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Biomedical subjects

W W Chang

Publications and source records attributed to W W Chang.

At least 19 recordsLinked to original sources

Development of hematogenous pneumococcal meningitis in adult mice: the role of TNF-alpha.

Bacterial penetration across the blood-brain barrier (BBB) into the central nervous system is the first step in development of meningitis. The role of tumor necrosis factor-alpha (TNF-alpha) in the penetration process was examined with peripheral infection of Streptococcus pneumoniae type 6. After intraperitoneal infection of S. pneumoniae type 6, the BBB opening was increased continuously from 6 h and the mice died of septic shock within 36 h due to bacterial overgrowth. The bacteria crossed the BBB and began to deposit in brain at 6 h post infection. There was strong staining of TNF-alpha on blood vessels of brain from 6 h to 24 h post infection. Anti-TNF-alpha antibody blocked both the BBB opening and the entrance of circulatory S. pneumoniae type 6 into brain, indicating that TNF-alpha played an important role in controlling the opening of BBB. Furthermore, an adult murine model of hematogenous pneumococcal meningitis was developed that is based on opening of the BBB by TNF-alpha and controlling the degree of bacteremia by cefazolin antibiotic. In conclusion, hematogenous meningitis developed as TNF-alpha initiated BBB opening, peripheral bacteria entered into the brain and formed bacterial emboli, and then progressed to meningitis.

Animals↗

Gastric schwannoma found incidentally 19 years after a horizontal gastroplasty for morbid obesity.

This report represents the first known case of a gastric schwannoma in a patient subsequent to a gastric stapling and partitioning procedure for morbid obesity. The submucosal tumor found in the collapsed distal portion of the stomach was merely an incidental finding and it appeared that all of the patient's ongoing symptomatology (nausea and vomiting after meals) was a reflection of the chronic obstruction that was present at the gastric partitioning staple-line. No correlation between gastric stapling and partitioning and the development of gastric schwannoma is known or is suggested in this report.

Diagnosis, Differential↗

Patterns of protein synthesis and tolerance of anoxia in root tips of maize seedlings acclimated to a low-oxygen environment, and identification of proteins by mass spectrometry.

Tolerance of anoxia in maize root tips is greatly improved when seedlings are pretreated with 2 to 4 h of hypoxia. We describe the patterns of protein synthesis during hypoxic acclimation and anoxia. We quantified the incorporation of [(35)S]methionine into total protein and 262 individual proteins under different oxygen tensions. Proteins synthesized most rapidly under normoxic conditions continued to account for most of the proteins synthesized during hypoxic acclimation, while the production of a very few proteins was selectively enhanced. When acclimated root tips were placed under anoxia, protein synthesis was depressed and no "new" proteins were detected. We present evidence that protein synthesis during acclimation, but not during subsequent anoxia, is crucial for acclimation. The complex and quantitative changes in protein synthesis during acclimation necessitate identification of large numbers of individual proteins. We show that mass spectrometry can be effectively used to identify plant proteins arrayed by two-dimensional gel electrophoresis. Of the 48 protein spots analyzed, 46 were identified by matching to the protein database. We describe the expression of proteins involved in a wide range of cellular functions, including previously reported anaerobic proteins, and discuss their possible roles in adaptation of plants to low-oxygen stress.

Adaptation, Physiological↗

Chinese dialect identification using segmental and prosodic features.

Several approaches to Chinese dialect identification based on segmental and prosodic features of speech are described in this paper. When using segmental information only, the system performs phonotactic analysis after speech utterances have been tokenized into sequences of broad phonetic classes. The second scheme comprises prosodic models which are trained to capture tone sequence information for individual dialects. Also proposed is a novel approach that examines differences between Chinese dialects at broad phonetic and prosodic levels. These algorithms were evaluated via a multispeaker read-speech mode. Simulation results indicate that the combined use of segmental and prosodic features allows the proposed system to discriminate among three major Chinese dialects spoken in Taiwan with 93.0% accuracy.

Adolescent↗

Sarcoidosis after renal transplantation.

This is the case of a 41-year-old renal transplant recipient taking tacrolimus immunosuppressive therapy, who had a large pleural effusion, found on a chest radiograph during the work-up of digital clubbing. The patient had undergone a renal transplant 17 months earlier for end-stage renal disease secondary to immunoglobulin A nephropathy. Analysis of the effusion fluid demonstrated a lymphocytic exudate. Biopsy specimens of pleural and lung tissues showed noncaseating granulomas. Fluid and tissue cultures were negative for viral, fungal, and bacterial pathogens. Diagnosis of sarcoidosis was established by identification of noncaseating granulomas in pleural and lung tissue, the exclusion of other conditions, and rapid resolution of the effusion after the institution of corticosteroid therapy. The patient has remained free of pulmonary symptoms and had normal chest radiographs during the 20-month follow-up period.

