusion syndrome after carotid stenting--a case report.

The hyperperfusion syndrome is a recognized complication of carotid endarterectomy. Reports of cerebral hyperperfusion injury following internal carotid artery angioplasty and stenting are few We report a case of 76-year-old hypertensive man who was admitted to our hospital for assessment 2 years after experiencing an ischemic stroke of right hemisphere. Angiography confirmed 60% stenosis of left internal carotid artery (ICA). Percutaneous transluminal stenting of left internal carotid artery was performed without any immediate complications. Two hours after the procedure, the patient suddenly deteriorated. Computed tomography (CT) of the brain revealed extensive intracerebral hemorrhage and he died 5 days later. There was precipitating migranous headache, and his blood pressure was moderately elevated at the time of deterioration. Sentinel headache could solely indicate the early sign of hyperperfusion injury after carotid stenting, especially in the presence of arterial hypertension. Patients with sentinel headache after angioplasty should be recognized early and they deserve intensive study for other features of cerebral hyperperfusion injury and prompt early management.

Acetazolamide↗

Alkaloid-fullerene systems through photocycloaddition reactions.

The photocycloaddition of tertiary amines to ¿60fullerene (C(60)) is an interesting and useful reaction. We wished to extend the applications of this type of reaction through an investigation of the photoaddition of alkaloids to C(60) for the purpose of synthesizing novel and complex photoadducts that are difficult to obtain by usual methods. Irradiation of tazettine (2) or gramine (3) with C(60) in toluene leads to formation of one monoadduct (6 or 7), whereas scandine (1a) or 10-hydroxyscandine (1b) reacts with C(60) photochemically to give two products, the expected ¿6,6 monoadduct (5a, 5b) and a new type of monoadduct with a bis-¿6, 6 closed structure (4a, 4b). These new structures were characterized by UV-vis, FT-IR, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, ROESY, HMQC (heteronuclear multiple-quantum coherence), and HMBC (heteronuclear multiple-bond connectivity) spectroscopy. The techniques of time-of-flight secondary ion MS (TOF-SIMS) and field desorption MS (FD-MS) were used for the mass determination. (3)He NMR analysis of the product mixture from photoaddition of 1a to C(60) containing a (3)He atom ((3)He@C(60)) led to two peaks at -9.091 and -11.090 ppm relative to gaseous (3)He, consistent with formation of a ¿6, 6-closed monoadduct and a bis-¿6,6 closed adduct. Presumably, the bis-¿6, 6 closed adducts are formed by an intramolecular ¿2 + 2 cycloaddition of the vinyl group to the adjacent 6,6-ring junction of C(60) after the initial photocycloaddition.

Alkaloids↗

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Aged↗

High-pressure and stark hole-burning studies of chlorosome antennas from Chlorobium tepidum.

Results from high-pressure and Stark hole-burning experiments on isolated chlorosomes from the green sulfur bacterium Chlorobium tepidum are presented, as well as Stark hole-burning data for bacteriochlorophyll c (BChl c) monomers in a poly(vinyl butyral) copolymer film. Large linear pressure shift rates of -0.44 and -0.54 cm(-1)/MPa were observed for the chlorosome BChl c Q(y)-band at 100 K and the lowest Q(y)-exciton level at 12 K, respectively. It is argued that approximately half of the latter shift rate is due to electron exchange coupling between BChl c molecules. The similarity between the above shift rates and those observed for the B875 and B850 BChl a rings of the light-harvesting complexes of purple bacteria is emphasized. For BChl c monomer, fDeltamu++ = 0.35 D, where Deltamu+ is the dipole moment change for the Q(y) transition and f is the local field correction factor. The data establish that Deltamu+ is dominated by the matrix-induced contribution. The change in polarizability (Deltaalpha) for the Q(y) transition of the BChl c monomer is estimated at 19 A(3), which is essentially identical to that of the Chl a monomer. Interestingly, no Stark effects were observed for the lowest exciton level of the chlorosomes (maximum Stark field of 10(5) V/cm). Possible explanations for this are given, and these include consideration of structural models for the chlorosome BChl c aggregates.

Bacterial Proteins↗

Four new naphthylisoquinoline alkaloids from Ancistrocladus tectorius.

