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Biomedical subjects

B Lin

Publications and source records attributed to B Lin.

At least 163 records · Page 9Linked to original sources

Characterization of PepB, a group B streptococcal oligopeptidase.

Group B streptococci were recently reported to possess a cell-associated collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate N-(3-[2-furyl]acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly purified enzyme nor crude group B streptococcal cell lysate solubilized a film of reconstituted rat tail collagen, an activity regarded as obligatory for a true collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced amino acid sequence showed 66.4% identity to the PepF oligopeptidase from Lactococcus lactis, a member of the M3 or thimet family of zinc metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase activity and degraded a variety of small bioactive peptides, including bradykinin, neurotensin, and peptide fragments of substance P and adrenocorticotropin.

Amino Acid Sequence↗

Implications of reengineering in health care.

Currently the United States spends 12 percent of its gross national product on health care, far more than any other industrialized nation. Technology accounts for 15 percent to 50 percent of the rise in hospital costs. No country is immune from public calls for strategic developments to maintain or lower costs and guarantee high quality while maintaining access for all patients. To achieve these goals of adequate access, high quality, and greater efficiency, hospitals must discard complicated and unwieldy administrative practices that have evolved. How to best deploy technology in health service organizations requires a strategic perspective that results in operational break-throughs. Accelerated alignment of clinical and management processes, systems integration, and health care process redesign are required to achieve the goals of lower costs, higher quality, and greater access. An environmental background of reengineering is presented for health service organizations to use in their processes. Some critical relationships between reengineering and total quality management (TQM) in the health care setting are addressed. Implications of reengineering for health service organizations are offered to facilitate the implementation of the concept.

Health Expenditures↗

[A study of treatment modalities for nonresectable primary liver cancer].

This paper reports the results of multimodality treatment in 200 patients with nonresectable primary liver carcinoma (PLC) from April 1964 to July 1993. PLC was verified histologically in all cases. They were divided into two groups according to the methods of treatment. In group 1, 115 cases received anticancer agents by hepatic artery infusion (HAI). The 1- and 2-year survival rate was 10.4% and 1.7%, respectively and only one patient survived 65 months. In group 2, 85 cases received multimodality treatments by various combinations of hepatic artery chemoembolization (HACE), hepatic artery ligation (HAL), microwave coagulation (MIC) of tumor and ethanol injection into tumor (EIT). The 1-, 2-, 3- and 5-year survival rate was 34.1%, 21.2%, 12.0% and 6.7%, respectively. Five patients had been alive for 41 to 63 months and second-stage hepatic resection performed in another 6 patients. The results suggest that multimodality treatment is an effective approach to improve the long-term survival of patients with nonresectable PLC.

Adult↗

[Changes of plasma levels of monoamines in normal pregnancy and pregnancy-induced hypertension women and their significance].

OBJECTIVE: To study the changes of plasma levels of monoamines in pregnant women and investigate the relationship between the monoamines and pregnancy induced hypertension (PIH). METHODS: Using fluorescence spectrophotometry, we determined the contents of plasma monoamines in 130 normal pregnant (NP), 32 normal non-pregnant (NNP), and 58 PIH women. RESULTS: The levels of norepinephrine (NE) in NP from the 2nd trimester to parturiency were more markedly increased than those of the 1st trimester and of NNP (P < 0.05). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were also obviously increased at the 2nd and 3rd trimester respectively (P < 0.05). Compared with NP, the contents of DA in moderate and severe PIH were markedly and very markedly decreased respectively (P < 0.05 and P < 0.01), while the levels of 5-HT in PIH increased significantly (P < 0.05). NE in PIH was also tending to increase. CONCLUSION: The changes of monoamines may be one of the causes of small artery spasm in PIH.

Adult↗

Combined postischemic hypothermia and delayed MK-801 treatment attenuates neurobehavioral deficits associated with transient global ischemia in rats.

