Biomedical subjects

S H Han

Publications and source records attributed to S H Han.

At least 91 records · Page 5Linked to original sources

PubMed1999

Comparison of munc-18 and cdk5 expression in the nervous system during mouse embryogenesis.

Cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator, p35, are essential for the proper migration of neurons. While the defects in p35 null mice are largely confined to the cerebral cortex, the anomalies in cdk5 nullizygous mice are also evident in the hippocampus and cerebellum. This suggested that additional cyclin-like activators, such as Munc-18, must be coexpressed with Cdk5 in some migrating neurons. Therefore, the expression patterns of munc-18 and cdk5 were determined in the developing mouse nervous system by in situ hybridization. In the embryonic day 11.5-13.5 developing neocortex, cdk5 was expressed in the proliferative zone and also in migratory and postmitotic neurons. In contrast, munc-18 messenger RNA was only detected in postmigratory, differentiated neurons. In the cerebellum and the hippocampus, cdk5 was expressed in proliferative, migrating and postmigratory neurons, while munc-18 was expressed in migrating and postmigratory neurons. This supports the hypothesis that Munc-18 could compensate for the loss of p35 in migrating neurons in the hippocampus and cerebellum, but not the cerebral cortex. Munc-18 levels increased substantially during late embryogenesis and into adulthood. Therefore, the function of Munc-18 is most likely relevant to mature neurons and any redundancy with p35 in migration is probably fortuitous.

Animals↗

PubMed1999

Characterization of allergens from Penicillium oxalicum and P. notatum by immunoblotting and N-terminal amino acid sequence analysis.

BACKGROUND: Penicillium species are important causative agents of extrinsic bronchial asthma. However, little is known about the allergens of these ubiquitous fungal species. Objective The object was to analyse the composition, the allergenic cross-reactivity and the N-terminal sequences of allergens from two prevalent airborne Penicillium species, P. oxalicum and P. notatum. METHODS: The allergenic composition and the immunoglobulin (Ig)E cross-reactivity were analysed by immunoblot and immunoblot inhibition, respectively, using sera from asthmatic patients. The N-terminal amino acid sequences of major allergens were determined by Edman degradation. Allergens identified were also characterized by immunoblotting using monoclonal antibody (MoAb) PCM39 against the alkaline serine proteinase major allergen of P. citrinum. RESULTS: Among the 70 asthmatic sera tested, 18 (26%) and 17 (24%) had IgE immunoblot reactivity towards components of P. oxalicum and P. notatum, respectively. Major allergens (> 80% frequency of IgE-binding) from both species are the 34 and 30 kDa proteins of P. oxalicum and the 34 and 32 kDa proteins of P. notatum. IgE cross-reactivity among these major allergens and the 33 kDa major allergen of P. citrinum can be detected by immunoblot inhibition studies. The N-terminal amino acid sequences of the 34 kDa allergen of P. oxalicum and of the 32 and the 28 kDa allergens of P. notatum share homology with sequences of the vacuolar serine proteinase from Aspergillus fumigatus. The N-terminal amino acid sequence of the 34 kDa allergen of P. notatum shows sequence homology with that of alkaline serine proteinase from P. citrinum. Results obtained from immunoblotting showed that MoAb PCM39 reacted with the 34, 30 and 16 kDa IgE-binding components of P. oxalicum, and with the 34, 32 and 28 kDa IgE-binding components of P. notatum. CONCLUSIONS: Results obtained suggest that the 34 kDa major allergen of P. oxalicum may be a vacuolar serine proteinase. The 34 and the 32 kDa major allergens of P. notatum may be the alkaline and the vacuolar serine proteinases of P. notatum, respectively. The 30 and 16 kDa IgE-binding components of P. oxalicum and the 28 kDa IgE-binding component of P. notatum may be breakdown products of the 34 and the 32 kDa major vacuolar serine proteinase allergens of P. oxalicum and P. notatum, respectively.

Adult↗

PubMed1999

Sequence polymorphism of the group 1 allergen of Bermuda grass pollen.

