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Biomedical subjects

R Y Lin

Publications and source records attributed to R Y Lin.

At least 37 records · Page 2Linked to original sources

Monophosphoryl lipid A stimulated up-regulation of nitric oxide synthase and nitric oxide release by human monocytes in vitro.

Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) with reduced toxicity which has been shown to modulate various immune functions in monocytes. We examined whether human monocytes can be stimulated to produce nitric oxide (NO) and its catalytic enzyme nitric oxide synthase (NOS). Monocytes were stimulated with LPS or MPL and both NOS and NO (as nitrite) production were measured. MPL at high doses (> 100 micrograms/ml) stimulated monocytes to release NO that was significantly greater than both the control and LPS-treated monocytes (p < 0.05). NO release by control cells and the LPS treated cells was not significantly different. Both arginase and N-monomethyl arginine (NMLA) inhibited the MPL stimulated release of NO (p < 0.01). MPL significantly increased inducible NOS (iNOS) expression as measured by both fluorescent microscopy and flow cytometry (p < 0.05). Similarly, both soluble NOS (sNOS) and particulate NOS (pNOS) activity were significantly up-regulated by MPL (p < 0.05). Significant correlations were found between pNOS expression and sNOS release (r = 0.72, p < 0.0001) and between 12 h NO release and sNOS production (r = 0.44, p < 0.005). These experiments confirm that human monocytes can be stimulated with MPL to produce NO in vitro and suggest that up-regulation of pNOS does not preclude NO release.

Adjuvants, Immunologic↗

Early parenteral corticosteroid administration in acute asthma.

To test the hypothesis that early parenteral corticosteroid administration may be associated with a rapid improvement in airflow obstruction in adult asthmatic patients, a randomized, double-blind placebo-controlled study was carried out. Forty-five adult asthmatic patients, with initial peak expiratory flow rates (PEFRs) of < 200 L/sec received an intravenous bolus of either 125 mg methylprednisolone (MP) or normal saline before any other emergency department treatments. This was immediately followed by 3 aerosol treatments of 2.5 mg of albuterol separated by 20-minute intervals. PEFRs and heart rates were measured over a 1-hour time frame. There was not a significantly higher rate of increase of PEFR in the MP group compared with the saline group. Similarly, the rate of increase in percent PEFR showed a trend to being higher in the saline group (P = .061). There was no significant difference in the proportion of hospitalizations and side effects between the two groups. Adjustment for other variables did not result in a model showing an enhanced PEFR improvement with MP treatment. This study does not support the concept that corticosteroid treatment effects are beneficial within the first hour after administration. Further studies of rapid-acting modalities to enhance bronchodilation are needed in treating acute asthmatics.

Acute Disease↗

Nasal mucosal cell alterations in HIV-infected patients.

Patients with HIV infection often have nasopharyngeal symptoms related to inflammatory or infectious diseases of the upper respiratory tract. In this study, we examined specific nasal mucosal cytologic alterations in adult patients with HIV infection for associations with nasopharyngeal symptoms and other clinical parameters. Mucosal cytology was obtained in 62 patients from an urban HIV clinic using a plastic curettelike probe. The quantities of goblet cells, vacuolated cells, and leukocytes were determined and analyzed for associations with various clinical aspects of these patients and specifically with the presence or absence of prolonged (> 2-week duration) nasopharyngeal symptoms. Goblet cell, but not vacuolated cell, increases were observed in samples in which nasal eosinophilia was present and in samples obtained from April to October without specific associations with nasopharyngeal symptoms or histories of atopic disease. A history of allergic rhinitis or recent upper respiratory infection was significantly associated with increased proportions and total numbers of epithelial cells that showed vacuolization. In patients with prolonged nasopharyngeal symptoms, significantly higher numbers of nasal leukocytes were observed but higher proportions of vacuolated cells were not. Scores of tests for abnormal physical findings in the nose were higher for patients with prolonged nasopharyngeal symptoms than for those without. Peripheral blood CD4 concentrations, gender, nasal substance abuse history, and other comorbidities did not influence either vacuolated cell or goblet cell quantities. These data show that prolonged nasopharyngeal symptoms in HIV infection are associated with a certain nasal cellular pattern. It is conceivable that this pattern relates to recurrent or prolonged nasal inflammation secondary to upper respiratory infection.

