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Biomedical subjects

K Lin

Publications and source records attributed to K Lin.

At least 19 recordsLinked to original sources
PubMed2002

The effect of different psychological profiles and timings of stress exposure on humoral immune response.

The aim of this study was to analyse the effects of different timings of stress exposure on humoral immune response in mice previously distinguished by their own psychological profile. The Swiss mice were submitted to two different protocols of social confrontation, based on the timing of stress exposure in relation to an immune challenge: animals socially confronted daily for 2 weeks (SINT) and another group confronted daily for 3 weeks (LINT). Control groups were individually housed in a different room. All groups were intraperitoneally injected with sheep red blood cells (SRBC). The SINT group was challenged on the 1st and 7th days of confrontation, whereas the LINT group was challenged on the 7th and 14th days. Two days prior to the period of social conflict, the animals were tested in the elevated plus-maze (PM). The SINT protocol caused a more depressed primary immune response in the submissive mice than that observed in the dominants. The LINT protocol induced a marked increase in the primary immune response, which was more evident in the dominant mice, whilst no changes were observed in the secondary immune response. In the control and dominant groups, the correlation analysis attributed a higher anti-SRBC titre to the more anxious animals; by contrast, higher anti-SRBC titres were found in the less anxious submissive mice. These studies show that different physiological and behavioural adaptations to environmental demands over time, as well as different psychological profiles, constitute important factors to a better understanding of neuro-immune interactions.

Adaptation, Psychological↗
PubMed2002

Wide distribution of Plasmodium ovale in Myanmar.

The presence of Plasmodium ovale has never been previously reported in Myanmar. Using blood samples obtained in many villages across the country between 1996 and 2000, molecular diagnosis of Plasmodium species was made with semi- or full-nested polymerase chain reaction (PCR) with species-specific primers, followed by agarose gel electrophoresis to detect amplification products. The presence of P. ovale was also confirmed with the another PCR-based diagnosis, the microtiterplate hybridization (MPH) method using species-specific probes. Both methods target the A type of the small subunit ribosomal RNA gene of the four human malaria parasites. Plasmodium ovale DNA was amplified in samples from 65 (4.9%) of 1323 PCR-positive patients, with perfect agreement between results obtained by nested PCR and MPH. Only four P. ovale-infected patients had single-species infection; all others were coinfected with P. falciparum, P. vivax and/or P. malariae. Quadruple infections were observed in six subjects. Parasites with typical P. ovale morphology were found in only 19 patients by conventional microscopy of Giemsa-stained thin smears or fluorescence microscopy of acridine orange-stained thin smears. Plasmodium ovale infections were found in villages situated in the southern, central and western regions of Myanmar, suggesting that P. ovale may be widely distributed in this country.

Adolescent↗
PubMed2002

Chronic lymphocytic leukaemia developing in the course of chronic myeloid leukaemia.

Both chronic myeloid leukaemia (CML) and chronic lymphocytic leukaemia (CLL) are rare illnesses. Their co-existence has been previously reported, typically with CML following CLL. We report to our knowledge the first case of CLL developing some years after initial diagnosis of Philadelphia (Ph) chromosome positive CML. We provide molecular evidence that CLL arose in a Ph negative clone. The implications of the findings are discussed.

Benzamides↗
PubMed2001

Colloidal interactions in suspensions of rods.

We report direct measurements of entropic interactions of colloidal spheres in suspensions of rodlike fd bacteriophage. We investigate the influence of sphere size, rod concentration, and ionic strength on these interactions. Although the results compare favorably with a recent calculation, small discrepancies reveal entropic effects due to rod flexibility. At high salt concentrations, the potential turns repulsive as a result of viral adsorption on the spheres and viral bridging between the spheres.

Biophysical Phenomena↗
PubMed2001

TNFalpha promoter region gene polymorphisms in carbamazepine-hypersensitive patients.

OBJECTIVE: To evaluate whether the major histocompatibility complex contains susceptibility genes for carbamazepine hypersensitivity. Carbamazepine hypersensitivity is immune-mediated, although factors determining its occurrence and severity are unknown. METHODS: Using PCR in 60 carbamazepine-hypersensitive patients, 37 with nonserious (Group I) and 23 with serious (Group II) reactions, and 313 control subjects (63 patients on carbamazepine without adverse effects and 250 healthy volunteers), the association with polymorphisms in the promoter region of the tumor necrosis factor alpha (TNFalpha) gene (positions -308 and -238), and with HLA-DR3 and -DQ2 was determined. RESULTS: The frequency of the variant allele (TNF2) at the -308 position was increased in Group II but not Group I carbamazepine-hypersensitive patients compared with all control subjects (p = 0.01; OR = 2.4), as was the frequency of HLA-DR3 (p = 0.01; OR = 3.3), HLA-DQ2 (p = 0.04; OR = 2.7), and the TNF2-DR3-DQ2 haplotypes (p = 0.02; OR = 3.2). None of the alleles were independently associated with serious carbamazepine hypersensitivity. For the -238 polymorphism, there was a difference in the genotype, but not in the allelic, frequencies between Group II hypersensitive patients and all control subjects. CONCLUSIONS: The TNF2 allele was associated with severe, but not nonserious, carbamazepine hypersensitivity reactions, suggesting that hypersecretion of tumor necrosis factor alpha may be a determinant of the severity of tissue damage. However, the association of the TNF2 allele with carbamazepine hypersensitivity was not independent of HLA-DR3 and -DQ2, and therefore the possibility that it constitutes a passive component of the TNF2-DR3-DQ2 haplotype cannot be excluded.

