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Biomedical subjects

L Xu

Publications and source records attributed to L Xu.

At least 739 records · Page 41Linked to original sources

Allergen-induced airway responses in rats pretreated with Sephadex.

Even though the eosinophil is potentially an important contributor to airway narrowing during the late allergic airway response, direct evidence of its participation is lacking. Therefore, we examined the effects of eosinophilia induced by Sephadex on the magnitude of the late airway response of sensitized rats following allergen challenge. Brown Norway rats were actively sensitized to ovalbumin (OA). At the same time and 14 days later, a test group was administered Sephadex G200 (0.5 mg intravenously). The animals were challenged with an aerosol of OA and pulmonary resistance (RL) was measured over 6 h. The early response to OA reached a peak more rapidly and the magnitude of the late response, measured as the area under the curve of RL against time, was significantly greater in the Sephadex-treated group (48.3; geometric mean) compared to the control animals (18.9; p < 0.02). The percentage of eosinophils was increased in the bronchoalveolar lavage of Sephadex-treated animals (4%) compared to the controls (0.9%; p < 0.02) following OA challenge. These results demonstrate that Sephadex induces eosinophilia in Brown Norway rats and is associated with an increase in the late allergic airway response. This is consistent with the hypothesis that the eosinophil is an important determinant of the late response.

Administration, Inhalation↗

Salivary proteolysis of histidine-rich polypeptides and the antifungal activity of peptide degradation products.

Incubation of purified synthetic histidine-rich polypeptides, HRP-2, -3, -4, -5, -6 (histatins), with diluted human parotid saliva yielded a series of peptide degradation products whose structures could be determined by gas-phase sequencing of cationic polyacrylamide gel electroblots. Sequencing indicated that two and sometimes three peptides were present in the same Coomassie blue-stained band. By comparing different individuals' salivas it was observed that structural variation occurs, perhaps due to differences in the concentrations or specific activities of salivary proteases. Based on the structural data, four proteolytic enzyme activities are proposed. A trypsin-like and chymotrypsin-like enzymatic activity(s) appear to represent the most active salivary protease; however, both an alanine-lysine endopeptidase and a histidine peptidase activity are also present in parotid saliva. In comparison to HRP-4 or HRP-6, degraded products were less active as antifungal agents against Candida albicans both in blastospore and germ-tube assays.

Amino Acid Sequence↗

Cryoglobulinemia with vasculitis associated with hepatitis C virus infection.

Essential mixed cryoglobulinemia is frequently associated with chronic hepatitis. This report presents four cases of cryoglobulinemia with vasculitis associated with chronic hepatitis related to hepatitis C virus infection. Hepatitis C virus infection was ascertained in the four patients by both the presence in the serum of anti-HCV antibodies detected by the four-antigen recombinant immunoblot assay and of HCV RNA detected by polymerase chain reaction. In two patients tested, anti-HCV antibodies were not detected after centrifugation in the purified cryoglobulin but were detected in the supernatant. HCV RNA was detected in the purified cryoglobulin in all four patients and was detected in the supernatant in three patients. In one patient receiving recombinant interferon alfa, serum aminotransferases normalized and cryoglobulin disappeared; in another patient receiving recombinant interferon alfa, serum aminotransferases remained high and the cryoglobulin persisted. The presence of HCV RNA in the cryoglobulin and the parallelism of the changes of the cryoglobulinemia and of the serum aminotransferases during recombinant interferon alfa administration suggest that HCV infection is responsible for the production of cryoglobulinemia and vasculitis. It is proposed that HCV infection is a cause of cryoglobulinemia associated with chronic hepatitis.

Adult↗

Effect of culture conditions on mast cell eicosanoid synthesis.

When mast cells are grown in culture from mouse bone marrow cells, some cells are in suspension and some attach. The cells in suspension released leukotrienes and thromboxane when stimulated. Removal from the attached cells increased eicosanoid formation in the suspended cells two- to six-fold. The upregulation of arachidonic acid metabolism seemed to be due to an increase in phospholipase activity. The attached cells resembled macrophages in morphology, but stained positively for mast cells and produced PGD2 an arachidonic acid metabolite which is characteristic for mast cells. The attached cells did not synthesize eicosanoids when stimulated with IgE/antigen or A23187. Addition of arachidonic acid caused cyclooxygenase product formation but not leukotrienes. No 5-lipoxygenase was detected by immunoblot analysis. Lack of eicosanoid synthesis was, therefore, due to the loss of 5-lipoxygenase and phospholipase activity, while the cyclooxygenase was preserved. These experiments demonstrate that attachment of mast cells to plastic can significantly alter their eicosanoid metabolism.

Animals↗

Prevalence and aetiology of profound deafness in the general population of Sichuan, China.