Adult↗

Decreasing hepatitis D virus infection in Taiwan: an analysis of contributory factors.

Superinfection of hepatitis D virus (HDV) among hepatitis B virus (HBV) carriers is mainly through heterosexual contact in Taiwan. This study investigated the change of HDV endemicity and its associated contributory factors. Seventy-seven patients with acute HDV superinfection among 527 consecutive exacerbating hepatitis B surface antigen (HBsAg) carriers were identified over the past 12 years. The prevalence decreased significantly by each 3-year period from June 1983 to May 1995 (23.7, 15.5, 13.1 and 4.2%, respectively, P < 0.001). This trend was more significant in the hepatitis B e antigen (HBeAg)-negative group (P < 0.001) than in the HBeAg-positive group (P = 0.073). Subjects with a history of paid sex and prostitutes were also recruited for analysis both in 1989 and 1996. Although not statistically significant, there was a trend showing a decrease in the prevalence of serum antibody against HDV (anti-HDV) in each risk group: it was lower in 1996 among HBsAg-positive brothel-goers (10.3 vs 6.9%), licensed prostitutes (54.5 vs 50%) and unlicensed prostitutes (36.1 vs 30.8%). Accumulation of anti-HDV-positive subjects in risk groups may mask the actual decrease of new HDV-infected cases. The prevalence of the HBsAg carrier rate among all prostitutes has significantly decreased (18.3 vs 12.2%, P = 0.015). The efficacy of each preventive strategy was examined and mapped with the trend. It was concluded that active preventive measures directed against promiscuity and sexually transmitted disease and the promotion of disposable needles may have contributed to the decrease in HDV endemicity.

Adolescent↗

Vasopressin-induced amber-like skin necrosis.

Case reports about vasopressin-induced cutaneous necrosis are not frequent. Here we report a further case, of which skin manifestations included not only mottling, cyanosis, ecchymosis, bullae and gangrene, but also amber-like change in focal areas. Besides, intermittent paling of the skin with or without deep pain sensation of the limbs over non-injection sites was observed that might be a warning sign of impending skin necrosis. Based on the literature about vasopressin-induced skin necrosis we discuss the possible role of coagulation enhancement of this molecule.

Esophageal and Gastric Varices↗

Neutrophil rheologic changes in septic shock.

Decreases in effective capillary blood flow during septic shock may be related to changes in neutrophil rheology which contribute to microvascular occlusion. The purpose of this study was to examine neutrophil deformability, adherence, and aggregation in patients with severe sepsis and septic shock. Neutrophils were isolated from six patients with septic shock (SS), 12 patients with severe sepsis (S), six noninfected critically ill patients (CINS), and nine normal volunteers (N). Neutrophil deformability was determined by examining filtration through 5-microm filters. Neutrophil aggregation was measured by aggregometry and leukergy. Neutrophil adherence was examined by assessing the binding of latex beads to neutrophils. Patients with S and SS demonstrated decreased neutrophil filterability of 27 +/- 2% and 16 +/- 5%, respectively (p < 0.01), in comparison with N subjects, 55 +/- 4% and CINS patients, 58 +/- 2%. Preincubation of neutrophils from S and SS patients with cytochalasin D significantly increased the percent filtration of neutrophils. Neutrophil aggregation, measured by aggregometry, was increased in SS patients, 16 +/- 4% (p < 0.01) compared with N subjects, 1 +/- 0.2% and CINS patients, 1 +/- 0.2%. Incubation of neutrophils of SS patients with anti-CD11/CD18 significantly increased the filtration of isolated neutrophils to 46 +/- 3% (p < 0.01) and decreased aggregation to 7 +/- 2%. Neutrophil adherence was not increased in S or SS patients. These observations suggest that neutrophil deformability is decreased in patients with S and SS. Increased leukoaggregation may also contribute to decreased filterability of neutrophils in SS patients. These mechanisms may play a role in impaired microvascular flow in septic shock.