Adrenal Cortex Hormones↗

Primary non-Hodgkin's lymphoma of the common bile duct.

Primary non-Hodgkin's lymphoma of the common bile duct is rare. To date, nine cases have been recorded in the literature. We report an additional case of a 39-yr-old woman presented with obstructive jaundice. Pathological studies of the surgical specimen disclosed that the wall of the common bile duct was transmurally infiltrated by non-Hodgkin's lymphoma of diffuse large cell type of B-cell lineage intimately associated with reticular fibers. The patient received postoperative brachytherapy, followed by six cycles of chemotherapy according to the CHOP regimen. There is no evidence of lymphoma recurrence 13 months after the surgery. Our analysis of the reported cases indicates that common bile duct non-Hodgkin's lymphoma is a rapidly progressive disease, terminating in death within a year. A complete surgical resection of the lymphoma followed by chemotherapy has shown a promising result.

Adult↗

Immunocytochemical expression of the 70 kD heat shock protein in ischaemic bowel disease.

Heat shock proteins (HSPs) are a family of polypeptides which are induced in response to diverse forms of cell injury including hyperthermia, anoxia, ethanol, heavy metals, and others, with a presumably protective function. Among several species of HSPs, the 70 kD protein (HSP70) is the most abundant and consistently induced in mammalian cells. Anti-HSP70 monoclonal antibody and a standard immunocytochemical method were used to study the expression of HSP70 in 28 surgical specimens of small and large intestines from patients with ischaemic bowel disease. Strong immunoreactivity was observed in viable, regenerating cells of both the crypt and surface epithelium within or adjacent to the necrotic foci in 86 per cent of the ischaemic bowel specimens. Staining was mostly cytoplasmic, but focally both cytoplasmic and nuclear. Smooth muscle cells of the muscularis mucosae in the ischaemic areas of some cases also showed immunoreactivity. On the other hand, HSP70 was not expressed in control specimens of small and large intestine or in colonic specimens of Crohn's disease, ulcerative colitis, and adenocarcinoma. These findings suggest a possible role of HSP70 in intestinal epithelial and smooth muscle cell response to ischaemic injury, especially in the recovery phase.

Aged↗

A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.

PURPOSE: Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure. METHODS: Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion. RESULTS: Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a). CONCLUSIONS: These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.

Adult↗

Cytomegalovirus recurrence in seropositive pregnant women attending obstetric clinics.

To understand reasons for cytomegalovirus (CMV) recurrence, a cohort of 350 CMV-seropositive pregnant women attending obstetric clinics in Taiwan was examined for cervical or urinary CMV shedding. Urine specimens were collected from 350 women and cervical secretion specimens were collected from 220 women. We measured the association of various factors with CMV recurrence, which was defined as viral shedding identified by the presence of a CMV-specific gene sequence amplified by the polymerase chain reaction in seropositive individuals. CMV recurrence status was independently associated with a sexual activity composite variable, which was defined by three sexual activity indicators: age at first sexual intercourse, total years of sexual experience, and average frequency of sexual intercourse prior to pregnancy. Pregnant women with a history of genital tract infection were more likely than women without such history to experience cervical CMV recurrence. Similarly, pregnant women with previous urinary tract infections were more likely to experience urinary CMV recurrence. The findings indicate that multiple exposure to CMV by sexual activity prior to pregnancy is an important determinant of CMV recurrence during pregnancy.

Antibodies, Viral↗

Cytomegalovirus transmission in special-care centers for mentally retarded children.

This study aimed to determine whether special-care centers for mentally retarded children are high-risk settings for cytomegalovirus (CMV) transmission. Serum and urine specimens obtained from 311 mentally retarded children aged 3 to 12 in three centers were compared for CMV seropositivity and CMV viruria with specimens from 360 normal children of the same ages. A seropositivity rate of 73.5% and a viruria rate of 8.7% were found among the children attending special-care centers. These rates were significantly higher than the 59.2% seropositivity and 1.7% viruria found among normal children. By logistic regression analysis, it was shown that the prevalence of CMV viruria in the class/center was one of the most important determinants for acquiring CMV infection. The data suggest that acquisition of CMV from playmates or classmates occurs frequently in special-care centers and that horizontal transmission of virus is the most plausible explanation for the higher prevalence of CMV infection among mentally retarded children.

Antibodies, Viral↗

Seroepidemiology of cytomegalovirus infection among children between the ages of 4 and 12 years in Taiwan.

