Search PubMed⌕ Search

Biomedical subjects

H H Chen

Publications and source records attributed to H H Chen.

At least 37 records · Page 2Linked to original sources

Role of the natriuretic peptides in the cardiorenal and humoral actions of omapatrilat: insights from experimental heart failure.

Vasopeptidase (VP) inhibitors are novel molecules that co-inhibit neutral endopeptidase 24.11 (NEP), which degrades natriuretic peptides and angiotensin-converting enzyme (ACE). We review the biology of the natriuretic peptide system and a recent study of the role for the natriuretic peptide system in the mechanism of action of omapatrilat (the most clinically advanced VP inhibitor). This study compared the cardiorenal and humoral actions of omapatrilat with those of ACE inhibition. The actions of omapatrilat were further defined in the presence and absence of a natriuretic peptide receptor antagonist. This investigation provided insight into a unique new pharmacologic agent that has beneficial renal actions in experimental mild heart failure that exceed those seen with ACE inhibition alone and that are linked to the natriuretic peptide system.

Angiotensin-Converting Enzyme Inhibitors↗

Functional characterization of Marek's disease virus (MDV) origin-binding protein (OBP): analysis of its origin-binding properties.

In previous studies, we identified a Marek's disease virus (MDV) origin-binding protein (OBP) gene that is highly homologous to the herpes simplex virus type 1 UL9 gene that encodes an OBP and functions as an initiator protein for viral DNA replication. In this study, a protein of 95 kDa was produced in coupled in vitro transcription-translation reaction with the plasmid containing the wild type MDV OBP gene. The in vitro synthesized protein was detected by immunoprecipitation with a penta-histidine specific monoclonal antibody. Further characterization of MDV OBP was accomplished using electrophoretic mobility shift assay (EMSA) with the in vitro expressed MDV OBP using a double-stranded (ds) 26-mer oligonucleotide as the probe, which was designed from the putative MDV OBP binding site present in the serotype 1 or 2 MDV replication origin. The EMSA results indicated that MDV OBP could form a protein-DNA complex with the ds 26-mer oligonucleotide designed from serotype 1 or 2 replication origin. A series of 26-mer oligonucleotides with two-base-pair (bp) substitution across the putative MDV OBP binding site were used in competitive EMSA to determine the recognition sequence for the MDV OBP. The results demonstrated that the recognition sequence for MDV OBP was the TTCGCACC that is a subset of a 9-bp element (CGTTCGCAC) conserved in the replication origins of alphaherpesviruses. Furthermore, the results of EMSA with a series of deletion mutants from the N-terminus of MDV OBP indicated that the origin-binding domain was located at the amino acids region 528 to 841 of the wild-type MDV OBP. Taken together, our results suggest that the MDV OBP gene encodes an OBP of MDV.

Amino Acid Sequence↗

Renal biopsy in pregnancies complicated by undetermined renal disease.

BACKGROUND: The aim of this retrospective study was to verify the role of renal biopsy in pregnancies complicated by renal dysfunction. METHODS: A series of 15 percutaneous renal biopsies performed in 15 pregnant women with renal disease presenting during pregnancy over the past 10 years (1990-1999) were reviewed. RESULTS: All the patients underwent renal biopsy before 30 weeks of gestation. The indications for renal biopsy were renal dysfunction of unknown cause or symptomatic nephrotic syndrome (NS). Patients with toxemia were excluded. Eight women had lupus nephritis, including five with diffuse crescenteric changes and three with a mesangial proliferative pattern. Three had chronic glomerulonephritis (CGN), two had mesangial proliferative glomerulonephritis and one each had diabetic nephrosclerosis and endocapillary proliferative glomerulonephritis. There were no significant complications except in one patient who experienced gross hematuria. Early induction of labor was recommended for the four patients with diabetic nephrosclerosis or CGM. The other 11 patients received intravenous pulse methylprednisolone or high dose oral prednisolone therapy. The responses to steroid therapy in these 11 patients were as follows: five achieved complete remission of NS, three achieved incomplete remission, and three achieved partial remission. After 2 years' follow-up, seven mothers achieved complete remission, three had died, three developed chronic renal failure (CRF), and two progressed to end stage renal failure (ESRF) requiring chronic hemodialysis. Fourteen of the 15 pregnancies resulted in live births and the other child was stillborn. CONCLUSIONS: Renal biopsy performed during pregnancy is not contraindicated. The results of histopathological studies are extremely useful in counseling regarding continuation or termination of pregnancy, potential maternal and fetal outcome, and recommending specific therapeutic modalities.

