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Biomedical subjects

S Chin

Publications and source records attributed to S Chin.

At least 73 records · Page 4Linked to original sources

Severe destruction of the neural integration mechanism for upward eye movements in bilateral internuclear ophthalmoplegia.

The visually elicited saccades and smooth pursuits of a 24-year-old man with bilateral internuclear ophthalmoplegia were recorded with an infrared limbus reflection technique. Although the amplitude-peak velocity relationship of saccades appeared to be normal, all the upward saccades were hypermetric and were followed by postsaccadic exponential drifts. The time constant of the postsaccadic exponential drifts was 248 +/- 19.5 ms (mean +/- SD). Upward pursuit eye movements were also severely disturbed, and only movements with a short duration (mean 113.8 ms) and low gain (mean 0.51) were frequently observed. Thus, the transformation of a pulse velocity signal for saccades and of a step velocity signal for smooth pursuits into step and ramp position commands, respectively, was almost completely lost for upward eye movements in this patient because of bilateral lesions of the medial longitudinal fasciculus.

Adult↗

[The functional significance of coronary collateral circulation during sudden coronary occlusion].

The functional significance of the coronary collateral circulation remains controversial. It has been suggested that collateral circulation possibly helps prevent myocardial ischemia. Seventeen target lesions in 15 patients were studied to determine the relationship between the extent of the coronary collateral circulation and the degree of ventricular dysfunction during percutaneous transluminal coronary angioplasty (PTCA). During the first balloon inflation, diastolic indices such as left ventricular end-diastolic pressure, max negative dP/dt and the time constant of early relaxation were measured immediately before and at 60 sec following balloon inflation. During the second inflation, the contralateral and ipsilateral collateral circulations were evaluated. The latter was graded as follows: 0 = none; I = filling of side branches only; II = partial filling of the epicardial segment; and III = complete filling of the epicardial segment. Following balloon inflation, a significant increase was noted in the time constant of early relaxation in patients with grade 0 collateral circulation (40 +/- 7 to 47 +/- 7 msec: p < 0.01) and grade II collateral circulation (52 +/- 12 to 56 +/- 13 msec: p < 0.05). The percent increase in the time constant of early relaxation of patients with grade 0 and I collateral circulations exceeded that of patients with grade II (p < 0.05) or grade III collateral circulation (p < 0.05). Left ventricular end-diastolic pressure was elevated in all groups during PTCA. There was no significant difference in the percent increase of left ventricular end-diastolic pressure (LVEDP) between the 4 groups. However, LVEDP before PTCA was higher in patients with grade III collateral circulation than in patients in the other groups. Max negative dP/dt did not change significantly in any group. In conclusion, collateral circulation helps prevent myocardial ischemia during acute coronary occlusion, which is most precisely shown by the time constant of early relaxation. The degree of this protective function of collateral circulation seems to vary.

Aged↗

Isolation and characterization of the rat chromosomal gene for a polypeptide (pS1) antigenically related to statin.

Increasing evidence shows the existence of nonproliferation-specific gene(s) whose expression is mostly present in growth-arrested cells. One member of this gene family has been identified by previous work as a nuclear protein of 57,000 Da, termed statin. Logical extensions of statin research are to identify the genomic and cDNA clones encoding for statin and to study the regulation of statin gene expression. During the search for the statin gene, we have identified a cDNA clone and a genomic clone named S1 and S10, respectively, by screening a rat brain lambda gt11 expression library with the statin antibody and subsequently using S1 cDNA as a probe to screen a rat genomic cosmid library. Here, we report the cloning and sequencing of the S1 cDNA and S10 genomic clones. Primary sequence analyses indicate that the derived amino acid sequence of S1 shares high homology (greater than 92.6%) with human elongation factor 1 alpha (EF-1 alpha), whereas the 5'- and 3'-untranslated regions are less than 20% homologous. Despite the unusually high degree of similarity between S1 and human EF-1 alpha at the amino acid sequence level, their protein products are different and immunologically distinct. The in vitro transcription and translation product of S1 (pS1), a 49,000-Da polypeptide, reacts only with the monoclonal antibody against statin; this antibody exhibits no antigenic reaction to the EF-1 alpha protein. Northern blot analysis shows that the S1 message is most abundant in G0 phase of 3T3 mouse fibroblasts, but becomes significantly reduced in G1 and S phase cells. EF-1 alpha messages do not show such dramatic changes during cell cycle phase transition. These findings suggest that the expression of the identified S1 cDNA clone is specific for nonproliferating cells and that the in vitro translation product of the S1 cDNA is recognized by the statin antibody. Genomic Southern blots indicate that S1 cDNA is encoded by a single copy gene in the rat genome and is a unique member of the EF-1 alpha/S1 supermultigene family. DNA sequence analysis demonstrates that the rat S1 transcription unit is 12 kilobase pairs in length and contains seven introns. The organization of exons is virtually identical between S1 and human EF-1 alpha. In contrast, neither a TATA box nor a CAAT box is located in the proximal 5'-flanking regions from positions -1 to -1359 of the S1 gene, where we could expect to find the regulatory region containing the elements controlling gene expression; no evident sequence homology to the human EF-1 alpha gene is detected in this region.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Block of L-type calcium channels by charged dihydropyridines. Sensitivity to side of application and calcium.

