Search PubMed⌕ Search

Biomedical subjects

J L Chen

Publications and source records attributed to J L Chen.

At least 127 records · Page 7Linked to original sources

Parenchymal microvascular systems and cerebral atrophy in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are hypertensive, hyperactive, and hydrocephalic; furthermore SHR have smaller brain volume and weight than age-matched, normotensive Wistar-Kyoto rats (WKY). At 6-7 months of age, local cerebral glucose is sizably lower in SHR than WKY. The hypothesis that these several abnormalities of SHR lead to variations in cerebral microvascular bed morphology was tested in 6-7-month-old SHR and WKY by quantitating various parameters of small, intermediate, and large parenchymal microvessels (grouped by luminal diameter) in 21 brain areas. Within each rat strain, the microvascular bed properties such as vessel profile frequency (density) varied considerably among the 21 brain areas. In opposition to the hypothesis, mean luminal diameter as well as profile frequency, surface area, and luminal volume of the microvascular beds per unit tissue mass were virtually identical in each brain area of SHR and WKY for the three groups of microvessels. These findings coupled with the reports of less tissue per structure but similar density of neurons throughout the brain of SHR and WKY indicate that there are fewer neurons and less vascular tissue per brain structure in 6-7-month-old SHR than WKY; in addition, they suggest a linkage between the size of parenchymal microvascular beds and the surrounding nervous tissue.

Animals↗

Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators.

The general transcription factor TFIID is a multiprotein complex containing the TATA-binding protein and several associated factors (TAFs), some of which may function as coactivators that are essential for activated, but not basal, transcription. Here we describe the isolation and characterization of the first gene encoding a TAF protein. The deduced amino acid sequence of TAF110 revealed the presence of several glutamine- and serine/threonine-rich regions reminiscent of the protein-protein interaction domains of the regulatory transcription factor Sp1 that are involved in transcription activation and multimerization. In both Drosophila cells and yeast, TAF110 specifically interacts with the glutamine-rich activation domains of Sp1. Moreover, purified Sp1 selectively binds recombinant TAF110 in vitro. These findings taken together suggest that TAF110 may function as a coactivator by serving as a site of protein-protein contact between activators like Sp1 and the TFIID complex.

Amino Acid Sequence↗

Drosophila TFIIA-L is processed into two subunits that are associated with the TBP/TAF complex.

The basal factor TFIIA has been shown to act early during initiation in both the mammalian and yeast transcription systems, but a TFIIA-like activity has not been identified in Drosophila. While characterizing the Drosophila TFIID complex, we discovered that a 30-kD protein that cofractionated with dTFIID was homologous to the previously identified, large subunit of yeast TFIIA. Here, we report the cloning and biochemical characterization of Drosophila TFIIA-L. Coimmunoprecipitation studies with anti-dTBP, anti-dTFIIA-L, and anti-TAF antibodies indicated a tight association of the endogenous dTFIIA and dTFIID. However, dTFIIA could be dissociated from dTFIID under conditions that did not elute the TAFs, and the eluted material had mobility shift and transcriptional activities associated with TFIIA. Peptide sequence and Western analysis with antibodies raised against the amino- and carboxy-terminal portions of recombinant dTFIIA-L revealed that a precursor 48-kD species was cleaved in vivo, giving rise to the 30- and 20-kD subunits of dTFIIA that remain associated with each other and with dTFIID. Protein-protein interaction assays identified dTBP and dTAFII110 as targets for binding TFIIA in the TFIID complex. These results suggest that TFIIA may form a specific complex with both TAFs and other components of the transcriptional machinery during formation of the initiation complex.

Amino Acid Sequence↗

Molecular cloning and characterization of dTAFII30 alpha and dTAFII30 beta: two small subunits of Drosophila TFIID.

The multisubunit transcription factor TFIID is an essential component of the RNA polymerase II initiation apparatus. Recent studies suggest that TFIID subunits, or TAFs associated with the TATA-binding protein (TBP), play a critical role in modulating transcriptional activation by sequence-specific DNA-binding factors. Thus far, six of the largest TAFs associated with Drosophila TFIID have been cloned and partially characterized. Here, we report the molecular cloning, expression, and subunit interaction specificities of two small molecular mass TAFs. Both dTAFII30 alpha and dTAFII30 beta are associated with TFIID via interactions with other TAFs, including dTAFII250, dTAFII150, and dTAFII110. In addition, dTAFII30 alpha also contacts dTBP. The carboxy-terminal half of dTAFII110 was found to contact a short 67-amino-acid region of dTAFII30 alpha, which is predicted to form two potential alpha-helices, one of which is amphipathic. Interestingly, dTAFII30 alpha also appears to multimerize through its carboxy-terminal region. Although neither dTAFII30 alpha nor dTAFII30 beta have been found to interact with specific activators thus far, it is intriguing that both bind other TAFs such as dTAFII110 and dTAFII150, which are the targets of activation domains. Our studies suggest that both of the small subunits of TFIID play a role in the assembly of the complex and may contribute to the stability of multiple TAF-TAF interactions.