Adolescent↗
PubMed2001

The 5' flanking region of the human bone morphogenetic protein-7 gene.

We describe here the cloning and characterization of the 5' flanking region of the human Bone Morphogenetic Protein-7 (BMP-7) gene from a 3.3 kb genomic DNA fragment. Functional analysis by transient transfection using the luciferase reporter gene indicated that this region had a low basal promoter activity in human Wilm's tumor derived renal (G401) and rat osteoblast (ROS 17/2.8) cell lines. Sequential deletion analysis of the promoter revealed sequences whose presence correlated with decreased expression of the reporter gene. Coexpression of transcription factors involved in epithelial/mesenchymal interactions during kidney and eye development dramatically stimulated the expression of the reporter gene from the putative BMP-7 promoter. Finally, a subset of agents that upregulated the expression of the reporter gene from the cloned promoter were also shown to increase the expression of the endogenous BMP-7 in G401 and ROS cell lines in vitro.

Amino Acid Sequence↗
PubMed2001

Sedimentation studies reveal a direct role of phosphorylation in Smad3:Smad4 homo- and hetero-trimerization.

SMAD proteins are known to oligomerize and hetero-associate during their activation and translocation to the nucleus for transcriptional control. Analytical ultracentrifuge studies on Smad3 and Smad4 protein constructs are presented to clarify the model of homo- and hetero-oligomerization and the role of phosphorylation in the activation process. These constructs all exhibit a tendency to form disulfide cross-linked aggregates, primarily dimers, and a strong reducing agent, TCEP, was found to be required to determine the best estimates for reversible association models and equilibrium constants. A Smad4 construct, S4AF, consisting of the middle linker (L) domain and the C-terminal (C) domain, is shown to be a monomer, while a Smad3 construct, S3LC, consisting of the LC domains, is shown to form a trimer with an affinity K(3) = (1.2-3.1) x 10(9) M(-2). A Smad3 construct that mimics phosphorylation at the C-terminal target sequence, S3LC(3E), has 17--35-fold enhanced ability to form trimer over that of the wild-type construct, S3LC. S4AF associates with either S3LC or S3LC(3E) to form a hetero-trimer. In each case, the hetero-trimer is favored over the formation of the homo-trimer. Despite high sequence homology between Smad3 and Smad4, a chimeric Smad4 construct with an engineered Smad3 C-terminal pseudo-phosphorylation sequence, S4AF(3E), shows no tendency to form trimer. This suggests a Smad4-specific sequence insert inhibits homo-trimer formation, or other domains or sequences in S3LC are required in addition to the target sequence to mediate the formation of trimer. These results represent a direct molecular measure of the importance of hetero-trimerization and phosphorylation in the TGF-beta-activated Smad protein signal transduction process.

Animals↗
PubMed2001

Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.

We evaluated the role of endogenous angiotensins at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of spontaneous baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved using rats anesthetized and maintained with pentobarbital sodium. Bilateral microinjection of angiotensin II (ANG II) or its active metabolite angiotensin III (ANG III) (5, 10, or 20 pmol) into the NRVL significantly suppressed the spontaneous BRR response, as represented by the magnitude of transfer function between systemic arterial pressure and heart rate signals. The inhibitory effect of ANG III (20 pmol) was discernibly reversed by coadministration with its peptide antagonist, [Ile(7)]ANG III (1.6 nmol), or the nonpeptide AT(2) receptor antagonist, PD-123319 (1.6 nmol), but not by the nonpeptide AT(1) receptor antagonist, losartan (1.6 nmol). On the other hand, the peptide antagonist, [Sar(1), Ile(8)]ANG II (1.6 nmol) or both non-peptide antagonists appreciably reversed the suppressive action of ANG II (20 pmol). Whereas losartan produced minimal effect, blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of PD-123319, [Sar(1), Ile(8)]ANG II or [Ile(7)]ANG III elicited significant enhancement of the spontaneous BRR response. We conclude that under physiologic conditions both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the spontaneous BRR response by acting selectively on the AT(2) subtype receptors at the NRVL.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed2001

