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Biomedical subjects

K L Chen

Publications and source records attributed to K L Chen.

35 records · Page 2Linked to original sources

Clinical study of Mycoplasma pneumoniae pneumonia.

From 1982 to 1991, we experienced 76 patients with Mycoplasma pneumoniae pneumonia which were confirmed by serologic tests. There were 32 (42%) male and 44 (58%) female patients. One patient had underlying disease of diabetes mellitus while the other patients were in good health. The age ranged from 9 months old to 72 years old. All the patients complained of fever and coughing; 63% had dry cough and 37% had sputum production. Upper respiratory tract complaints such as rhinorrhea, sore throat, or earache were noted in 57% of the patients. Fifty-five percent of the patients had GI symptoms of anorexia, nausea, vomiting, or diarrhea. Other complaints included myalgia/arthralgia (29%), headache (30%), and general malaise (32%). Dyspnea (17%) and chest pain (20%) were occasional complaints. Seventy-one percent of the patients had WBC counts < 10000/cu mm and 29% > 10000/cu mm. The mean value of C-reactive protein (CRP) was 53.1 micrograms/ml, while 16% of the patients had a CRP value above 100 micrograms/ml. Thirty-one percent of the patients were noted to have a transient elevation of serum transaminase. Four different patterns of infiltration were seen in chest radiographic manifestation: 1) peribronchial and perivascular interstitial infiltrates (18.4%), 2) nonhomogeneous patchy consolidations (22.4%), 3) homogeneous acinar consolidations (27.6%), and 4) mixed interstitial and alveolar infiltrates (27.6%). Interstitial infiltration was more commonly seen in pediatric than adult patients (46% vs 20%). Other features of the radiologic manifestation were as follows: unilateral lesions in 80% of patients, single lobe lesions in 77%, lower lobe predominant in 69%, pleural effusion in 7%, and radiographic deterioration in 10%. Mycoplasmal pneumonia should be considered in the differential diagnosis of community-acquired pneumonias.

Adolescent↗

The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication.

Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy.

Base Sequence↗

A yeast artificial chromosome contig spanning the Charcot-Marie-Tooth disease type 1A duplication region.

A contiguous set of 43 overlapping yeast artificial chromosome (YAC) clones has been developed for the Charcot-Marie-Tooth disease type 1A (CMT1A) duplication region of chromosome 17p11.2. The contig spans approximately 2.0 Mb and can be represented in a minimum of five overlapping YACs. The YAC clones were isolated from two total human genomic YAC libraries and from YAC libraries made from rodent-human hybrid cell lines. YAC clones were isolated from the libraries by polymerase chain reaction (PCR) technique. Localization to chromosome 17p11.2 was confirmed by fluorescence in situ hybridization. Overlap between the YAC clones was detected by inter-Alu PCR amplification of the YACs and by cross hybridization of the YACs with YAC insert ends obtained by Vectorette PCR. This YAC contig is a useful resource for analyzing and mapping all the genes contained within the CMT1A duplication.

Base Sequence↗

Ultrasonography of chest diseases: analysis of 154 cases.

Sonographic characteristics of various chest diseases in 154 cases were analysed according to margin of the lesion, internal echogenecity, posterior echo enhancement, air bronchogram etc. We intended to present the basic sonographic patterns of common chest diseases. The study included 10 normal cases, 10 cases with lung abscesses, 31 cases of pneumonia, 24 cases of tumors, 11 cases of obstructive atelectasis, 8 cases of pleuropericarcadial effusions, 10 cases of minimal effusions, 6 cases with pleural thickening, 32 cases of massive pleural effusion with simple compression atelectasis and 12 cases of pneumonia with parapneumonic effusion. Sonographically, normal lung showed hyperechoic zone beneath the chest wall. Identification of arc or ring-shaped wall favored lung abscess. Air bronchogram could only be found in pneumonia. Mass showed various internal echogenecity. The internal echogenecity in obstructive atelectasis was very homogeneous which could not be found in tumor. Pleural thickening showed linear hyperechogenecity beneath the chest wall. In minimal effusion, the line of the diaphragm could be easily identified. Pleuropericardial effusion could be easily diagnosed by chest sonography. The line of the pericarcadium could be clearly identified. The internal echogenecity of massive effusion were various. The internal echogenecity of simple compression atelectasis showed very homogeneous hyperdense internal echogenecity. The internal echogenecity of lung parenchyma in pneumonia with parapneumonic effusion was similar to that of pneumonia. Obstructive atelectasis, mass, consolidation and encapsulated effusion could be differentiated by chest sonography without much difficulty. Sonography could aid chest radiography by giving more morphologic information and was cheaper than computed tomography.

