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Biomedical subjects

K Liu

Publications and source records attributed to K Liu.

At least 217 records · Page 12Linked to original sources
PubMed1998

PRAK, a novel protein kinase regulated by the p38 MAP kinase.

We have identified and cloned a novel serine/ threonine kinase, p38-regulated/activated protein kinase (PRAK). PRAK is a 471 amino acid protein with 20-30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAP-K2/3. PRAK was found to be expressed in all human tissues and cell lines examined. In HeLa cells, PRAK was activated in response to cellular stress and proinflammatory cytokines. PRAK activity was regulated by p38alpha and p38beta both in vitro and in vivo and Thr182 was shown to be the regulatory phosphorylation site. Activated PRAK in turn phosphorylated small heat shock protein 27 (HSP27) at the physiologically relevant sites. An in-gel kinase assay demonstrated that PRAK is a major stress-activated kinase that can phosphorylate small heat shock protein, suggesting a potential role for PRAK in mediating stress-induced HSP27 phosphorylation in vivo.

Amino Acid Sequence↗
PubMed1998

A novel palindromic triple-stranded structure formed by homopyrimidine dodecamer d-CTTCTCCTCTTC and homopurine hexamer d-GAAGAG.

We have carried out NMR and molecular mechanics studies on a complex formed when a palindromic homopyrimidine dodecamer (d-CTTCTCCTCTTC) and a homopurine hexamer (d-GAAGAG) are mixed in 1:1 molar ratio in aqueous solutions. Such studies unequivocally establish that two strands of each oligomer combine to form a triple-stranded DNA structure with a palindromic symmetry and with six T.A:T and six C+. G:C hydrogen-bonded base triads. The two purine strands are placed head to head, with their 3' ends facing each other in the center of the structure. One-half of each pyrimidine strand contains protonated and the other half contains non-protonated cytosines. The two half segments containing protonated cytosines are hydrogen bonded to each of the two purine hexamers through Hoogsteen T.A and C+.G base pairing. The segments containing non-protonated cytosines are involved in Watson-Crick (A:T and G:C) base pairing. This leads to a palindromic triplex with a C2-dyad symmetry with respect to the center of the structure. The complex is less stable at neutral pH, but the cytosines involved in Hoogsteen base pairing remain protonated even under these conditions. Molecular mechanics calculations using NMR constraints have provided a detailed three-dimensional structure of the complex. The entire stretches of purine, and the pyrimidine nucleotides have a conformation close to B-DNA.

Base Composition↗
PubMed1998

Improvement of ischemic damage in gerbil hippocampal neurons by procaine.

Acute cerebral ischemia induces membrane depolarization in the neuron, thereby incurring the simultaneous influx of various ions such as Na+ and Ca2+. Since procaine possesses the ability to inhibit the release of Ca2+ from intracellular Ca2+ stores to the cytosol as well as the ability to block Na+ channels, the effects of procaine on ischemia were investigated in the present study in gerbils both in vivo and in vitro. The histologic outcome was evaluated 7 days after 3 min of transient forebrain ischemia by assessing delayed neuronal death in hippocampal CA1 pyramidal cells in animals administered procaine (0.2, 0.4, or 2 micromol) intracerebroventricularly 10 min before ischemia and in animals given saline. The changes in the direct-current potential shift in the hippocampal CA1 area were measured using an identical animal model. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effects of procaine (10, 50, and 100 micromol/l) on the Ca2+ accumulation were examined. Additionally, the effect of procaine (100 micromol/l) in a Ca2+-free condition was investigated. The histologic outcome was improved and the onset of the ischemia-induced membrane depolarization was prolonged by the preischemic administration of procaine. The increase in the intracellular concentration of Ca2+ induced by the in vitro hypoxia was suppressed by the perfusion of procaine-containing mediums (50 and 100 micromol/l), regarding both the initiation and the extent of the increase. A hypoxia-induced intracellular Ca2+ elevation in the Ca2+-free condition was observed, and the perfusion with procaine (100 micromol/l) inhibited this elevation. Procaine helps protect neurons from ischemia by suppressing the direct-current potential shift and by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the extracellular space.

Anesthetics, Local↗
PubMed1998

Catalytic domain of the p120 Ras GAP binds to RAb5 and stimulates its GTPase activity.