Distribution of glucose-6-phosphate dehydrogenase mutations in Southeast Asia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a heterogeneous enzyme abnormality with high frequency in tropical areas. We performed population screening and molecular studies of G6PD variants to clarify their distribution and features in Southeast Asia. A total of 4317 participants (2019 males, 2298 females) from 16 ethnic groups in Myanmar, Lao in Laos, and Amboinese in Indonesia were screened with a single-step screening method. The prevalence of G6PD-deficient males ranged from 0% (the Akha) to 10.8% (the Shan). These G6PD-deficient individuals and 12 G6PD-deficient patients who had been diagnosed at hospitals in Indonesia and Malaysia were subjected to molecular analysis by a combination of polymerase-chain-reaction-based single-strand conformation polymorphism analysis and direct sequencing. Ten different missense mutations were identified in 63 G6PD-deficient individuals (50 hemizygotes, 11 heterozygotes, and 2 homozygotes) from 14 ethnic groups. One missense mutation (1291 G-->A) found in an Indonesian Chinese, viz., G6PD Surabaya, was previously unknown. The 487 G-->A (G6PD Mahidol) mutation was widely seen in Myanmar, 383 T-->C (G6PD Vanua Lava) was specifically found among Amboinese, 871 G-->A (G6PD Viangchan) was observed mainly in Lao, and 592 C-->T (G6PD Coimbra) was found in Malaysian aborigines (Orang Asli). The other five mutations, 95 A-->G (G6PD Gaohe), 1003 G-->A (G6PD Chatham), 1360 C-->T (G6PD Union), 1376 G-->T (G6PD Canton), and 1388 G-->A (G6PD Kaiping) were identified mostly in accordance with distributions reported previously.

Amino Acid Substitution↗
PubMed2001

The wisdom of hormone-replacement therapy in survivors of ovarian and endometrial cancer.

This article reviews the relationship between estrogen replacement therapy (ERT) and hormone replacement therapy (HRT) in the development of endometrial, ovarian, and breast cancers. The wisdom of HRT in survivors of ovarian and endometrial cancers is reviewed by critically analyzing recent data. Because of methodological limitations in the reported studies, there are no definite data to support the safety of ERT and HRT in survivors of ovarian or endometrial cancer.

Endometrial Neoplasms↗
PubMed2001

Structural basis of Smad1 activation by receptor kinase phosphorylation.

Phosphorylation of Smad1 at the conserved carboxyl terminal SVS sequence activates BMP signaling. Here we report the crystal structure of the Smad1 MH2 domain in a conformation that reveals the structural effects of phosphorylation and a molecular mechanism for activation. Within a trimeric subunit assembly, the SVS sequence docks near two putative phosphoserine binding pockets of the neighboring molecule, in a position ready to interact upon phosphorylation. The MH2 domain undergoes concerted conformational changes upon activation, which signal Smad1 dissociation from the receptor kinase for subsequent heteromeric assembly with Smad4. Biochemical and modeling studies reveal unique favorable interactions within the Smad1/Smad4 heteromeric interface, providing a structural basis for their association in signaling.

Allosteric Regulation↗
PubMed2001

Lymphatic mapping and sentinel node identification for colorectal cancer.

The primary treatment of resectable CRC is surgical resection. Postoperative adjuvant therapies are recommended when lymph node metastases are found (stage III). There is evidence that about 20% of node negative CRC cases (stage II) are understaged, i.e., they are actually node positive (stage III). New intraoperative procedures (lymphatic mapping and sentinel node identification) that are able to detect occult macro- and micrometastases. Molecular assessment of nodal disease should improve the current staging criteria for colon cancer and could influence recommendation for adjuvant treatment.

Biomarkers, Tumor↗
PubMed2001

Pre-transplant cardiac testing for kidney-pancreas transplant candidates and association with cardiac outcomes.

BACKGROUND: Coronary artery disease is a major cause of mortality following renal transplantation, especially in those patients with diabetes. The accurate prediction of cardiac risk is therefore a major focus of the pre-transplant evaluation. The objective of this study was to retrospectively evaluate the ability of non-invasive cardiac testing (standard echocardiography, stress echocardiography, exercise tolerance testing, and nuclear myocardial perfusion) performed within 1 yr of kidney-pancreas transplant to predict post-transplant myocardial infarction. METHODS: Clinical history and pre-transplant cardiac testing performed within 1 yr prior to transplantation were reviewed in a non-blinded fashion for 165 kidney-pancreas transplantation patients receiving allografts between June 1990 and May 1998. The predictive values of clinical symptoms and cardiac testing for cardiac events (fatal and non-fatal myocardial infarctions) up to 1 yr post-transplant were calculated. RESULTS: Clinical history had a negative predictive value of 98% for cardiac events occurring within 1 yr following testing and 97% within 1 yr post-transplant. Collectively, non-invasive testing had a negative predictive value of 97% for 1 yr post-testing and 1 yr post-transplant. CONCLUSION: Clinical history alone is highly suggestive but not sufficient for the prediction of post-kidney-pancreas transplant myocardial infarction. Although a useful supplement, cardiac testing does not predict all cardiac events out to 1 yr post-testing. In this high-risk patient population with diabetes and renal failure, other methods of risk assessment are needed to more accurately predict long-term cardiac outcome for patients awaiting transplantation.