We have studied block of L-type calcium channels by intracellular and extracellular application of the ionized dihydropyridine derivatives amlodipine and SDZ 207-180. We find that extracellular application of either drug causes voltage-dependent block of calcium channels. However, neither drug is effective when applied intracellularly. The insensitivity of calcium channels to intracellular drug is not due to the low concentrations of cytosolic calcium, because voltage-dependent block by ionized amlodipine, SDZ 207-180, and the neutral drug nisoldipine persists under conditions in which Ca0 is buffered by EGTA. In fact, the time course of the development of block by the ionized but not neutral drug molecules studied, is slower in the presence than in the absence of calcium. Our results indicate that the DHP binding site of the L-type calcium channel is close to the extracellular surface of the cell membrane and that ionized DHP molecules may interact with the receptor in a manner that is uniquely affected by calcium.

Amlodipine↗

Deaths from falls in children: how far is fatal?

The outcome of injury was determined in 317 children who were brought to a children's trauma center with a history from the caretaker that the child had fallen. Cases in which the clinicians' judgment was that an incorrect history had been given were included along with cases in which the history was not questioned. Seven deaths occurred in 100 children who fell 4 feet or less. One death occurred in 117 children who fell 10 feet to 45 feet. The 7 children who died in short falls all had other factors in their cases which suggested false histories. When children incur fatal injuries in falls of less than 4 feet, the history is incorrect. Long falls with an outdoor component are likely to be reliable data points for studies of children's injuribility.

Accidental Falls↗

[Resection of mediastinal teratoma in a patient with cardiac tamponade due to pericardial perforation].

Benign teratoma of the mediastinum causes a variety of complications if left untreated, but reports of pericardial perforation have been rare. We report a case of mediastinal teratoma that perforated the pericardium and induced clinical cardiac tamponade. The patient was a 46-year-old male, who was admitted due to sudden chest pain. Since chest CT and echocardiography suggested perforation of the pericardium by a mediastinal teratoma, pericardial drainage was carried out. However, heart failure could not be resolved, and the tumor was resected on the 5th hospital day. From the intraoperative and pathologic findings, mature type mediastinal teratoma was found to have perforated the pericardium, causing massive influx of yellowish fluid from the cyst of the tumor. There have been only 10 cases reported to date in Japan and abroad in which mediastinal teratoma was complicated by cardiac tamponade.

Cardiac Tamponade↗

Using a pocket computer to calculate monitor units--outline of a program in BASIC.

A pocket computer was programmed in BASIC to calculate monitor units for a dual energy linear accelerator. Because of the relatively large RAM memory, it was possible to input the TMR (or the PDD) tables for both energies as DATA. The program was written with the intention of providing a back-up check of the hand calculations.

Humans↗

The use of tri(n-butyl)phosphate detergent mixtures to inactivate hepatitis viruses and human immunodeficiency virus in plasma and plasma's subsequent fractionation.