Aged↗

GB virus-C/hepatitis G virus infection in prostitutes: possible role of sexual transmission.

The modes of transmission of GB virus-C/hepatitis G virus (GBV-C/HGV) other than by blood transfusion are largely unknown. The prevalence of GBV-C/HGV viremia and the associated risk factors in 145 female prostitutes were examined. The seroprevalence of hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), and GBV-C/HGV RNA were 14%, 18%, and 11%, respectively. The demographic characteristics were similar between subjects with and without HBsAg. In contrast, those with HCV or GBV-C/HGV infection had practised longer as prostitutes and received blood transfusion more frequently. Moreover, the prevalence of GBV-C/HGV RNA and anti-HCV tended to increase in parallel with the duration of prostitution. These results suggest that like HCV, sexual transmission of GBV-C/HGV occurs and the risk increased with prolonged duration of exposure. The transmission efficiency between GBV-C/HGV and HCV appears to be similar.

Adult↗

Frequency of the CCR5 delta 32 mutant allele in HIV-1-positive patients, female sex workers, and a normal population in Taiwan.

A specific 32-nucleotide deletion mutant of the CCR5 gene (Accr5), the coreceptor gene for human immunodeficiency virus type 1 (HIV-1), can effectively suppress the transmission and pathogenesis of the virus. Individuals homozygous for the delta ccr5 allele resist primary macrophage-tropic HIV-1 infection, despite multiple high-risk sexual exposures. This gene deletion is relatively common among Caucasians but uncommon among Africans, Asians, and South Americans. We used polymerase chain reaction (PCR) technology to determine the frequency of the delta ccr5 allele in a Taiwanese population with diverse health status and social backgrounds. Subjects included 24 HIV-1-infected persons in the northern and southern parts of Taiwan; 131 HIV-1 high-risk, licensed female sex workers in the northern part of the island (21% of whom were aborigines); and 187 unrelated, healthy, HIV-1-negative individuals in southern Taiwan. PCR with primers encompassing the entire CCR5 gene was used to explore possible deletions at regions other than the 32-nucleotide area in the female sex workers. No ccr5 deletions were detected, indicating that they are rare or absent in the Taiwanese population. This finding implies that delta ccr5 is not likely to be part of the defense against the spread of HIV-1-infection in Taiwanese.

Acquired Immunodeficiency Syndrome↗

The arterial anatomy of larynx transplantation: microsurgical revascularization of the larynx.

Advances in immunosuppression and selective reinnervation may soon make laryngeal transplantation a potential therapy for patients undergoing total laryngectomy. Successful transplantation requires a clear delineation of those vessels necessary to completely revascularize the larynx. Our hypothesis is that the arterial inflow provided by a single superior thyroid artery is sufficient to revascularize the entire larynx. To test this hypothesis, 8 cadavers were studied via either barium latex injection (n = 4) to assess contralateral tissue perfusion or India ink (n = 4), to determine the degree of mucosal perfusion. Following injection via a single superior thyroid artery, all larynges demonstrated either complete, bilateral tissue perfusion evidenced by x-ray visualization of the barium latex injected specimen or bilateral mucosal staining with India ink. We conclude that bilateral perfusion of the entire larynx transplant, including laryngeal and epiglottic mucosa, would occur after revascularization of a single superior thyroid artery. These findings suggest that reliable revascularization of a larynx transplant is technically possible using modern microsurgical techniques.

Adult↗

The role of the fetal fibroblast and transforming growth factor-beta in a model of human fetal wound repair.

