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Biomedical subjects

H H Chen

Publications and source records attributed to H H Chen.

At least 19 recordsLinked to original sources
PubMed1998

A 2.9-kilobase noncoding nuclear RNA functions in the establishment of persistent Hz-1 viral infection.

Differential viral gene expression during both productive and persistent infections of Hz-1 virus in insect cells was elucidated. Despite more than 100 viral transcripts being expressed during productive viral infection, massive viral gene shutoff was observed during viral persistency, leaving the 2.9-kb persistence-associated transcript 1 (PAT1) as the only detectable viral RNA. Persistence-associated gene 1 (pag1), which encodes PAT1, was cloned and found to contain no significant open reading frames. PAT1 is not associated with the cellular translation machinery and is located exclusively in the nucleus. Further experiments showed that PAT1 is functional in the establishment of persistent Hz-1 viral infection in the cells. All the evidence collectively indicates that PAT1 is a novel nuclear transcript of viral origin. Our results showed that although PAT1 and XIST RNA, a mammalian X-inactive specific transcript, are transcribed by different genes, they have interesting similarities.

Animals↗
PubMed1997

Effects of subacute lead exposure on [3H]MK-801 binding in hippocampus and cerebral cortex in the adult rat.

We used the NMDA receptor non-competitive antagonist, [3H]MK-801, as a ligand for an autoradiographic study to determine the effects of lead on NMDA receptor in the rat brain. Adult male rats were administered lead acetate, 100 mg/kg, or sodium acetate, 36 mg/kg (control), by i.p. for 7 days. High lead levels were detected in blood (41.1 microg/dl) and in brain (16.7-29.4 microg/g). Concentrations of lead in brain regions were not significantly different. The [3H]MK-801 binding was heterogeneously distributed throughout the rat brain with the following order of binding densities: hippocampal formation > cortex > caudate-putamen > thalamus > brainstem. Lead exposure produced a significant decrease in [3H]MK-801 binding to the NMDA receptor in the hippocampal formation including CA2 stratum radiatum, CA3 stratum radiatum, hilus dentate gyrus and presubiculum, and in the cerebral cortex including agranular insular, cingulate, entorhinal, orbital, parietal and perirhinal areas. The hippocampal formation is known as a critical neural structure for learning and memory processes, whereas, cortical and subcortical regions have been demonstrated to be involved in the modulation of complex behavioral processes. The NMDA receptor has been demonstrated to play a key role in synaptic plasticity underlying learning and memory. Lead-induced alterations of NMDA receptors in the hippocampal formation and cortical areas may play a role in lead-induced neurotoxicity.

Animals↗
PubMed1997

Effects of chronic lead exposure on [3H]MK-801 binding in the brain of rat.

We have used quantitative autoradiographic methods to determine the effects of chronic lead exposure on N-methyl-D-aspartate (NMDA) receptors in the brain of female rat. Rats were exposed pre- and post-natally from day 4 +/- 1 post conception with 1000 ppm lead in their drinking water. This treatment continued after weaning. No effects of lead on [3H]MK-801 binding were found at PN 28. However, lead caused a significant increase in [3H]MK-801 binding in the hippocampus including CA1 and CA2, and in the occipital and temporal cortical areas at PN 56 and at PN 112. An increase in binding was also found in the entorhinal cortex and the dentate gyrus at PN 112. Because the NMDA receptor is involved in learning and memory, the lead-induced disruption of NMDA receptors in the hippocampus and cortex may be associated with the cation-induced cognition deficits.

Animals↗
PubMed1997

Persistence in muscle of an adenoviral vector that lacks all viral genes.

Genetic correction of inherited muscle diseases, such as Duchenne muscular dystrophy, will require long term expression of the recombinant protein following gene transfer. We have shown previously that a new adenoviral vector that lacks all viral genes expressed both full-length dystrophin and beta-galactosidase in mdx (dystrophin-deficient) mouse muscle. We observed a significant histologic improvement of vector-transduced mdx muscle before the eventual loss of vector-encoded transgene expression. In this study, we investigated whether an immunological response against vector-encoded beta-galactosidase contributed to the loss of vector expression and affected vector persistence in muscle. Intramuscular vector injection in control normal mice resulted in an early and complete loss of beta-galactosidase expression accompanied by predominantly CD4+ and CD8+ lymphocytic infiltration and a significant loss of vector DNA. In contrast, intramuscular vector injection in lacZ transgenic mice resulted in persistent expression of beta-galactosidase for at least 84 days with no evidence of inflammation or significant loss of vector DNA. Our studies demonstrate that, in the absence of an immune response induced by beta-galactosidase expression, an adenoviral vector lacking all viral genes is stably maintained in muscle.

Adenoviridae↗
PubMed1997

Shear stress induction of the tissue factor gene.

