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Biomedical subjects

B Lin

Publications and source records attributed to B Lin.

At least 217 records · Page 12Linked to original sources

Calcium antagonists in the treatment of experimental cerebral ischemia.

Calcium ion functions widely as an intracellular messenger and regulator. Intracellular calcium dyshomeostasis occurs during hypoxic/ischemic cell injury, and pharmacological antagonism of calcium entry into neurons has been considered to be of potential therapeutic value. Calcium antagonists, in addition, tend to improve cerebral perfusion of both the normal and abnormal (post-ischemic) brain. Studies of these agents have shown variable degrees of cerebroprotection in focal and global ischemia models. (S)-Emopamil is a phenylalkylamine-type calcium channel blocker which also exhibits stereoselective antagonism of the serotonin S2 receptor and has excellent blood-brain barrier penetrability. Protection of hippocampal CA1 neurons has been demonstrated with pre-ischemic administration of (S)-emopamil in global ischemia models. Our laboratory has compared the efficacy of pre- vs. post-ischemic (S)-emopamil treatment on neuronal necrosis resulting from 10 min of transient normothermic global ischemia in the rat. (S)-Emopamil pre-treatment, 20 mg/kg i.p., 30 min prior to ischemia, with a second dose 2.5 h later, resulted in 1.8-2.4 fold increases in numbers of surviving CA1 pyramidal neurons. Post-ischemic administration was ineffective. Intracerebral microdialysis has revealed a partial attenuation of dopamine release with pre-ischemic (S)-emopamil administration. In focal cerebral ischemia (middle cerebral artery occlusion in the rat), our laboratory has demonstrated a marked reduction in cortical infarct volume with (S)-emopamil pre- or post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Digital replantation. A ten-year retrospective study.

Eight hundred and two digits (592 complete amputation and 210 incomplete amputations) of 549 patients were replanted. The male to female ratio was 3:1 and the age range 1-63 years. 728 digits survived and 74 digits failed. The overall survival rate was 90.8%. Special varieties of complicated amputation were encountered in this series: (1) distal segment replantation, 139 digits, 131 digits (94%) survived; (2) digital replantation of children, 45 cases, 78 digits, average age 3.8 years, the youngest being 1 year old, 68 digits survived (88.7%); (3) rotational avulsion amputation of thumb, 26 digits, 23 digits (88.4%) survived; (4) bilateral digit amputation, 8 cases, 44 digits amputated, 38 digits replanted, including 9 digits of a ten-digit guillotined case. All the digits were salvaged. We conclude that thorough debridement, meticulous anastomosis of blood vessels and timely management of vascular crisis are keys to high survival rate, while judicious selection of indication, proper internal fixation of bone, anastomosis of as many blood vessels as possible, attentive repair of nerves and tendons, sound rehabilitation program are important measures in improving postoperative function.

Adolescent↗

The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae.

Sequencing of the neurofibromatosis gene (NF1) revealed a striking similarity among NF1, yeast IRA proteins, and mammalian GAP (GTPase-activating protein). Using both genetic and biochemical assays, we demonstrate that this homology domain of the NF1 protein interacts with ras proteins. First, expression of this NF1 domain suppressed the heat shock-sensitive phenotype of yeast ira1 and ira2 mutants. Second, this NF1 domain, after purification as a glutathione S-transferase (GST) fusion protein, strongly stimulated the GTPase activity of yeast RAS2 and human H-ras proteins. The GST-NF1 protein, however, did not stimulate the GTPase activity of oncogenic mutant ras proteins, H-rasVal-12 and yeast RAS2Val-19 mutants, or a yeast RAS2 effector mutant. These results establish that this NF1 domain has ras GAP activity similar to that found with IRA2 protein and mammalian GAP, and therefore may also regulate ras function in vivo.

Cloning, Molecular↗

[Involvement of oxytocin in spinal cord in acupuncture analgesia].

The influence of intrathecal injection of oxytocin (OT), anti-OT serum (AOTS) and naloxone on pain threshold and electroacupuncture (EA) analgesia in rats was investigated. The tail-flick induced by potassium iontophoresis was used to measure the pain threshold. The increase in pain threshold was observed within 70 min after OT injection (100 ng), and it was much more effective than that of the ACSF injection (P less than 0.001). The OT administration could enhance the EA analgesia. This effect was of dose-related. Although injection of AOTS did not affect the pain threshold, it diminished EA analgesia. Furthermore, injection of naloxone did not influence the action of OT on EA analgesia. Our results showed that OT in spinal cord plays an important role in the EA analgesia, and its effects is independent of endogenous opiate peptides.

Acupuncture Analgesia↗

[Effects of clonidine and norepinephrine on rabbit pulmonary artery strips with or without endothelium].

