Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 433 records · Page 24Linked to original sources

PubMed1997

Detoxication of tyramine by the flavin-containing monooxygenase: stereoselective formation of the trans oxime.

In the presence of pig or adult human liver microsomes, tyramine was metabolized to the corresponding trans oxime through the intermediacy of the hydroxylamine. The requisite intermediate, (4-hydroxyphenethyl)hydroxylamine, was retroreduced to tyramine or converted stereoselectively to the trans oxime in the presence of pig or adult human liver microsomes. Studies of the effect of metabolic inhibitors suggested that formation of the trans oxime and retroreduction of the hydroxylamine were largely dependent on NADPH and the flavin-containing monooxygenase (FMO) and cytochrome P450, respectively. The conclusion that FMO was predominantly responsible for trans oxime formation in human liver microsomes was based on the effect of incubation conditions on tyramine N-oxygenation and the observation that cDNA-expressed human FMO3 also N-oxygenated tyramine to give exclusively the trans oxime. The synthetic hydroxylamine and oxime metabolites of tyramine were examined for affinity to human and animal dopamine and serotonin receptors and the human dopamine transporter. For all of the receptors and for the transporter examined, the avidity of the hydroxylamine and oximes was greater than 10 microM and beyond the effective concentration for physiological relevance. The results suggested that tyramine was sequentially N-oxygenated in the presence of pig and human liver microsomes and cDNA-expressed FMO3 to the hydroxylamine and then to the di-N-hydroxylamine that was spontaneously dehydrated to the trans oxime. This may be facilitated by FMO through a nondissociative substrate-enzyme interaction. Based on the biogenic amine receptor or transporter affinity for the hydroxylamine and oxime metabolites of tyramine, N-oxygenation of tyramine by pig or human liver FMO may represent a detoxication reaction that terminates the pharmacological activity of tyramine.

Adult↗

PubMed1997

Human flavin-containing monooxygenase form 3: cDNA expression of the enzymes containing amino acid substitutions observed in individuals with trimethylaminuria.

Trimethylaminuria is an autosomal recessive human disorder affecting a small part of the population as an inherited polymorphism. Individuals diagnosed with trimethylaminuria excrete relatively large amounts of trimethylamine in their urine, sweat, and breath, and this results in a fishy odor characteristic of trimethylamine. Activity of the human flavin-containing monooxygenase (FMO) has been proposed to be deficient in trimethylaminuria patients causing a decrease in the metabolism of trimethylamine that results in a fishy body odor. Cohorts of Australian, American, and British individuals suffering from trimethylaminuria have been identified. The human FMO3 cDNA was amplified from lymphocytes of affected patients. We report preliminary evidence of substitutions detected by screening of the cDNA and genomic DNA. The variant human FMO3 cDNA was constructed from wild type human FMO3 cDNA by site-directed mutagenesis as maltose-binding protein fusions. Five distinct human FMO3 mutants were expressed as fusion proteins in Escherichia coli and compared with wild type human FMO3 maltose-binding proteins (FMO3-MBP) for the N-oxygenation of 10-[(N,N-dimethylamino)pentyl]-2-(trifluoromethyl)phenothiazine, tyramine, and trimethylamine. Human Lys158 FMO3-MBP and, to a greater extent, human Glu158 FMO3-MBP efficiently N-oxygenated the three amine substrates. Human Lys158 Ile66 FMO3-MBP, Glu158 Ile66 FMO3-MBP, Lys158 Leu153 FMO3-MBP, and Glu158 Leu153 FMO3-MBP were all constructed as mutants identified as possible FMO3 variants responsible for trimethylaminuria and were found to be inactive as N-oxygenases. The results suggest that mutations at codons 66 and 153 of FMO3 can cause trimethylaminuria in humans. We observed a common polymorphism of Lys to Glu at codon 158 of FMO3 that segregated with almost equal allele frequencies in a number of control Australian and North American samples studied. The Lys158 to Glu158 human FMO3 polymorphism does not decrease trimethylamine N-oxygenation for the cDNA-expressed enzyme and thus does not appear to be causative of trimethyaminuria. The data show that the functional activity of human FMO3 can be significantly altered by amino acid changes that have been observed in individuals with clinically diagnosed trimethylaminuria.

DNA, Complementary↗

PubMed1997

cDNA sequence analysis of cardiotoxin variants from Taiwan cobra.

Five cDNAs encoding cardiotoxin variants were constructed from the cellular RNA isolated from the venom glands of Naja naja atra by reverse transcription-polymerase chain reaction. A high degree of nucleotide sequence homology was observed between these variants and other determined ones. Among them, a novel cardiotoxin 6 had 61 amino acid residues rather than 60 ones that usually observed with Naja naja atra cardiotoxins. The other cardiotoxin variants were the homologues of cardiotoxins 1, V or N with one or two amino acid substitutions, respectively. These results probably reflect the involvement of RNA editing in the production of cardiotoxin variants in the venom of Taiwan cobra.