Using flow channel, we report that the application of a laminar shear stress induced a transient increase of tissue factor (TF) procoagulant activity in human umbilical vein endothelial cells (HUVEC), which was accompanied by a rapid and transient induction of the TF mRNA in the HUVEC. Functional analysis of the 2.2 kb TF 5' promoter indicated that a GC-rich region containing three copies each of the EGR-1 and Sp1 sites was required for induction. Mutation of the Sp1 sites, but not the EGR-1 sites, attenuated the response of TF promoter to shear stress. Thus, Sp1 is a newly defined shear stress responsive element. Electrophoretic mobility shift assays showed there was no increase in binding of nuclear extracts from sheared cells to an Sp1 consensus site. In contrast, immunoblotting of these nuclear extracts with antibody against transcription factor Sp1 demonstrated that shear stress increased the phosphorylation of Sp1. We also showed that shear stress, like the phosphatase inhibitor okadaic acid, increased the transcriptional activity of Sp1. These findings suggest that the shear stress induction of TF gene expression is mediated through an increased Sp1 transcriptional activity with a concomitant hyperphosphorylation of Sp1.

Endothelium, Vascular↗
PubMed1997

Stapled colonic J-pouch-anal anastomosis without a diverting colostomy for rectal carcinoma.

PURPOSE: Colonic J-pouch reconstruction is designed to improve functional outcome of coloanal anastomosis. Most surgeons use a diverting colostomy to avoid severe pelvic sepsis caused by anastomotic breakdown. METHODS: We report the outcome of 30 consecutive patients with colonic J-pouch-anal anastomosis without a diverting colostomy performed between November 1992 and October 1993. All patients had carcinoma of the lower two-thirds of the rectum. Patients were seen every three months. Functional results were compared with those of 21 rectal cancer patients with straight coloanal anastomosis who underwent surgery in the same period and 20 normal patients. RESULTS: There were two anastomotic leakages and one postoperative death. After one year, patients with pouch anastomosis had significantly less frequency of defecation and rectal urgency compared with those with straight anastomosis (P < 0.01); 48 percent of patients with straight anastomosis had more than five bowel movements per day, whereas all patients with pouch anastomosis had five or less bowel movements per day. Manometric studies showed maximum tolerable volume was significantly higher in patients with pouch anastomosis (81 vs. 152 ml; P < 0.01). CONCLUSIONS: Stapled colonic J-pouch-anal anastomosis without a diverting colostomy is a reliable procedure that provides good, long-term functional results.

Adult↗
PubMed1997

Developmental lead exposure and two-way active avoidance training alter the distribution of protein kinase C activity in the rat hippocampus.

Long-term exposure to a low level of lead is associated with learning deficits. Several types of learning have been correlated to hippocampal protein kinase C (PKC) activation. This study was designed to determine if there is a correlation between the effects of lead on hippocampal PKC activation and those on learning performance. Rats were exposed to 0.2% (w/v) lead acetate at different developmental stages including a maternally exposed group, a postweaning exposed group, and a continuously exposed group. The continuously lead exposed rats tended to avoid less frequently and not respond more frequently in two-way active avoidance training than did controls. This training process was associated with translocation of hippocampal PKC activity from cytosol to membrane. Two-way analysis of variance of data indicates that there is a significant training and lead treatment interaction in the ratio of membrane to cytosolic PKC activity (F3,32 = 3.013; p = 0.044). The interaction is attributable to the absence of the training-induced PKC translocation in the continuously lead exposed rats. In addition, no significant changes were observed in learning performance and training-induced hippocampal PKC activation after maternal and postweaning lead exposure. Continuous and longer duration of lead exposure appears to affect the learning performance and hippocampal PKC activation. These data suggest that a change in the activation of hippocampal PKC may be involved in the lead-induced deficit in learning.

Analysis of Variance↗
PubMed1997

Abrupt, severe hypertension associated with dissection of a renal artery during selective catheterization.

A 23-year-old woman with longstanding renovascular disease associated with intimal dysplasia presented with stage I-II hypertension 6 years following bilateral percutaneous renal artery angioplasties (associated with normotension after antihypertensive agents). Following the diagnostic selective left renal arteriogram, blood pressure (BP) rose from 140/90 mm Hg to 200/130 mm Hg over 30-40min. Reassessment angiography revealed a proximal intimal dissection with the development of a lengthy false lumen. Attempts to cross the dissected area for stent placement were unsuccessful. To avoid the consequences of severe and accelerated hypertension, intravenous enalaprilat was administered (which lowered BP to 160-170/100 mm Hg) and the patient underwent emergency aortorenal bypass surgery. Fortunately, the BP normalised post-operatively and renal function remained normal. This case illustrates the possibility that catheterisation of a renal artery may lead to acute, severe hypertension by creating an acutely ischaemic kidney through intimal or medial arterial dissection. In such cases, pharmacologic blockade with angiotensin-converting enzyme inhibitors may provide stabilisation of BP to allow surgical revascularisation to proceed safely.