Ras is a master GTPase switch controlling multiple signal transduction cascades in the regulation of cell proliferation and differentiation. Rab5 is a local GTPase switch that is localized on early endosomes and controls early endosome fusion. This study demonstrates that the catalytic domain of p120 GTPase-activating protein (GAP), a well known Ras GAP, is able to interact physically with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5, however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6, indicating that it is not a generic GAP for the Rab family of GTPases that regulate intracellular membrane fusion during endocytosis and exocytosis. The findings indicate a level of structural similarity between Ras and Rab5 unexpected from their primary sequences. They also suggest a possible signal transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.

Catalysis↗
PubMed1998

Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry.

Silicon is possibly important in human physiology in protecting against the toxic effects of aluminium, but the kinetics of uptake and excretion of silicic acid, the bioavailable form, are not well characterised. We have used 32Si as a tracer in a human uptake experiment to determine a gastrointestinal uptake factor for silicic acid, and to elucidate the kinetics of renal elimination. Urine collections were made for extending intervals from 2 to 12 h over 2 days following ingestion by a single human subject of a neutral silicic acid solution containing tracer levels of 32Si (t1/2 approximately 150 y). Silicon was isolated as SiO2 and the 32Si content determined by accelerator mass spectrometry (AMS), using a gas-filled magnet technique to eliminate a prolific isobaric interference from 32S. Silicon uptake appears to have been essentially complete within 2 h of ingestion. Elimination occurred by two simultaneous first-order processes with half-lives of 2.7 and 11.3 h, representing around 90% and 10%, respectively, of the total output. The rapidly eliminated 32Si was probably retained in the extracellular fluid volume, whilst the slower component may represent intracellular uptake and release. Elimination of absorbed 32Si was essentially complete after 48 h and was equivalent to 36% of the ingested dose. This establishes only a lower limit for gastrointestinal absorption as, although there was no evidence for longer term retention of additional 32Si, the possibility could not be excluded by these results.

Administration, Oral↗
PubMed1998

Demonstration of myxoid change in fine-needle aspiration of synovial sarcoma: a case report.

We report a case of synovial sarcoma with extensive myxoid change diagnosed by fine-needle aspiration. The patient is a 46-year-old woman who presented with a right paratibial mass. Aspiration cytology demonstrated a spindle cell neoplasm consistent with a synovial sarcoma but containing a prominent myxoid matrix. The clinical suspicion and cytologic diagnosis of a synovial sarcoma was confirmed by histologic and immunohistochemical findings. The cytologic differential diagnosis of spindle cell neoplasms with extensive myxoid change should be broadened to include synovial sarcoma.

Biomarkers, Tumor↗
PubMed1998

Logistic regression analysis of myxoid sarcomas: a cytologic study.

The objective of this study was to identify key diagnostic cytologic criteria for the most common myxoid sarcomas studied by fine-needle aspiration cytology. We reviewed 27 myxoid malignant fibrous histiocytomas, 8 chordomas, 16 chondrosarcomas, and 12 myxoid liposarcomas in which both cytologic specimens and final histopathologic diagnoses were available. All specimens were coded as to the presence or absence of the following variables: high cellularity, low cellularity, tissue fragments, epithelial fragments, pale/loose ground substance, dense ground substance, chondroid fragments, large amount of myxoid material, small amount of myxoid material, capillary vessel networks, pleomorphism, binucleate cells, multinucleate cells, physaliphorous cells, cells in lacunae, signet ring cells, lipoblasts, fibroblast-like cells, histiocyte-like cells, stellate cells, long filamentous cells, short spindle cells, osteoclastic giant cells, nuclei with pointed ends, nuclei with cigar-shaped ends, fish-hook nuclei, round/ovoid nuclei, naked nuclei, large nucleoli, small nucleoli, mitotic figures, abnormal mitotic figures, intracytoplasmic hemosiderin deposits, background cells, fat, cytoplasmic vacuoles, and pleomorphic giant cells. A logistic regression analysis was performed to identify the variables predictive of myxoid malignant fibrous histiocytoma, chordoma, myxoid chondrosarcoma, and myxoid liposarcoma. The statistical analysis selected pleomorphic giant cells and the presence of fibroblast-like cells as most predictive of malignant fibrous histiocytoma, physaliphorous cells as most closely associated with chordoma, chondroid fragments as most predictive of chondrosarcoma, and lipoblasts as most predictive of liposarcoma. While myxoid lesions have many overlapping cytologic features, key criteria including the presence of lipoblasts, physaliphorous cells, chondroid fragments, and pleomorphic giant cells are useful in subclassifying these neoplasms.