Four new naphthylisoquinoline alkaloids, ancistrotectoriline A (1), ancistrotectoriline B (2), 6-O-methyl-4'-O-demethylancistrocladine (3), and 6-O-methyl-4'-O-demethylhamatine (4), were isolated from the stems and leaves of Ancistrocladus tectorius, collected from Hainan Province, Southern China. Their structures were elucidated using MS and NMR methods.

Alkaloids↗

Programmed cell death in plant reproduction.

Reproductive development is a rich arena to showcase programmed cell death in plants. After floral induction, the first act of reproductive development in some plants is the selective killing of cells destined to differentiate into an unwanted sexual organ. Production of functional pollen grains relies significantly on deterioration and death of the anther tapetum, a tissue whose main function appears to nurture and decorate the pollen grains with critical surface molecules. Degeneration and death in a number of anther tissues result ultimately in anther rupture and dispersal of pollen grains. Female sporogenesis frequently begins with the death of all but one of the meiotic derivatives, with surrounding nucellar cells degenerating in concert with embryo sac expansion. Female tissues that interact with pollen undergo dramatic degeneration, including death, to ensure the encounter of compatible male and female gametes. Pollen and pistil interact to kill invading pollen from an incompatible source. Most observations on cell death in reproductive tissues have been on the histological and cytological levels. We discuss various cell death phenomena in reproductive development with a view towards understanding the biochemical and molecular mechanisms that underlie these processes.

Apoptosis↗

A pollen tube growth-promoting arabinogalactan protein from nicotiana alata is similar to the tobacco TTS protein.

Upon germination on the stigma, pollen tubes elongate in the stylar transmitting tract, aided by female factors, with speed and directionality not mimicked in in vitro pollen tube growth cultures. We have shown that a stylar transmitting tissue arabinogalactan protein (AGP) from Nicotiana tabacum (tobacco), TTS protein, stimulates pollen tube growth in vivo and in vitro and attracts pollen tubes grown in a semi-in vivo culture system. It has been reported that the self-incompatible Nicotiana alata produced a stylar glycoprotein, GaRSGP, which had a backbone polypeptide that shared 97% identity with those of TTS proteins but some of its properties were different from those described for TTS proteins. We report here the characterization of a family of stylar transmitting tissue glycoproteins from N. alata that is virtually identical to tobacco TTS proteins and which we refer to as NaTTS proteins. Like their tobacco counterparts, NaTTS proteins are recognized by the traditional AGP-diagnostic reagent beta-glucosyl Yariv reagent, and they are also recognized by JIM13, a monoclonal antibody against AGP. NaTTS proteins also stimulate pollen tube elongation in vitro and attract pollen tubes in a semi-in vivo pollen tube culture system. Biochemical and immunological characterization of NaTTS proteins revealed that they have extraordinary variability in the extent of sugar modifications of their polypeptide backbones. The extent of sugar modifications on NaTTS proteins significantly affects their biochemical properties, influences how they interact with the transmitting tissue extracellular matrix, and affects their solubility from this matrix. Our results suggest that the strategy used to purify GaRSGP only recovered a less glycosylated, more tightly extracellular matrix-bound sub-population of the entire spectrum of N. alata TTS proteins.

Electrophoresis, Gel, Two-Dimensional↗

Dissemination of CTX-M-3 and CMY-2 beta-lactamases among clinical isolates of Escherichia coli in southern Taiwan.

