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Biomedical subjects

J K Lim

Publications and source records attributed to J K Lim.

At least 55 records · Page 3Linked to original sources

Pharmacological evaluation of GS-389, a novel tetrahydroisoquinoline analog related to higenamine, on vascular smooth muscle.

The effects of GS-389, a novel tetrahydroisoquinoline analog, on isolated rat and mouse thoracic aorta rings, were investigated. Both GS-389 and papaverine induced endothelium-independent, concentration-dependent relaxations of the rat and mouse aortae precontracted with phenylephrine (PE). The GS-389-induced inhibition of the contractile response to PE was noncompetitive. The initial phasic contraction to PE elicited in Ca(2+)-free media was also attenuated by pretreatment with GS-389, indicating that GS-389 may interfere with the release of intracellular Ca2+ and/or the effects of intracellular Ca2+ release. GS-389 potentiated the vasodilatory effects of isoproterenol and sodium nitroprusside in rat and mouse aortae. GS-389 significantly increased cGMP levels in the rat aorta and inhibited cGMP phosphodiesterase from the rabbit brain. Methylene blue, but not propranolol, inhibited the vasodilatory effect of GS-389. These results suggest that the vasorelaxant effect of GS-389 may be due, at least in part, to inhibition of cGMP metabolism.

Alkaloids↗

Hemangiopericytoma of the hand: a literature review and case study.

We present a case of hemangiopericytoma of the hand. We also attempt to differentiate hemangiopericytoma from glomus tumor with a summary of the history and a comprehensive review of the literature demonstrating the malignant character of the neoplasm, and we offer some guidelines for treatment.

Angiography, Digital Subtraction↗

Relative bioavailability of oral sustained-release and regular-release oxprenolol tablets at steady-state.

The relative bioavailability of a test sustained-release (SR) oxprenolol tablet against an approved regular-release (RR) tablet has been investigated at steady-state. In a randomized two-way crossover study, one tablet of 160 mg SR oxprenolol once every 24 h and one tablet of 80 mg RR oxprenolol once every 12 h were given to 12 healthy volunteers for 5 days. Blood samples were collected from each subject just prior to each dose-administration on days 1 through 4, and at scheduled time points on day 5 and analysed for oxprenolol concentration using HPLC. The SR tablet resulted in 42 per cent reduction in mean peak drug levels (p = 0.0341) and a statistically non-significant 14 per cent increase in mean trough levels (p = 0.8357) than the RR tablet. However it required 160 per cent longer time to reach average steady-state concentrations (Css) on day 5 (1.38 h for SR versus 0.53 h for RR; p = 0.0205). The mean area under the plasma drug concentration-time curve at steady state (AUC96-120) with the SR tablet was approximately 18 per cent lower than that observed with the RR tablet, and the degree of fluctuation (DF) was reduced by 30 per cent (2.81 for SR versus 4.11 for RR; p = 0.0069). On average, a single dose of SR tablet and two doses of RR tablets maintained the drug levels above a constant Css of 204.6 ng ml-1 for 7.88 and 7.65 h, respectively (p = 0.3513).

Adult↗

Optimization of high-performance liquid chromatographic analysis for isoxazolyl penicillins using factorial design.

A 3 X 3 factorial design has been used to study the effects of pH and acetonitrile concentration of the eluents on the retention and resolution of cloxacillin, flucloxacillin and dicloxacillin on a C18 column. The logarithm of the capacity factors of these solutes have been found to vary linearly with the pH and quadratically with the acetonitrile content. The equations generated have been employed to predict experimental conditions necessary for an optimum separation. The chromatographic condition selected has been applied to the quantitation of flucloxacillin in human plasma using dicloxacillin as the interval standard. Sample preparation consists of protein precipitation and solid-phase extraction. The detection limit of the assay at 220 nm for flucloxacillin is in the region of 0.1 microgram/ml. This assay has been employed in a study of the relative bioavailability of two commercial flucloxacillin sodium capsules in ten healthy volunteers.

Adult↗

Intrachromosomal rearrangements mediated by hobo transposons in Drosophila melanogaster.