BACKGROUND: Cyn d 1, the major allergen of Bermuda grass pollen, consists of a number of isoforms. OBJECTIVE: To examine the extent of sequence variation of Cyn d 1 isoforms at the molecular level. METHODS: A Bermuda grass pollen lambdaZAP II cDNA expression library was immunoscreened with anti-Cyn d 1 monoclonal antibodies. The reactive clones were isolated, subcloned into Escherichia coli, and sequenced. Some of them were expressed in the yeast Pichia pastoris to obtain recombinant Cyn d 1 proteins. RESULTS: Ten cDNA clones were obtained, all these clones encode the full length of Cyn d 1 protein. Their deduced mature proteins can be grouped into: the long ones with 246 amino acids, and the short ones with 244 amino acids. The last two amino acids (AG) of the long Cyn d 1 are deleted in the short Cyn d 1. The remaining amino acid sequences share more than 98% identity; a total of nine amino acid variations were observed. Two recombinant Cyn d 1 proteins (rCyn d 3-2 and rCyn d 5-4) with three amino acid substitutions showed differential IgE-binding profiles. CONCLUSION: The present study extended our understanding of the primary structure of isoforms of Cyn d 1.

Allergens↗

PubMed1999

Expression of myosin heavy chain mRNA in rat laryngeal muscles.

The composition of myosin heavy chain mRNA was analysed quantitatively in 5 intrinsic laryngeal muscles of rats, using a competitive polymerase chain reaction. Intrinsic laryngeal muscles with the fastest contraction times, e.g. ventricular thyroarytenoid muscle. lateral cricoarytenoid muscle. and vocalis muscle, contained 2 fast isoforms, comprising mainly type 2B myosin heavy chains (52.1, 44.6 and 8.2%, respectively) and type 2X myosin heavy chains (21.9, 37.6 and 80.8%, respectively). Conversely, muscles with slower contraction times, such as posterior cricoarytenoid muscle and cricothyroid muscle, contained more than 85% of 2 fast isoforms; mainly type 2X myosin heavy chains (52.4-72.1%, respectively) and type 2A myosin heavy chains (34.6-25.2%, respectively). The results show a strong correlation between the composition of fast myosin heavy chain isoforms and muscle contraction times. Type 2L myosin heavy chain transcripts specific for laryngeal muscles and extra-ocular muscles were expressed in the order of ventricular thyroarytenoid (9.5%) > lateral cricoarytenoid (4.8%) > vocalis (2.5%) > posterior cricoarytenoid muscle (0.9%), but were not expressed in cricothyroid muscle. Neonatal myosin heavy chain was also expressed in all laryngeal muscles, ranging from 0.04 to 3%, but embryonic myosin heavy chain was expressed in ventricular thyroarytenoid, posterior cricoarytenoid and cricothyroid muscle at very low levels. These results suggest that intrinsic laryngeal muscles have different expression patterns for myosin heavy chain isoforms and may have different regulatory roles related to their functional requirement.

Animals↗

PubMed1999

High level expression of soluble angiogenin in Escherichia coli.

Human angiogenin was genetically engineered and contained the E. coli Omp A signal sequence for secreting soluble angiogenin to the periplasm under tac promoter control. The angiogenin sequence was encoded in a single gene and expressed as a 14.4 kilodalton soluble protein in E. coli. It was purified by CM-Sepharose ion-exchange chromatography and by a heparin-Sepharose affinity chromatography procedure. The biological activity of angiogenin was established by its ability to inhibit mRNA-dependent rabbit reticulocyte cell-free translation.

Bacterial Outer Membrane Proteins↗

PubMed1999

Undetectable serum thyroglobulin in a patient with metastatic follicular thyroid cancer.

The case of a 54-year-old woman with metastatic follicular thyroid cancer and undetectable serum thyroglobulin is presented. Many years after the patient had a subtotal thyroidectomy for a large goiter that had no clear evidence of malignancy, metastatic bone disease developed. When the bone metastases were detected and during the follow-up period, serum thyroglobulin values remained undetectable, but radioiodine uptake in the metastases was abundant. This case indicates that the combination of 1-131 scintigraphy and serum thyroglobulin values is superior to the measurement of serum thyroglobulin alone in detecting well-differentiated, metastatic thyroid cancer.

Adenocarcinoma, Follicular↗

PubMed1999

Algorithm for recipient vessel selection in free tissue transfer to the lower extremity.