The treatment of plasma with organic solvent/detergent mixtures at the time of plasma collection or pooling could reduce the exposure of technical staff to infectious viruses and enhance the viral safety of the final product. Treatment of plasma for 4 hours with 2-percent tri(n-butyl)phosphate (TNBP) at 37 degrees C, with 1-percent TNBP and 1-percent polyoxyethylensorbitan monooleate (Tween 80) at 30 degrees C, or with 1-percent TNBP and 1-percent polyoxyethylene ethers, (Triton X-45) at 30 degrees C resulted in the rapid and complete inactivation of greater than or equal to 10(4) tissue culture-infectious doses (TCID50) of vesicular stomatitis and Sindbis viruses, which are used as surrogates. Treatment of plasma with TNBP and TNBP and Tween-80 was shown to inactivate greater than or equal to 10(4) TCID50 of human immunodeficiency virus. TNBP treatment of plasma contaminated with 10(6) chimpanzee-infectious doses (CID50) of hepatitis B virus and 10(5) CID50 of non-A,non-B hepatitis virus prevented the transmission of hepatitis to chimpanzees. Immediately after treatment of plasma with 2-percent TNBP, the recovery of factors VIII, IX, and V and antithrombin III was 80, 90, 40, and 100 percent, respectively. Recovery of all factors was greater than or equal to 90 percent after treatment with TNBP and detergent mixtures. Treated plasma was fractionated by standard techniques into antihemophilic factor and prothrombin complex concentrates, immune globulin, and albumin. Prior treatment with TNBP or TNBP and detergent did not affect the separations of desired proteins. Therefore, it appears possible to inactivate viruses in plasma before the execution of standard fractionation procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Cellular electrophysiology of amlodipine: probing the cardiac L-type calcium channel.

The electrophysiologic properties of amlodipine in single guinea-pig ventricular cells were investigated. The degree of ionization of the drug molecule was found to affect both the development of and the recovery from block of L-type calcium channels. Under alkaline conditions, when most of the drug is in a neutral form, the actions of amlodipine resemble previously described neutral dihydropyridine (DHP) compounds. Under these conditions, calcium channel block by amlodipine is reversibly regulated by cell membrane potential, i.e., block is more pronounced at voltages positive to -50 mV and completely relieved at voltages negative to -80 mV. When the drug molecule is ionized, block develops very slowly at positive membrane potentials and is very difficult to relieve on returning the membrane potential to more negative voltages. It is concluded that the degree of ionization of the drug molecule limits access to the DHP receptor and that the drug-bound receptor can be titrated by extracellular hydrogen ions. These results place limitations on the location of the DHP receptor within the cardiac sarcolemmal membrane.

Amlodipine↗

Waardenburg syndrome type I in a child with de novo inversion (2)(q35q37.3).

We report on a child with Waardenburg syndrome type I and a paracentric inversion of chromosome 2. This 20 month-old boy has dystopia canthorum, sensorineural deafness, heterochromia iridis, partially albinotic ocular fundi, and partial leukodermia. He does not have mental retardation or any skeletal abnormalities. Family history was unremarkable. Cytogenetic studies demonstrated that the patient has a paracentric inversion (2)(q35q37.3); his parents have normal chromosomes. These findings suggest that the locus of the gene for Waardenburg syndrome type I may be at 2q35 or 2q37.3.

Abnormalities, Multiple↗

Specificity of human anti-neurofilament autoantibodies.

The specificities and isotypes of human antibodies that react with neurofilament (NF) proteins were examined by Western blot analysis. Two-thirds of the subjects tested had antibodies to the 200 kDa high molecular weight neurofilament protein (NF-H), and fewer had antibodies to the low and middle molecular weight neurofilament proteins (NF-L and NF-M respectively). Human autoantibodies bound to both native and dephosphorylated NF-H, but some antibodies bound to dephosphorylated NF-H only, indicating the presence of at least two target epitopes. They also recognized a fusion protein containing a segment of the NF-H protein produced by a cDNA clone in Escherichia coli, indicating that they bind to unmodified peptide epitopes. The anti-NF-H antibodies were mostly IgG, but were frequently complexed to IgA or IgM antibodies, possibly with rheumatoid factor or anti-idiotypic activity. These characteristics of anti-NF-H antibodies are most consistent with a secondary immune response that is antigen driven and T-cell dependent.

Adult↗

Establishment of mouse thymic nurse cell clones from a spontaneous BALB/c thymic tumor.

This is the first report on the establishment of the readily identifiable and functioning thymic nurse cell (TNC) clones from the mouse thymus. In the course of the culture of an epithelial cell line using a medium with a low concentration of Ca2+ from the spontaneous BALB/c thymic tumor, lymphocytes as well as thymic stromal cells which were not apparently typical epithelial cells by light microscopy seemed to grow relatively well in one flask. The culture medium was exchanged with regular Dulbecco's modified Eagle's medium in the third week, and from that flask TNC clones were established together with lymphoblast cell clones. The established cells (IT-79MTNC3) were easily identified as TNC. They formed complexes with simultaneously established lymphoblast cells and were remarkably similar to those of fresh TNC and thymocytes. Cloned TNC could express Ia antigens. In co-culture experiments, cloned TNC together with recombinant interleukin 2 (rIL 2) appeared to support the growth of fetal thymocytes which with rIL 2 alone failed to proliferate. The supernatant of IT-79MTNC3 was previously found to contain the growth factor for some T cell clones. It remains to be solved whether the TNC affects fetal thymocytes through direct contact or secretes an active growth-promoting factor. Experiments along this line are now in progress.