The present study was designed to determine whether postischemic hypothermia, delayed MK-801 (dizocilpine) administration, or a combination of these treatments can provide lasting neurobehavioral protection following transient global ischemia in rats. Rats were subjected to 10 min of normothermic (37 degrees C) ischemia induced by 2-vessel occlusion and hypotension (50 mmHg) or sham procedures. Ischemia was followed by either: (a) 3 h at normothermic brain temperatures, (b) 3 h of postischemic brain hypothermia at 30 degrees C, (c) hypothermia coupled with MK-801 (4 mg/kg, i.p.) on postischemic days 3, 5 and 7, or (d) postischemic MK-801 treatment alone. Neurobehavioral evaluation 6-8 weeks following surgery showed that normothermic ischemia (NI) was associated with water maze navigational deficits, including performance on a simple place task involving finding a hidden platform maintained in one position for 6 days, and a learning set task in which the platform was moved to a different location each day (both P's < 0.02 vs. sham). NI was also associated with increased locomotion in an open field (P < 0.01 vs. sham). A combination of postischemic hypothermia and delayed MK-801 injections provided partial protection from ischemic-associated hyperactivity in the open field (P < 0.02 vs. NI), and robust protection from simple place task deficits (P < 0.02 vs. NI). Evidence for significant protective effects of MK-801 or hypothermia alone was observed in the learning set, during the final trial blocks each day. These results provide further evidence for neuroprotective effects of these treatments at chronic survival intervals, and indicate that the therapeutic window for attenuating ischemic damage is considerably longer than has heretofore been appreciated.

Animals↗

Determination of polyamines in serum by high-performance capillary zone electrophoresis with indirect ultraviolet detection.

A method for determining polyamines in serum by capillary zone electrophoresis (CZE) with indirect ultraviolet detection was established. The concentrations of polyamines in the sera of six healthy adults were determined and the results were in accordance with those obtained previously by high-performance liquid chromatography (HPLC). However, the CZE method is superior to HPLC in that it has high sensitivity, small sample consumption and easy sample pretreatment.

Adult↗

Structural analysis of the 5' region of mouse and human Huntington disease genes reveals conservation of putative promoter region and di- and trinucleotide polymorphisms.

We have previously cloned and characterized the murine homologue of the Huntington disease (HD) gene and shown that it maps to mouse chromosome 5 within a region of conserved synteny with human chromosome 4p16.3. Here we present a detailed comparison of the sequence of the putative promoter and the organization of the 5' genomic region of the murine (Hdh) and human HD genes encompassing the first five exons. We show that in this region these two genes share identical exon boundaries, but have different-size introns. Two dinucleotide (CT) and one trinucleotide intronic polymorphism in Hdh and an intronic CA polymorphism in the HD gene were identified. Comparison of 940-bp sequence 5' to the putative translation start site reveals a highly conserved region (78.8% nucleotide identity) between Hdh and the HD gene from nucleotide -56 to -206 (of Hdh). Neither Hdh nor the HD gene have typical TATA or CCAAT elements, but both show one putative AP2 binding site and numerous potential Sp1 binding sites. The high sequence identity between Hdh and the HD gene for approximately 200 bp 5' to the putative translation start site indicates that these sequences may play a role in regulating expression of the Huntington disease gene.

Animals↗

Genomic organization of the human alpha-adducin gene and its alternately spliced isoforms.

The cDNA for the human alpha-adducin gene has been cloned, and different alternately spliced forms have been identified. We report the complete genomic organization of the human alpha-adducin gene and these alternately spliced forms. The human alpha-adducin gene, spanning approximately 85 kb, consists of 16 exons ranging in size from 34 to 1892 bp. One of the spliced forms of the human alpha-adducin gene results from alternate use of the 5' splice donor site for exon 10, while another results in a truncated protein following insertion of 34 bp comprising exon 15, followed by a premature stop codon. This alternate spliced form of alpha-adducin is predicted to result in an altered carboxyl terminus that would eliminate a protein kinase and calmodulin binding site. Seven nucleotide substitutions and 4 insertion/deletions were also identified. The 5' region of the human alpha-adducin gene contains one Sp1 site, two AP2 sites, and two CAAT boxes. No TATA box was apparent, consistent with features of a housekeeping gene. We have mapped another cDNA within the first intron of the human alpha-adducin gene, suggesting overlapping genes in this 4p16.3 genomic region.

Alternative Splicing↗

Use of a tantalum-178 generator and a multiwire gamma camera to study the effect of the Mueller maneuver on left ventricular performance: comparison to hemodynamics and single photon emission computed tomography perfusion patterns.