Amino Acid Sequence↗

PubMed1997

cDNA sequence analysis of a novel neurotoxin homolog from Taiwan banded krait.

The cDNA encoding a novel protein was constructed from the cellular RNA isolated from the venom glands of Bungarus multicinctus (Taiwan banded krait) by reverse transcription-polymerase chain reaction. The deduced amino acid sequence of this novel protein contains 68 amino acid residues with 10 cysteine residues. Comparative sequence analyses show that it is structurally related to alpha-bungarotoxin and kappa-bungarotoxins from Bungarus multicinctus venom. Eight out of the ten cysteine residues in this protein are located at the homologous positions as those in the neurotoxins. However, instead of the fifth disulfide linkage appearing in loop II of alpha-bungarotoxin and kappa-bungarotoxins, the other two cysteine residues in this novel toxin are situated at the N-terminal region. Phylogenetic analyses suggest that it probably represents a small evolutionary divergence between the long and short neurotoxins.

Amino Acid Sequence↗

PubMed1997

First trial of home ECG and blood pressure telemonitoring system in Macau.

OBJECTIVE: To determine the feasibility of home monitoring of patients with cardiac disease or hypertension. METHODS: An improved home electrocardiographic and blood pressure telemonitoring system linked to a central workstation was tested in 10 patients in Macau for 3 months. RESULTS: The total number of connections was 1377. Of the automatic alarm connections, 32.5% were false positive, with the percentage of false positives ranging from 7.6 to 54.6 for different patients. Both patients and physicians found the system easy to use. CONCLUSIONS: Further investigation is required to match the number of patients with the system capacity. A more robust dysrhythmia detection algorithm is needed to reduce the number of false alarms. Nevertheless, the results were sufficiently good that the trial is being expanded.

Blood Pressure Determination↗

PubMed1997

A novel neurotoxin, cobrotoxin b, from Naja naja atra (Taiwan cobra) venom: purification, characterization, and gene organization.

A novel neurotoxin, cobrotoxin b, was isolated from Naja naja atra (Taiwan cobra) venom by successive chromatographies on gel filtration and SP-Sephadex C-25 columns. The yield of this novel toxin was 5% of that of cobrotoxin from the same venom. Its neurotoxicity determined as the inhibition of acetylcholine-induced muscle contractions was approximately 50% of that of cobrotoxin. Cobrotoxin b consists of 61 amino acid residues including 8 cysteine residues. Moreover, there are 12 amino acid substitutions between cobrotoxin b and cobrotoxin. The genomic DNA, with a size of 2,386bp, encoding the precursor of cobrotoxin b was isolated from the liver of N. naja atra. The gene consists of three exons separated by two introns. This exon/intron structure is essentially the same as that reported for the cobrotoxin gene. Moreover, the nucleotide sequences of the two neurotoxin genes exhibit 92% identity. These results highly suggest that the cobrotoxin b and cobrotoxin genes are derived from a common ancestor. Comparative analyses of cobrotoxin b and cobrotoxin precursors showed that the protein-coding regions of the exons are more diverse than introns, except for in the signal peptide domain. This indicates that the protein-coding regions may have arised via accelerated evolution. BLAST searches for sequence similarity in the GeneBank databases showed that intron 1 of the cobrotoxin b and cobrotoxin genes encodes a small nucleolar RNA (snoRNA). However, the snoRNA gene is absent from the gene encoding the Laticauda semifasciata erabutoxin c precursor (L. semifasciata and N. naja atra are sea and land snakes, respectively). Since previous studies suggested the potential mobility of snoRNA genes during evolution, we propose that intron insertions or deletions of snoRNA genes occurred with the evolutionary divergence between the sea snake and land snake neurotoxins.

Amino Acid Sequence↗

PubMed1997

Development of genetic vaccines for pathogenic genes: construction of attenuated vif DNA immunization cassettes.

OBJECTIVE: To develop a putative immunization cassette using HIV-1 vif accessory gene derived from HIV-1 clinical specimens as a component of a DNA vaccine for HIV-1. METHODS: vif genes were cloned from HIV-1-infected patients and the sequence variation present within the patients was analyzed. Prototypic genetic variants were selected and the ability of these clones to induce humoral and cellular immune responses was studied in animals. The selected protective genetic variants were biologically characterized through transcomplementation assays using primary cells infected with a vif-defective HIV-1 proviral clone. RESULTS: Analysis of vif variants from different patients revealed that vif is highly conserved with the open reading frame remaining intact in vivo. It was shown that attenuated vif clones from HIV-1-infected subjects can effectively induce both humoral and cellular responses against Vif protein in mice. Evaluation of the cellular responses in vitro using human cellular targets infected with a clinical HIV-1 isolate showed that vif clones could induce cellular responses capable of destroying the virus. CONCLUSIONS: The vif variants developed in this study exhibited non-productive phenotypes, yet were capable of inducing specific immune responses against HIV-1. These constructs could be used as part of a DNA vaccine strategy for HIV-1. This vaccine adaptation strategy could be used for the development of immunogens for any pathogen resulting in cross-reactive immunity and attenuated gene pathogenesis.