Amino Acid Sequence↗

Nicotine increases microvascular blood flow and flow velocity in three groups of brain areas.

To examine the mechanism of local cerebral blood flow (LCBF) elevation, nicotine (1.75 mg/kg sc) was administered to rats, and LCBF plus the distribution spaces of radiolabeled albumin (RISA) and red blood cells (RBC) in parenchymal microvessels were measured throughout the brain. Microvascular blood spaces and transit times were calculated from the data. From 1.5 to 3 min after nicotine administration, LCBF was raised by 40-150% in 16 of the brain areas and unaltered in the remaining 28 areas. The affected structures included parts of the visual-auditory, sensorimotor-cortical, and interpeduncular systems. RBC spaces were not changed by nicotine treatment. RISA and blood spaces were increased slightly but not significantly in some of the LCBF-affected areas but nowhere else. Nicotine seemingly elevates LCBF in the affected areas mainly by increasing linear velocity of flow through the microvascular beds. In agreement with this, mean transit time, which is inversely related to velocity, was decreased from 0.3-0.5 to approximately 0.2 s in the microvascular systems of the nicotine-affected areas.

Animals↗

Reperfusion arrhythmias in acute myocardial infarction.

In 27 patients with acute myocardial infarction (MI) and their infarct-related coronary artery being completely occluded who received thrombolytic therapy or percutaneous transluminal coronary angioplasty, reperfusion was confirmed by immediate coronary angiography in 24. Reperfusion arrhythmias (RA) occurred in 19 (79.2%) of the patients, including ventricular arrhythmias in 13 (54.2%). Ventricular fibrillation and sustained ventricular tachycardia developed in 2 (8.4%) and accelerated idioventricular rhythm in 5 (20.8%), the latter was a reliable indicator of coronary recanalization. Transient sinus bradycardia or AV block occurred in 10 (66.7%) of the 15 patients with inferoposterior MI. The occurrence of RA was not related to the duration of ischemia; ventricular RA was also not related to the location of MI and the occurrence and severity of ischemic arrhythmias before reperfusion.

Aged↗

[Clinical characteristics and coronary angiographic findings of spontaneous angina].

The clinical characteristics and coronary angiographic findings in 50 patients with spontaneous angina (SA) were studied. Coronary angiography did not disclose any severe fixed narrowing in 7 patients with SA only; the episodes of SA in these patients is the result of subtotal occlusion of a major coronary artery induced by spasm. 43 patients with both SA and effort angina (EA) had more severe coronary obstructive lesions. In these patients, the localization of electrocardiographic ischemia during episodes of SA and EA were always identical, indicating that the episodes of SA are related to the coronary narrowing lesions. Our study showed that incidence of SA was highest with 90% stenosis of the ischemia related artery, suggesting that besides coronary spasm, physiological coronary vasoconstriction or increase of coronary vasomotor tone could play an important role in the production of SA. In addition, turbulent flow, stasis, platelet aggregation and transient thrombosis might be individually responsible for episodes of SA in patients with severe coronary stenosis.

Adult↗

Sarcomatoid carcinoma of the lung. Immunohistochemical and ultrastructural studies of 14 cases.

The authors retrospectively reviewed data regarding 14 patients with sarcomatoid carcinomas of the lung seen and treated at M.D. Anderson Cancer Center from 1955 to 1986. The following were the histologic criteria for inclusion in the study: (1) the concurrent presence of malignant epithelial and sarcomatoid spindle cell components, and (2) positive immunoreactivity for antikeratin antibody or ultrastructural demonstration of epithelial differentiation in sarcomatoid tumors in which the epithelial component was inconspicuous. For the sarcomatoid components, the most frequent pattern was malignant fibrous histiocytoma, which was present in ten tumors. An unclassified sarcomatoid pattern was found in two cases and a fibrosarcomatous pattern in two remaining cases. Clinically, the median patient age was 59 years; 12 patients were male and 2 were female; 13 were smokers and 1 used snuff. Three patients had Stage I, ten had Stage III, and one had Stage IV disease. One patient with Stage I, seven with Stage III, and one with Stage IV disease died of their carcinomas 2 to 26 months after diagnosis (median survival time 12 months). All patients who had lymph node metastases at presentation died of disease. The authors concluded the following: (1) patients with sarcomatoid carcinoma of the lung usually presented at an advanced stage; (2) lymph node metastasis, as with a usual carcinoma of the lung, is an important prognostic factor; and (3) for all lung tumors with a sarcomatoid pattern, especially a malignant fibrous histiocytoma pattern, extensive samples should be obtained and immunoperoxidase or ultrastructural studies done to identify epithelial differentiation.