During the Mueller maneuver, there is a decrease in intrathoracic pressure and an increase in transmural left ventricular pressure. The changes in loading conditions cause transient left ventricular dysfunction. This study examined the effects of the Mueller maneuver on left ventricular performance using tantalum (Ta)-178 (half-life 9.3 min) and a multiwire gamma camera. First-pass radionuclide angiograms were obtained at baseline and during Mueller maneuver in 41 patients aged 58 +/- 10 years. In 34 patients, stress single photon emission computed tomography (SPECT) myocardial perfusion imaging with thallium-201 or sestamibi was also performed. Hemodynamic measurements during the Mueller maneuver (n = 10) showed a decrease in systemic pressure (139 +/- 25 mm Hg vs 123 +/- 24 mm Hg, p < 0.001) and pulmonary artery pressure (24 +/- 6 mm Hg vs 14 +/- 12 mm Hg, p = 0.01) and an increase in heart rate (67 +/- 10 bpm vs 75 +/- 14 beats/min, p = 0.001). Among the 34 patients who had perfusion imaging, the left ventricular ejection fraction remained unchanged or increased in 17 patients (group 1) (48% +/- 19% vs 49% +/- 21%, p not significant) and decreased (> or = 5%) in 17 patients (group 2) (55% +/- 13% vs 40% +/- 16%, p = 0.001). The stress SPECT images showed no or only fixed defects in 11 (65%) patients in group 1 and 3 (18%) patients in group 2 (p = 0.02), and reversible defects in 6 (35%) patients in group 1 and 14 (82%) patients in group 2 (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Vaccination of sheep against Schistosoma japonicum with either glutathione S-transferase, keyhole limpet haemocyanin or the freeze/thaw schistosomula/BCG vaccine.

The protective potential of glutathione S-transferase (GST), keyhole limpet haemocyanin (KLH) and the freeze/thaw (F/T) schistosomula/BCG vaccine was evaluated against Schistosoma japonicum in the natural sheep host. Groups of ten sheep each were vaccinated as follows: Group I: 2 x F/T 30,000 schistosomula+BCG 3 x 10(8) organisms, with a 2 week interval between vaccinations (F/T 'Low'). Group II: 3 x F/T 20,000 schistosomula+BCG 3 x 10(8), with 4 week interval (F/T 'High'). Group III: 2 x GST 0.24 mg+FCA (Freund's complete adjuvant) with 2 week interval (GST 'Low'). Group IV: 3 x GST 0.24 mg+FCA, with 4 week interval (GST 'High'). Group V: 2 x KLH 1.0 mg in phosphate-buffered saline (PBS), with 2 week interval (KLH 'Low'). Group VI: 3 x KLH 1.0 mg in PBS, with 4 week interval (KLH 'High'). Group VII: control (not vaccinated). Specific antibody, detected by GST-enzyme-linked immunosorbent assay (ELISA) and KLH-ELISA on the day after the last vaccination and 1, 2 and 3 weeks post-challenge, was found in all GST- or KLH-vaccinated groups. The same was found in F/T schistosomula-vaccinated groups against crude adult worm antigen (AWA). In Western blotting all GST-vaccinated sera recognized 26 kDa and 28 kDa bands on the challenge day and at 3 and 11 weeks post-challenge. Mean faecal egg counts between Weeks 6 and 10 post-challenge were reduced in a statistically significant way at five time points in the four groups, i.e. 83.38% (P < 0.005) in Group II, 49.29% (P < 0.025) in Group III, 47.9% (P < 0.05) and 71.15% (P < 0.01) in Group IV, 52.0% (P < 0.025) and 66.38% (P < 0.025) in Group VI. On autopsy and perfusion 1 week after the last faecal count, adult worm reductions were obtained of 40.36% (P < 0.05) in Group I, 37.26% (P < 0.025) in Group II, 24.73% (not significant) in Group III, 35.93% (P < 0.025) in Group IV, 27.46% (P < 0.05) in Group V and 33.81% (P < 0.01) in Group VI. Mean tissue egg densities were also reduced significantly in Groups III, IV and VI, especially in Group IV vaccinated animals. Mean liver egg granuloma diameters of the vaccinated groups were found to be less than those of the controls but there was no statistical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of delayed MK-801 (dizocilpine) treatment with or without immediate postischemic hypothermia on chronic neuronal survival after global forebrain ischemia in rats.

