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Biomedical subjects

C S Lin

Publications and source records attributed to C S Lin.

At least 199 records · Page 11Linked to original sources

Ischemic damage in the striatum of adult gerbils: relative sparing of somatostatinergic and cholinergic interneurons contrasts with loss of efferent neurons.

The pattern of ischemia-induced cell death was examined with histochemical methods in the striatum of adult gerbils 4 and 7 days after transient forebrain ischemia. The results showed a massive loss of immunoreactivity to enkephalin and tachykinins, peptides present in striatal efferent neurons. In contrast, neurons expressing acetylcholinesterase activity, or choline acetyltransferase immunoreactivity, as well as neurons immunoreactive for somatostatin, were relatively preserved in areas of severe neuronal loss. The selective vulnerability of subpopulations of striatal neurons to transient ischemia in the adult is similar to that observed in the neonate and after local injections of agonists of N-methyl-D-aspartate receptors, but not of agonists of other glutamate receptor subtypes. It also presents striking similarities to the pattern of neuronal death observed in Huntington's disease. The results further support a role for overstimulation of a subtype of excitatory amino acid receptor in ischemia-induced cell death and show that the selective sparing of subpopulations of striatal interneurons after ischemic injury is not related to immaturity of these neurons but also occurs in the adult.

Acetylcholinesterase↗

Applicability of fixed brain slice for ultrastructural study.

A new method is described to study the dendritic morphology and axonal collaterals from fixed slice preparations. Either rhodamine or fluorescein conjugated horseradish peroxidase was used to fill single projecting neurons intracellularly. The identification of projecting neurons was labelled first with rhodamine-coated latex microspheres. After the diaminobenzidine reaction, the filling of detailed morphological characteristics can be examined at both the light and electron microscopic levels. The advantages of this technique are discussed.

Animals↗

Selective neocortical and thalamic cell death in the gerbil after transient ischemia.

In animal models of transients ischemia, selective vulnerability and delayed neuronal death in the hippocampus have been extensively described. However, little is known about selective damage in the neocortex and the thalamus, even though deficits in sensorimotor function are common in humans surviving hypoxic/ischemic episodes. This study investigated the neurodegenerative effects of transient ischemia in the gerbil neocortex and thalamus with use of Cresyl Violet and silver impregnation staining methods. In addition, immunohistochemistry of an astrocyte-associated protein, glial fibrillary acidic protein, was used to assess the astrocytic response to ischemia. Pyramidal cells in layers 3 and 6 of somatosensory and auditory cortex were exceptionally sensitive to ischemia, whereas the neurons in layers 2, 4 and 5 were more resistant to ischemia. More pyramidal cells were killed in layer 3 than in layer 6. This bilaminar pattern of neuronal death developed after periods of ischemia ranging from 3 to 10 min and was identifiable at post-ischemic survival times of 6 h to one month. Somatodendritic argyrophilia in the neocortex was identified as early as 6-12 h after 5 min of ischemia. The greatest number of degenerating cortical neurons were stained two to four days after ischemia. With 10 min of ischemia, argyrophilic neurites and neurons were also found as early as 8 h after the occlusion. The most extensive damage was noted in the ventroposterior nucleus, the medial geniculate nucleus, and the intralaminar nuclei two to four days after ischemia. Thus, selective vulnerability and delayed neuronal death are evident in both the neocortex and the thalamus after transient ischemia. These regions need to be examined when considering the efficacy of potential neuroprotective drugs.

Animals↗

Induction of transcription from the long terminal repeat of Moloney murine sarcoma provirus by UV-irradiation, x-irradiation, and phorbol ester.

The long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MuSV) was used as a model system to study the stress response of mammalian cells to physical carcinogens. The chloramphenicol acetyltransferase (CAT) gene was inserted between two Mo-MuSV LTRs, and the LTR-CAT-LTR construct was used for virus production and was integrated into the genome of NIH 3T3 cells in the proviral form. This construct was used to assure that the integrated CAT gene was driven by the promoter of the LTR. Expression of the CAT gene was stimulated 4-fold by UV irradiation, and the peak of activity was observed at 18 hr. In contrast, stimulation of the CAT expression after x-irradiation was 2-fold and occurred at 6 hr. Phorbol myristate acetate also stimulated CAT activity 4-fold with a peak at 6 hr. Down-regulation of protein kinase C blocked totally the response to x-irradiation but only partially the response to UV. The protein kinase inhibitor H7 blocked the response to treatment by UV, x-ray, and phorbol ester.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Fimbrin is a homologue of the cytoplasmic phosphoprotein plastin and has domains homologous with calmodulin and actin gelation proteins.