People with profound deafness were surveyed in the general population of Sichuan. The results showed that the overall prevalence in Sichuan was 0.186 per cent (236/126,876) of the general population, males 0.212 per cent (135/63,741), females 0.159 per cent (101/63,135) (p < or = 0.05). Two hundred and fifteen (92 per cent) cases were older than 10 years, but 227 (96 per cent) lost their hearing under the age of 10 years, 192 (80 per cent) under five years, and 104 (44 per cent) were congenital. There was no significant difference in prevalence of deafness between the population located in urban and rural areas. However, the population living in the flat area and mountain area had a much higher prevalence than that of the hill people (p < or = 0.05). Amongst the nationalities investigated, there existed significant differences in prevalence. Both the population of the Hui and the Lisu presented a significantly higher prevalence of profound deafness than that of the others. In aetiology, genetic factors may account for 43 per cent (101/236) of the cases, amongst which, autosomal recessive (AR) deafness is 92 per cent (95/104) and autosomal dominant (AD) 5.4 per cent. Environmental factors were thought to be responsible for 35.6 per cent (84/236) of cases, including infectious diseases (31 per cent), ototoxic antibiotics (2.6 per cent), injury (1.7 per cent), and asphyxia (0.4 per cent). The number of cases of unknown origin were 20.3 per cent. It is suggested that, in China, the importance of genetic factors in hearing impairment should be emphasized. In addition, infectious diseases and ototoxicity play an important role in causing deafness.

Adolescent↗

Effects of local anesthetics on single channel behavior of skeletal muscle calcium release channel.

The effects of the two local anesthetics tetracaine and procaine and a quaternary amine derivative of lidocaine, QX314, on sarcoplasmic reticulum (SR) Ca2+ release have been examined by incorporating the purified rabbit skeletal muscle Ca2+ release channel complex into planar lipid bilayers. Recordings of potassium ion currents through single channels showed that Ca(2+)- and ATP-gated channel activity was reduced by the addition of the tertiary amines tetracaine and procaine to the cis (cytoplasmic side of SR membrane) or trans (SR lumenal) side of the bilayer. Channel open probability was lowered twofold at tetracaine and procaine concentrations of approximately 150 microM and 4 mM, respectively. Hill coefficients of 2.0 and greater indicated that the two drugs inhibited channel activity by binding to two or more cooperatively interacting sites. Unitary conductance of the K(+)-conducting channel was not changed by 1 mM tetracaine in the cis and trans chambers. In contrast, cis millimolar concentrations of the quaternary amine QX314 induced a fast blocking effect at positive holding potentials without an apparent change in channel open probability. A voltage-dependent block was observed at high concentrations (millimolar) of tetracaine, procaine, and QX314 in the presence of 2 microM ryanodine which induced the formation of a long open subconductance. Vesicle-45Ca2+ ion flux measurements also indicated an inhibition of the SR Ca2+ release channel by tetracaine and procaine. These results indicate that local anesthetics bind to two or more cooperatively interacting high-affinity regulatory sites of the Ca2+ release channel in or close to the SR membrane. Voltage-dependent blockade of the channel by QX314 in the absence of ryanodine, and by QX314, procaine and tetracaine in the presence of ryanodine, indicated one low-affinity site within the conduction pathway of the channel. Our results further suggest that tetracaine and procaine may primarily inhibit excitation-contraction coupling in skeletal muscle by binding to the high-affinity, regulatory sites of the SR Ca2+ release channel.

Anesthetics, Local↗

Safety and short-term toxicity of a novel cationic lipid formulation for human gene therapy.

Among the potential nonviral vectors for human gene therapy are DNA-liposome complexes. In a recent clinical study, this delivery system has been utilized. In this report, a novel cationic lipid, dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium (DMRIE), has been substituted into the DNA-liposome complex with dioleoyl phosphatidylethanolamine (DOPE), which both improves transfection efficiencies and allows increased doses of DNA to be delivered in vivo. The safety and toxicity of this DNA-liposome complex has been evaluated in two species, mice and pigs. The efficacy of DMRIE/DOPE in inducing an antitumor response in mice after transfer of a foreign MHC has been confirmed. No abnormalities were detected after administration of up to 1,000-fold higher concentrations of DNA and lipid than could be tolerated in vivo previously. Examination of serum biochemical enzymes, pathologic examination of tissue, and analysis of cardiac function in mice and pigs revealed no toxicities related to this treatment. This improved cationic lipid formulation is well-tolerated in vivo and could therefore allow higher dose administration and potentially greater efficiency of gene transfer for gene therapy.

Animals↗

Ryanodine sensitive calcium release channel from left ventricle, septum, and atrium of canine heart.