Animals↗

Purification and analysis of a sex-specific antibody.

Analysis of the male-specific H-Y antigen is difficult, in part, because of the tendency of "male-specific" antisera to bind cell surface components found in male and in female cells. Some insight as to the nature of that difficulty is provided by biochemical evaluation of H-Y antibody. In this study, purification of a monoclonal H-Y antibody with ammonium sulfate or Protein-A Sepharose, revealed the possibility of microheterogeneity. Despite evidence of multiple subtypes, Protein-A elution profiles suggested that the male-specific activity of the antibody resided in an IgG2a moiety. This was borne out by decreased activity after absorption of the IgG2a subtype with male cells, and by reaction of the monoclonal antibody with mouse subtype-specific antisera in an ELISA. Combined analysis using biological (absorption), biochemical (EF and PAGE) and immunological (ELISA) methods could find applicability in other complex systems.

Animals↗

[Diastolic dysfunction and its relation to myocardial fibrosis in essential hypertension].

This study elucidated diastolic left ventricular dysfunction and whether myocardial interstitial fibrosis correlates with diastolic dysfunction in mild to moderate systemic hypertension (HT). Six normotensive subjects, 18 hypertensive patients without left ventricular hypertrophy (LVH) and 10 hypertensive patients with significant LVH were evaluated. M-mode echocardiography was used to determine fractional shortening (FS), isovolumic relaxation time (IRT), and left ventricular filling volume during rapid and slow filling periods and the atrial contraction period (RFV, SFV, ACV). The quotients of the left ventricular filling volume and the end-diastolic volume and stroke volume were also calculated. Simultaneous biventriculography was used to determine the end-diastolic thickness of the interventricular septum and posterior wall. Right ventricular endomyocardial biopsies were performed to calculate the percentages of fibrosis. The FS was normal in all groups. The percentages of fibrosis in the two HT groups were significantly greater than those in the normals. The IRT of the HT groups was significantly greater, and the RFV, RFV/EDV and RFV/SV were significantly less than those of the normals. Multiple regression analysis showed that the wall thickness and the percentages of fibrosis correlated significantly with IRT, RFV, RFV/EDV and RFV/SV. The standard coefficients of correlation of wall thickness and the percentages of fibrosis were 0.333 and 0.239 in respect to IRT, and -0.304 and -0.473 in respect to RFV. There were significant correlations between the percentages of fibrosis and RFV (r = -0.675), RFV/EDV (r = -0.664) and RFV/SV (r = -0.602) in the normals and in cases of HT without LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

Tri(n-butyl) phosphate/detergent treatment of licensed therapeutic and experimental blood derivatives.

Incubation of an AHF concentrate with 0.3% tri(n-butyl)phosphate (TNBP) and 0.2% sodium cholate was shown to inactivate at least 10,000 infectious doses of lipid-enveloped viruses, including hepatitis B and non-A, non-B viruses and HTLV-III [Prince et al., Lancet i, pp. 706-710, 1986]. The use of TNBP/detergent combinations for virus sterilization was evaluated further to determine its effect on the structure and function of a wide variety of blood proteins. Vesicular stomatitis and Sindbis viruses were used as markers of virus inactivation. TNBP/detergent treatment did not significantly alter the function of AHF, factor VII, factor IX, factor X, fibrinogen, factor XIII, fibronectin, anti-HBsAg and anti-HA in normal serum globulin, haptoglobin, tumor necrosis factor, alpha-interferon, and both native and chemically polymerized stroma-free hemoglobin. As compared with partially purified derivatives, the extent of virus sterilization of plasma and component cryoprecipitate with 0.3% TNBP and 0.2% sodium cholate at ambient temperature could be improved by raising the TNBP concentration and temperature. Virus sterilization by TNBP/detergent mixtures appears to be generally applicable to blood protein derivatives.

Antiviral Agents↗