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Biomedical subjects

D M Wu

Publications and source records attributed to D M Wu.

32 records · Page 2Linked to original sources

Lipotropes alter casein gene expression in bovine mammary acinar culture.

Lipotropes (methyl group containing nutrients, including methionine and choline, folic acid, and vitamin B(12)) are essential for cell proliferation and differentiation of mammary tissues. Lipotropes interact in the supply and regulation of intracellular methyl group pools, thereby affecting synthesis and methylation of DNA. To determine the effect of lipotropes on milk protein gene expression, acini isolated from mammary tissues of lactating cows were cultured in one of three treatment media: (1) control, (2) lipotrope deficient, and (3) lipotrope supplemented. beta-Casein mRNA was determined by Northern blotting, and milk protein secretion was measured by a pulse-chase method. The level of beta-casein mRNA was lower in cells grown in lipotrope-deficient medium than in cells grown in the lipotrope-supplemented and control media. Acinar cells cultured in lipotrope-deficient medium also had approximately threefold less milk protein secretion than that of cells in either control or lipotrope-supplemented media. Protein secretion did not differ in the control and lipotrope-supplemented groups. The present study indicates that lipotrope deficiency suppresses total protein secretion and beta-casein gene expression in bovine mammary alveolar epithelial cells in culture.

Journal Article↗

Na+/Ca2+ exchange current in myocytes isolated from rat hypertrophied heart.

Effects of myocardial hypertrophy on the Na+/Ca2+ exchange current in isolated rat cardiac myocytes were investigated, using whole cell patch techniques. Goldblatt 2-kidney, one-clip technique was used to induce cardiomyocyte hypertrophy. The results demonstrated that the Ni(2+)-sensitive Na+/Ca2+ exchange current density was larger in hypertrophied cells than that in normal cells. At a holding potential of mV, the outward current densities were 1.53 +/- 0.31 pA/pF in normal cells and 2.62 +/- 0.53 pA/pF in hypertrophied cells (P < 0.01). At a holding potential of -100 mV, the inward current densities were 0.42 +/- 0.14 pA/pF in normal cells and 1.12 +/- 0.33 pA/pF in hypertrophied cells (P < 0.001). The results suggest that during myocardial hypertrophy the Na+/Ca2+ exchange current is significantly increased.

Animals↗

Conservation of structure and function between human and murine IL-16.

IL-16 is a proinflammatory cytokine that signals via CD4, inducing chemotactic and immunomodulatory responses of CD4+ lymphocytes, monocytes, and eosinophils. Comparative analysis of murine and human IL-16 homologs could reveal conserved structures that would help to identify key functional regions of these cytokines. To that end, we cloned the murine IL-16 cDNA and found a high degree of amino acid similarity comparing the predicted murine and human IL-16 precursor proteins (pro-IL-16). The highest similarity (82.1%) was found in the C-terminal region, which is cleaved from pro-IL-16 to yield biologically active IL-16. Chemotaxis experiments with IL-16 of murine and human origin, using murine splenocytes or human T lymphocytes as targets, showed cross-species stimulation of motility. Synthetic oligopeptides and anti-peptide Ab were produced, based on the sequences of three predicted hydrophilic domains of IL-16 potentially presented in exposed positions. None of these peptides had intrinsic IL-16 bioactivity, but one (corresponding to a hydrophilic C-terminal domain of IL-16) partially displaced binding of OKT4 mAb to human lymphocytes. This peptide, and its cognate Ab, also inhibited IL-16 chemoattractant activity for human and murine cells. These studies demonstrate a high degree of structural and functional similarity between human and murine IL-16 and suggest that amino acids in the C terminus are critical for its chemoattractant function. The data suggest cross-species conservation of IL-16 receptor structures as well. Inhibitory peptides may be useful in disease states where the proinflammatory functions of IL-16 are detrimental to the host.

Amino Acid Sequence↗

Processing and activation of pro-interleukin-16 by caspase-3.