Relaxing responses of strips of rabbit pulmonary artery (RPA) with endothelium (+E) to norepinephrine (NE) during sustained contraction with KCl 20 mmol/L in the presence of propranolol (Pro) 10 mumol/L and prazosin (Pra) 1 mumol/L were more sensitive than those without endothelium (-E) to NE. These responses were inhibited by yohimbine (Yoh) 1 mumol/L. However, the relaxing responses of the strips to clonidine (Clo) were not different between RPA strips +E and -E in the presence of Pro+ Pra or Pro + Pra + Yoh 1 mumol/L. Relaxing responses of RPA strips -E precontracted by phenylephrine (PE) 1 mumol/L to Pra and Clo were greater than that of those precontracted by KCl 20 mmol/L. The relaxing responses of these strips precontracted by PE to Pra were larger than those precontracted by PE mumol/L; but that of those precontracted by PE and Clo to Yoh were not different. The results suggest that integrity of the endothelium is an important factor in the relaxing responses of RPA strips to NE. The relaxing effect of Clo on RPA strips precontracted by KCl 20 mmol/L may be due to alpha 1-adrenoceptor blockade on smooth muscle cells of the RPA strips.

Animals↗

Hepadna virus nucleocapsid and surface antigens and the antigen-specific antibodies associated with hepatocyte plasma membranes in experimental woodchuck acute hepatitis.

Hepatocyte plasma membranes purified from five woodchucks with distinct serologic and histologic patterns of experimentally induced acute woodchuck hepatitis virus (WHV) infection were studied to determine the virus antigens expression and anti-viral specificity of the bound immunoglobulins. WHV core, e, and surface antigens (WHcAg, WHeAg, and WHsAg, respectively) were analyzed with the use of immunoblotting technique both in the native form of these membranes and in the membranes treated with high molar urea or a nonionic detergent. The eluted material was tested either for the presence of WHV antigens or reactivity of the antibodies directed to the virus antigens. The data revealed that acute WHV infection is accompanied by hepatocyte plasma membrane expression of all three viral antigens tested. In all cases, native membranes displayed both WHeAg and WHsAg, whereas WHcAg presence was detected in hepatocyte plasma membranes after their disruption with urea or a detergent. The data indicated that a part or, in some instances, even the whole detectable WHcAg specificity can be incorporated into plasma membrane structure in such a way that it is not accessible for recognition by the specific antibodies (anti-WHc), suggesting at least a partial functional disability of this antigen as a target for immunologic reactions in in vivo conditions. In contrast, WHeAg specificity was detectable in all native membrane preparations studied and its expression was not evidently influenced by the employed treatments, whereas that of WHsAg tended to decline. Further, anti-WHc reactivity was identified in all membrane eluates tested, but antibodies to WHeAg (anti-WHe) were exclusively found in the material eluted from membranes originating from woodchucks with borderline histologic activity of acute hepatitis, which cleared away e antigen from the serum shortly before liver perfusion. Antibodies to WHsAg (anti-WHs) did not show up in the eluates. The present findings demonstrated that WHeAg specificity is not only exposed on the surface of infected hepatocytes, but is also relatively more easily accessible for serologic recognition than that of WHcAg in acute WHV infection. The above observation suggests that e antigen can serve as a potential plasma membrane target for hepatocytolytic attack in addition to that of WHsAg or WHcAg. Moreover, the results of this study demonstrated an apparent relationship between low histologic activity of liver inflammation, e antigen clearance from the circulation, and detectability of hepatocyte plasma membrane-bound anti-e antibodies in acute hepadna viral hepatitis.

Acute Disease↗

Colony formation of CFU-MK and other hemopoietic progenitors in patients with acute non-lymphoblastic leukemia at diagnosis and following complete remission.

Blood and marrow mononuclear cells were cultured in methylcellulose and plasma clot. In patients with acute non-lymphoblastic leukemia (ANLL) at diagnosis, marrow multipotential progenitors (CFU-Mix), megakaryocyte progenitors (CFU-MK) and granulocyte-monocyte progenitors (CFU-GM) were reduced or undetectable (all p less than 0.01). Two to 4 weeks after completion of induction therapy, marrow CFU-Mix returned to normal level (p greater than 0.05), CFU-MK and CFU-GM reached levels significantly higher than normal controls (both p less than 0.01), and circulating CFU-Mix, CFU-MK and CFU-GM were about 3, 6 and 6 times normal controls respectively (all p less than 0.01). During maintenance therapy CFU-Mix remained in low normal range (p greater than 0.05) and CFU-MK and CFU-GM were significantly reduced (both p less than 0.01). In patients at relapse CFU-Mix was undetectable (p less than 0.01) and CFU-MK and CFU-GM were undetectable or reduced (both p less than 0.01). The percentages of CFU-MK and CFU-GM in cell cycle S-phase as analysed by ara-c suicide technique were 51.4 +/- 5.8 and 52.3 +/- 2.3 two weeks after the completion of induction therapy, and 61.1 +/- 7.9 and 53.8 +/- 8.7 during maintenance therapy, all significantly higher than normal controls (all p less than 0.01). Our results suggest that chemotherapy may not result in severe damage to CFU-Mix, and that cell culture technique may be helpful in assessing prognosis.

Adolescent↗

The use of fluorescent probes in pharmaceutical analysis.