The fetus heals skin wounds without scar formation. Human fetal skin that is transplanted to a subcutaneous location on an adult athymic mouse and subsequently wounded heals without scar formation, whereas the same fetal skin heals with scar formation when transplanted to a cutaneous location. To characterize the healing process of human fetal skin in these two locations, species-specific human and mouse DNA probes were constructed and used to probe graft wounds under high stringency in situ hybridization conditions. Immunostaining for species-specific fibroblasts, macrophages, and neutrophils was also performed. The cutaneous human fetal graft healed with scar and showed an influx of adult mouse fibroblasts and macrophages. In contrast, subcutaneous human fetal grafts showed exclusively human fetal fibroblasts in the wound environment, an absence of inflammatory cells, and scar-free repair. Thus, the highly organized collagen deposition in scarless human fetal wound repair appears to be intrinsic to the human fetal fibroblast and occurs in the absence of an adult-like inflammatory response. One important cytokine involved in wound repair is transforming growth factor-beta (TGF beta). TGF beta promotes inflammatory cell recruitment and collagen deposition in healing wounds. To determine the role of TGF beta 1 in fetal wound healing, in situ hybridization for TGF beta 1 mRNA expression, immunostaining for TGF beta protein, and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF beta 1 slow release disk. TGF beta 1 RNA expression and TGF beta protein were found in wounded adult skin. Neither TGF beta 1 mRNA upregulation nor TGF beta protein was detected in human fetal skin after wounding. However, when exogenous TGF beta 1 was added to human fetal skin, induction of TGF beta 1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. Thus, non-scarring fetal skin is relatively TGF beta 1 deficient when compared to scarring adult skin. Furthermore, when exogenous TGF beta is added to fetal skin, scarring occurs. TGF beta appears to be an important modulator in scar formation. With a more thorough understanding of scarless repair mechanisms, clinical induction of scarless healing in adults and children soon may be possible.

Adult↗

The pattern of inflammation in rat sepsis due to enterotoxin-producing Staphylococcus aureus: a comparison with ischemia-reperfusion injury.

Sepsis and trauma have similarities in their immunopathologic profiles. Both conditions can result in multi-system organ failure which is sometimes associated with cytokine generation and inflammatory cell activation. Furthermore, decreases in peripheral blood monocyte expression of HLA-DR have been noted in both human sepsis and trauma. However, the magnitude, onset, and time course of such stimuli are often difficult to ascertain in human studies. Thus, to study a more detailed in vivo immunologic profile in these conditions, rat models were employed. Our aim was to describe and analyze cytokine and peripheral blood immunophenotype patterns in bacterially induced rat sepsis and to compare this to rat ischemia-reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion. Two bacterial doses which were either lethal or sublethal at 24-48 hours were utilized. Peripheral blood neutrophils and B-lymphocytes were studied for expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose injection resulted in significantly higher levels of neutrophil CD11b/c expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A expression was also higher in lethal sepsis. Gamma interferon levels were significantly higher in lethal sepsis compared with ischemia-reperfusion (p = 0.005). Studies over time showed that CD11b expression and interferon gamma were both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on the other hand remained elevated at comparable levels at 6 and 24 hr in lethal sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with enterotoxin producing staphylococcus results in phasic alterations in neutrophil CD11b and plasma interferon levels prior to death. In analogy to the findings of monocyte decreases in DR expression observed in human trauma and sepsis, rat B-cell I-A expression showed decreases in sublethal sepsis as well as in ischemia-reperfusion injury. However, this was not observed in lethal sepsis. These findings have implications in understanding the immunologic/inflammatory changes observed in human sepsis and trauma.

Animals↗

Characterization of S-AKAP84, a novel developmentally regulated A kinase anchor protein of male germ cells.