Adult↗

Estimating the benefits of adjuvant systemic therapy for women with early breast cancer.

BACKGROUND: Prognostic factors are commonly used to help identify women with node-negative breast cancer at high risk of recurrence. Although many are available, knowing which risk factor or combination of factors to use to estimate prognosis for an individual woman is often difficult. This study documented the baseline prognoses for a group of women with node-negative breast cancers, and estimated the potential benefits of adjuvant systemic therapy. METHODS: Ten-year, actuarial, cause-specific survival based on tumour size and histological grade using data from the Swedish Two-County Trial of mammographic screening was calculated for 1200 women with node-negative cancers of less than 30 mm diameter. The benefits of adjuvant systemic therapy for these women were then estimated using the published odds reductions in death from adjuvant systemic therapy from the Early Breast Cancer Trialists' Collaborative Group overview. RESULTS: The absolute 10-year survival benefits for subgroups of women based on tumour size and histological grade were estimated for women aged under 50 years by the addition of chemotherapy, and over 50 years by the addition of tamoxifen and/or chemotherapy. CONCLUSION: Decisions about adjuvant systemic therapy in women with node-negative breast cancer need to be individualized, taking into account treatment efficacy and toxicity. The quantitative methods presented in this paper facilitate such decisions.

Adult↗

The thymidylate synthase gene of Hz-1 virus: a gene captured from its lepidopteran host.

The sequence analysis of a thymidylate synthase gene was identified in the Hz-1 virus HindIII-D fragment. The viral thymidylate synthase gene encodes a protein of 295 amino acids, and is closely related to that of insect, mammals and herpesvirus. The thymidylate synthase gene identified was a genuine viral gene in that it was only detected in cells infected with Hz-1 virus but not in the mock infected cells, by Southern blot analysis and by RT-PCR. Results of phylogenetic analysis based on non-synonymous and amino acid distances suggested that the TS gene of Hz-1 virus was grouped closely with that of Bombyx mori. High bootstrap values confirmed that the thymidylate synthase of Hz-1 virus was acquired by a capture event from its lepidopteran host. Results of both sequence divergences and phylogenetic analysis suggested that TS genes in insect viruses, Hz-1, CIV, and MsEPV may have a different history or originated from different capture events.

Amino Acid Sequence↗

Risk factors for surgical site infection after elective resection of the colon and rectum: a single-center prospective study of 2,809 consecutive patients.

OBJECTIVE: To identify the risk factors for surgical site infection (SSI) in patients undergoing elective resection of the colon and rectum. SUMMARY BACKGROUND DATA: SSI causes a substantial number of deaths and complications. Determining risk factors for SSI may provide information on reducing complications and improving outcome. METHODS: The authors performed a prospective study of 2,809 consecutive patients undergoing elective colorectal resection via laparotomy between February 1995 and December 1998 at a single institution. The outcome of interest was SSI, which was classified as being incisional or organ/space with or without clinical leakage. A likelihood ratio forward regression model was used to assess the independent association of variables with SSIs. RESULTS: The overall SSI, incisional SSI, and organ/space SSI with and without clinical anastomotic leakage rates were 4.7%, 3%, 2%, and 0.8%, respectively. Risk factors for overall SSI were American Society of Anesthesiology (ASA) score 2 or 3 (odd ratio [OR] = 1.7), male gender (OR = 1.5), surgeons (OR = 1.3-3.3), types of operation (OR = 0.3-2.1), creation of ostomy (OR = 2.1), contaminated wound (OR = 2.9), use of drainage (OR = 1.6), and intra- or postoperative blood transfusion (1-3 units, OR = 5.3; >/=4 units, OR = 6.2). However, SSIs at specific sites differed from each other with respect to the risk factors. Among a variety of risk factors, only blood transfusion was consistently associated with a risk of SSI at any specific site. CONCLUSIONS: In addition to ASA score and surgical wound class, blood transfusion, creation of ostomy, types of operation, use of drainage, sex, and surgeons were important in predicting SSIs after elective colorectal resection.

