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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 433 records · Page 24Linked to original sources

Dysfunctional platelet glycoprotein IIb/IIIa associated with a platelet release defect: a family study.

We are reporting on a 36-year-old white female with a bleeding history attributed to dysfunctional platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and a coexisting platelet release defect. Platelet aggregation studies (PAS) revealed markedly diminished to absent responses to ADP, epinephrine, collagen and arachidonic acid; the ristocetin response was normal. ATP content was normal with poor release to the agonists as measured by luminescent technique. DDAVP infusion shortened bleeding time from 13.5 min to 8.0 and 12 min (at 1 and 2 hours). Flow cytometry and immunoblotting revealed normal amounts of GPIIb and diminished GPIIIa (50% of control). Using a previously reported ELISA which measures the binding of GPIIb/IIIa to immobilized fibrinogen, the patient's platelet extract showed no binding to fibrinogen. Both the father and mother were found to have decreased PAS responses and normal amounts of GPIIb/IIIa determined by both Western blot and flow cytometry. However, the ELISA showed decreased binding of their GPIIb/IIIa to fibrinogen (71% and 62% as compared to controls, respectively). The patient's dysfunctional fibrinogen receptor was clearly demonstrated by the ELISA. The parents had moderately reduced GPIIb/IIIa function in this assay, but they did not demonstrate a reduced GPIIIa as was noted in the patient. The parents' PAS indicated a platelet release defect. These findings suggest an inherited platelet release defect and a dysfunctional GPIIIa. The partial response to DDAVP would be compatible with the presence of a platelet release defect.

Adult↗

Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia.

We previously described an ELISA to measure the inhibition of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti-platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV-related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV-related ITP, whereas in non-HIV ITP, inhibition was only partially due to CIC; anti-platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV-related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV-seronegative ITP patients, the decrease or disappearance of anti-platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti-platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti-platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti-idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV-seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count.

Antibodies↗

Nucleus ambiguus of the rabbit: cytoarchitectural subdivision and myotopical and neurotopic representations.

The cytoarchitectural subdivisions of the nucleus ambiguus of the rabbit and its myotopical and neurotopical representations were investigated with HRP labeling. The nucleus was subdivided into the compact cell group (CoG), the medial and lateral scattered cell groups (SGm and SGl), and the diffuse cell group (DiG). The CoG was formed by esophageal, pharyngeal constrictor, and palatal motoneurons in the rostral half of the nucleus. The SGm and SGl were located medial and lateral to the CoG, respectively, in the rostral one-third of the nucleus. Stylopharyngeal and cricothyroid motoneurons were located in the most rostral one-fifth of the SGm and the remaining four-fifths, respectively, whereas the SGl was not labeled with HRP injections into the palatal, pharyngeal, esophageal, and laryngeal muscles. The DiG was formed by recurrent laryngeal motoneurons in the caudal two-thirds of the nucleus. Neurons of origin for the glossopharyngeal nerve occupied the stylopharyngeal region, with a few of them scattered in the CoG and SGl. Neurons giving rise to axons in the superior laryngeal nerve occupied the cricothyroid region, with a few of them scattered in the pharyngeal constrictor region; whereas the pharyngeal vagal branch originated from the pharyngeal constrictor and palatal regions. Neurons of the DiG, SGl, and esophageal region contributed to the infranodosal vagus nerve; esophageal fibers of the recurrent laryngeal nerve originated from the dorsal esophageal region. Laryngeal fibers of the recurrent laryngeal nerve originated from the DiG, the caudal neurons of which had axons traversing the cranial accessory root.

Accessory Nerve↗

Longitudinal Gompertzian analysis of non-Hodgkin's lymphoma mortality in the US, 1979-1988: demonstration of the environmental basis for rising overall mortality.

Between 1979 and 1988, annual crude non-Hodgkin's lymphoma mortality rates (per 100,000) in the United States increased from 3.43 to 6.34 among men (an 85% increase in only 10 years) and, among women, increased from 2.82 to 5.71 (a 102% increase). Age-specific mortality rates for non-Hodgkin's lymphoma from 1979 through 1988 were subjected to longitudinal Gompertzian analysis, a method that may be able to identify and distinguish among genetic, environmental and competitive influences upon evolving mortality trends. The results of this analysis suggest that the basis for the dramatic rise in non-Hodgkin's lymphoma mortality is due to worsening environmental influences. The capability to distinguish between environmental and competitive influences upon evolving mortality patterns has significant public health policy implications.