Adult↗

Flow cytometric DNA analysis of pleural effusions.

A total of 71 cases of pleural effusion in patients with and without cancer were analyzed by conventional cytology and flow cytometry (FCM) in order to detect cells with an abnormal DNA content (aneuploidy). For cytologic examination, the samples were prepared using standard techniques. Sample for FCM analysis were centrifuged and exposed to hypotonic solution containing detergent and propidium iodide. Thirty-eight patients had pleural effusion due to benign disease, whilst 33 patients had primary lung cancer. All 38 patients with benign pleural effusions showed FCM diploidy. There were 17 aneuploidy (52%) and 16 diploidy (48%) in the 33 patients with lung cancer by FCM analysis. Four of these 33 effusions were cytologically negative, however, FCM showed aneuploidy in 2 of these 4 patients. Based on these results, FCM analysis combined with conventional cytopathology yielded 100% specificity, 94% sensitivity and 100% predictive value of positive result. There were no false-positive results but 2 false-negative results. These findings suggest that FCM is a rapid and useful technique in the analysis of pleural effusion and can be a very useful adjunct to conventional cytopathology.

DNA↗

Generation and fluorescent in situ hybridization mapping of yeast artificial chromosomes of 1p, 17p, 17q, and 19q from a hybrid cell line by high-density screening of an amplified library.

A yeast artificial chromosome (YAC) library has been constructed from a somatic cell hybrid containing a t(1p;19q) chromosome and chromosome 17. After amplification, part of this library was analyzed by high-density colony filter screening with a repetitive human DNA probe (Alu). The human YACs distinguished by the screening were further analyzed by Alu fingerprinting and Alu PCR. Fluorescent in situ hybridization (FISH) was performed to localize the YACs to subchromosomal regions of chromosome 1p, 17, or 19q. We have obtained a panel of 123 individual YACs with a mean size of 160 kb, and 77 of these were regionally localized by FISH: 33 to 1p, 10 to 17p, 25 to 17q, and 9 to 19q. The YACs cover a total of 19.7 Mb or 9% of the 220 Mb of human DNA contained in the hybrid. No overlapping YACs have yet been detected. These YACs are available upon request and should be helpful in mapping studies of disease loci, e.g., Charcot-Marie-Tooth disease, Miller-Dieker syndrome, hereditary breast tumor, myotonic dystrophy, and malignant hyperthermia.

Chromosome Mapping↗

A preliminary study on the therapeutic effects of a calcium antagonist (diltiazem) on primary congestive cardiomyopathy. A clinical survey of 15 cases.

The clinical effects of diltiazem in 15 patients with congestive cardiomyopathy were observed. Symptoms were controlled in 66% and cardiac enlargement improved in 73.3%. There was a decrease in cardiac silhouette on X-ray in 18.82 +/- 3.2% (p less than 0.01), with an increase of EF(%), CO, CI and a decrease of TPR on two-dimensional (2-D) echocardiogram (p less than 0.01). Prior to treatment, the cardiac status of 8 cases was grade III and 7 cases grade IV; after treatment 1 case was grade I, 8 grade II, 5 grade III and 1 grade IV. This improvement might be due to the blockade of calcium channels and the fact that diltiazem has the least negative inotropic effect among the calcium antagonists. The dosage, route of administration, and prevention of side effects are discussed.

Adolescent↗

An HRP study of the motoneurons supplying the rat hypobranchial muscles: central localization, peripheral axon course and soma size.

The locations of motoneurons (MNs) supplying the rat hypobranchial muscles (lingual, geniohyoid, and infrahyoid) and the peripheral courses of axons of these MNs were investigated by using a method of HRP injection into the hypoglossal nerve or these muscles in combination with severing of the hypoglossal and/or cervical components of the plexus hypoglossocervicalis. Moreover, some sizes of the MNs were investigated in both transverse and horizontal sections. The hypobranchial MNs formed a sequence of cell columns extending caudally from the hypoglossal nucleus, via the supraspinal nucleus, to the medial and then the ventrolateral subnuclei of the ventral horn of C1 to C3. The lingual and geniohyoid MNs were located in the hypoglossal nucleus. The majority of their axons passed solely through the hypoglossal nerve, whereas a small number of axons, whose somata lay in the caudal hypoglossal nucleus, passed through the first cervical nerve and then through the ansa cervicalis to reach the hypoglossal nerve. The infrahyoid MNs were located in the supraspinal nucleus and the ventral horn, and their axons passed through the first to third cervical nerves. The hypobranchial MNs were divided into three groups according to their size: the lingual, the geniohyoid and thyrohyoid, and lastly the other infrahyoid MNs, in order of smaller to larger size. The sizes of lingual, geniohyoid, and thyrohyoid MNs displayed a unimodal distribution both in transverse and horizontal sections, whereas the other infrahyoid MNs showed a bimodal distribution.