OBJECTIVE: The aim was to consider the possibility that functionally distinct forms of the ryanodine sensitive calcium release channel are expressed in different regions of heart. METHODS: Membranous fractions enriched in ryanodine binding activity were isolated from canine left ventricular free wall, interventricular septum, and atrium. Ryanodine receptors (RyR) were purified by sucrose density gradient centrifugation, following solubilisation of sarcoplasmic reticular membranes with the detergent Chaps. Single channel currents were measured, upon reconstitution of sarcoplasmic reticular vesicles and the purified RyR into planar lipid bilayers. RESULTS: Ryanodine sensitive Ca2+ release channels from three different regions of canine heart displayed the same [3H]ryanodine binding and single channel characteristics. CONCLUSIONS: The left ventricular free wall, septum, and atrium of canine heart may express functionally related, if not identical, ryanodine receptor/Ca2+ release channels.

Animals↗

Total gastrectomy via thoracotomy for cancer of the cardia or fundus of the stomach (report of 90 cases).

From 1978 through 1990, 90 total gastrectomies with esophagojejunostomy via thoracotomy were performed for the treatment of cancer of the cardia or fundus of the stomach in our hospital. Eighty-five patients were in TNM-stage III and five in stage IV. The 30-day postresectional mortality was 1.1%, and the 5-year survival rate was 13.8%. 14CO2 breathing test and clinical evaluation of 34 postoperative patients (not included in the 90 patients) showed that total gastrectomy may decrease the incidence of positive residual cancer along the incision lines, and may help to avoid small stomach syndrome. There was no statistical difference in postoperative fat absorption between patients treated by ordinary proximal subtotal gastrectomy and those receiving total gastrectomy via thoracotomy.

Adult↗

[Study on antibacterial proteins from rabbit bladder mucosa].

Acid-soluble extract of rabbit bladder mucosa was obtained by washing out the bladder of normal female New Zealand rabbit with 1% acetic acid in the presence of proteinase inhibitors. Acid urea polyacrylamide electrophoresis (AU-PAGE) analysis indicated that the extract had more than 10 main protein bands. The currently-known antibiotic peptides, e. g. lysozyme and defensin-like molecules were not found in this material. When tested for antibacterial activity by using ultrasensitive radial diffusion assay, the acid-soluble extract effectively killed E. coli ML-35P. The gel overlay assay showed that the anti-bacterial activity of the acid-soluble extract was relevant to two protein bands referred to as rabbit bladder protein 1 (Rab BP-1) and rabbit bladder protein 2 (Rab BP-2). The Rab BP-1 and Rab BP-2 accounted for 2.5% and 1.2% of the total acid-soluble extract proteins, respectively. These results suggest that the long recognized ability of the normal rabbit bladder wall to kill adherent E. coli may result from the presence of endogenous antibacterial proteins associated with its mucosa.

Animals↗

[Hyperselective posterior rhizotomy in the treatment of spasticity of paralytic limbs].

108 cases of spasticity of paralytic limbs were treated successfully with hyperselective posterior rhizotomy (SPR). Among them, 100 had cerebral palsy, 2 hemiplegia, 2 paraplegia, 3 sequelae of cerebral injury, and 1 multiple sclerosis. Cervical SPR was performed in 12 cases and lumbosacral SPR in 96 cases. After laminectomy, the posterior nerve roots were split into some rootlets, and the lower threshold rootlets were divided after electrical stimulation. Follow up for 6-30 months showed an effective rate of 95% and an improvement rate of 81%.

Adolescent↗

Hyperselective posterior rhizotomy in treatment of spasticity of paralytic limbs.

One hundred and eight patients with spasticity of the paralytic limbs were treated successfully with hyperselective posterior rhizotomy (SPR). Of the 108 patients, 100 had cerebral palsy, 2 hemiplegia, 3 sequelae of cerebral injury, 2 paraplegia and 1 multiple sclerosis. Twelve patients received cervical SPR and 96 lumbosacral SPR. Laminectomy is performed to open the dura and to separate the posterior spinal root into several rootlets. The lower threshold rootlets were divided after electrical stimulation. Follow-up for 6 to 30 months showed that the effective rate of reducing spasticity was over 95% and functional improvement rate over 80%.

Adolescent↗

Misdiagnosis of lung cancer in patients under age 40--a clinical analysis of 47 cases.

Diagnosis of lung cancer in 47 patients aged younger than 40 years was delayed as a result of misdiagnosis, accounting for 70.1% of all cases of lung cancer in those aged less than 40 years treated in PUMC Hospital in the same period. Pulmonary tuberculosis and tuberculous pleurisy were diagnosed in 26 cases (55.3%). Pulmonary inflammation was suspected in 24 cases (51.1%). The delay in diagnosis was one to three months in 28 cases and longer than 3 months in 19 cases. Twenty-eight (59.6%) of the 47 patients underwent surgery, including exploratory thoracotomy (21.4%) and pneumonectomy (40.9%). The five-year survival rates in the resectable group and in the non-surgical group were 31.6% and 5.3%, respectively. We recommend that accessory examinations should be performed wherever possible in younger patients with suggestive pulmonary nodules in order to collect sufficient evidence to confirm or rule out the diagnosis of lung cancer and thereby reduce the rate of misdiagnosis in such younger people.