Coronary Angiography↗
PubMed2001

The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization.

Smad proteins mediate the transforming growth factor beta responses. C-terminal phosphorylation of R-Smads leads to the recruitment of Smad4 and the formation of active signaling complexes. We investigated the mechanism of phosphorylation-induced Smad complex formation with an activating pseudo-phosphorylated Smad3. Pseudo-phosphorylated Smad3 has a greater propensity to homotrimerize, and recruits Smad4 to form a heterotrimer containing two Smad3 and one Smad4. The trimeric interaction is mediated through conserved interfaces to which tumorigenic mutations map. Furthermore, a conserved Arg residue within the L3 loop, located near the C-terminal phosphorylation sites of the neighboring subunit, is essential for trimerization. We propose that the phosphorylated C-terminal residues interact with the L3 loop of the neighboring subunit to stabilize the trimer interaction.

Animals↗
PubMed2001

Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling.

The lifespan of Caenorhabditis elegans is regulated by the insulin/insulin-like growth factor (IGF)-1 receptor homolog DAF-2, which signals through a conserved phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Mutants in this pathway remain youthful and active much longer than normal animals and can live more than twice as long. This lifespan extension requires DAF-16, a forkhead/winged-helix transcription factor. DAF-16 is thought to be the main target of the DAF-2 pathway. Insulin/IGF-1 signaling is thought to lead to phosphorylation of DAF-16 by AKT activity, which in turn shortens lifespan. Here, we show that the DAF-2 pathway prevents DAF-16 accumulation in nuclei. Disrupting Akt-consensus phosphorylation sites in DAF-16 causes nuclear accumulation in wild-type animals, but, surprisingly, has little effect on lifespan. Thus the DAF-2 pathway must have additional outputs. Lifespan in C. elegans can be extended by perturbing sensory neurons or germ cells. In both cases, lifespan extension requires DAF-16. We find that both sensory neurons and germline activity regulate DAF-16 accumulation in nuclei, but the nuclear localization patterns are different. Together these findings reveal unexpected complexity in the DAF-16-dependent pathways that regulate aging.

Animals↗
PubMed2001

Surfactant and inhaled nitric oxide in rats alleviate acute lung injury induced by intestinal ischemia and reperfusion.

BACKGROUND: Respiratory distress and acute lung injury (ALI) are severe complications of intestinal ischemia and reperfusion injury (I/R). The authors hypothesize that a combined surfactant and inhaled nitric oxide (iNO) may alleviate I/R-induced ALI. METHODS: Adult rats (body weight 285 to 315 g, n = 45) were allocated randomly to either a negative control group (N-Control, n = 9) with only sham laparotomy, or groups (n = 9 each) for induction of I/R by occlusion of superior mesenteric artery, followed by treatment with (1) surfactant at 100 mg/kg (Surf), (2) iNO at 20 ppm (NO), (3) both surfactant and iNO (SNO), or (4) no surfactant no iNO (a positive control, P-Control). Mechanical ventilation was provided for 120 minutes with variable peak insufflation pressure and FIO2 to achieve adequate arterial pH, PaO2, and PaCO2. Blood gas values, dynamic lung compliance (Cdyn), and airway resistance (Raw) were measured during the 2-hour treatment. Lung wet-to-dry weight ratio (W/D), histopathology, and morphometric analysis of alveolar expansion (V(V)) were determined at the end of the experiment. RESULTS: After 120 minutes of treatment, the SNO group had the highest PaO2 and Cdyn values, close to that of the N-Control group. The Surf, NO, and SNO groups had higher V(V) and lower CV (V(V)) values than the P-Control, but modest decrease of W/D values. The NO group had moderately improved PaO2 but Cdyn and V(V) were as low as that of the P-Control. The lungs of the SNO group had significantly alleviated edema and neutrophil infiltration compared with the P-Control. CONCLUSIONS: The combined surfactant and iNO treatment alleviated rat ALI induced by I/R, and exerted effects better than the use of surfactant or iNO alone.

Administration, Inhalation↗