AIDS Vaccines↗

PubMed1997

False aneurysm with median nerve palsy after iatrogenic brachial artery puncture.

We report on a case in which a patient on oral anticoagulation for her aortic valve replacement, with an International Normalised Ratio of 2.13, developed a false aneurysm of the brachial artery after a routine arterial puncture, despite direct pressure to the aspiration site. The false aneurysm was complicated by the development of median nerve palsy.

Aneurysm, False↗

PubMed1997

Three new members of the mouse prolactin/growth hormone family are homologous to proteins expressed in the rat.

A search of a mouse expressed sequence tag database for novel messenger RNAs (mRNAs) in the PRL/GH family has identified three clones that are homologous to the rat PRL-like protein A (PLP-A), PRL-like protein B (PLP-B), and decidual/trophoblast PRL-related protein (d/tPRP). Full-length complementary DNA clones for each of these three mouse mRNAs have been sequenced. Mouse PLP-A is predicted to be synthesized as a precursor of 227 residues and secreted as a glycoprotein of 196 amino acids; the secreted protein shares 78% identity with rat PLP-A. The open reading frame for mouse PLP-B encodes a protein of 230 residues; the putative mature glycoprotein of 201 amino acids is 66% identical to rat PLP-B. The third mouse complementary DNA clone encodes a precursor protein of 240 residues and a secreted glycoprotein of 211 amino acids with 64% identity to rat d/tPRP. All three mouse mRNAs are expressed specifically in the placenta or decidua. The highest levels of the PLP-A mRNA are detected on day 12, at which time expression is localized to a subset of trophoblast giant cells, especially those cells that line maternal blood sinuses. PLP-B mRNA levels are high on day 10 in decidual cells and on day 12 in spongiotrophoblasts. The mRNA similar to rat d/tPRP is present at high levels even earlier in gestation (day 8) and is localized to the decidual layer. The identification of PRL-related mRNAs in common between the mouse and rat indicates that the encoded hormones are evolutionarily conserved and, therefore, likely to play important roles in reproductive physiology.

Amino Acid Sequence↗

PubMed1997

Two novel members of the prolactin/growth hormone family are expressed in the mouse placenta.

Two novel members of the mouse PRL/GH family have been identified through a search of an expressed sequence tag database. The encoded proteins do not appear to be homologs of other known members of this hormone family. One of these proteins, designated PRL-like protein E (PLP-E), is predicted to be synthesized as a precursor of 265 amino acids, modified by N-linked glycosylation, and secreted as a mature glycoprotein of 236 residues. The second clone encodes a protein of 253 residues with consensus sites for N-linked glycosylation; the secreted form of the protein, designated PRL-like protein F (PLP-F), is predicted to be 223 amino acids in length. Both of these messenger RNAs are expressed specifically in the placenta, with peak levels of PLP-E on days 10-12 and of PLP-F on days 14-16. Expression of PLP-E is restricted to the trophoblast giant cells, whereas PLP-F is synthesized only in the spongiotrophoblasts. The genes for both of these proteins map to a 700-kilobase region of mouse chromosome 13 that includes other members of the PRL/GH family.

Amino Acid Sequence↗

PubMed1997

A home electrocardiography and blood pressure telemonitoring system.

A home electrocardiography (ECG) and blood pressure telemonitoring system for cardiac patients was installed in the Macau region. The monitoring centre was established in the emergency unit at the Government Hospital of Macau. The first users were 10 cardiovascular patients selected by a physician. The average age of these users was 61 years (range 30-78). The results of a three-month trial showed that the system was easy to operate and technically reliable. It was found to be helpful for cardiac patients. The most significant problem during the trial was electrical noise from the ECG electrodes.

Adult↗

PubMed1997

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

OBJECTIVE: Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS: In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS: The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or > or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS: Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

Adult↗

PubMed1997

Dexamethasone inhibits mucous glycoprotein secretion via a phospholipase A2-dependent mechanism in cultured chinchilla middle ear epithelial cells.