Adolescent↗

Effect of shock wave therapy on acute fractures of the tibia: a study in a dog model.

The effect of shock wave therapy on acute fractures of the tibia was studied in eight adult dogs. A fracture with a 3-mm gap was created in both tibias and the fractures were fixed internally with a small metallic plate and screws. Each of the right limbs received 2,000 impulses of shock waves at 14 kV whereas the left limbs were used as controls. The evaluations included the callus formations based on serial radiographic examinations at 1, 4, 8, and 12 weeks and histologic examinations at 12 weeks for tissue distribution including bone tissues. Based on radiographic findings, there was no statistically significant difference in the amount of callus formation between the treated and the control groups at 8 weeks or less. However, the radiographic findings at 12 weeks statistically showed more callus formations in the treated group. In histologic examinations, there was significantly more cortical bone formation in the treated group at 12 weeks and the bone tissues were thicker, denser, and heavier. Shock wave therapy enhanced callus formation and induced cortical bone formation in acute fractures in dogs at 12 weeks. The effect of shock wave therapy seemed to be time-dependent at 3 months.

Animals↗

Endogenous natriuretic peptides participate in renal and humoral actions of acute vasopeptidase inhibition in experimental mild heart failure.

Mild heart failure is characterized by increases in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in the absence of activation of the renin-angiotensin-aldosterone system (RAAS). Vasopeptidase (VP) inhibitors are novel molecules that coinhibit neutral endopeptidase 24.11, which degrades the natriuretic peptides (NPs) and ACE. In a well-characterized canine model of mild heart failure produced by ventricular pacing at 180 bpm for 10 days, we defined the renal and humoral actions of acute VP inhibition with omapatrilat (OMA, n=6) and acute ACE inhibition (n=5) alone with fosinoprilat. We also sought to determine whether the NPs participate in the renal actions of acute VP inhibition by the administration of OMA together with an intrarenal administration of the NP receptor antagonist HS-142-1 (n=5). OMA resulted in a greater natriuretic response than did ACE inhibition in association with increases in plasma cGMP, ANP, BNP, urinary cGMP, urinary ANP excretion, and glomerular filtration rate (P<0.05 for OMA versus ACE inhibition). Plasma renin activity was increased only in the group subjected to ACE inhibition. Administration of intrarenal HS-142-1 attenuated the renal properties of OMA in association with a decrease in urinary cGMP excretion despite similar increases in plasma ANP and BNP. This study provides new insight into a unique new pharmacological agent that has beneficial renal actions in experimental mild heart failure beyond the actions that are observed with ACE inhibition alone and that are linked to the NP system.

Angiotensin-Converting Enzyme Inhibitors↗

Acute paraplegia in a patient with spinal tophi: a case report.

A 28-year-old man with a 5-year history of gouty arthritis suffered from an acute episode of lower back pain. He visited a rehabilitative clinic and received physical therapy following his examination. Weakness and numbness of both lower legs developed rapidly after physical therapy. He was sent to our hospital with complete paralysis of both lower limbs and complete sensory loss below the umbilicus 3 hours after the physical therapy. No peripheral tophi were found. Myelography showed an extrinsic compression of the dura sac at T10. Emergency decompressive laminectomy of T9 to T11 was performed. During the surgery, caseous material was found deposited in the ligamentum flavum and the left T9 to T10 facet joint, with indentation of the dura sac. The pathologic diagnosis was spinal tophi. After surgery, the patient's neurologic function recovered rapidly. It was suspected that inappropriate physical therapy might have aggravated acute inflammation of spinal gout and resulted in a rapid deterioration of neurologic function. Though gout is a chronic medical disease, an acute attack of spinal gout may be disastrous and requires emergency neurosurgical intervention.

Acute Disease↗

[The influence of hyaluronic acid and basic fibroblast growth factor on the proliferation of ligamentous cells].