Adolescent↗

The isolation and structural elucidation of four novel triterpene lactones, pseudolarolides A, B, C, and D, from Pseudolarix kaempferi.

Four novel triterpene lactones, pseudolarolides A [1], B [2], C [3], and D [4], were isolated from the seeds of Pseudolarix kaempferi. Their structures and stereochemistry were elucidated from spectral data. Compound 2 shows potent cytotoxicity against three human cancer cell lines, KB (nasopharyngeal), A-549 (lung), and HCT-8 (colon), and against a murine leukemia cell line (P-388) with ED50 values of 0.49, 0.67, 0.73, and 0.79 micrograms/ml, respectively.

Animals↗

The deduced amino acid sequences of human platelet and frontal cortex monoamine oxidase B are identical.

Monoamine oxidases (MAOs) A and B play important roles in the metabolism of neuroactive, vasoactive amines. Human platelets contain only MAO B, often used as an indicator of brain MAO B. The validity of this model remained to be evaluated. This report describes the molecular cloning of human MAO B from frontal cortex and platelets. Two overlapping PCR-amplified clones of human platelet MAO B and four PCR-amplified clones of human frontal cortex MAO B covering the entire coding region were sequenced using five internal oligomers and M13 reverse and forward primers. The nucleotide sequences of human MAO B cDNA from platelet and frontal cortex were identical to that of human liver MAO B except for three nucleotides that differed in frontal cortex: nucleotides 440 A-->G, 794 C-->T, and 825 C-->T. Whether or not these differences are artifactual, all three represent silent mutations, which would not alter the amino acid of the encoded polypeptides. Thus, the deduced amino acid sequences of MAO B from frontal cortex, platelet, and liver are identical. These findings indicate the validity of using platelet MAO B mRNA as a marker for brain MAO B and provide a new approach to study the role of brain MAO B in humans.

Amino Acid Sequence↗

Influence of age and hemodynamics on myocardial blood flow and flow reserve.

BACKGROUND: Aging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. METHODS AND RESULTS: Myocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31 +/- 9 versus 64 +/- 9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895 +/- 1070 versus 8634 +/- 1890; P < 0.01). Myocardial blood flow at rest averaged 0.76 +/- 0.17 mL.min-1.g-1 in the younger volunteers and 0.92 +/- 0.25 mL.min-1.g-1 in the older volunteers (P < 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0 +/- 0.8 versus 2.7 +/- 0.6 mL.min-1.g-1; P = NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1 +/- 0.9 versus 3.0 +/- 0.70; P < 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. CONCLUSIONS: Aging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Adult↗

Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction.

BACKGROUND: Metabolic imaging with positron emission tomography (PET) can detect tissue viability in clinical infarct regions. With appropriate tracer kinetic models and serial PET imaging, regional myocardial blood flow and rates of metabolism can now be quantified in patients with recent myocardial infarctions. METHODS AND RESULTS: Serial PET imaging with [13N]ammonia, [11C]acetate, and 18F-deoxyglucose was performed in 22 patients with recent infarctions to measure regional blood flow (in milliliters per gram per minute), glucose metabolism (in micromoles per gram per minute), and oxidative metabolism (in clearance rate per minute). Hypoperfused clinical infarct regions were classified as "PET mismatch" if 18F was increased relative to 13N activity or "PET match" if 13N and 18F activities were reduced concordantly. Blood flows differed significantly between normal, mismatch, and match segments (0.83 +/- 0.20, 0.57 +/- 0.20, and 0.32 +/- 0.12 mL.g-1.min-1, respectively). The relation between oxidative metabolism and blood flow was piecewise linear and differed significantly between PET mismatch and PET match. Oxidative metabolism was less severely reduced than blood flow in mismatch regions but but reduced in proportion to blood flow in match regions. There was considerable overlap of blood flows between both types of PET segments. CONCLUSIONS: Quantification of regional blood flow and substrate metabolism in postinfarction patients revealed alterations in the relation between substrate delivery and consumption demonstrated previously only in invasive animal experiments. The preserved oxidative metabolism in myocardium with PET mismatches may be ascribed to a regional increase in oxygen extraction. Such increase together with preserved glucose utilization may be the prerequisite for survival of ischemically injured myocardium.