Adult↗

Epidemiologic study of lung cancer mortality in workers exposed to titanium tetrachloride.

A study was done to examine whether workers exposed to titanium tetrachloride had significantly higher risks of lung cancer, chronic respiratory disease, pleural thickening/plaques, or pulmonary fibrosis than referent groups. A total of 2477 employees from two titanium dioxide plants were studied. Of that group, 969 employees exposed to titanium tetrachloride were observed from 1956 through 1985 for cancer and chronic respiratory disease incidence and from 1935 through 1983 for mortality. A cross-sectional sample of 398 employees was evaluated for chest roentgenogram abnormalities. Cohort analyses showed that the risk of developing lung cancer and other fatal respiratory diseases was not statistically significantly higher for the titanium tetrachloride-exposed workers than for the referent group. Nested case-control analyses found no statistically significant association between titanium tetrachloride exposure and risk of lung cancer, chronic respiratory disease, and chest roentgenogram abnormalities. No cases of pulmonary fibrosis were observed among titanium tetrachloride-exposed employees. Smoking was found to be a strong predictor of lung cancer mortality in the nonexposed employees with an increased risk of dying from lung cancer up to 7-fold higher in current smokers than in nonsmokers.

Case-Control Studies↗

The Laerdal pocket mask: effects of increasing supplementary oxygen flow.

To determine the effect of increasing supplementary oxygen flow during ventilation with the Laerdal pocket mask 24 subjects ventilated a modified recording mannikin for four 90 s periods using the mask with oxygen flows of 5 l, 10 l, 15 l and 20 l.min-1. Oxygen concentration increased and carbon dioxide concentration decreased with increasing oxygen flow. Tidal volume also increased with oxygen flow. The delivered oxygen concentrations were lower than previously reported at all four rates; however, mask function improved with increasing flow up to 20 l.

Adult↗

Psychiatric disturbances associated with ganciclovir therapy.

OBJECTIVE: To report a case of possible ganciclovir-induced psychiatric disturbances. CASE SUMMARY: A patient with AIDS who had no known psychiatric history and mild renal dysfunction experienced exacerbation of cytomegalovirus retinitis and was treated with ganciclovir 5 mg/kg iv q12h. The patient complained of nightmares and developed visual hallucinations and severe agitation on day 15 of ganciclovir therapy. The problems resolved after haloperidol administration and ganciclovir withdrawal and reappeared when the same regimen was reinstituted. However, the patient was able to tolerate the maintenance dose of ganciclovir at 5 mg/kg/d along with haloperidol later without further episodes of visual hallucinations. DISCUSSION: Case reports in the literature on ganciclovir-or its analog, acyclovir-, induced psychiatric disturbances were reviewed and compared. The potential relationship between ganciclovir accumulation in patients with renal insufficiency and the observed central nervous system problems in our patient was postulated. CONCLUSIONS: It is likely that ganciclovir accumulation contributed to the acute psychotic episodes observed in our patient. Adjusting ganciclovir dosage based on the patient's renal function is probably the only approach required to prevent or reduce the incidence of these episodes.

Acquired Immunodeficiency Syndrome↗

[A study on the regulation of ACTH secretion in rat pituitary cells].

In addition to method of ACTH RIA, a rat pituitary cell perfusion system was developed for the assessment of pituitary cells in stimulating and inhibiting ACTH secretion induced by some substances. Hypothalamic extract stimulated the ACTH secretion in a dose-dependent manner. AVP, cAMP, Ca2+, K+, noradrenaline, metoclopramide and haloperidol also had some stimulating effect. Dexamethasone and dopamine inhibited the basal ACTH secretion of pituitary cell and antagonized the effect of the various stimulating substances. Cyproheptadine could antagonize the effect of some of the stimulating substances while GABA had no marked inhibiting effect.

Adrenocorticotropic Hormone↗

Immunization strategies for the production of rat monoclonal anti-idiotope antibodies.