Adenocarcinoma↗

Role of first exon/intron sequences in the regulation of myc family oncogenic potency.

cis-Acting sequence elements that participate in the regulation of myc family gene expression in normal tissues and that serve as potential targets for the deregulation of expression in tumors have been localized to the first exon/intron region of all three myc family genes. To test directly the importance of these cis elements in the tumor-associated deregulation of myc family gene expression, we have compared the oncogenic activities of complete (exons 1, 2 and 3) and truncated (exons 2 and 3 only) c-, N- and L-myc expression constructs in the rat embryo fibroblast (REF) cooperation assay. Removal of the first exon/intron region from each construct was associated with a dramatic increase in oncogenic potency by several criteria. Analysis of N-myc/ras-transformed cell lines demonstrated (i) fewer transfected N-myc gene copies and an overall higher level of steady-state N-myc mRNA with the truncated N-myc expression construct and (ii) the presence of a significant block to transcriptional elongation in the first exon of the complete N-myc expression construct. These results indicate that the first exon of N-myc plays an important role in governing oncogenic potency, possibly through transcriptional control mechanisms.

Animals↗

[Dynamic observations of the optic cup and its modes of damages in glaucoma].

Changes in the optic disk and retinal nerve fiber layer are the sole objective indicators of glaucomatous damages. Many investigators held that damages in the optic nerves in glaucoma preceded changes in the visual functions. The optic cups and visual fields of 106 primary open angle glaucoma eyes and 207 eyes of glaucoma suspects were followed up an average 16.6 months. Among 35 eyes that developed changes in the optic cup, the cup changes preceded the visual field changes in 78%, and both changes occurred simultaneously in 22%.

Adolescent↗

Gene transfer and bone marrow transplantation with special reference to Gaucher's disease.

Gene therapy following gene transfer into hematopoietic cells is now being investigated for several genetic disorders (1). The candidate diseases under consideration and active experimental investigation are disorders that can be fully or partially corrected by allogeneic bone marrow transplantation, where the gene defect is known and the normal gene has been cloned and characterized. Together with ADA deficiency Gaucher's disease is a leading candidate among these disorders. We have developed high titer retroviral vectors containing the glucocerebrosidase gene that can transduce murine bone marrow stem cells with high efficiency and will result in high levels of human glucocerebrosidase in macrophages of long-term reconstituted mice. "Gene therapy" for Gaucher's disease has therefore been accomplished in the mouse. We have also developed high titer amphotropic vectors containing the glucocerebrosidase gene that can transduce human CD34+ hematopoietic progenitors with a high degree of efficiency. Up to 70% of CFU-GM colonies from these infected CD34+ cells contained the transferred gene as determined by PCR. Our vectors can also correct the enzyme deficiency of hematopoietic cells from Gaucher patients following gene transfer.

Animals↗

Optic disc morphology in eyes after nonarteritic anterior ischemic optic neuropathy.

PURPOSE: Parapapillary chorioretinal atrophy, neuroretinal rim loss, and a decrease of retinal vessel diameter have been described to occur in glaucomatous eyes. This study was conducted to evaluate the frequency and degree of these signs in nonarteritic anterior ischemic optic neuropathy (AION). METHODS: We evaluated morphometrically and compared stereo color optic disc photographs of 17 patients after AION, 184 patients with primary open-angle glaucoma, and 98 normal subjects. RESULTS: The optic disc area and retinal vessel diameter were significantly smaller and the visibility of the retinal nerve fiber bundles was significantly reduced in patients after nonarteritic AION compared with that of the normal subjects. The optic disc shape, area, and form of zones alpha and beta of the parapapillary chorioretinal atrophy and the size and form of the neuroretinal rim did not differ significantly between these two groups. In the group of eyes with glaucoma, the neuroretinal rim was significantly smaller and the parapapillary chorioretinal atrophy was significantly larger than in the group of eyes with AION. Visibility of the retinal nerve fiber bundles and retinal vessel caliber did not differ statistically between the eyes with AION and those with glaucoma. CONCLUSIONS: These results indicate that the parapapillary chorioretinal atrophy is not larger in eyes after nonarteritic AION compared with normal eyes. They show that the area and shape of the neuroretinal rim, as determined planimetrically, may not markedly change after nonarteritic AION. They confirm previous reports on a small optic disc size as a risk factor for nonarteritic AION. They agree with findings of a reduced retinal vessel caliber in eyes with optic nerve damage, independently of the cause.

Adult↗