Biomedical subjects

T P Lin

Publications and source records attributed to T P Lin.

At least 37 records · Page 2Linked to original sources

PubMed1998

Drug resistance patterns of tuberculosis in Taiwan.

To evaluate the patterns of drug resistance of Mycobacterium tuberculosis in Taiwan, a total of 1,091 isolates collected from patients from January 1996 through December 1996 were tested for drug susceptibility using the absolute concentration method at the Taiwan Provincial Chronic Disease Control Bureau. The overall drug rate of resistance to at least one drug was 35.5%. Among the 249 isolates from patients who had never been treated for tuberculosis, 16.1% were resistant to one or more drugs; 1.6% were resistant to at least isoniazid and rifampin. Of 200 patients with prior antituberculosis treatment, 67.0% had isolates resistant to one or more drugs and 46.0% had isolates resistant to at least isoniazid and rifampin. We conclude that drug-resistant M. tuberculosis is an important issue in tuberculosis treatment in Taiwan, especially when dealing with patients with a prior history of antituberculosis treatment. More aggressive interventions, such as directly observed therapy, short-course, are needed to improve the cure rate of pulmonary tuberculosis and to decrease resistance rates.

Adolescent↗

PubMed1997

In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch repair.

In vitro studies have shown that loss of DNA mismatch repair due to lack of either hMSH2 or hMLH1 activity results in low-level resistance to cisplatin but not to oxaliplatin, an analogue that produces a different type of DNA adduct. No information is currently available on whether this low-level resistance is sufficient to result in enrichment of mismatch repair-deficient cells during drug exposure in vitro or to account for clinical failure of treatment in vivo. Mixed populations of cells containing a minority of DNA mismatch repair-deficient cells constitutively expressing green fluorescence protein were exposed repeatedly in vitro to cisplatin and oxaliplatin. Treatment with cisplatin resulted in a gradual enrichment for DNA mismatch repair-deficient cells, whereas treatment with oxaliplatin did not. MSH2-/- and MSH2+/+ embryonic stem cells were established as xenografts in athymic nude mice. Animals were treated 48 h after tumor implantation with a single LD10 dose of either cisplatin or oxaliplatin. MSH2-/- tumors were significantly less responsive to cisplatin than MSH2+/+ tumors, whereas there was no difference in sensitivity to oxaliplatin. These results demonstrate that the degree of cisplatin resistance conferred by loss of DNA mismatch repair is sufficient to produce both enrichment of mismatch repair-deficient cells during treatment in vitro and a large difference in clinical responsiveness in vivo. The results identify loss of DNA mismatch repair as a mechanism of resistance to cisplatin but not oxaliplatin.

Adenocarcinoma↗

PubMed1997

A prospective clinical study of isoniazid-rifampicin-pyrazinamide-induced liver injury in an area endemic for hepatitis B.

In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug-induced liver injury in hepatitis B surface antigen (HBsAg)-positive carriers and non-carriers, in an area endemic for hepatitis B, we prospectively followed 240 patients (154 male, 86 female; mean age 40 years) who had received daily isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of pulmonary tuberculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post-treatment follow-up were excluded from the study. Thirty-one (13%) patients were positive for serum HBsAg before treatment. Sixty-three (26%; 95% CI: 21-32%) patients developed antituberculous drug-induced liver injury. The incidence of drug-induced liver injury was significantly more frequent in patients > 35 years of age than in patients < or = 35 years of age (33 vs 17%; P < 0.05), but was not different between HBsAg carriers and non-carriers (29 vs 26%; P > 0.05). Using step-wise logistic regression analysis, patient age > 35 years was the only independent variable for predicting antituberculous drug-induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum ALT levels in antituberculous drug-induced liver injury were not significantly different between HBsAg carriers and non-carriers. Only one 61-year-old HBsAg carrier developed severe jaundice after 6 months antituberculous therapy; he subsequently died of hepatic failure. In conclusion, the incidence of antituberculous drug-induced liver injury was significantly higher in patients > 35 years of age than in patients < or = 35 years of age, but was not different between HBsAg carriers and non-carriers. Mortality occurred in an aged HBsAg carrier superimposed with antituberculous drug-induced liver injury.

Adult↗

PubMed1997

Serodiagnosis of tuberculosis. A study comparing three specific mycobacterial antigens.

To compare the efficacy of different mycobacterial specific antigens and to assess the applicability of the combination of several different antigens in the diagnosis of tuberculosis, three ELISA tests derived by Antigen 60, 38kda, and Kp90 were evaluated in 594 Chinese patients (312 patients with active pulmonary tuberculosis and 282 control subjects). Quantified levels of sensitivity and specificity were compared with those in the nontuberculous control groups. Antigen 60 IgG (sensitivity and specificity, 80.77 and 88.4%) was more antigenic and more effective in its determination than was 38kda IgG (sensitivity and specificity, 64.21 and 80.74%) and Kp90 IgA (sensitivity and specificity, 62.58 and 66.3%). The clinical significance of the difference, however, was not striking: negative predictive value of Antigen 60, 38kda, and Kp90 was 93, 86 and 83%, respectively; positive predictive value of Antigen 60, 38kda, and Kp90 was 71, 54, and 39%, respectively. Combination of different antigens could improve the sensitivity and specificity by no more than 10%, with the sacrifice of the opposite parameter by no less than 20%. The same improvement in sensitivity could be easily achieved by adjusting the cutoff values in the ELISA test by a single antigen. We conclude that the sensitivity and specificity of presently available antigens for serodiagnosis of tuberculosis still remains limited at around 80%, which makes it a poor diagnostic tool for disease confirmation. In low incidence areas, its clinical value may be useful in disease exclusion. A combination of several different antigens provides no more improved diagnostic yield than what can be provided by cutoff value adjustment in a single antigen serologic test.