Adipocytes↗
PubMed1998

"Dedifferentiated" chordoma: a case report of the cytomorphologic findings on fine-needle aspiration.

Chordomas are relatively rare neoplasms occurring at both ends of a neuro axis. The majority follow an indolent course of multiple local recurrences, ultimately leading to the patient's death. Rare examples have been associated with sarcomatous components, usually resembling malignant fibrous histiocytoma, fibrosarcoma, or osteosarcoma. These tumors have followed a more aggressive course, with poor response to treatment and death following a relatively short time course. Cytologic material from a single case obtained by fine-needle aspiration revealed a high-grade malignancy composed of short atypical spindle cells containing modest amounts of granular cytoplasm. Physaliphorous cells were absent, and myxoid material was not a significant component of the smears. Rare polygonal cells with foamy cytoplasm were identified. Histologic study revealed a high-grade spindle-cell sarcoma in which were scattered small aggregates of vacuolated cells resembling physaliphorous cells. Anaplastic giant cells were present, and the overall appearance of the neoplasm resembled a malignant fibrous histiocytoma. Despite the radiographic appearance of a conventional chordoma in this case, the cytologic findings were indicative of a high-grade sarcoma consistent with a dedifferentiated chordoma.

Adult↗
PubMed1998

S-nitroso-N-acetylcysteine protects skeletal muscle against reperfusion injury.

The effects of a nitric oxide (NO) donor on microcirculation and contractile function of reperfused skeletal muscle were studied. Rat cremaster muscles underwent 5 hours of ischemia and 90 minutes of reperfusion and were divided into two groups systemically infused with S-nitroso-N-acetylcysteine (SNAC, 100 nmol/min) and phosphate-buffered saline (PBS), respectively. The results showed that the vessels in the SNAC group had more rapid and complete recovery than that in controls. A significant difference was found from 10 to 40 minutes and at 90 minutes in 10-20-microm arterioles, from 10 to 90 minutes in 20-40-microm arterioles, and at 10 and 90 minutes in 40-70-microm arteries. When compared to controls, SNAC-treated muscles showed larger fluorescein filling areas at 15, 30, 60, and 90 minutes and greater isometric tetanic contractile forces in response to stimulation frequencies of 40, 70, 100, and 120 Hz. The data indicate that supplementation of exogenous NO could effectively improve microcirculation and contractile function of skeletal muscle during early reperfusion.

Acetylcysteine↗
PubMed1998

Halofuginone inhibits neointimal formation of cultured rat aorta in a concentration-dependent fashion in vitro.

Halofuginone, an anticoccidial quinoazolinone, can specifically inhibit collagen type alpha1 (I) synthesis and gene expression, and also inhibits cultured smooth muscle cell proliferation. The aim of this study was to investigate the effect of halofuginone on neointimal formation of rat aorta after culture in a concentration-dependent manner in vitro. Thoracic aorta of Wistar rats was removed and manipulated to damage the endothelium under sterile conditions, and culture for 15 days in halofuginone-free or halofuginone-added culture medium (n = 20). Segments of cultured aorta were studied by histologic and immunohistochemical methods. Proliferation of neointimal layers consisting of loose multilayer cellular structure was observed in the halofuginone-free control group after 15 days of rat aorta culture, and neointimal formation was significantly decreased as an increasing concentration of halofuginone was added. As with precultured fresh aorta, no intimal proliferation was observed in the cultured segments of aorta with 500 ng/ml halofuginone added to culture medium. The proliferation of cell nuclear antigen index was significantly higher in the halofuginone-free control group than that in the halofuginone-added groups. The present results suggest that halofuginone can inhibit neointimal formation of rat aorta after culture in a concentration-dependent fashion in vitro.

Animals↗
PubMed1998

Hormone secretion by cell culture of human GH-PRL secreting pituitary adenomas: effects of bromocriptine.

Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is unclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.

Adenoma↗
PubMed1998

Recombinant human glial growth factor 2 (rhGGF2) improves functional recovery of crushed peripheral nerve (a double-blind study).