Fimbrin is an actin-bundling protein found in intestinal microvilli, hair cell stereocilia, and fibroblast filopodia. The complete protein sequence (630 residues) of chicken intestine fimbrin has been determined from two full-length cDNA clones. The sequence encodes a small amino-terminal domain (115 residues) that is homologous with two calcium-binding sites of calmodulin and a large carboxy-terminal domain (500 residues) consisting of a fourfold-repeated 125-residue sequence. This repeat is homologous with the actin-binding domain of alpha-actinin and the amino-terminal domains of dystrophin, actin-gelation protein, and beta-spectrin. The presence of this duplicated domain in fimbrin links actin bundling proteins and gelation proteins into a common family of actin cross-linking proteins. Fimbrin is also homologous in sequence with human L-plastin and T-plastin. L-plastin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to IL 1 or phorbol myristate acetate. T-plastin is found in cells of solid tissues where it does not become phosphorylated. Neoplastic cells derived from solid tissues express both isoforms. The differences in expression, sequence, and phosphorylation suggest possible functional differences between fimbrin isoforms.

Actins↗

Acral melanoma. A clinicopathologic study of 28 patients.

Clinical and histopathologic analyses of 28 cases of acral melanoma in the last 24 years were carried out in this study. Of our 81 patients with cutaneous malignant melanoma, 28 (35%) had acral melanoma. The mean patient age was 59 years old. The two most commonly involved sites were the soles and toes. The preferential sites for metastasis were the lymph nodes, followed by the lungs, bone, and liver in descending order. Histologically, all skin biopsy specimens showed biphasic growth patterns and consisted of either spindle cells or epithelioid cells or both. The treatment was in all cases mainly surgical and, in patients at advanced stage, chemotherapy was added. The mean survival time for the series was 34.03 months, while the 3-year survival rate was only 29%.

Adult↗

Correction of the N-terminal sequences of the human plastin isoforms by using anchored polymerase chain reaction: identification of a potential calcium-binding domain.

Plastins are a family of at least three cytoplasmic protein isoforms that are expressed differentially between cells of the hematopoietic lineages and cells of solid tissues. Expression of the L-plastin isoform appears to be restricted to replicating blood cells, and the two T-plastin isoforms appear to be restricted to replicating cells of solid tissues. However, L-plastin is induced in many human solid tumor-derived cells. We used the anchored polymerase chain reaction technique to amplify and clone the missing 5' ends of plastin mRNAs. We found that both plastin isoforms contain a potential calcium binding site near the N terminus.

Amino Acid Sequence↗

A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin.

CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation. In addition to their clinical importance in the prevention of allograft rejection, cyclosporin A and FK-506 represent important reagents for the study of the molecular mechanisms of lymphocyte activation. Cyclosporin A, a cyclic undecapeptide and FK-506, a macrolide, although chemically distinct, inhibit similar lymphocyte activation responses. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for interleukins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so be interacting with distinct cytosolic proteins. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity.

Amino Acid Isomerases↗

A rapid procedure to identify newborn transgenic mice.

We have developed a rapid procedure to identify newborn transgenic mice containing foreign genetic material in their genome. The protocol involves collagenase digestion of a small amount of tail tissue which can be taken very early after birth, phenol and chloroform extraction, polymerase chain reaction, and polyacrylamide gel electrophoresis. The entire procedure, from tissue biopsy to final results, can be completed in 1 day.

Animals↗

Cutaneous chylous reflux.

Two cases of cutaneous chylous reflux are described. Both patients had many translucent white vesicles from which milk-like fluid wept intermittently. Lymphangiogram revealed dilated, tortuous lymphatic vessels and dermal backflow. Electron microscopic studies showed an abnormal ultrastructure of the dilated lymphatics.

Adult↗

Proteolytic cleavage of tetanus toxin increases activity.