OBJECTIVE: To observe the effects of hyaluronic acid (HA) and basic fibroblast growth factor (bFGF) on the proliferation of the cells from medial collateral ligament (MCL) and anterior cruciate ligament (ACL) cells. METHODS: The MCL cells and ACL cells of mature New Zealand white rabbit were cultured, while HA, bFGF or HA and bFGF were added to the cell culture media, the cellular proliferation was assayed by MTT method. RESULTS: HA only had no effect on the preoliferation of ACL cells, but had a small stimulatory effect on the proliferation of MCL cells. The addition of 1 ng/ml bFGF enhanced the proliferation of both MCL and ACL cells significantly, and this enhancement was maximal in the concentration of 50 ng/ml. However, the enhancement of proliferation of MCL and ACL cells could be achieved when the combination of HA in concentration of 100 micrograms/ml and bFGF in concentration of 100 ng/ml. CONCLUSION: It is evident that bFGF can enhance the proliferation of the ligament cells. HA can maintain the normal growth of ACL cells with no effect on the proliferation of the cells, while HA has a small stimulatory effect on the proliferation of MCL cells. However, when bFGF is coordinated with HA, more improvement of cellular proliferation can be achieved. HA can be used as a potential carrier for bFGF to enhance the healing of ligamentous tissue injuries.

Animals↗

Low cholesterol in erythrocyte membranes and high lipoperoxides in erythrocytes are the potential risk factors for cerebral hemorrhagic stroke in human.

OBJECTIVE: To explore the association of risk for human cerebral hemorrhage with blood cholesterol, free radicals, oxidation and lipoperoxidation. METHODS: 351 cerebral hemorrhage patients (CHP) in the acute phase and 100 healthy adult volunteers (HAV) were investigated by testing the contents of cholesterol (CH), lipoperoxides (LPO), nitric oxide (NO), vitamin C (VC) and vitamin E (VE) and activities of superoxide dismutase (SOD) in plasma and erythrocytes (RBC), and by assessing the contents of CH and LPO in RBC with spectrophotometric assays. RESULTS: Compared with the average values (AV) of the above biochemical parameters (BP) in the HAV group, the AV of CH in plasma and RBC, VC and VE in plasma as well as SOD in plasma and RBC in the CHP group were significantly decreased (P = 0.0000), while the AV of the LPO in plasma and RBC as well as NO in plasma in the CHP group were significantly increased (P = 0.0000). The findings of linear correlation analysis for the CHP group showed that the above biochemical parameters were significantly correlated with both intracranial hemorrhagic sizes (IHS) and neurotic functional defective scales (NDS). The findings of stepwise correlation analysis for the CHA group suggested that HIS was closely correlated with the values of CH and LPO in RBC as well as NO and VE in plasma, and that NDS was closely correlated with the values of CH and LPO in RBC as well as NO and VC in plasma. CONCLUSIONS: The findings of the present study suggest that marked low RBC cholesterol and marked high RBC lipoperoxides may constitute the potential main risk factors for human cerebral hemorrhage, and that the oxidative and lipoperoxidative stress in the CHP bodies is pathologically aggravated, leading to the oxidative and lipoperoxidative damages in the CHP.

Adult↗

Recurrent hypertensive intracerebral hemorrhage among Taiwanese.

Hypertensive intracerebral hemorrhage (HICH) was once thought to be a one-time event with very rare recurrence, but recent studies have revealed that the recurrent hemorrhage due to hypertension is not unusual. The purpose of this study was to determine the clinical characteristics of HICH among Taiwanese. From June 1988 to December 1999, 1421 HICH patients were admitted to our hospital. Among them, 68 patients (4.8%) had recurrent HICH. We reviewed their medical records and computed tomographic findings. There were 46 males and 22 females (M/F = 2.1) with a mean age of 59.9 +/- 11.9 years at the onset of the second hemorrhage. The median interval between the first two hemorrhages was 22.5 months (range: 1-107 months). Most of the recurrence was within two years of the first hemorrhage (within 1 year in 27.9%, within 1-2 years in 25%). The location of the second hemorrhage was typical for HICH (putamen in 44.1%, thalamus in 33.8%, cerebellum in 5.9%, pons in 4.4%, and caudate nucleus in 1.5%) except for 7 patients (10.3%) who had lobar hematoma. Forty-nine patients (72%) had both hemorrhages located in the supratentorium and in most of them (40 patients) the recurrent HICH occurred contralaterally to the first one. Putaminal-thalamic pattern was the most common (23.5%), followed by the putaminal-putaminal pattern (20.6%). The mortality rate of the second HICH was 17.6%. Seven patients (10.3%) experienced more than 2 episodes of hemorrhages. This report found that the recurrent HICH was not rare among Taiwanese. A substantial proportion (19.1%) of recurrence was after 5 years. The male predominance and risk factor for recurrent HICH require further study.