Acute Disease↗
PubMed1997

Complications in patients with palmar hyperhidrosis treated with transthoracic endoscopic sympathectomy.

OBJECTIVE: To assess the complications in a group of patients with palmar hyperhidrosis treated with transthoracic endoscopic sympathectomy. The extraordinarily high incidence of postoperative compensatory hyperhidrosis in our series is stressed and explained. METHODS: The retrospective study included chart reviews and outpatient assessments. Seventy-two patients underwent T2 or T2-T3 endoscopic sympathectomy for primary palmar hyperhidrosis. Patients' hyperhidrosis severity, precipitating factors, postoperative complications, surgical results, and satisfaction were assessed. Severity of palmar hyperhidrosis and compensatory hyperhidrosis was classified by two grading scales. RESULTS: The success rate of sympathectomy was 93%. All patients except one suffered from compensatory sweating, which was the main cause of patients' dissatisfaction postoperatively. Seventeen percent of the patients (12 of 72 patients) experienced new symptoms of gustatory sweating (facial sweating associated with eating). Twenty-one patients experienced other complications, including pneumothorax, Horner's syndrome, nasal obstruction, and intercostal neuralgia. CONCLUSION: Transthoracic endoscopic sympathectomy is an effective and simple modality to treat palmar hyperhidrosis. However, all patients need to be warned of the common complications, particularly compensatory hyperhidrosis, before surgery.

Adult↗
PubMed1997

Prognostic significance of altered cerebral blood flow velocity in acute head trauma.

From July 1992 to January 1993, 31 patients with acute closed head injuries underwent blood flow velocity (BFV) measurement in the middle cerebral artery by transcranial Doppler ultrasound. Eighteen patients had abnormal changes of BFV (group A) and 13 patients had normal BFV (group B). In group A, there were eight deaths (44%) and the Glasgow Outcome Scale score was 2.6 +/- 0.4 (mean +/- SEM). On admission, 14 group A patients had decreased BFV, including nine patients with evidence of early cerebral circulatory arrest (CCA). During hospitalization, eight group. A patients were diagnosed with global hyperemia, including two patients who had early CCA. Another six in group A had ultrasound recordings consistent with vasospasm, and three of these six also experienced early CCA. The renaming four patients in group A had persistently low BFV, progressing from early CCA. In group B there were two deaths (15%) and the mean Glasgow Outcome Scale score was 4.0 +/- 0.5. Group A had higher mortality (Fisher's exact test, p = 0.128) and a significantly higher rate of unfavorable functional outcome than group B. To evaluate the prognostic significance of these BFV changes, group A was subdivided into global hyperemia, vasopasm and early CCA subgroups. Both the vasospasm and early CCA subgroups had significantly lower Glasgow Coma Scale scores on admission and a higher rate of unfavorable functional outcomes than group B. All five survivors with vasospasm and/or early CCA showed ischemic morbidity on follow-up cranial computed tomography; though those with global hyperemia did not. There were no significant differences in the Glasgow Coma Scale score on admission, mortality or functional outcome between global hyperemia patients and group B patients. Global hyperemia may represent a recovery stage of impaired cerebral hemodynamics. This stage may occur transiently and has no major impact on morbidity or mortality. Vasospasm and early CCA may be closely related to ischemic complications, and may provide clinical information for selecting appropriate therapy in acute head trauma.

Acute Disease↗
PubMed1997

Modified reverse sural artery flap.

BACKGROUND: Reverse sural artery flap is a useful flap for defect reconstruction in the distal leg, ankle and heel. The major problem encountered with the reverse sural artery flap is its unreliability. It may be compromised by venous congestion and peripheral arterial insufficiency when the flap is transferred with its pedicle tunneled subcutaneously. METHODS: In this study we describe modifications of this procedure consisting of a wider pedicle during flap design and transferring it without passing the pedicle through a subcutaneous tunnel. The pedicle is then divided in a second-stage operation. Four patients with defects at various locations over the distal leg and heel had reconstruction with reverse sural artery flap in this fashion. RESULTS: No failure developed among these cases and the wounds healed without complication. These patients were satisfied with this procedure. CONCLUSION: Reverse flow flap vascularity is maintained and its viability is ensured with this technical modification.

Aged↗
PubMed1996

Construction of a chimeric Theiler's murine encephalomyelitis virus containing the leader gene of foot-and-mouth disease virus.