The proper selection of a recipient vessel is essential for the success of free tissue transfer, especially when the transfer is to the lower extremity. However, a general agreement on which vessel to use has not been reached yet. Conflicting data have been reported on the survival and outcome of the transferred flaps, depending on the vessel used or the location of anastomosis. The aim of this study was to identify the patterns and problems in the selection of recipient vessels for free tissue transfer to the lower extremity and to establish a general guideline for proper selection. From September of 1990 to December of 1997, 50 consecutive, microvascular, free tissue transfers were performed on the lower extremity. The causes requiring soft-tissue coverage included trauma (25), unstable scar (11), chronic osteomyelitis (7), and tumors (7). The mean follow-up period was 22.4 months (range, 2 to 41 months). In 25 cases, the posterior tibial vessel was used as the recipient vessel. The microvascular anastomosis was done proximal to the zone of injury in 45 cases. The two most important factors in the selection of a recipient vessel are the site of injury and the vascular status of the lower extremity. Less important factors include the flap to be used, method, and site of microvascular anastomosis. All the currently feasible options for recipient vessels are included, and the opinions of other surgeons are reviewed. A general guideline is established, and an algorithm for the proper selection of a recipient vessel is proposed. This algorithm is a fast and convenient guide for evaluating the wound and planning the free flap to the lower extremity.

Adolescent↗

PubMed1999

Stability of neural networks and solitons of field theory.

The layers of a feed-forward neural network are interpreted as a cascade of field theories. The stability of the neural network is interpreted as the topological stability of kink solutions. An explicit example is shown for a three-class problem with their field theoretical Lagrangian equations.

Journal Article↗

PubMed1999

The respiratory burst activity of activated eosinophils in atopic asthmatics.

Although activated eosinophils in peribronchial tissue and peripheral blood are increased in patients with asthma, the mechanisms contributing to their presence and causing airway hyperreactivity are not well established. Recently, the respiratory burst activity on activated eosinophils can be evaluated by dual staining with monoclonal antibody EG2 and 2,7-dichlorofluorescein diacetate, which can be analyzed with the FACS analyzer. The severity of allergy and airway hyperreactivity can be evaluated by allergen-specific IgE and airway hyperresponsiveness to methacholine. In this study we evaluated the cell numbers with respiratory burst activity on activated eosinophils and correlated these cell numbers with the allergen-specific IgE and airway hyperresponsiveness to methacholine. Results showed that the cell number with respiratory burst activity of activated eosinophils was increased in those patients with more hyperresponsiveness to methacholine and correlated with PD20 of methacholine with r = -0.643 and p = 0.01. The number of activated eosinophils was also correlated with allergen-specific IgE with r = 0.641 and p = 0.025. There were increased cell numbers of activated eosinophils (EG2(+)/PMN) and cells with respiratory burst activity (DCF+EG2(+)/PMN) in the unstable asthmatic patients when compared to those of stable asthmatic patients. These results suggest that there is in vivo activation of eosinophils in the asthmatic patients, especially in the unstable patients and patients who have airways more hyperreponsive to methacholine. We concluded that the cell numbers with respiratory burst activity of activated eosinophils cannot only reflect the airway hyperresponsiveness but also the disease severity of asthmatic patients.

Administration, Inhalation↗

PubMed1999

The importance of serine proteinases as aeroallergens associated with asthma.

Penicillium and Aspergillus species have been identified as prevalent indoor airborne fungi that are associated with extrinsic bronchial asthma. We have recently analyzed the IgE-binding components in 8 prevalent Penicillium and Aspergillus species (P. citrinum, P. notatum, P. oxalicum, P. brevicompactum, A. fumigatus, A. flavus, A. oryzae and A. niger) by immunoblotting and N-terminal amino acid sequence analysis. Our results show that the alkaline and/or vacuolar serine proteinases are the major allergens in these prevalent fungal species. IgE cross-reactivity among these major allergens was also detected. Results obtained provide an important basis for clinical allergy. In addition, monoclonal antibodies against alkaline and/or vacuolar serine proteinase allergens have been generated. These antibodies can be applied for the standardization of allergenic extracts.

Air Pollutants↗

PubMed1999

Alkaline serine proteinase is a major allergen of Aspergillus flavus, a prevalent airborne Aspergillus species in the Taipei area.