In mammalian spermatozoa, most of the type II alpha isoform of cAMP-dependent protein kinase (PKAII alpha) is anchored at the cytoplasmic surface of a specialized array of mitochondria in the flagellar cytoskeleton. This places the catalytic subunits of PKAII alpha in proximity with potential target substrates in the cytoskeleton. The mechanism by which PKAII alpha is anchored at the outer surface of germ cell mitochondria has not been elucidated. We now report the cloning of a cDNA that encodes a novel, germ cell A kinase anchor protein (AKAP) designated S-AKAP84. S-AKAP84 comprises 593 amino acids and contains a centrally located domain that avidly binds regulatory subunits (RII alpha and RII beta) of PKAII alpha and PKAII beta. The 3.2-kilobase S-AKAP84 mRNA and the cognate S-AKAP84 RII binding protein are expressed principally in the male germ cell lineage. Expression of S-AKAP84 is tightly regulated during development. The protein accumulates as spermatids undergo nuclear condensation and tail elongation. The timing of S-AKAP84 expression is correlated with the de novo accumulation of RII alpha and RII beta subunits and the migration of mitochondria from the cytoplasm (round spermatids) to the cytoskeleton (midpiece in elongating spermatids). Residues 1-30 at the NH2 terminus of S-AKAP84 constitute a putative signal/anchor sequence that may target the protein to the outer mitochondrial membrane. Immunofluorescence analysis demonstrated that S-AKAP84 is co-localized with mitochondria in the flagellum.

A Kinase Anchor Proteins↗

A model of scarless human fetal wound repair is deficient in transforming growth factor beta.

Human fetal skin heals via scarless regeneration, whereas adult skin heals with scar. Scarless repair may reflect a distinct cytokine milieu. We studied the role of the cytokine transforming growth factor beta (TGF beta) using an established model of scarless human fetal skin repair in which human fetal skin is transplanted into a subcutaneous pocket on the flank of an adult nude mouse. In this model, wounded 16-week-gestation human fetal skin heals without scar, whereas wounded adult skin heals with scar. Seven days after transplantation, incisional wounds were made in the skin grafts. In the first phase of the study, wounds were harvested from 1 hour to 4 weeks postwounding, and immunohistochemistry was performed for TGF beta (isoform nonspecific), TGF beta 1, and TGF beta 2. Scarfree wounds in the fetal skin grafts did not show TGF beta staining. In contrast, wounds in adult grafts that heal with scar demonstrated isoform nonspecific TGF beta staining from 6 hours through 21 days, TGF beta 1 from 6 hours through 21 days, and TGF beta 2 from 12 hours through 7 days. In the second phase of the study, a slow-release disk with 0.01, 0.1, 1.0, or 10 micrograms of TGF beta 1 was placed beneath the fetal skin graft at the time of wounding. Fourteen days postwounding, there was marked scarring in the fetal grafts treated with TGF beta 1, and the size of the scar was proportional to the amount of TGF beta 1 applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urinary hyaluronic acid is a Wilms' tumor marker.

Wilms' tumor is a renal neoplasm that is histologically similar to fetal kidney tissue. Both Wilms' tumor and the fetal kidney have high levels of the glycosaminoglycan hyaluronic acid (HA) in the extracellular matrix. Preliminary studies suggest that urinary HA levels are elevated in Wilms' tumor patients. To test the utility of urinary HA as a Wilms' tumor marker, the authors compared HA levels in urine specimens from 105 Wilms' tumor patients with those of 17 age-matched controls. Preoperative urine samples (n = 92), early postoperative samples, obtained from 1 to 3 weeks after surgery (n = 63), and late postoperative samples, obtained from 1 to 6 months after surgery (n = 58) were collected from patients at 30 institutions between 1989 and 1993. The HA levels were determined in triplicate by a competitive enzyme-linked immunosorbent binding assay. Seventy-four percent of the preoperative urine specimens contained elevated HA levels compared with the controls. The preoperative HA levels were significantly higher than the early postoperative (P < .01), late postoperative (P < .01), and control levels (P < .01). There was significant correlation between preoperative HA levels and clinical tumor staging. The mean preoperative HA level for patients with histological evidence of nephroblastomatosis was higher than that for patients without nephroblastomatosis. In the late postoperative period, patients with relapse or persistent disease had higher levels of urinary HA than did the disease-free patients (P < .05). In Wilms' tumor patients, urinary HA levels are elevated preoperatively and decline progressively after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