The foot-and-mouth disease virus (FMDV) leader coding region (Lb) was cloned into a full-length cDNA of the DA strain of Theiler's murine encephalomyelitis virus (TMEV) replacing the complete L coding region of TMEV. This construct, pDAFSSC1-Lb, was engineered to contain cleavage sites, at the 3' end of the Lb coding region, for both the FMDV Lb and the TMEV 3C proteases. Transcripts derived from this construct were translated in a cell-free system. Analysis of the translation products showed efficient synthesis and processing of TMEV structural and nonstructural proteins as well as a major band that comigrated with FMDV Lb and was reactive with Lb antiserum. A small plaque virus was recovered from BHK-21 cells transfected with RNA derived from pDAFSSC1-Lb. RT-PCR of RNA isolated from DAFSSC1-Lb virus demonstrated a product corresponding in size and sequence to FMDV Lb. DAFSSC1-Lb virus grew slower than parental virus, DAFSSC1, and to a lower titer. The pattern of viral proteins synthesized in DAFSSC1-Lb virus-infected cells was very similar to the pattern in DAFSSC1 virus-infected cells except that significant amounts of FMDV Lb were produced. In addition, extracts from DAFSSC1-Lb-virus-infected cells cleaved an exogenous source of the translation initiation factor, p220, while DAFSSC1-virus-infected extracts did not. Chimeric viruses that contain coding regions from different picornaviral genera may be valuable tools in investigating the function of particular viral proteins and in studying disease pathogenesis.

Animals↗
PubMed1996

Chronic osteomyelitis of the spine managed with a free flap of latissimus dorsi. A case report.

STUDY DESIGN: A patient with intractable spinal osteomyelitis who underwent surgery 12 times with persistent exposed bone is presented. OBJECTIVES: To demonstrate the effectiveness of free-flap grafting for managing difficult spinal osteomyelitis wounds. SUMMARY OF BACKGROUND DATA: Conventional procedures can usually achieve wound closure, but they may not work for advanced cases. METHODS: A free latissimus dorsi flap was transferred for reconstruction. The muscle component was used to obliterate the dead space and cover the exposed bone, and the skin component was used for tension-free closure of the wound. RESULTS: The wound healed dramatically. There was no recurrence of infection at 2-year follow-up evaluation. CONCLUSIONS: For an intractable spinal osteomyelitis wound, a free flap should be considered, although the surgery is difficult. Technical precautions in performing this operation are given.

Chronic Disease↗
PubMed1996

A new adenoviral vector: Replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and beta-galactosidase.

Adenoviral vector-mediated gene transfer offers significant potential for gene therapy of many human diseases. However, progress has been slowed by several limitations. First, the insert capacity of currently available adenoviral vectors is limited to 8 kb of foreign DNA. Second, the expression of viral proteins in infected cells is believed to trigger a cellular immune response that results in inflammation and in only transient expression of the transferred gene. We report the development of a new adenoviral vector that has all viral coding sequences removed. Thus, large inserts are accommodated and expression of all viral proteins is eliminated. The first application of this vector system carries a dual expression cassette comprising 28.2 kb of nonviral DNA that includes the full-length murine dystrophin cDNA under control of a large muscle-specific promoter and a lacZ reporter construct. Using this vector, we demonstrate independent expression of both genes in primary mdx (dystrophin-deficient) muscle cells.

Adenoviridae↗
PubMed1996

Tumour development, histology and grade of breast cancers: prognosis and progression.

Using 1,973 breast tumours from women aged 40-69 participating in the Swedish two-county trial of mammographic screening for breast cancer, we examined the effect of histological type on prognosis and sojourn time (the duration of the preclinical screen-detectable phase) by age. The hypothesis of dedifferentiation, according to which a cancer of mixed malignancy grade drifts towards grade 3 as the more poorly differentiated part of the tumour grows faster than the well-differentiated part, was also assessed. Ductal carcinoma in situ, invasive ductal carcinoma of grade 1, mucinous carcinoma and tubular carcinoma were all associated with good survival. Ductal carcinoma of grade 3 was associated with poor survival. Ductal carcinoma of grade 2, lobular and medullary carcinoma were associated with intermediate survival. These patterns were much the same in women aged 40-49 as in women aged 50-69. In women aged 40-49, sojourn time was estimated at about 2 years regardless of histological type. For women aged 50-69, there was a marked association of sojourn time with histological type, the shortest sojourn time being observed for lobular (2 years) and medullary (1.2 years) carcinoma, and the longest for ductal carcinoma grade 1 (7.7 years) and tubular carcinoma (7.1 years). There was strong evidence of a potential to dedifferentiation. A mover-stayer mixture of Markov chain models estimated that, in women aged 40-54, 91% of ductal tumours have the potential to dedifferentiate and, in women aged 55-69, 38% of ductal tumours have such a potential.

Adult↗