The recurring intrachromosomal rearrangements observed in an unstable X chromosome, designated Uc, of Drosophila melanogaster are shown to be mediated by hobo transposable elements. Each of 29 chromosome rearrangement breakpoints in 16 gross aberrations detected in the Uc-derived X chromosomes had a hobo element. In one particular unstable X chromosome line selected for detailed studies, a hobo element was found in each of the five hot spots for rearrangements. Furthermore, hobo elements at deletion hot spots were found to lie in the same orientation, whereas those hobo elements at inversion hot spots were in the opposite orientation. The restriction maps of two phage lambda clones containing rearrangement breakpoints indicated that a hobo element was inserted exactly at the breakpoints. Pairing of hobo elements in the same chromosome followed by recombination between the paired hobo elements is suggested as the explanation for the intrachromosomal aberrations observed in the Uc X chromosomes. A clear qualitative difference among the hobo elements in their ability to participate in rearrangement formation was noted. It was also found that each of the 11 recessive lethal mutations mapped in the 6F1-2 doublet had a hobo element in the doublet, whereas none of the 16 independent revertants of the mutation had a hobo element in the site. This observation indicates that hobo movement is responsible for production and subsequent instability of recessive lethal mutations in the 6F region of the Uc X chromosomes.

Animals↗

Spontaneous formation of compound X chromosomes in Drosophila melanogaster.

Males carrying different X chromosomes were tested for the ability to produce daughters with attached-X chromosomes. This ability is characteristic of males carrying an X chromosome derived from 59b-z, a multiply marked X chromosome, and is especially pronounced in males carrying the unstable 59b-z chromosomes Uc and Uc-lr. Recombination experiments with one of the Uc-lr chromosomes showed that the formation of compound chromosomes depends on two widely separated segments. One of these is proximal to the forked locus and is probably proximal to the carnation locus. This segment may contain the actual site of chromosome attachment. The other essential segment lies between the crossveinless and vermilion loci and may contain multiple factors that influence the attachment process.

Animals↗

Cytogenetics of Notch mutations arising in the unstable X chromosome Uc of Drosophila melanogaster.

A derivative of the unstable X chromosome, Uc, isolated in 1978 is still unstable and exhibits most of the genetic properties characteristic of the original Uc. This derivative, Df(1)cm-In, contains an inversion of the genes between bands 6F1-2 and 3D3-5 and a lethal deficiency between 6D5-7 and 6F1-2. This chromosome generated Notch mutations at a rate of 3.47 +/- 0.32% during seven consecutive generations. Cytological analysis of 50 Notch mutations of independent origin in the Df(1)cm-In chromosome showed that all of the 50 had an apparently identical deletion involving the region between 3D3-5 and 3C7-8 of the X chromosome. The results of in situ hybridization indicated that the extent of deletion in all of the 20 Notch deficiencies sampled from the 50 mentioned above involves about 10 kb of the sequences from the 3' end of the Notch locus. In addition to hypermutability and the accumulation of site-specific chromosome breaks, the Df(1)cm-In chromosome reinverts its inversion to the normal sequence and exhibits use of the existing chromosome breakpoints to generate new rearrangements.

Animals↗

Phospholipid dependency of carp brain and liver mitochondrial monoamine oxidase.

The effects of lipid-protein interactions on carp brain and liver mitochondrial MAO with respect to substrate and inhibitor preference, thermostability and Arrhenius parameters were studied and compared. Treatment with phospholipase A2, C or D decreased MAO activities towards 5-hydroxytryptamine (5-HT), beta-phenylethylamine and tyramine similarly, accompanied by great changes in their apparent affinities for MAO, but not by changes in Vmax values. Minimum phospholipid binding to mitochondria might be essential for enzyme activity. Among these activities, 5-HT deamination was the most sensitive to the changes in mitochondrial phospholipids and bulk lipid phase transition (fluidity). Sensitivity of MAO to clorgyline or l-deprenyl was not affected by these phospholipase treatments. Of the phospholipids tested, only phosphatidylinositol significantly activated MAO activity towards 5-HT in both intact and phospholipase-treated mitochondria.