Coronary Angiography↗

Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration.

Atrophy and dysfunction of certain neurons, including cholinergic neurons in the basal forebrain, are key features of the neuropathology of Alzheimer's disease (AD). Since all individuals with Down syndrome (DS) develop AD neuropathology by the 4th decade, we reasoned that a genetic model of DS, the trisomy 16 (Ts 16) mouse, may provide an animal model to study the neurodegeneration in AD. Ts 16 mice fail to survive birth; to evaluate neurons for long periods in vivo required transplantation of fetal tissue. We previously demonstrated that Ts 16 basal forebrain cholinergic neurons (BFCNs) undergo age-related atrophy similar to DS and AD, and now show that a specific neurotrophic factor, nerve growth factor (NGF), acts to reverse Ts 16-induced atrophy of BFCNs and stimulates hypertrophy of these cells. As NGF levels were not decreased in the host, abnormalities intrinsic to Ts 16 BFCNs presumably caused the atrophy. Our results suggest that NGF may be useful in reversing cholinergic neurodegeneration in DS and AD.

Aging↗

Tumoral calcinosis, a clinical report of eleven cases.

Clinical observations of 11 new cases of tumoral calcinosis are reported. The condition is characterized by calcified masses of varying size in the region of major joints. Surgical excision is recommended in selected cases determined by the size of the lesion, the deformity present and functional complaints. In this series surgical excision was done in 6 patients, and the diagnosis was confirmed histopathologically. After a complete excision of the tumor, no recurrences were seen in 5 cases with a mean follow-up time of 25 months. Incomplete excision led to multiple recurrences in one patient.

Adult↗

Recent advances in studies on traditional Chinese anti-aging materia medica.

Presented in this paper is a report of our studies on 386 traditional effective anti-aging medications, the effects of which on cell generation, survival time, immunomodulation, improvement of visceral and metabolic functions, and anti-infection, and their trace element contents were further summarized and analysed. This suggests that the investigations of traditional anti-aging materia medica in China are now well under way and some effective drugs and compound prescriptions have been explored, such as Ginseng, Radix Astragali seu Hedysari, Radix Angelicae Sinensis, Herba Epimedii, Cordyceps, Ganoderma Lucidum seu Japonicum, Radix Polygoni Multiflori, Radix Acanthopanacis Senticosi, Rhizoma Polygonati, Fructus Lycii, and Poria. However, all of these preliminary results remain to be further investigated.

Aging↗

[The isolation of Vibrio alginolyticus bacteriophage].

We identified 4 bacteriophages of V. alginolyticus in 29 ones, which were first isolated from seafood. According to their character of the plaques, they were classified into two kinds: one plaque was clear, the other was opaque. The size of these plaques were different and their diameters are 0.5-3.0mm. By electron microscopy observation, they could be classified into two kinds; one has a long axie and hexagemal head, and a thin-long tail, the other has an equal axie hexagenal head and a very short tail, but the edges and corners aren't clear. The multiplication valence of the phages attained to 10(8-9) pfu/ml. Total lysis rate of 4 bacteriophages was 72.22% to V. alginolyticus. However, the lysis rate of single phage was 9.72-44.4%. 4 bacteriophages all had high host specificity. Cross-lysis reaction wasn't found in the test of original solution of bacteriophages to 612 strains of different genus bacteria and 697 strains of genus Vibrio, but they only showed 39% cross-lysis rate to V. parahaemolyticus and most part of this phenomenon disappeared at 10 RTD of the phages. Thus, the obvious relation of consanguinity was showed between two kinds of bacteria strains.

Bacteriophages↗

[Gastric emptying time with 99mTc-resin solid experiment meal].