To determine risk factors responsible for primary cytomegalovirus (CMV) infection in Taiwan, samples of blood for antibody to CMV were obtained from 362 children aged 4 to 12 years: 58% were found to be positive for anti-CMV IgG antibody. Logistic regression analysis showed that seropositivity correlated with age, method of delivery, duration of breast feeding, and younger age of mother. Neither socioeconomic status nor crowded living conditions showed significant correlation with CMV seropositivity. Primary CMV infection in Taiwan appears to be less related to socioeconomic status shown in western countries, and, since the majority of pregnant women were seropositive in Taiwan, two of the major sources of primary CMV transmission are infected breast milk and the infected genital tract.

Adult↗

Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells.

Interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. We have reported that IL-1 inhibited hCG-induced cAMP and testosterone formation. In the present study we evaluated the effect of IL-1 on Leydig cell cholesterol side-chain cleavage cytochrome P450 (P450scc) mRNA levels. P450scc is the rate-limiting enzyme for Leydig cell steroidogenesis. Highly purified Leydig cells were prepared from adult Sprague-Dawley male rats (55-65 day-old) using the combination of elutriation and Percoll gradient. Purified Leydig cells were then cultured with or without IL-1 beta (1-100 ng/ml) and recombinant human monocyte-derived IL-1 receptor antagonist (250 ng/ml) for 24 h. hCG (10 ng/ml), 8-bromo-cAMP (0.1 mM), or 4 beta-phorbol 12 beta-myristate 13 alpha-acetate was then added, and cultures were continued for an additional 6 h. P450scc mRNA levels of Leydig cells were very low to undetectable after 24 h in culture and could be stimulated by the addition of either hCG (10 ng/ml) or 8-bromo-cAMP (0.1 mM), but the addition of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate had no effect. P450scc mRNA levels increased as early as 2 h after the addition of hCG. Furthermore, cycloheximide (1 microgram/ml) markedly blocked hCG-induced P450scc mRNA expression. This indicates that synthesis of a labile new protein(s) is required for the induction of P450scc mRNA by hCG. IL-1 beta inhibited hCG-stimulated testosterone formation and P450scc mRNA expression in a dose-dependent manner. The inhibitory effects of IL-1 beta could be reversed by the concomitant addition of IL-1 receptor antagonist. Our results suggest that P450scc mRNA levels of Leydig cells are modulated by IL-1. This may be one mechanism that could explain the inhibitory effects of IL-1 on Leydig cell steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Human chorionic gonadotropin up-regulates insulin-like growth factor-I receptor gene expression of Leydig cells.

The effects of hCG, 8-bromo-cAMP, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, and forskolin on insulin-like growth factor-I (IGF-I) receptor gene expression of Leydig cells were studied. The treatment of purified Leydig cells with hCG caused a dose-dependent increase in [125I]IGF-I binding to Leydig cells without changes in binding affinity, indicating that the increased binding was due to increased receptor numbers and not to increased affinity. The minimal time required for hCG to induce IGF-I binding was 6 h, and it had reached a plateau at 16 h. 8-Bromo-cAMP (1 mM) increased IGF-I binding about 2-fold, and forskolin (10 microM) increased binding about 51%. Using the ribonuclease protection assay, we found that hCG and 8-bromo-cAMP could increase IGF-I receptor mRNA expression as early as 2 h before the increase in IGF-I binding. The induction by hCG was over 3.5-fold at 4 h and decreased to about 2-fold at 6 h. 4 beta-Phorbol 12 beta-myristate 13 alpha-acetate had a very small effect on IGF-I receptor mRNA levels (1.5-fold increase at 2 h and no changes at 4 and 6 h). In conclusion, IGF-I receptors can be up-regulated by hCG, 8-bromo-cAMP, and forskolin. The up-regulation of IGF-I receptor number is associated with transient increases in IGF-I receptor mRNA levels. This could be a mechanism by which hCG and IGF-I interact to enhance Leydig cell steroidogenesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Interleukin-1 beta induces interleukin-1 alpha messenger ribonucleic acid expression in primary cultures of Leydig cells.

Previously, we have reported that interleukin-1 (IL-1) can modulate Leydig cell steroidogenesis. Recently, IL-1-like material has been shown to be present in the testis; however, the cellular source of this material remains unclear. In the present study we found that human recombinant IL-1 beta (1-100 ng/ml) caused dose-dependent increases in IL-1 alpha mRNA expression in Leydig cells. Similar to that reported in other tissues, IL-1 alpha mRNA from Leydig cells is mainly 2.2 kilobases. IL-1 alpha mRNA expression in Leydig cells was detectable as early as 2 h after the addition of IL-1 beta (10 ng/ml) and persisted for up to 24 h. Lipopolysaccharide also stimulated IL-1 alpha mRNA expression in these cells, but phorbol ester had no effect. Our results indicate that Leydig cells are a potential source of IL-1, which has both autocrine and paracrine effects.