Inhibition or attenuation of mucous hypersecretion in middle ear epithelium is a key step toward resolution of mucoid otitis media. Mucous hypersecretion induced by platelet-activating factor (PAF) in cultured Chinchilla middle ear epithelial cells is dependent on arachidonic acid metabolites via PAF receptors, suggestive of the role of phospholipase A2 (PLA2) in mucous glycoprotein (MGP) secretion. In this study, dexamethasone added to cultured Chinchilla middle ear epithelial cells inhibited baseline and PAF-induced MGP secretion in a concentration-dependent manner. A definite time lag (16 h) was observed between administration of dexamethasone and MGP inhibition. This inhibition was reversed by the addition of exogenous PLA2 (the rate-limiting enzyme of arachidonic acid metabolism) and actinomycin D (an inhibitor of mRNA synthesis). This suggests that dexamethasone inhibits baseline and PAF-induced MGP secretion via a PLA2-dependent mechanism.

Animals↗

PubMed1997

An evaluation of the functional status of the residents of a geriatric residential facility in South Africa.

An increase in dependent elderly people together with a change in social structure from extended to nuclear families is resulting in institutionalization of the elderly. Since training of health care personnel is not keeping pace with the demands for health care, many institutions for the elderly are forced to function without the necessary health personnel. The purpose of the present study was to examine the functional status of the residents of one geriatric facility without health care personnel in Durban, South Africa. Functional status of each of the 101 residents was assessed using the Barthel Index. The results show that although overall Barthel Index scores showed that ageing or pathology did not influence numbers of functional elderly, individual analysis of items indicated that the majority of the residents could not perform basic functional tasks like feeding, bathing and climbing stairs.

Activities of Daily Living↗

PubMed1997

[Comparison between radiotherapy and radiotherapy after laser operation and neck block dissection in the treatment of nasopharyngeal cancer].

Two groups of patients who suffered from nasopharyngeal carcinoma were treated by different methods. Group one of 67 patients accepted radiotherapy after laser operation and neck block dissection. Group two of 42 patients were treated by radiotherapy only. The survival rate after five years was 76.1% in group one, and 46.9% in group two. The curative results showed that group one was superior to group two. Nd: YAG laser treatment of the original lesion followed by neck block dissection of the metastatic lymph nodes and radiotherapy can yet be regasded as a new method.

Adult↗

PubMed1997

[The results of questionnaire of basic concepts about asthma management and prevention for respiratory professionals in Beijing's hospitals at different levels].

OBJECTIVE: To evaluate the information of basic concepts about asthma management and prevention collected from respiralogy professionals in Beijing's hospitals at different levels and provide the basis of drawing up a work plan for Asthma Management and Prevention Committee. METHODS: Fifty-five hospitals including municipal hospitals, urban district hospitals and county hospitals of suburban district were involved and four hundred and thirty-six respiralogy professionals consisting of resident physician and physician-in-charge were asked using questionnaire method. RESULTS: The respiralogy professionals at different level hospitals have some confused ideas in the definition of asthma, the importance of inhalation and anti-inflammatory therapy and the value of peak flow meter. The results of quetionnaire of respiralogy professionals in municipal hospitals were superior to that in urban district hospitals and county hospitals of suburban district. CONCLUSION: The physician education of asthma management and prevention is an important task. Special attention should be paid on the hospitals at basic level.

Asthma↗

PubMed1997

[Limitations of the common pre-processing method in the signal-averaged electrocardiogram].

The isolation of the micro potentials from electrocardiogram using coherence averaging technique requires perfect signal alignment. The purpose of this paper was to assess the reliability of the maximum correlation coefficient (MCC) method by computer simulation. The ability of signal recognition, the impacts of correlation-window-width and threshold on accuracy of temporal alignment and on averaged results were analyzed. The results showed that the MCC method was totally insensitive to amplitude variation and relatively insensitive to the duration variation. In the process of signal alignment, the narrower correlation-window-width, the less sensitivity of the maximum correlation coefficient to the misalignment would be. With the threshold of 0.99, the window-width of both 40 and 100 ms induced the deformation on averaged result in time and frequency domain. The simulation results suggested that the deficiencies of MCC method could impose serious limitations on reliability of isolating the atrial and ventricular late potentials.

Computer Simulation↗

PubMed1997

[Painful mild scoliosis in the elderly].

We followed up and analysised 25 patients with slight painful scoliosis including symptoms, signs, images, as well as treatment and effects. The results showed that the mild scoliosis with rotation in lumbar and thoracic-lumbar region will develop and aggraviate with age. In the elderly, it may cause severe low-back pain intermittent claudication and neurological defect of lower extremities due to stenosis and spondylolethesis. We think this kind of patients should be treated with the anterior Zielke operation in early stage in order to correct rotation and prevent the later stage problems. If the symptoms and signs as described above have occured, surgical decompression and internal fixation should be recommended, the operative treatment is more effective than the non-operative treatment.

Aged↗