A total of 1,210 clinical isolates of Escherichia coli collected from a university hospital in southern Taiwan were screened for production of extended-spectrum beta-lactamases (ESBLs). Expression of classical ESBLs (resistant to extended-spectrum beta-lactam agents and susceptible to beta-lactam inhibitors) was inferred in 18 isolates by the phenotypic confirmatory test. These included 10 isolates producing CTX-M-3, 2 strains carrying SHV-12, 1 strain harboring SHV-5, 1 strain expressing TEM-10, and 4 strains producing unidentifiable ESBLs with a pI of 8.05, 8.0, or 7.4. Eighteen isolates that showed decreased susceptibilities to ceftazidime and/or cefotaxime, negative results for the confirmatory test, and high-level resistance to cefoxitin (MICs of >/=128 microg/ml) were also investigated. Five isolates were found to produce CMY-2 AmpC enzymes, one isolate carried both CTX-M-3 and CMY-2, and the remaining three and nine isolates expressed putative AmpC beta-lactamases with pIs of >9.0 and 8.9, respectively. Thus, together with the isolate producing CTX-M-3 and CMY-2, 19 (1.6%) isolates produced classical ESBLs. Pulsed-field gel electrophoresis revealed that all isolates carrying CTX-M-3 and/or CMY-2 were genetically unrelated, indicating that dissemination of resistance plasmids was responsible for the spread of these two enzymes among E. coli in this area. Among the 16 isolates expressing CTX-M-3 and/or CMY-2, 5 might have colonized outside the hospital environment. Our data indicate that CTX-M-3 and CMY-2, two beta-lactamases initially identified in Europe, have been disseminated to and are prevalent in Taiwan.

Adult↗

Prevalence of polyclonal mefA-containing isolates among erythromycin-resistant group A streptococci in Southern Taiwan.

A total of 204 nonrepetitive isolates of group A streptococci (GAS), including 107 randomly collected between 1992 and 1995 and 66 and 31 consecutively collected in 1997 and 1998, respectively, from a university hospital in southern Taiwan were examined to determine the prevalence and mechanisms of erythromycin resistance among these isolates. Resistance to erythromycin was detected in 129 isolates (63.2%) by the agar dilution test. Of these, 42 isolates (32.6%) were assigned to the constitutive macrolide, lincosamide, and streptogramin B resistance (cMLS) phenotype, and all carried the ermB gene; 4 (3.1%) were assigned to the inducible MLS resistance (iMLS) phenotype, and all harbored the ermTR gene; and 83 (64.3%) were erythromycin resistant but susceptible to clindamycin (M phenotype), and all possessed the mefA gene. Distributed by years, the rates of erythromycin resistance and different phenotypes were 61.7% (53.0% cMLS, 6.1% iMLS, and 40.9% M phenotype) between 1992 and 1995, 62.1% (12.2% cMLS and 87.8% M phenotype) in 1997, and 71. 0% (9.1% cMLS and 90.9% M phenotype) in 1998. Pulsed-field gel electrophoresis showed that all but 2 cMLS isolates were clonal in origin, and 17 clones were detected among the M-phenotype isolates. These results indicate that the high incidence and increasing rate of erythromycin-resistant GAS in southern Taiwan are due to the prevalence of multiple M-phenotype clones and that clindamycin may be the drug of choice for the treatment of infections with GAS in penicillin-hypersensitive patients in this area.

Anti-Bacterial Agents↗

The Chinese herbal medicine Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001) exerts anticonvulsant effects against different experimental models of seizure in rats.

We evaluated the anticonvulsant effect of Chai-Hu-Long-Ku-Mu-Li-Tan (TW-001), a Chinese herbal medicine, and its mechanisms in several standard rodent models of generalized seizure. TW-001 (4 g/kg, p.o.) significantly increased the threshold for tonic electroconvulsions and the threshold for tonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ). In the s.c. PTZ seizure test, both the incidence and severity of seizures were decreased by TW-001. TW-001 (1-10 mg/ml) did not alter resting membrane potential or input resistance of the hippocampal CA1 neurons, but elicited a reversible suppression of stimulus-triggered epileptiform activity in area CA1 and spontaneously occuring epileptiform burst discharges in area CA3 elicited by picrotoxin. Both field excitatory postsynaptic potentials and population spikes were reversibly depressed by TW-001 (0.5-15 mg/ml) in a concentration-dependent manner. The sensitivity of postsynaptic neurons to a glutamate-receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate, was not altered by TW-001 (10 mg/ml). However, TW-001 (5 mg/ml) clearly increased the magnitude of paired-pulse facilitation. TW-001 (5-10 mg/ml) reversibly limited the repetitive firing and reduced the maximal rate of rise of action potentials elicited by injection of depolarizing current pulses (0.4 nA, 200 ms) into the pyramidal cells. TW-001 (1-10 mg/ml) exerted a concentration-dependent reduction of the tetrodotoxin-sensitive sodium currents and high voltage-activated calcium currents. These results suggest that TW-001 is an interesting new anticonvulsant agent that exerts its anticonvulsant activity through inhibition of sodium and calcium channels, stabilizing neuronal membrane excitability and inhibiting glutamate release.