Even though many pharmaceuticals show native fluorescence, there is also an important group of compounds which is not fluorescent. A main object of studies is to make them fluorescent, principally by using fluorescent probes through derivatisation reactions. An account of the fluorescent probes more widely used for the determination of drugs and related compounds is presented in this review paper. A wide variety of fluorescent probes is described on the basis of their ability to react specifically with various functional groups. Attention is focused on derivatisation reactions used in spectrofluorimetry and chromatographic techniques (HPLC, TLC) with fluorimetric detection. The review covers only those fluorescent probes whose use involves a chemical reaction with the analyte, and not those methods that involve physico-chemical interactions such as sensitised or charge transfer processes. Many of these derivatisation reactions have been widely used in the detection of primary and secondary amines. Reagents such as dansyl chloride, fluorescamine, o-phtalaldehyde are very well known. Other reagents have also been developed for other functional groups, for example dansyl hydrazine for compounds with a carbonyl function or 4-bromomethyl-7-methoxy-coumarin for acidic compounds . Acid chlorides such as dansyl chloride may also react with different functional groups carrying active hydrogens as do phenols. The use and development of new fluorescent probes in pharmaceutical analysis is a subject for further studies.

Journal Article↗

Vacuum ultraviolet circular dichroism of keratan sulfate.

The vacuum ultraviolet CD of keratan sulfate reveals an intense negative CD band at 171 nm. Its intensity can be rationalized with a recently proposed quadrant rule in terms of the acetamido group being slightly tilted toward the hexosaminidic linkage oxygen. The same structural feature accounts for the particularly intense negative n-pi CD band near 210 nm.

Animals↗

Electronic imaging system for direct and rapid quantitation of fluorescence from electrophoretic gels: application to ethidium bromide-stained DNA.

We have built an electronic imaging system based on a modified charge-coupled-device television camera that directly quantitates the distribution of fluorescence from electrophoretic gels, chromatograms, and other stationary sources. Exposure times can exceed 1 min. Unlike the photographic system that it replaces, the response of the camera is directly proportional to the intensity of incident fluorescence, and image data are digitized and stored in computer memory ready for analysis immediately upon completion of an exposure. We describe procedures for the display, normalization, and archival storage of image data and programs that use images of ethidium bromide-stained DNA in alkaline agarose gels to quantitate single-strand breaks in DNA.

DNA↗

Activation of transforming potential of the human insulin receptor gene.

A retrovirus containing part of the human insulin receptor (hIR) gene was constructed by replacing ros sequences in the avian sarcoma virus UR2 with hIR cDNA sequences coding for 46 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains of the beta subunit of hIR. The resulting virus, named UIR, contains the hIR sequence fused to the 5' portion of the UR2 gag gene coding for p19. UIR is capable of transforming chicken embryo fibroblasts and promoting formation of colonies in soft agar; however, it does not form tumors in vivo. A variant that arose from the parental UIR is capable of efficiently inducing sarcomas in vivo. UIR-transformed cells exhibit higher rates of glucose uptake and growth than normal cells. The 4-kilobase UIR genome codes for a membrane-associated, glycosylated gag-hIR fusion protein of 75 kDa designated P75gag-hir. P75gag-hir contains a protein tyrosine kinase activity that is capable of undergoing autophosphorylation and of phosphorylating foreign substrates in vitro; it is phosphorylated at both serine and tyrosine residues in vivo.

Animals↗

Spontaneous regression of cardiac rhabdomyoma in tuberous sclerosis.

Life-threatening cardiac rhabdomyoma in a newborn infant regressed spontaneously within a 5 month period. Since cardiac surgery for rhabdomyoma is dangerous in infancy, medical management should be considered if symptomatology is not severe. When a fetal arrhythmia is diagnosed, antenatal ultrasound examination for presence of cardiac tumors is warranted.

Heart Neoplasms↗

Regulation of the expression of proto-oncogene c-src by alternative RNA splicing in chicken skeletal muscle.

Expression of the c-src locus in skeletal muscle of the chicken was found to be different from other tissues. A 4 kilobases (kb) cellular src (c-src) mRNA, which most likely codes for pp60c-src, is expressed in various chicken tissues examined, and most of its approximately 2.2 kb non-coding sequences are present at the 3' end of the RNA molecule. Whereas the 4 kb RNA is also expressed in embryonic chicken muscle, it disappears shortly before hatching and is replaced by a smaller-sized class of c-src mRNAs of 2.8 to 3.3 kb. The transition of expression from the 4 kb to the 2.8-3.3 kb RNA in skeletal muscle occurs shortly before hatching of the chicken and persists into adulthood. The two classes of the c-src mRNA share sequences both within the 5' coding and the 3' non-coding regions of pp60c-src, however, the 2.8 to 3.3 kb RNA lacks most of the kinase domain, but it contains upstream c-src sequences missing in the 4 kb RNA. The two classes of c-src mRNA most likely are generated by alternative splicing, and the smaller c-src RNA most likely codes for a product other than tyrosine protein kinase.

Age Factors↗