Animals↗

Effects of higenamine on isolated heart adrenoceptor of rabbit.

In the present study, effects of higenamine on various mechanical parameters of rabbit left atria as influenced by propranolol were investigated and compared to those of epinephrine. The following results are obtained: Higenamine, in a dose-dependent manner, increased the rate of tension development and shortened both the time to peak tension and the total duration of contraction. These effects of higenamine were competitively blocked by propranolol. The pA2 values of higenamine and epinephrine against propranolol were 8.58 +/- 0.14, 7.50 +/- 0.82 respectively, and the slopes by Schild plots were 0.97 and 0.99 with higenamine and epinephrine, respectively. The results indicate that the positive inotropic action of higenamine is likely due to stimulation of cardiac adrenoceptors.

Alkaloids↗

Treatment of comminuted trochanteric femoral fractures with Dimon Hughston displacement fixation and acrylic cement--a preliminary report of sixteen cases.

A new method for the treatment of unstable intertrochanteric fracture of the femur is proposed. This consists of stabilizing the fracture with a Dimon and Hughston medial displacement osteotomy and then restoring the cortical defect at the fracture site with methylmethacrylate cement (Dimon and Hughston, 1967). A preliminary trial on sixteen patients showed the excellent stability of the fracture achievable by this method. No mechanical failure was encountered, even though patients were all starting to walk and bearing full weight within the first week. No infection or non-union occurred. Early walking by the elderly patient suffering from a comminuted trochanteric fracture is important to counter the ill effects of decubitus associated with this fracture.

Aged↗

Homologue destabilization by a putative transposable element in Drosophila melanogaster.

We postulate the presence of a transposable element, designated the L factor, to explain the properties of an unstable X chromosome and its derivatives. These chromosomes generate recessive lethal mutations at high rates, as does a stable X chromosome that has been associated with them for only one generation. The stable X chromosome does not become highly mutable in the absence of the unstable X chromosome, even when autosomes from the unstable stock are present. These facts suggest that the L factor is confined to the X chromosome and that it transposes to other X chromosomes paired with it. We propose the term "homologue destabilization" to denote the change in the stable chromosome brought about by this transposition. The lethal mutations caused by the L factor occur preferentially in the region around the cut wing locus (ct) and are sometimes associated with recognizable chromosome aberrations. The breakpoints of these aberrations are most often in the vicinity of ct, implying that the L factor is located near ct on the unstable chromosome, but it may reside at other sites as well. Alternately, the ct region may simply be a preferred target for the insertion of this transposable element.

Animals↗

Fecal bulk, energy intake, and serum cholesterol: regression response of serum cholesterol to apparent digestibility of dry matter and suboptimal energy intake in rats on fiber-fat diet.

Two experiments were conducted in the rat to determine the relationships of serum cholesterol (SC, mg/dl), apparent digestibility of dry matter (DDM, %), and digested energy intake (DE, kcal/day) at suboptimal level of energy. The energies in diet and feces were determined by calorimetry. DE as percentage of the National Research Council requirement (DE%) was suboptimal (70 to 85%). The experiments had four to five isofibrous diets, and no fiber diets, supplemented with 0.2% crystalline cholesterol (CChol). Animals in experiment 1 were fed varying amounts of feed with 18% coconut oil in the diets where as these in experiment 2 were given fixed amounts of feed with either 6 or 18% oil. The following regressions (p less than 0.001) for SC were found: experiment 1: -1157.7 -5.97 DDM +105.5 CCI -1.48 CCI2 (r2 0.35), where CCI = CChol, mg/day; -1888.4 -2.66 DE +120.97 CCI -1.62 CCI2 (r2 0.37). Experiment 2: 762.99 -6.15 DDM -0.8 fat cal % -0.87DE% (r2 0.31), where fat cal % = fat calories % of DE. Data indicate that at suboptimal energy intake, SC was inversely related to (1) DDM, (2) fat cal, and (3) total energy intake. Liver cholesterol lowering effect of the dietary fiber was also observed. The above findings help to elucidate various conflicting reports related to diet and blood cholesterol.

Animals↗