Action Potentials↗

High resolution MRI of adrenal glands in patients with primary aldosteronism.

BACKGROUND: We studied the role of high-resolution magnetic resonance imaging (MRI) of the adrenal glands using a surface coil in patients with primary aldosteronism to differentiate aldosterone-producing adenomas (APA) from idiopathic hyperplasia of the adrenal gland (IHA). The data obtained were used to decide on surgical or nonsurgical treatment for patients. METHODS: High-resolution MRI with SE T1WI, FSE T2WI and paired in- and out-phase images of the adrenal glands of 41 patients with clinically documented primary aldosteronism were collected. The images were reviewed in comparison with other differentiating tests. RESULTS: Nineteen of the 41 patients were diagnosed with APA on MRI. Surgical and pathologic proof of APA was obtained in 10 cases and solitary macronodular hyperplasia was found in one case. Among these 11 cases, there were no false positive findings on MRI, while correct detectability of high-resolution computerized tomography (CT) was 62.5% (5/8); for adrenal venous sampling, it was 37.5% (3/8); and for NP-59 adrenal scanning, it was 42.9% (3/7). In eight cases with biochemically favored APA and no surgical proof, MRI and CT showed the same lesion detection rate, while there was no concordance with venous sampling, and concordance of only 33.3% (2/6) for adrenal scanning. In the remaining 22 patients without focal lesions on MRI, there was poor concordance among the four test modalities, with frequently conflicting results. CONCLUSIONS: In patients with definitive results of noninvasive biochemical tests for APA, and positive findings of unilateral, focal adrenal lesion on MRI or CT, unilateral adrenalectomy may be justified without further tedious and invasive examinations. CT should still be the first screening test; however, high-resolution MRI is a useful diagnostic supplement for patients with strong clinical evidence of APA and negative or equivocal findings on CT.

Adrenal Glands↗

Myopia: gene-environment interaction.

INTRODUCTION: Myopia has reached epidemic proportions in Japan, Hong Kong, Taiwan and Singapore. This review summarises the evidence for environmental and genetic factors as well as gene-environment interaction for myopia for both epidemiologic studies as well as animal models. METHODS: A literature review was conducted after a Medline search on articles on the genetic or environmental aetiology of myopia in animal or epidemiologic studies. Articles on the methodology of gene-environment studies were also reviewed. All articles reviewed were articles published in peer-reviewed journals. RESULTS: Cross-sectional studies have found a positive association between myopia and near work activity such as reading and writing. Likewise, laboratory research has shown that environmental factors such as visual deprivation may lead to the development of myopia in animals. While linkage studies in humans are currently being conducted to identify possible markers for myopia in the human genome, several neurotransmitters, modulators and growth factors that influence refractive development have already been identified in animal models that may help identify candidate genes. Epidemiologic studies have also evaluated the combined effects of hereditary factors, environmental factors and gene-environment interaction on myopia development. CONCLUSIONS: Both genes and environmental factors may be related to myopia. There are no conclusive studies at present, however, that identify the nature and extent of possible gene-environment interaction. Further linkage analysis, affected sib-pair studies, and family-based association studies may better identify the nature of gene-environment interaction.

Animals↗

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.

Adult↗

Structure, interaction and electron transfer between cytochrome b5, its E44A and/or E56A mutants and cytochrome c.