Animals↗

Hepatitis B viral polymerase fusion proteins are biologically active and can interact with the hepatitis C virus core protein in vivo.

Hepadnaviruses and retroviruses are evolutionarily related families because they both require a process of reverse transcription for genome replication. However, hepadnaviruses produce polymerase (pol) and core proteins separately, while retroviruses synthesize a gag-pol fusion protein that is subsequently cleaved by a virally encoded protease to release a functional polymerase. To test whether an additional sequence at the N-terminus of pol in hepatitis B virus (HBV) interferes with its function, we created two plasmids expressing core-pol fusion proteins, core144-pol and core31-pol. Secreted particles obtained from HuH-7 cells, which were cotransfected with a core-pol fusion protein-expressing plasmid and a core-expressing plasmid, showed a positive signal of HBV DNA by the endogenous polymerase assay, indicating that the core-pol fusion proteins retain DNA priming, polymerization and RNase H activities. The fusion protein was detected in the cytoplasm of transfected cells and in secreted virions by immunoprecipitation. Furthermore, we found by immunofluorescence staining that the HBV core-pol fusion protein colocalized with the hepatitis C virus (HCV) core protein in cytoplasm and in lipid droplets. Immunoprecipitation studies showed that the anti-HCV core complex contained the HBV core-pol fusion protein while the anti-HBV pol complex contained the HCV core protein, which supports the hypothesis that the HCV core protein can form a complex with the HBV core-pol fusion protein.

Cytoplasm↗

Larger trinucleotide repeat size in the androgen receptor gene of infertile men with extremely severe oligozoospermia.

Androgens are significant regulators of human spermatogenesis. Their action is mediated through the androgen receptor (AR), which binds to the androgen responsive element on DNA and regulates gene transcription. Men become infertile with spinobulbar muscular atrophy (Kennedy disease) caused by a trinucleotide repeat expansion, > or = 40 CAG repeats, in the AR gene located on the X chromosome. In this prospective study, we investigated whether the variable size, larger repeats, of this trinucleotide could alter AR function and result in impaired spermatogenesis. A total of 69 infertile men were studied. Clinical and laboratory analysis showed idiopathic, nonobstructive azoospermia in 16 men, extremely severe oligozoospermia in 27 men (< 1 million sperm/mL), and severe oligozoospermia in 26 men (1 to 5 million sperm/mL). Fertile control men (n = 45) were selected by documented paternity proven by linkage analysis. Leukocyte DNA was analyzed by polymerase chain reaction (PCR) amplification across the AR repeat region. Accurate size determination of the PCR product using an ABI 373 DNA sequencer allowed precise calculation of CAG repeat sizes. The AR gene was not analyzed for other types of mutations. The difference in CAG repeat size between infertile men and proven fertile controls was statistically significant, P = .03. Patients with extremely severe oligozoospermia had significantly longer CAG repeat tracts (mean, 25.4 +/- 4.0; P = .0005; range 20-39) than controls (mean, 22 +/- 2.8; range 12-30) or patients with severe oligozoospermia (mean, 22.2 +/- 2.3; range 18-26). None of the 26 infertile men with sperm counts < 1 million/mL had < or = 19 CAG repeats compared with 6 out of 45 controls (13%; P = .06). This study suggests that some men with severe impairment of spermatogenesis have longer trinucleotide repeats in the AR gene. Although direct evidence is missing, lower affinity between androgen and the AR protein or decreased AR protein availability with longer repeats could be responsible for a diminished androgen effect on spermatogenesis. Two of the patients in the extremely severe oligozoospermia group had 35 and 39 CAG repeats, respectively (normal range is 11 to 33). Although not yet considered a mutation, longer trinucleotide repeats are unstable and might either expand or contract between generations. If they expand, conception through the use of intracytoplasmic sperm injection (ICSI), could result in the son of an

Humans↗