Actins↗

Crypt alterations and collagen deposition in hyperplastic polyps of colorectum.

In order to investigate the nature of hyperplastic polyps in the colorectum, 44 longitudinally sectioned crypts from biopsied polyps were analyzed morphometrically and compared with 81 control crypts. Although the crypts in hyperplastic polyps were longer and wider, containing more cells, their cell density was less, particularly in the serrated epithelium. In these crypts, both the tall and short epithelial cells contained cytoplasmic vacuoles, even in the surface epithelium. These cells exhibited increased expression of carcinoembryonic antigen. The subepithelial collagen table was of similar thickness in the polyp and control colonic mucosa, but it extended down along the cryptal wall to a greater depth in the polyp. These and other data indicate an aberrant differentiation of cryptal epithelial cells in the polyp. On upward migration to the surface, these cells appeared to undergo an arrested maturational process. Hence, the hyperplastic polyp may be considered a disease of epithelial cell differentiation.

Biopsy↗

Reproductive factors and colon cancers.

In Los Angeles County, the age-adjusted incidence rate of colon cancer in men is almost 30% higher than that in women; however, in the descending and sigmoid colon, age-specific incidence rates for women are higher than those for men before age 55. Since menstrual and/or reproductive factors may be involved in producing this crossover in age-specific rates, they were examined in a population-based case-control study involving 327 white women with adenocarcinoma of the colon and age-, race- and neighbourhood-matched controls. After adjustment for other factors associated with colon cancer in this study (family history of large bowel cancer, total fat intake, calcium, weight and activity level), ever having been pregnant was protective (RR = 0.56, 95% CI = 0.33-0.97). For one to two pregnancies, the RR was 0.76 (CI = 0.42-1.37); for three or more pregnancies, the RR was 0.45 (CI = 0.25-0.81). However, the relationship between the number of pregnancies and colon cancer risk was actually U-shaped, with risk decreasing with successive pregnancies up to four and then increasing with additional pregnancies. The U-shaped relationship was present for incomplete as well as for full-term pregnancies and was more striking for cancers occurring in the distal (descending and sigmoid) than proximal (caecum to splenic flexure) colon. Risk was not related to age at menarche or use of exogenous oestrogens, but delayed natural menopause was weakly protective in the proximal but not distal colon. The crossover in incidence rates in the distal colon can be completely accounted for by the pregnancy effect. The U-shape of the pregnancy curve suggests the possibility of competing factors, some protective, especially after one or several pregnancies, and others conferring increasing risk with successive pregnancies, regardless of the pregnancy outcome.

Adenocarcinoma↗

Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid patients.

The significance of hepatic changes in methotrexate-treated RA patients is unclear at this time. In our group of RA patients, there was a slight increase in the incidence of triaditis and fat during methotrexate therapy. Disease duration greater than or equal to 10 years was associated with increased hepatic triaditis before treatment. Age greater than 50 years was associated with increased hepatic fat before and after treatment. It appears that patients' ages and duration of underlying RA account for some changes, independent of methotrexate therapy. Several of our patients changed from higher to lower histologic grade or had an apparent decrease in fibrosis, fat, or triaditis on the pathologists' reports and the blind readings of the repeat biopsies. This may be explained by sampling error. More importantly, some of these changes may not be of clinical significance. One report of methotrexate-induced cirrhosis in patients with psoriasis demonstrated that in all but one of 14 patients who continued receiving methotrexate the cirrhosis decrease or did not progress. This may also be true of the hepatic fibrosis seen in RA after methotrexate treatment. In this study, there did not appear to be changes seen on pretreatment liver biopsy that were predictive of subsequent fibrosis or cirrhosis. Our data indicate that pretreatment biopsy is unwarranted in a population similar to ours. However, our practice has been to try to avoid methotrexate in patients with diabetes, prior liver disease, alcoholism, or obesity because of previous reports suggesting that these patients are at increased risk for the development of cirrhosis. Only the above-mentioned patient, eventually diagnosed as having cirrhosis, might have been handled differently. Including the study, none of the approximately 700 RA patients in the literature having liver biopsies after methotrexate therapy have developed cirrhosis consequent to its use. Most of these had received a total dose of approximately 1,500 mg in small weekly doses, and alcohol was prohibited. Below this cumulative dose the risk of clinically significant liver damage in carefully selected patients is very low. In view of this experience, the recommendation that RA patients have liver biopsies after 1,500 mg of methotrexate (a holdover from the psoriasis literature) may be too conservative in low-risk RA patients, provided methotrexate is administered weekly and alcohol is prohibited. Recognizing that the absolute need for biopsy is unproven, a more realistic milestone for those choosing biopsy might be after each 2,000 to 2,500 mg.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