Interleukin-16, a proinflammatory cytokine produced in CD8(+) lymphocytes, is synthesized as a precursor protein (pro-IL-16). It is postulated that the C-terminal region of pro-IL-16 is cleaved, releasing bioactive IL-16. To characterize IL-16 cleavage, we transfected COS cells with a cDNA encoding a approximately 50-kDa form of pro-IL-16. Transfected COS cells released a approximately 20-kDa IL-16 cleavage product shown to consist of the 121 C-terminal residues of pro-IL-16 by immunoblotting and amino acid sequencing. Cleaved IL-16, but not pro-IL-16, exhibited lymphocyte chemoattractant activity. A C-terminal approximately 20-kDa IL-16 polypeptide was also released when pro-IL-16 was treated with concanavalin A-stimulated CD8(+) lymphocyte lysate. Cleavage occurred after an Asp, suggesting involvement of a caspase (interleukin-1beta-converting enzyme/CED-3) family protease. Using recombinant caspases and granzyme B, we determined that pro-IL-16 cleavage is mediated only by caspase-3. Relevance to pro-IL-16 processing in primary lymphocytes was supported by identifying the p20 subunit of activated caspase-3 in stimulated CD8(+) lymphocytes and by inhibition of CD8(+) lymphocyte lysate-mediated cleavage with Ac-DEVD-CHO. Pro-IL-16 is a substrate for caspase-3, and cleavage by this enzyme releases biologically active IL-16 from its inactive precursor.

Amino Acid Sequence↗

Underregistration of neonatal deaths: an empirical study of the accuracy of infantile vital statistics in Taiwan.

STUDY OBJECTIVE: The accuracy of the official statistic on infant deaths in Taiwan has been questioned. This study aimed to survey infant deaths nationwide, to measure associated vital statistics, and compare them with the official statistics to assess accuracy. DESIGN AND PARTICIPANTS: A nationwide survey of all gestational outcomes occurring at > or = 20 weeks' gestation over a three day study period (15-17 May 1989) was conducted to collect data from 23 counties and cities nationwide using a two stage data collection procedure. MAIN RESULTS: The survey derived infant death rate was 9.72 per 1000 live births, which was higher than the reported official statistic of 5.71 per 1000 live births. A more detailed examination of data on infant deaths showed that the estimated neonatal death rate of 6.68 per 1000 live births (95% confidence intervals: 3.33, 11.96 per 1000 live births) was significantly higher than the published official statistic of 1.94 per 1000 live births, while the postneonatal mortality of 3.04 per 1000 live births was comparable to the reported statistic of 3.37 per 1000 live births. CONCLUSIONS: This study empirically documented the underregistration of infant deaths in Taiwan, particularly those occurring during the first 27 days of life.

Data Collection↗

Primary ureteral carcinoma. Report of 15 cases and comparison of the effectiveness of diagnostic methods.

Fifteen cases of primary urothelial carcinomas of the ureter are reported (14 transitional cell carcinoma and 1 mixed transitional cell carcinoma and squamous cell carcinoma). There was a clear male predominance (11/4); the peak incidence was in the sixth decade. Most tumors originated from the distal third of the ureter. Multicentricity and high recurrence rate after partial ureterectomy were noted. The clinical signs were hematuria and flank pain. Urine cytology and IVU were diagnostic in a limited number of cases. Retrograde pyelography was very helpful. CT showed to be the image modality of choice for diagnosis and preoperative staging.

Aged↗

Epstein-Barr virus in gastric carcinoma in Suzhou, China and Osaka, Japan: association with clinico-pathologic factors and HLA-subtype.

Information on geographic differences of Epstein-Barr virus (EBV) positivity and association with HLA in gastric carcinoma are limited. Therefore, the association of gastric carcinoma with EBV was examined in 118 patients from Suzhou, China, where the incidence of nasopharyngeal carcinoma (NPC) is high, and in 216 patients from Osaka, Japan, where the incidence of NPC is low, NPC being one of the EBV-associated carcinomas. Expression of HLA-A2 was also examined in some of these cases. The EBV genome was evidenced by PCR and in the tumor cells by in situ hybridization in 7/90 and 9/151 of cases from Suzhou and Osaka, respectively. Immunohistochemistry revealed that cancer cells in all cases with EBV did not express latent membrane protein-I. Type A was found in all cases positive for EBV. Among several histologic and clinical factors, only age of patients showed a correlation with EBV positivity: patients over 60 showed a higher frequency than patients below 60 years of age (p < 0.05). Typing of the HLA-A locus was possible in 16 cases positive for the EBV genome: 3 of 4 cases from Suzhou and 4 of 7 from Osaka were positive for HLA-A2 products. Severe lymphoid cell infiltration was found in 2 of 7 cases and 1 of 4 cases with and without the HLA-A2 type, respectively. The reported frequency of EBV positivity in Chinese living in Taiwan and in Japanese living in Hawaii is higher than in Suzhou, China, and Osaka, Japan, respectively. Our findings suggest that EBV association with gastric carcinoma is influenced by environmental and cultural factors.