In contrast to intraischemic hypothermia, immediate postischemic hypothermia (30 degrees C) has been shown to delay but not chronically protect the CA1 hippocampus from transient global forebrain ischemia. The inability of a relatively short postischemic hypothermic period to protect chronically might involve a delayed or secondary injury mechanism. We determined whether delayed treatment with the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine), alone or in combination with immediate postischemic hypothermia, would chronically protect histopathologically. Wistar rats underwent 10 min of normothermic forebrain ischemia induced by bilateral common carotid artery occlusion plus hypotension (50 mg Hg). Four ischemia groups were studied after normothermic (37 degrees C) ischemia: no treatment; 3 h of immediate postischemic hypothermia (30 degrees C); delayed MK-801 treatment (4 mg/kg) on postischemic days 3, 5, and 7; and postischemic hypothermia combined with multiple MK-801 treatments. Two months after the ischemic insult, rats were perfusion-fixed for quantitative histopathological assessment. Postischemic hypothermia alone or MK-801 treatment alone failed to protect the CA1 hippocampus chronically. However, immediate postischemic hypothermia combined with delayed MK-801 treatment led to significant increases in normal CA1 neuron counts per microscopic field compared with normothermic ischemia. For example, neuronal counts within the hippocampal CA1 areas were 58 +/- 39 (mean +/- SD) in normothermic ischemic rats compared with 395 +/- 198 in rats treated with postischemic hypothermia and MK-801. Chronic survival also led to pronounced striatal damage. Within the dorsolateral striatum, significant protection was documented with either postischemic hypothermia alone or delayed MK-801 treatment alone.

Animals↗

Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation.

To obtain direct evidence of oxygen radical activity in the course of cerebral ischemia under different intraischemic temperatures, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) following salicylate administration. Wistar rats were subjected to 20 min of global forebrain ischemia by two-vessel occlusion plus systemic hypotension (50 mm Hg). Intraischemic striatal temperature was maintained as normothermic (37 degrees C), hypothermic (30 degrees C), or hyperthermic (39 degrees C) but was held at 37 degrees C before and following ischemia. Salicylate was administered either systemically (200 mg/kg, i.p.) or by continuous infusion (5 mM) through a microdialysis probe implanted in the striatum. Striatal extracellular fluid was sampled at regular intervals before, during, and after ischemia, and levels of 2,3- and 2,5-DHBA were assayed by HPLC with electrochemical detection. Following systemic administration of salicylate, stable baseline levels of 2,3- and 2,5-DHBA were observed before ischemia. During 20 min of normothermic ischemia, a 50% reduction in mean levels of both DHBAs was documented, suggesting a baseline level of hydroxyl radical that was diminished during ischemia, presumably owing to oxygen restriction to tissue at that time. During recirculation, 2,3- and 2,5-DHBA levels increased by 2.5- and 2.8-fold, respectively. Levels of 2,3-DHBA remained elevated during 1 h of reperfusion, whereas the increase in 2,5-DHBA persisted for 2 h. The increases in 2,3- and 2,5-DHBA levels observed following hyperthermic ischemia were significantly higher (3.8- and fivefold, respectively). In contrast, no significant changes in DHBA levels were observed following hypothermic ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of the transcription factor C/EBP beta in expression of a rat pregnancy-specific glycoprotein gene.

Pregnancy-specific glycoproteins (PSGs), which are the major placental proteins, and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. To understand the molecular mechanisms underlying the control of PSG expression, we characterized the promoter elements of a rodent PSG gene, rnCGM3, and showed that DNA elements at nucleotides -326 to -185 (PI) relative to the translation start site of rnCGM3 function as a promoter. The rnCGM3 PI promoter contains two placental factor binding sites, PISI and PISII. Both are transcription activation elements. In the present report, we screened a placental expression cDNA library with a rnCGM3-PISII probe (nucleotides -263 to -233) encompassing two overlapping palindromes (TGTTGCTCAACATGTTG) and demonstrated that the PISII-binding factor is C/EBP beta, a leucine zipper family of transcription factor. Gel mobility-shift and transient expression analyses showed that C/EBP beta and C/EBP isoforms, C/EBP alpha and C/EBP delta, bind to the PISII element and trans-activate rnCGM3 gene expression. Deletion of PISII from the rnCGM3 PI promoter greatly reduced the basal as well as the C/EBP-activated rnCGM3 expression. Gel supershift assays demonstrated that C/EBP beta is the placental isoform that binds to the PISII site rnCGM3. Moreover, C/EBP beta is expressed in high levels in the placenta, ovary, liver, lung, heart, and spleen, in contrast to C/EBP alpha, which is expressed primarily in the liver and only low levels in the placenta. Our results demonstrate that C/EBP beta is one of the transcription factors that positively regulate rnCGM3 expression during pregnancy.