Adult↗

Regulation of phospholipase D activity and ceramide production in daunorubicin-induced apoptosis in A-431 cells.

We demonstrated here that daunorubicin induced apoptosis in A-431 cells, a human epidermoid carcinoma cell line. Treatment of cells with daunorubicin induced chromatin condensation, nuclear fragmentation, internucleosomal DNA degradation, and the proteolytic cleavage of PKC-delta and poly(ADP-ribose) polymerase in A-431 cells. Daunorubicin, as well as sphingomyelinase (SMase) and the exogenous cell-permeable ceramide analogue C(2)-ceramide, inhibited phospholipase D activity stimulated by phorbol 12-myristate 13-acetate or epidermal growth factor (EGF). Like ceramide, daunorubicin also decreased EGF-induced diacylglycerol generation. However, no increase in ceramide level was observed in daunorubicin-induced apoptosis in A-431 cells. Moreover, treatment of A-431 cells with exogenous cell-permeable C(2)-ceramide or SMase did not induce apoptosis. These results indicate that daunorubicin induces apoptosis in A-431 cells via a mechanism that does not involve increased ceramide formation.

Apoptosis↗

Subcutaneous administration of brain natriuretic peptide in experimental heart failure.

OBJECTIVES: The objective of this investigation was to define for the first time the cardiorenal and humoral actions of repeated short-term administration of subcutaneous (SQ) brain natriuretic peptide (BNP) administration during the evolution of experimental heart failure. BACKGROUND: The rationale of this study was based on BNP as a vasodilating, natriuretic, renin-inhibiting and lusitropic peptide of cardiac origin. METHODS: First, we defined the cardiorenal and humoral responses to acute low and high dose (5 microg/kg or 25 microg/kg) of SQBNP in experimental heart failure to establish the acute efficacy of an SQ delivery. Second, we characterized the response to 10 days of repeated short-term administration of BNP during the evolution of experimental heart failure produced by rapid ventricular pacing. RESULTS: Plasma BNP and 3',5'-cyclic guanosine monophosphate rapidly increased and peaked at 30 min after acute SQBNP administration with increases in urinary sodium excretion, urine flow and renal blood flow in association with reductions in cardiac filling pressures. After 10 days of repeated short-term administration of SQBNP, cardiac output was increased and systemic vascular resistance and pulmonary capillary wedge pressure were decreased, as compared with untreated dogs with heart failure. CONCLUSIONS: This study demonstrated for the first time that repeated short-term administration of SQ BNP administration for 10 days during the evolution of left ventricular dysfunction in a canine model results in an improvement in cardiovascular hemodynamics. This investigation supports a potential novel strategy for the chronic administration of BNP in the therapeutics of heart failure.

Animals↗

Chromatin fine structure profiles for a developmentally regulated gene: reorganization of the lysozyme locus before trans-activator binding and gene expression.

The chicken lysozyme locus is activated in a stepwise fashion during myeloid differentiation. We have used this locus as a model to study at high resolution changes in chromatin structure both in chicken cell lines representing various stages of macrophage differentiation and in primary cells from transgenic mice. In this study we have addressed the question of whether chromatin rearrangements can be detected in myeloid precursor cells at a stage well before overt transcription of the lysozyme gene begins. In addition to restriction enzyme accessibility assays and DMS footprinting, we have applied new, very sensitive techniques to assay for chromatin changes. Particularly informative was UV photofootprinting, using terminal transferase-dependent PCR and nonradioactive detection. We find that the basic chromatin structure in lysozyme nonexpressing hematopoietic precursor cells is highly similar to the pattern found in fully differentiated lysozyme-expressing cells. In addition, we find that only in nonexpressing cells are dimethylsulfate footprints and UV photofootprints affected by trichostatin, an inhibitor of histone deacetylation. These results are interpreted to mean that most chromatin pattern formation is complete before the binding of end-stage trans-activators, supporting the notion that heritable chromatin structure is central to the stable epigenetic programs that guide development.

Animals↗

Immunocytochemical localization of putative gamma-aminobutyric acid receptor subunits in the head ganglia of Periplaneta americana using an anti-RDL C-terminal antibody.