BACKGROUND: Aspergillus species are prevalent indoor airborne fungi and have been identified to be a causative agent of human allergic disorders. In the present study, we identified, purified and characterized the allergen(s) from Aspergillus flavus, a predominant airborne Aspergillus species in the Taipei area. METHODS: The IgE-binding components of A. flavus were identified by SDS-PAGE immunoblotting with sera from asthmatic patients. The N-terminal amino acid sequences of the major allergens were determined by Edman degradation. The allergenic cross-reactivity among allergens from different fungi was analyzed by immunoblot inhibition using sera from asthmatic patients. The detected major allergen was purified from the culture medium. It was further characterized in terms of its N-terminal amino acid sequence, its IgE-binding activity and its enzymatic activity. RESULTS: The results of the immunoblot analysis indicate that a 34-kD component that has high IgE-binding (63%) frequency is a major allergen of A. flavus. The N-terminus of this 34-kD major allergen (GLTTQKSAP) has high sequence identity with that of the 34-kD alkaline serine proteinase major allergen of A. oryzae. Results from immunoblot inhibition studies indicate that IgE cross-reactivity occurs among the 34-kD major allergens of A. flavus, A. fumigatus and Penicillium citrinum. The 34-kD major allergen of A. flavus was purified from the culture medium by ammonium sulfate precipitation and DEAE ion exchange chromatography. The N-terminal amino acid sequence of the purified allergen (Asp fl 13) is identical to that determined previously for the 34-kD major allergen in the crude extract of A. flavus. The IgE immunoblot reactivity to the 34-kD major allergen in the crude extract can be dose-dependently inhibited by the purified Asp fl 13. The degree of IgE binding to the 34-kD major allergen in the crude extract correlates with that of the purified Asp fl 13 in sera of 8 asthmatic patients. The purified Asp fl 13 has proteolytic activity with casein as substrate at pH 8.0. This enzymatic activity can be inhibited by either phenylmethylsulfonyl fluoride or diethylpyrocarbonate. CONCLUSION: Our results suggest that the 34-kD alkaline serine proteinase is a major allergen of A. flavus. There was IgE cross-reactivity among allergens of A. flavus, A. fumigatus and P. citrinum.

Adolescent↗

PubMed1999

Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine.

Because chlorofluorocarbons (CFCs) contribute to depletion of stratospheric ozone, CFC-containing metered-dose inhalers (MDIs) such as Ventolin and Proventil are being phased out of production. In terms of delivery of albuterol to the lungs, we compared an alternative delivery system, the Spiros dry-powder inhaler (DPI), with Ventolin, using a methacholine challenge-based clinical bioassay. Twenty-four adults and adolescents with asthma completed this double-blind, four-period crossover study. Doses evaluated were one and three actuations each of Spiros and Ventolin (90- and 270-microgram albuterol base). A methacholine challenge (Cockcroft method) was initiated 3 h before and 0.25 h after albuterol. Predose PC(20)FEV(1) values were not significantly different between study days. Postdose PC(20)FEV(1) results met standard bioassay study validity criteria: i.e., a significant dose-response relationship was present (p = 0.0002); tests for deviation from parallelism and overlap of dose-response curves were nonsignificant (p = 0.08, 0.69). By using Finney 2-by-2 bioassay analysis, we estimate that each Spiros actuation delivers 1.12 times as much albuterol to the airways as one Ventolin actuation (90% confidence interval, 0.68 to 1.94). There were no significant differences in markers of systemic effects (vital signs, potassium, and blood glucose concentrations). We conclude that Spiros and Ventolin inhalers deliver comparable quantities of albuterol to the airways.

Adolescent↗

PubMed1999

Effects of glucocorticoids and cyclosporine on IL-2 and I kappa B alpha mRNA expression in human peripheral blood mononuclear cells.

To evaluate molecular mechanisms that might account for the heterogeneity in the in vitro responsiveness of individual subjects' peripheral blood mononuclear cells (PBMC) to immunosuppressive drugs, the authors quantitated in normal human cells the suppressive effects of the glucocorticoids prednisolone and methylprednisolone and of cyclosporine on interleukin-2 (IL-2) mRNA expression and IL-2 production, as well as the stimulatory effect of these drugs on IkappaBalpha mRNA expression. As expected, cyclosporine was significantly more suppressive than either glucocorticoid of IL-2 mRNA expression and IL-2 production by mitogen-stimulated PBMC, with variable degrees of inhibition in cells from individual subjects. The authors confirmed in human PBMC the stimulation of IkappaBalphamRNA expression by the glucocorticoid reported by others in HeLa and transfected Jurkat cell lines. In addition, the authors observed a stimulatory effect on IkappaBalpha mRNA expression by cyclosporine as well in 8 of 10 PBMC preparations studied, suggesting a possible role of calcineurin in the regulation of IkappaBalpha production. Interindividual variability in the intracellular mechanisms of action, possibly based on molecular polymorphisms, might be one factor contributing to differences among patients in their clinical responses to treatment with such drugs.