Anti-idiotypic antibodies are powerful reagents for the study of immunoregulation, and have potential interest as vaccines against tumors and infectious diseases. Three immunization strategies for the production of rat monoclonal anti-idiotope antibodies have been compared in this paper. Male Wistar rats were immunized i.p. and at multiple subcutaneous sites with 750 micrograms of purified monoclonal antibody against Plasmodium falciparum for three times and subsequently boosted by (1) intraperitoneal injection with 750 micrograms of the immunogen, (2) intravenous inoculation with 400 micrograms of the IgG, and (3) intrasplenic immunization with 200 micrograms of the idiotype. With the intraperitoneal boost method, the frequency of hybrids with anti-idiotope activity was 0.3-0.9% with 62.8-85.2% of the seeded wells containing hybrids. In the intravenous boost group, the percentage of hybrids demonstrating anti-idiotope activity increased to 11.0-13.3% with 80.2-97.9% of the hybrid efficiency. When immunized by the intrasplenic boost route, the frequency of anti-idiotope hybrids generated rose to 12.9-16.4% with 82.3-96.6% of the hybrid efficiency. There was no obvious effect of the boost immunizing methods on the generation of rat monoclonal anti-mouse IgG antibodies. These results indicated that the multiple-site immunization followed by intravenous or intrasplenic boost injection was an appropriate immunizing method for the production of monoclonal anti-idiotope antibodies.

Animals↗

The renal excretory activity of atrial natriuretic factor is independent of renal prostaglandins in humans.

Since renal prostaglandins may contribute to natriuresis induced by endogenous atrial natriuretic factor (ANF), acute volume expansion (AVL), a known stimulus of ANF and prostaglandins, was induced in 8 healthy women in order to test whether the consequent sodium and water diuresis is altered by prostaglandin inhibition. AVL (i.v. infusion of a 2 liter 5% glucose solution in 1 h) was infused after placebo and after inhibition of prostaglandins with diclofenac (200 mg/day orally for 4 days), in a double blind randomized cross-over fashion. Urinary eicosanoids (PGE2, PGF2 alpha, 6-ketoPGF1 alpha, TXB2--RIA), plasma ANF (RIA) and urinary electrolytes were determined before, during and after AVL under both placebo and diclofenac regimes. During placebo, AVL induced sustained increases in plasma ANF (174% at peak, p less than 0.001 ANOVA), excretion of the four eicosanoids (149%-1172%, p less than 0.005-0.001), urinary volume (UV, 815%, p less than 0.001), natriuresis (UNa, 98%, p less than 0.005) and in kaliuresis (UK, 90%, p less than 0.001). Cyclooxygenase inhibition resulted in a reduction of over 70% in both baseline values and AVL-induced increase of eicosanoids. It did not alter either baseline levels or AVL-stimulated ANF, UV, UNa and UK in relation to placebo. The present results suggest that the diuretic and natriuretic activity of ANF is not mediated by renal PGs in humans.

Adult↗

The protective role of zinc in the toxic action of coal dust upon mouse macrophages.

Macrophages from mice were cultured at 37 degrees C with 1640 medium containing 10% bovine serum. The macrophage suspension was made from 50 Swiss mice and was cultured in the following groups: control group; coal dust group (with added coal dust particles (10 micrograms/ml) smaller than 4 microns diameter); subdivided zinc-coal dust group (as coal dust group with zinc added in three different concentrations--namely, 10 ppm, 30 ppm, and 60 ppm). Cells were examined by light microscopy. Obvious differences were found in the rate of cell deaths between the coal dust group and the zinc-coal dust group after culture for 48 hours. The cell membranes were ruptured after culturing with coal dust, and the presence of zinc appeared in some degree to protect cell membranes from damage caused by the dust. Staining the cells with Gomori's modified method, showed that acid phosphatase particles in the zinc-coal dust group were more numerous than in the coal dust group. The results indicate that the trace element zinc may play an important part in protecting against the cytotoxic action of coal dust.

Acid Phosphatase↗

[Indirect immunoperoxidase staining technique with frozen sections of schistosome for serodiagnosis of latent schistosomiasis].

Indirect immunoperoxidase staining technique using frozen sections of adult worm as antigen (IIP-AWA) was carried out to detect antibodies against schistosome antigens (AWAb) for the diagnosis of existing infection of schistosomiasis in COPT positive cases. Sera from 229 COPT positive and 135 COPT negative cases in Shanghai County, where schistosomiasis had been eradicated for more than 5 years, were tested. Sera from 122 patients with positive stool hatching from an endemic area were served as positive controls. The positive rates of the three groups were 96.9%, 5.2%, and 100% respectively. The staining pattern of the worm sections was mainly diffused at serum dilutions 1:4 to 1:16. 149 sero-positive cases were treated with pyquiton (60 mg/kg.2d) and re-examined 1, 1.5, and 2.5 years post-treatment. The negative conversion rate of IIP-AWA was considerably higher than that of COPT (80% vs. 61.1%) at the first year, but no significant difference was observed after 2.5 years (85.5% vs. 83.6%). With the decreasing antibody titer, the staining pattern of worm sections changed from diffused to focal pattern, mostly in the gut. The results suggest that the presence of detectable AWAb in untreated patients or patients treated 2 years ago with pyquiton possibly indicate latent schistosomiasis. IIP-AWA is of practical value in screening populations for latent schistosomiasis in areas where the disease had been under control.

Animals↗