Half gastric emptying time (GET1/2) was measured by using radionuclide gamma-photography with 99mTc-resin solid experiment meal. The results were as follows: 1. GET1/2 in the normal controls (10 cases) was 51.62 +/- 3.69 minutes. 2. GET1/2 in mild chronic atrophic gastritis (CAG) patients was 51.68 +/- 9.20 Min, not significantly different with the normal controls (P > 0.05). GET1/2 in 15 cases with moderate and severe CAG was 70.39 +/- 14.86 Min, which was apparently longer than that in normal controls (P < 0.01). 3. There was no significant difference in GET1/2 between carcinoma of the gastric corpus, fundus and cardia (50.77 +/- 2.73 Min) as well as the normal controls (P > 0.05). GET1/2 of the cancer of gastric antrum was 89.06 +/- 19.55 Min, being longer than that in normal controls (P < 0.01). 4. No obvious difference was observed between the GET1/2 of patients with corpus and fundus peptic ulcer (55.36 +/- 6.80 Min.) and the normal controls (P > 0.05). It was apparently longer in patients with antral peptic ulcer (76.62 +/- 16.96 Min.) than in patients with ulcers of corpus, fundus and normal controls (P < 0.01). 5. GET1/2 in patients with duodenal ulcer (42.49 +/- 6.26 Min.) was apparently shorter than those with gastric ulcer and normal controls. 6. GET1/2 in diabetic patients was 70.01 +/- 29, 46 Min, it was obviously longer in those patients with autonomic nervous dysfunction (84.03 +/- 22.31 Min.) than that those without (34.14 +/- 7.90 Min.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Site-directed mutagenesis of monoamine oxidase A and B: role of cysteines.

Nine cysteines are found in the deduced amino acid sequences of both human liver monoamine oxidase (MAO)-A and MAO-B. The role of these cysteine residues in MAO-A and -B catalytic activity was studied by site-directed mutagenesis, whereby each cysteine residue was converted to serine. The wild-type and mutant cDNAs were then transiently transfected into COS cells and assayed for MAO-A and -B catalytic activity using 5-[3H]hydroxytryptamine and [14C]phenylethylamine, respectively, as substrates. Catalytic activities were retained in seven MAO-A cysteine to serine mutants (mutations at residues 165, 210, 266, 306, 321, 323, and 398) and in six MAO-B cysteine to serine mutants (mutations at residues 5, 172, 192, 297, 312, and 389). Kinetic parameters (Km) of these mutants were also similar to those of the wild-type enzymes, indicating that these cysteines are not necessary for enzymatic activity. Substitution of MAO-A Cys-374 and -406 and MAO-B Cys-156, -365, and -397 with serine resulted in complete loss of MAO-A and -B catalytic activity. The loss of catalytic activity was not due to unsuccessful transfection of the mutants, as indicated by either Northern blot or Western blot analysis. The loss of catalytic activity in the MAO-A Ser-406 and MAO-B Ser-397 mutants may be due to the prevention of covalent binding of the enzyme to the cofactor FAD, which is necessary for catalytic activity. The loss of catalytic activity of MAO-A Ser-374 and MAO-B Ser-156 and -365 suggests that these cysteines are important for catalytic activity, but whether they are involved in forming the active site or are important for the appropriate conformation of MAO-A and -B remains to be studied.

Animals↗

[An applied study on the method of multi-factorial quantitative-risk assessment (MFQRA) for mass screening of colorectal cancer].

This paper reported an actual effectiveness evaluation for MFQRA, as a primary screening procedure, applied in a mass screening for colorectal cancer since 1989 to 1990 among a general population with the age of 30 and above in Jia-shan county where is a high incidence area of colorectal cancer in this nation. Results of this paper demonstrated that (1) attributable degree (AD) can identify subpopulations or subgroups with different incidence risks from a general population, and provide evidence for decision-making of advanced screening procedures and even for prevention of colorectal cancer; (2) Sensitivity of MFQRA was much higher, compared to conventional fecal occult blood test (FOBT) and symptomatic screening methods (65.89% vs 34%-50%); (3) Multiple tests with FOBT by reverse passive hemagglutination (RPHA) were effective and practical method for mass screening of colorectal cancer.

Adult↗