Site-directed mutagenesis has been used to produce variants of a tryptic fragment of bovine liver cytochrome b5 in which Glu44 and Glu56 are mutated to alanine. The reduction potentials measured by spectroelectrochemical titration (in the presence of 1 mM (Ru(NH3)6)3+, pH 7.0 and I=0.1 M) are 4.5, 6.0, 6.0 and 7.5 mV versus the standard hydrogen electrode (SHE) for the wild-type and E44A, E56A and E44/56A mutants of cytochrome b5, respectively. A comparative two-dimensional NMR study of cytochrome b5 and its E44/56A mutant in water solution has been achieved. Resonance assignments of side-chains have been completed successfully. The NMR results suggest that the secondary structures and global folding of the E44/56A mutant remain unchanged, but the mutation of both Glu44 and Glu56 to hydrophobic alanine may lead to the two helices containing mutated residues contracting towards the heme center. The inner mobility of the Gly42 approximately Glu44 segment in cytochrome b5 may be responsible for the difference of the binding mode between Glu44 and Glu56 with cytochrome c. The binding between cytochrome c and cytochrome b5 was studied by optical difference spectra of cytochrome c and variants of cytochrome b5. The association constants (KA) for the wild-type, E44A, E56A, and E44/56A mutants of cytochrome b5 with cytochrome c, are 4.70(+/-0. 10)x10(6) M-1, 1.88(+/-0.03)x10(6) M-1, 2.70(+/-0.13)x10(6) M-1, and 1.14(+/-0.05)x10(6) M-1, respectively. This is indicative that both Glu44 and Glu56 are involved in the complex formation between cytochrome b5 and cytochrome c. The reduction of horse heart ferricytochrome c by recombinant ferrocytochrome b5 and its mutants has been studied. The rate constant of the electron transfer reaction between ferricytochrome c and wild-type ferrocytochrome b5 (1.074(+/-0.49)x10(7) M-1 s-1) is higher than those of the mutant protein E44A (8.98(+/-0.20)x10(6) M-1 s-1), E56A (8.76(+/-0. 39)x10(6) M-1 s-1), and E44/56A (8.02(+/-0.38)x10(6) M-1 s-1) at 15 degreesC, pH 7.0, I=0.35 M. The rate constants are strongly dependent on ionic strength and temperature. These studies, by means of a series of techniques, provide conclusive results that the interaction between cytochrome b5 and cytochrome c is electrostatically guided, and, more importantly, that both Glu44 and Glu56 participate in the electron transfer reaction.

Alanine↗

Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability.

We previously demonstrated that vascular endothelial growth factor (VEGF)-elicited increase in the permeability of coronary venules was blocked by the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). The aim of this study was to delineate in more detail the signaling pathways upstream from NO production in VEGF-induced venular hyperpermeability. The apparent permeability coefficient of albumin (Pa) and endothelial cytosolic Ca2+ concentration ([Ca2+]i) were measured in intact perfused porcine coronary venules using fluorescence microscopy. VEGF (10(-10) M) induced a two- to threefold increase in Pa, which was blocked by a monoclonal antibody directed against the VEGF receptor Flk-1/KDR, the phospholipase C (PLC) antagonist U-73122, or the protein kinase C (PKC) antagonist bisindolylmaleimide (BIM). In 12 venules that displayed the [Ca2+]i response to bradykinin (10(-6) M) and ionomycin (10(-6) M), only 4 vessels responded to VEGF with a transient increase in [Ca2+]i. Furthermore, Western blot analysis of cultured human umbilical vein endothelial cells showed that VEGF increased tyrosine phosphorylation of PLC-gamma and serine phosphorylation of endothelial constitutive NO synthase (ecNOS). The hyperphosphorylation of PLC-gamma was greatly attenuated by the KDR receptor antibody and U-73122, but not by BIM or L-NMMA. In contrast, U-73122 and BIM were able to inhibit VEGF-elicited serine phosphorylation of ecNOS. The results suggest that VEGF induces venular hyperpermeability through a KDR receptor-mediated activation of PLC. In turn, ecNOS is activated by PLC-mediated PKC and/or cytosolic Ca2+ elevation stimulation.

Animals↗

Increase of intestinal Bifidobacterium and suppression of coliform bacteria with short-term yogurt ingestion.