Adenocarcinoma↗

[Effects of m-nifedipine and nifedipine on hemodynamics in renovascular hypertensive rats].

In the renovascular hypertensive myocardial hypertrophic rats of prevention and regressive groups, the blood pressure was lowered by m-nifedipine (m-Nif) or nifedipine (Nif) of 20 mg.kg-1.d-1, i.g., for 9 wk vs control (LVH) group (P < 0.01). From the isolated working hearts of prevention and regressive groups, it was found that AP, LVSP, +dp/dtmax, -dp/dtmax, CF, and CI values of m-Nif and Nif groups increased higher than that of LVH group, but LVEDP and T was lower in m-Nif and Nif groups. It was concluded that m-Nif exhibits the similar effects like Nif in prevention and reversion of renovascular hypertensive LVH and improvement of hemodynamics.

Animals↗

An outbreak of epidemic diarrhoea in adults caused by a new rotavirus in Anhui Province of China in the summer of 1983.

Shexian County of Anhui Province in East China experienced a severe outbreak of nonbacterial diarrhoea in May and June of 1983. Over 20,0000 cases were reported. Most were adults of 20 to 50 years old. The isolated virus was morphologically indistinguishable from ordinary infantile rotavirus, but CF and ELISA tests showed that the new virus lacked the common group-A antigen shared by ordinary rotavirus. Nine of 10 convalescent-phase and three paired sera of patients showed antibody positive, with a greater than four-fold antibody rise against new rotavirus in the CF test. Seventeen faecal samples from patients showed identical, and special, electropherotype. They all had a double-stranded RNA with 11 discrete segments. The RNA profiles were quite different from those of reference rotavirus Wa strain and ordinary infantile rotaviruses. Third and 4th segments were near to each other, 5th and 6th segments were very close, but 7th, 8th, and 9th segments were widely separated. This study indicates the new virus can be identified as part of a new group of rotaviruses. This new rotavirus has been incriminated as the causative agent of the epidemic.

Adult↗

Dopamine activates ATP-sensitive K+ currents in rat retinal pericytes.

The relatively sparse vasculature of the retina minimizes obstruction to incoming light, but also poses a challenge to fulfilling the metabolic demands of retinal neurons. An efficient process for distributing energy supplies to areas of need is likely to involve neuron-derived vasoactive signals. However, knowledge of the mechanisms by which capillary perfusion is regulated by neuron-to-vascular signaling is limited. Potential targets of vasoactive molecules released from nerve cells are the pericytes, which are positioned on the endothelial walls of microvessels and are thought to play a role in controlling the microcirculation. In this study, we assessed the effect of dopamine on pericyte physiology. Because dopaminergic neurites are closely associated with microvessels that express dopamine receptors, this molecule is a putative neuron-to-capillary signal, as well as neurotransmitter. We used the perforated-patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on microvessels freshly isolated from the adult rat retina. In 43% (58/134) of the sampled pericytes, we found that dopamine reversibly activated a hyperpolarizing current, which increased the membrane potential by 19 +/- 1 mV. This dopamine-induced current was inhibited by the ATP-sensitive potassium (KATP) channel blocker, glibenclamide. Consistent with a signaling pathway involving D1 dopamine receptors, adenylate cyclase and protein kinase A (PKA), the selective D1 antagonist, SCH23390, inhibited the hyperpolarizing effect of dopamine; the activator of adenylate cyclase, forskolin, mimicked the dopaminergic effect, and H89, which inhibits PKA, significantly reduced the hyperpolarization induced by dopamine. Taken together, our experiments indicate that a mechanism involving D1 dopamine receptors, adenylate cyclase, and PKA activates KATP currents in retinal pericytes. Our observations support the hypothesis that, in addition to being a neuromodulator, dopamine also serves as a signal linking neuronal activity with the function of the pericyte-containing microvasculature.

Adenosine Triphosphate↗