A polyclonal antibody raised against a 17 amino acid polypeptide (the predicted C-terminal sequence of the cloned Drosophila melanogaster gamma-aminobutyric acid (GABA) receptor subunit, RDL) was used to investigate the distribution of GABA receptor subunit(s) of this type in the nervous system of the cockroach Periplaneta americana. Intense staining was detected in the calyces of the mushroom bodies, glomeruli of the antennal lobes, lower central body, the corpora cardiaca and several cell layers of the medulla and the lobula regions of the optic lobe. The most intense immunocytochemical staining was in the suboesophageal ganglion. Control sections pre-incubated with the primary antibody and conjugated peptide were not stained. Thus, it appears that a GABA receptor subunit of the RDL type is located in cockroach brain regions involved in the processing of visual, olfactory and mechanosensory inputs to the nervous system. Since the corpora cardiaca reacted to this antiserum, this type of GABA receptor may also be involved in the regulation of neurosecretory activity.

Animals↗

RGS7 complex formation and colocalization with the Gbeta5 subunit in the adult rat brain and influence on Gbeta5gamma2-mediated PLCbeta signaling.

This study describes the colocalized distribution and dimeric complex formation between RGS7, a GTPase-activating protein for several heterotrimeric Galpha protein families, and the Gbeta5 subunit in the adult rat brain. Confocal dual immunofluorescence labeling studies indicated a broad regional specificity in the cellular coexpression between RGS7 and Gbeta5 within the cerebral cortical layers I and V-VI, hippocampal formation, caudate-putamen, medial habenula, most thalamic nuclei, and cerebellar molecular and granular layers. In all instances, Gbeta1-beta4 immunoreactivities exhibited no observable colocalization with RGS7, despite their widespread codistribution throughout similar neuronal networks. Coimmunoprecipitation studies confirmed the selective protein-protein interaction between RGS7 and Gbeta5 within brain regions that displayed immunohistochemical colocalization. The influence of RGS7 to modulate Gbeta5gamma2-mediated phosphatidyl inositol (PI) production was examined in COS-7-cotransfected cells. In the presence of Gbeta5gamma2 only, intracellular PI accumulation was increased by 25% above basal levels; addition of RGS7 produced no significant alteration in Gbeta5gamma2-mediated PI accumulation. A similar trend was exhibited when full-length RGS7 was substituted with an RGS7 construct lacking the Gbeta5-interacting region (G protein gamma-like domain; GGL domain) or with RGS4. In conclusion, RGS7/Gbeta5 dimers occurred within most brain regions in which both proteins were cellularly coexpressed. However, an influence of RGS7 on Gbeta5gamma2-mediated PLCbeta signaling activity was not apparent, athough this was in COS-7 cell transfection studies.

Animals↗

In vivo, high-resolution analysis of yeast and mammalian RNA-protein interactions, RNA structure, RNA splicing and ribozyme cleavage by use of terminal transferase-dependent PCR.

We have investigated the analysis of RNA by use of terminal transferase-dependent PCR (TDPCR), a procedure previously used for the analysis of DNA and chromatin [J. Komura and A.D.Riggs, Nucleic Acids Res.,26, 1807-1811 (1998)]. When preceded by reverse transcription (RT), TDPCR provides an extremely sensitive, versatile, quantitative and nucleotide-level assay for detecting RNA lesions or structures that block primer extension during the RT step. The procedure is: (i) RT using a gene-specific oligonucleotide; (ii) ribo-tailing of the single-stranded cDNA product by use of terminal deoxy-nucleotidyl transferase; (iii) ligation of a DNA linker to the tailed cDNA by use of T4 DNA ligase; and (iv) PCR using a nested, gene-specific primer and a linker-specific primer. This procedure combines the versatility of a primer extension assay with nucleotide-level resolution, the specificity of nested primers and the sensitivity of PCR. Band patterns obtained are reproducible and quantifiable. We successfully used the technique for the study of yeast RNA structure, splicing intermediates and ribozyme cleavage. Also, in vivo footprint experiments, using mammalian cells and RNase T1, revealed the binding of iron-responsive element binding protein to iron responsive elements in the mRNAs of transferrin receptor and ferritin H-chain.

Base Sequence↗