Animals↗

Methodological issues in patient satisfaction surveys.

Examines some of the methodological problems encountered in conducting patient satisfaction surveys, including the sampling frames, quality of survey data and instruments, non-response problems, and reporting and interpretation of results. Proposes guidelines and lays out an agenda for future research.

Data Collection↗

Pulmonary vasodilation to adrenomedullin: a novel peptide in humans.

The present study investigates the effects of human adrenomedullin (ADM) on the pulmonary vascular bed of isolated, blood-perfused rat lung. Because pulmonary blood flow and left atrial pressure were constant, changes in pulmonary arterial pressure directly reflect changes in pulmonary vascular resistance. Under conditions of resting (low) pulmonary vasomotor tone, intra-arterial bolus injections of ADM-(1-52) and two truncated sequences of ADM-(1-52) [ADM-(1-12) and ADM-(13-52)] did not alter pulmonary arterial pressure. When pulmonary vasomotor tone was increased by U-46619, a thromboxane A2 mimic, intra-arterial bolus injections of ADM-(1-52) and ADM-(13-52) at similar doses produced similar, dose-dependent reductions in pulmonary arterial pressure. On a molar basis, ADM-(1-52) had greater pulmonary vasodilator activity than isoproterenol. In contrast, ADM-(1-12) had no activity. When pulmonary vasomotor tone was actively increased to the same level using KCl, the pulmonary vasodilator activity of ADM-(13-52) was decreased 10-fold. The present data demonstrate that ADM-(1-52) dilates the pulmonary vascular bed and suggest that the pulmonary vasodilator activity of ADM is greater on pulmonary blood vessels preconstricted through a receptor-dependent mechanism. Because meclofenamate, nitro-L-arginine methyl ester, methysergide, BW A-1433U83, U-37883A, and calcitonin gene-related peptide [CGRP-(8-37)], a CGRP-receptor antagonist, did not alter the pulmonary vasodilator response to ADM-(1-52), the present data suggest that ADM dilates the pulmonary vascular bed independently of cyclooxygenase products, endothelium-derived relaxation factor, serotoninergic receptors, adenosine1 purinoreceptors, ATP-dependent potassium channels, and CGRP receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Brain temperature modulations during global ischemia fail to influence extracellular lactate levels in rats.

BACKGROUND AND PURPOSE: While brain tissue lactate increases during cerebral ischemia and is known to be important in the pathogenesis of ischemic brain injury, patterns of extracellular lactate accumulation have been less well characterized, and the influence of brain temperature has not been previously investigated. Mild brain temperature modulations are known to affect the outcome of ischemia dramatically. This study examined changes of extracellular lactate during and after global cerebral ischemia, in which intraischemic brain temperature was held at either 30 degrees C, 37 degrees C, or 39 degrees C. METHODS: Halothane-anesthetized fasted male Wistar rats underwent 20 minutes of global cerebral ischemia produced by bilateral carotid artery occlusions plus systemic hypotension (40 to 50 mm Hg). Rectal temperature was maintained at 37 degrees C throughout, and intraischemic brain temperature was held at either 30 degrees C (n = 6), 37 degrees C (n = 5), or 39 degrees C (n = 5). Before and after the ischemic insult, brain temperature was maintained at 37 degrees C in all groups. A microdialysis cannula was implanted in the right dorsolateral striatum and perfused with Ringer's solution. Dialysate samples were collected at 10-minute intervals before, during, and after ischemia and were analyzed for lactate by enzymatic-fluorometric techniques. RESULTS: In all groups, extracellular lactate rose during ischemia and peaked at 10 to 30 minutes of recirculation. Maximal extracellular lactate elevations were sevenfold, eightfold, and eightfold above control in the 30 degrees C, 37 degrees C, 39 degrees C groups, respectively. Significant elevations with respect to control were observed in all groups at 10 to 30 minutes of recirculation. In the 30 degrees C group, these elevations above control were also significant at the 10- and 20-minute ischemic time points (P = .001). At 30 minutes of recirculation, however, lactate levels were lower in the 30 degrees C rats than in the other groups. CONCLUSIONS: These data provide evidence that extracellular lactate accumulation is not a crucial determinant of ischemic brain injury. Our results suggest that the increased lactate release during ischemia and the accelerated clearance of lactate during recirculation might contribute in part to the neuroprotection of intraischemic hypothermia.

Animals↗