To determine whether ingestion of yogurt would alter human intestinal bacterial composition and whether Bifidobacterium numbers would increase in the intestine, 34 healthy volunteers were studied. The experimental period was 26 d, including an initial 8 d without yogurt, 10 d with three bottles (230 ml each) of AB yogurt per day (President Enterprise Corporation, Tainan, Taiwan), and 8 d without yogurt. Stool samples were taken at 3- to 4-d intervals. The bacteria of each fresh stool sample were promptly analyzed by dilution and culture on blood, MacConkey, Center for Disease Control and NNLP agars, the agar contained nalidixic acid, neomycin sulfate, LiCl, and paromomycin sulfate for aerobes, coliforms, anaerobes, and bifidobacteria, respectively. The number of bacteria was determined as colony-forming units per gram of dried stool. Results indicated that ingestion of AB yogurt increased the counts of anaerobic bacteria, suppressed aerobic bacteria, and significantly elevated the bifidus to coliform ratio. Arbitrarily primed polymerase chain reaction was used to differentiate the identity of bifidobacteria in four volunteers before and after yogurt ingestion and confirmed that B. bifidum ingested from the yogurt survived and proliferated in the stool throughout the experiment. However, the elevated bifidus to coliform ratio gradually diminished and disappeared after yogurt consumption was discontinued. In conclusion, ingestion of yogurt increased the numbers of stool bifidobacteria and suppressed coliform bacteria. The ingested bifidobacteria survived for more than 8 d after yogurt consumption was discontinued.

Adult↗

Unusual chromosome 9 variant with an extra G-dark and C-negative segment in the short arm, proximal to the centromere: a case study.

Polymorphic variation of constitutive heterochromatin in human chromosomes is commonly seen in clinical cytogenetic analyses. Normal variant can be confirmed with C-banding and are generally considered clinically insignificant. However, it may be a concern if an unusual variant chromosome is detected in a prenatal specimen. We report an unusual chromosome 9 variant with an extra G-dark and C-negative segment in the short arm, proximal to the centromere. This chromosome 9 variant has been previously reported in only nine independent families. Whether this is a rare variant or an underestimation requires further evaluation. Of note is that all probands so far reported in the literature are clinically normal.

Adult↗

A highly selective beta1-adrenergic blocker with partial beta2-agonist activity derived from ferulic acid, an active component of Ligusticum wallichii Franch.

Short-term injection of ferulinolol (0.1, 0.5, and 1.0 mg/kg, i.v.) produced dose-dependent bradycardia responses in pentobarbital-anesthetized Wistar rats, whereas it had no significant effects on the blood pressure. Ferulinolol markedly inhibited the tachycardia effects induced by (-)isoproterenol but did not show any blocking effect on the arterial pressor responses induced by (-)phenylephrine. These findings clearly suggested that ferulinolol had a beta-adrenergic blocking activity; nevertheless, it did not involve an alpha-adrenergic blocking action. In isolated guinea pig tissues, ferulinolol competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses. The parallel shift to the right of the concentration-response curve of (-)isoproterenol suggested that ferulinolol was a beta-adrenoceptor-competitive antagonist. The apparent pA2 values for ferulinolol on right atria, left atria, and trachea were 7.62 +/- 0.05, 7.54 +/- 0.01, and 6.28 +/- 0.11, respectively. Ferulinolol was more potent on the atria than on tracheal tissues, demonstrating that it possessed beta1-adrenoceptor selectivity. The intrinsic sympathomimetic activity (ISA) of ferulinolol and propranolol were determined on isolated atria and trachea from reserpine-treated guinea pig. Propranolol caused significantly negative inotropic and chronotropic effects at > or =1 microM, whereas ferulinolol possessed fewer cardiodepressant activities than propranolol. In reserpine-treated tracheal strips, ferulinolol produced dose-dependent relaxant responses, but propranolol was without effectiveness. Preincubating the preparations with ICI 118,551 (0.1, 1.0, and 10 nM), a beta2-adrenoceptor antagonist, significantly shifted the concentration-relaxation curves of ferulinolol to a region of higher concentrations. These results implied that ferulinolol had a partial beta2-agonist activity. Further, binding characteristics of ferulinolol and various beta-adrenoceptor antagonists were evaluated in [3H]CGP-12177 binding to rat ventricular or lung membranes. The Ki values of ferulinolol, atenolol, metoprolol, and (-)propranolol were 103, 262, 123, and 0.23 nM, respectively, in ventricular membranes, and 2,412, 7,539, 2,186, and 0.72 nM, respectively, in lung membranes. In conclusion, ferulinolol was found to be a highly selective beta1-adrenoceptor antagonist with partial beta2-agonist activity but was devoid of alpha-adrenoceptor blocking action.

Adrenergic beta-1 Receptor Antagonists↗