Cells, Cultured↗

PubMed1999

Neuro-Behcet's disease presenting with isolated unilateral lateral rectus muscle palsy.

The authors present the clinical findings of a 30-year-old female and a 29-year-old male who both had isolated unilateral lateral rectus muscle palsy in neuro-Behcet's disease. The clinical feature related to isolated abduscens nerve palsy was identified by CT, systemic assessment and extraocular examination. These patients' constellation of findings appear to be unique: it does not follow any previously reported pattern of ocular manifestations of neuro-Behcet's disease.

Abducens Nerve↗

PubMed1999

Effect of Helicobacter pylori infection on antral gastrin and somatostatin cells and on serum gastrin concentrations.

OBJECTIVES: Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted. RESULTS: Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p < 0.001). The number of G-cells per gastric gland was similar in infected and uninfected patients (7.1 +/- 3.1 vs 7.3 +/- 3.9, respectively, p > 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001). CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.

Case-Control Studies↗

PubMed1999

186Re-etidronate in breast cancer patients with metastatic bone pain.

UNLABELLED: The aim of this study was to evaluate the efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (etidronate) in breast cancer patients with painful bone metastases. METHODS: Thirty patients with advanced breast cancer who had metastatic bone pain were treated with 186Re-etidronate using different dosages in a noncomparative, open-label study. Twenty-four patients were evaluated for efficacy (6 patients had incomplete datasets). Dosages varied from 1295 to 2960 MBq (35 to 80 mCi). Efficacy was evaluated according to the multidimensional pain model using a paper-and-pencil diary. The diary was kept twice daily for 8-10 wk (2 wk before through 6-8 wk after 186Re-etidronate treatment). Response was determined with a strict criteria, in which pain intensity (PI), medication index (MI) and daily activities (DA) were core determinants. Response was defined as: (a) Reduced PI > or = 5% while MI and DA were at least constant; or (b) Reduced PI <25% in combination with improvement of MI or DA > or = 25%, without worsening of either factor. Duration of response should always exceed a minimum of 2 wk. RESULTS: Fifty-eight percent (n = 14) of all patients reported a response. The maximum follow-up period was 8 wk. Duration of response ranged from 2 to 8 wk (mean 4 wk). Patients (14/24) not only experienced considerable pain reduction, but in 12 patients this was also accompanied by noteworthy reduction in MI (> or = 25%). No clear dose-response relationship was found. CONCLUSION: With strict pain assessment criteria, 186Re-etidronate showed a response of 58% in the palliative treatment of metastatic bone pain originating from breast cancer.

Bone Neoplasms↗

PubMed1998

Down-regulation of protein kinase C: a potential mechanism for 2-amino-3-methylimidazo[4,5-f]quinoline-mediated immunosuppression.

Immunosuppressive mechanism of food-born mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), was studied in murine spleen cells. IQ suppressed the IL-2 secretion and its mRNA expression. Treatment of IQ also decreased PKC activity in both the membrane fraction and the cytosol fraction. Treatment of PMA resulted in the recovery of IQ-induced suppression of IL-2 production, but the addition of ionomycin (Io) had no effect. Subsequently, we examined the effect of IQ on the activation of NF-kappaB, AP-1, and NF-AT, which are key transcription factors for IL-2 transcription. The activation of NF-kappaB and AP-1 was markedly inhibited by IQ in PMA/PHA-stimulated cells. Meanwhile, NF-AT was not affected by IQ in PMA/Io-stimulated cells. These results suggest that the immunosuppression induced by IQ might be associated with the down-regulation of PKC and subsequent blockade of the activation of NF-kappaB and AP-1 in the IL-2 gene expression.

Animals↗

PubMed1998

[Palliative treatment of bone metastases with bone-seeking radionuclides].

The skeleton is a common site for metastases in patients with prostate and breast cancer. Beside analgesic therapy and external beam radiotherapy, the use of bone-seeking radiopharmaceuticals gives pain relief. Analogues of these pharmaceuticals are also applied in skeletal scintigraphy. They accumulate at the site of high osteoblast activity and in this way they exert a local favourable influence on metastases through their radiation (beta particles or conversion electrons). The bone-seeking radiopharmaceuticals include strontium-89 chloride and rhenium-186 hydroxyethylidenediphosphonate. The main adverse reaction that has been observed is myelosuppression.

Bone Marrow↗