Tetanus toxin is initially synthesized in the form of a single polypeptide chain and then proteolytically "nicked" by the bacteria to produce a two-chain structure joined by a disulfide bond. This two-chain form of the toxin is the form known to be biologically active. Whether such nicking is necessary for activity, as it is for certain other bacterial toxins, has not been demonstrated previously. Single-chain toxin preparations produced by salt extraction from the bacteria are characterized and compared with pure two-chain toxin obtained from extracellular filtrates. The ability of these various toxin preparations to produce paroxysmal activity in mouse spinal cord neurons grown in dissociated cell culture is described. The pure two-chain toxin is demonstrated to have greater activity than the single-chain toxin preparations. Indeed the activity of the single-chain toxin preparations can be explained by the small amounts of residual two-chain toxin present in these extracts. Using a protease from a toxin-minus strain of Clostridium tetani to convert a single-chain toxin preparation to two-chain toxin increases toxin activity. In vivo the single-chain toxin preparation is also less toxic. These findings indicate that proteolytic nicking of tetanus toxin increases activity. The unnicked, single-chain form of tetanus toxin may be a relatively nontoxic protoxin form of the toxin; this is a structure-function relationship similar to that of other bacterial protein toxins.

Animals↗

A digoxin-like immunoreactive substance and atrioventricular block induced by a Chinese medicine "kyushin".

The attempted suicide by 2 women with a kyushin overdose is reported. Kyushin caused them to produce a significant elevation of a serum digoxin-like immunoreactive substance (2.35 and 1.84 ng/ml) and symptoms of nausea, vomiting and general malaise. Their blood biochemistry and electrolytes were normal. In one patient, an electrocardiogram revealed a second degree Wenckebach atrioventricular block and T-wave change. Toad venom, a kyushin ingredient, is possibly responsible for the development of these clinical features and electrocardiographic changes.

Adult↗

Endoscopic sphincterotomy in the treatment of biliary tract diseases.

Endoscopic sphincterotomy (EST) was performed in 53 patients with biliary disease. Indications for sphincterotomy were: 48 patients with choledocholithiasis, 3 patients with malignant biliary obstruction, and 2 patients with papillary stenosis. The procedure was successful in 52 patients (98.1%). In patients with choledocholithiasis, the stones were successfully removed or passed out spontaneously in 42 patients (87.5%). Endoscopic retrograde biliary drainage (ERBD) was successfully carried out in 2 cases of malignant biliary obstruction after EST. The clinical and biochemical evidence of cholestasis resolved in both patients with papillary stenosis. Complications consisted of hemorrhage (2 patients) and cholangitis (1 patient), resulting in one death. The overall complication and mortality rates were 5.7% and 1.9% respectively. Thirty-two patients received regular ultrasound examination follow-up with a mean of 13.4 months. Two patients had recurrent common bile duct stones and one had restenosis of papilla. The conditions were managed by endoscopic therapy. Endoscopic sphincterotomy is a relatively safe and effective means of relieving extrahepatic cholestasis; however, its comparison with surgical techniques needs long-term, randomized studies.

Adult↗

[Investigation on serious diarrhea].

We made an etiologic and epidemiologic investigation on 92 cases of serious diarrhea patients treated at hospitals of different level in Longhai county in 1986. From 63 patients, pathogenic organisms were isolated with the case positive rate of 64.48%; There are totally 75 isolates with the strain positive rate of 81.52%, among which 50 strains were ETEC (66.67%). High incidence was in August and September, during which there were 77 cases accounting for 83.69% of total cases and pathogen isolation rate was the highest. The main pathogen was ETEC, most of them were ST-producing strains, whose toxigenic ability is stronger there was only 19.70% whose ratio of intestinal weight to body weight was less than 0.1000 and the rest 80.30% more than 0.1000 in baby mice test.

Adolescent↗

Effect of a Chinese medicine "kyushin" on serum digoxin concentration measurement in dogs.

The effect of the Chinese medicine kyushin administered orally on serum digoxin measurement was studied in an animal model. Administration of 6 pills of kyushin caused a significant increase in the serum concentration of a digoxin-like immunoreactive substance (DLIS). The DLIS concentration increased to a peak value of 1.14 ng/ml at 11/2 hours and declined to 0.5 ng/ml after 24 hours. A one-week administration of 10 pills of kyushin a day produced a steady-state DLIS concentration ranging from 0.91 to 1.07 ng/ml. Among the 7 different kyushin ingredients, toad venom (ch'an-su in Chinese) was the only drug that produced DLIS in the dogs' serum. The similarity in structures of digoxin and toad venom most likely plays an important role in producing a cross-reactivity of DLIS with immunoassay antibody to digoxin. Although these findings require confirmation in human beings, they suggest that this nonprescription drug may seriously compromise the accuracy and interpretation of digoxin concentration measurements.

Animals↗