This in vivo double-blind study evaluated the effect of recombinant human glial growth factor 2 (rhGGF2), a Schwann cell mitogen, on the recovery of motor function of rat sciatic nerve following crush injury. Seventy three rats were divided into three groups. Group I (n=5), sham operated; Groups II (n=34) and III (n=34) received a 100 g crush load for 2 h over a 5 mm segment of the sciatic nerve. Group III was treated with 1 mg/kg rhGGF2, via subcutaneous injection one day before nerve crush and daily for the following four days. Group II received an equivalent volume of saline as a control. Motor functional recovery was assessed by calculating the sciatic functional index (SFI) and the recovery rate of tetanic contractile force of the extensor digitorum longus (EDL) muscle. Recovery of nerve function was evident at day 11 after crush in the rhGGF2-treated animals, whereas the nerves in controls were still paralyzed. The rhGGF2-treated animals showed a significant improvement of the SFI between days 11-21 postoperatively when compared to controls. The isometric tetanic contractile force was stronger in the rhGGF2-treated group than in controls, with a significant difference at 40 to 70 Hz stimulus frequencies on day 4. Correlation analysis showed that tetanic contractile force had a linear correlation with the SFI. Histologic assessment indicated that the rhGGF2-treated animals showed less severe degeneration and earlier robust remyelination of axons than controls. The results suggest that treatment with rhGGF2 is effective in promoting nerve regeneration as seen in measurements of functional recovery and qualitative assessment of nerve morphology. The mechanism of GGF's protective effect may be related to its direct action on Schwann cells, stimulating their mitosis as well as inducing neurotrophic factors essential to neuronal maintenance and repair.

Animals↗
PubMed1998

The effects of 17beta-estradiol on ischemia-induced neuronal damage in the gerbil hippocampus.

The effects of 17beta-estradiol, a potent estrogen, on ischemia-induced neuronal damage, membrane depolarization and changes in intracellular Ca2+ concentration were studied in gerbil hippocampi. The histological outcome evaluated seven days after 3 min of transient forebrain ischemia in hippocampal CA1 pyramidal cells was improved by high doses of 17beta-estradiol (30 microg, i.c.v. and 4 mg/kg, i.p.), whereas low doses of 17beta-estradiol (3 and 10 microg, i.c.v.) showed no protective effect. Administration of 17beta-estradiol did not affect the changes in the direct current potential shift in ischemia in the hippocampal CA1 area at any dosage. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices. Pretreatment of 17beta-estradiol (4 mg/kg, injected i.p. 1 h before decapitation) suppressed the increase in the intracellular concentration of Ca2+ due to the in vitro hypoxia, affecting both the onset of the increase and the extent. The in vitro hypoxia in the Ca2+-free condition induced an elevation of the intracellular concentration of Ca2+, although the increase was gradual. Pretreatment of 17beta-estradiol (4 mg/kg, i.p.) also inhibited this elevation. These findings imply that high doses of 17beta-estradiol protect the neurons from ischemia by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the extracellular space.

Action Potentials↗
PubMed1998

Measurement of walking endurance and walking velocity with questionnaire: validation of the walking impairment questionnaire in men and women with peripheral arterial disease.

OBJECTIVES: The Walking Impairment Questionnaire (WIQ) was designed to measure community walking ability in patients with peripheral arterial disease (PAD) and intermittent claudication. We compared the WIQ scores to objective measures of walking in a heterogeneous group of patients with and without PAD. METHODS: The study was designed as a cross-sectional study, with the setting in an academic medical center. The subjects were patients with PAD (n = 145) who were identified from a noninvasive vascular laboratory at an academic medical center. The patients without PAD (n = 65) were identified from a general medicine practice. The average number of comorbidities was 2.03 for patients with PAD and 1.52 for patients without PAD. Among the patients with PAD, 28% had classical intermittent claudication symptoms and 55% had exertional leg symptoms other than claudication. The main outcome measures were the WIQ estimates of the patient-reported walking distance and walking speed on a scale of 0 to 100. Walking endurance was measured objectively with the 6-minute walk. Walking velocity was measured with a 4-m walk. PAD and PAD severity were defined with the ankle brachial index. RESULTS: The Spearman rank correlation coefficients (rho) between the WIQ distance score and the 6-minute walk score were 0.557 among patients with PAD (P <.001) and 0.484 among patients without PAD (P <.001). The correlation coefficients between the WIQ speed score and the usual-paced 4-m walk score were 0.528 among patients with PAD (P <.001) and 0.524 among patients without PAD (P <.001). The correlations were not affected by the presence versus the absence of intermittent claudication, by PAD severity, or by the presence of 2 or more versus less than 2 comorbid illnesses. The WIQ scores in the highest and lowest quartiles were the most closely associated with the objective measures of function. CONCLUSION: The WIQ is a valid measure of community walking ability in a heterogeneous group of patients with and without PAD. The WIQ discriminates best among patients in the highest and the lowest quartiles of walking speed and endurance.

Aged↗