Adult↗

PubMed1997

In vitro activity of ofloxacin against Mycobacterium tuberculosis.

For the past 3 years, ofloxacin has been widely used in treating patients with drug-resistant tuberculosis in Taiwan. To study its usefulness in treating these patients, 139 isolates of Mycobacterium tuberculosis from patients treated at the Taiwan Provincial Chronic Disease Control Bureau from September 1994 to September 1995 were tested to determine the in vitro antituberculosis activity of ofloxacin. Of these, 131 had not been previously exposed to ofloxacin, and 130 (99.2%) were susceptible to ofloxacin. Sixty-four isolates were found to be susceptible to all conventional antituberculosis drugs, and all of these were also susceptible to ofloxacin. Of the remaining 67 isolates that were resistant to one or more conventional antituberculosis drugs, 66 (98.5%) were susceptible to ofloxacin. There was no association between susceptibility to ofloxacin and susceptibility to conventional antituberculosis drugs among the isolates tested. Of the eight isolates of M. tuberculosis previously exposed to ofloxacin, seven (87.5%) were resistant. Our results indicate that patients with multidrug-resistant strains of M. tuberculosis who have not received prior ofloxacin treatment may be safely treated with ofloxacin even without knowing the result of pretreatment ofloxacin susceptibility tests. We also found that ofloxacin resistance emerges frequently. Therefore, an adequate combination of antituberculosis drugs, along with ofloxacin, should be prescribed to prevent the development of resistance to ofloxacin.

Anti-Infective Agents↗

PubMed1997

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

The prevalence and mortality rate of pulmonary tuberculosis in adults are high in Taiwan. Because the emergence of drug-resistant tuberculosis is one of the major causes of this sustained high tuberculosis mortality, surveillance of initial drug resistance is important. We tested Mycobacterium tuberculosis isolates from 1,935 newly diagnosed tuberculosis patients from January 1990 through December 1995 at the Taiwan Provincial Chronic Disease Control Bureau. The overall initial drug resistance rate was 12.3%; 8.7% of isolates were resistant to only one drug, 2.6% to two drugs, 0.7% to three drugs, and 0.3% to four drugs. The resistance rates to individual drugs were: streptomycin, 5.7%; isoniazid, 9.2%; ethambutol, 0.7%; and rifampin, 1.5%. The frequency of multidrug-resistant M. tuberculosis (resistant to at least isoniazid and rifampin) was 1.2%. In view of the high initial isoniazid resistance rate and low initial ethambutol resistance rate, ethambutol should be added to the regimen for the initial treatment of tuberculosis in Taiwan. The emergence of multidrug-resistant M. tuberculosis is ominous and should be considered when treating patients in Taiwan.

Adolescent↗

PubMed1996

Occurrence of a novel galactopinitol and its changes with other non-reducing sugars during development of Leucaena laucocephala seeds.

A new cyclitol which is abundant in the late developmental stages of leucaena (Leucaena leucocephala (Lam.) de Wit) seeds was identified by HPLC, NMR, and GC-MS as O-alpha-D-galactopyranosyl-(1-->1)-3-O-methyl-D-chiroinositol, a new galactopinitol. This galactopinitol was initially detected midway through seed development and increased to 10.2 mg (gDW)-1, but decreased in mature seeds to its about a half. Stachyose content increased greatly and remained the most abundant of the soluble sugars in mature seeds (25.6 mg (g DW)-1). Artificial drying at 73% relative humidity of 70 DPA immature seeds induced the accumulation of raffinose, stachyose, galactopinitol and galactinol, but the total amounts of these sugars were only about half of those found in mature seeds. Seed germination decreased following an initial increase after 8 d artificial drying to a moisture content of 24%, and this dehydration damage probably is because of underdevelopment of seed tissue. Galactopinitol changes in a similar fashion to the oligosaccharides during the late developmental stage and dehydration experiment, implying that galactopinitol may play a role in desiccation tolerance of leucaena seeds.

Carbohydrate Metabolism↗

PubMed1996

Treatment of multidrug-resistant tuberculosis in Taiwan.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Adult↗

PubMed1996

Rifabutin as salvage therapy for cases of chronic multidrug-resistant pulmonary tuberculosis in Taiwan.

This study was aimed at assessing the efficacy and tolerability of rifabutin for the re-treatment of cases of chronic, multidrug-resistant pulmonary tuberculosis. The study design was self-controlled, single center. Rifabutin was administered as part of an individual-tailored multidrug regimen. In-patients suffering from pulmonary tuberculosis, infected with Mycobacterium tuberculosis bacilli resistant to isoniazid, rifampicin and other drugs with progressive disease unresponsive to prior courses with standard anti-tuberculosis medications were treated. Overall, 43 patients were enrolled and treated with rifabutin at 300 or 450mg/day according to body weight in conjunction with available anti-tuberculous drugs for a mean time of 353 days (range 42-678). Of these, 36 met all eligibility criteria (i.e. positive baseline culture of sputum with bacilli resistant to rifampicin at least) and were retained for the analysis of efficacy. Seventeen patients (47%) achieved a sustained conversion to a negative culture of sputum in a mean time of 47.7 days with a range of 14-120 days. Treatment prevented deterioration in most patients and resulted in clinical and radiological cure or marked improvement in more than half of cases. No correlation was found between treatment outcome and use of medication concomitant to rifabutin or susceptibility of bacilli to the drugs used. Four deaths occurred due to disease progression, in no case being related to study drugs. Ten patients reported a total of 18 adverse events that led to treatment discontinuation in 5 cases. Rifabutin should be considered for inclusion in regimens for cases of pulmonary multidrug-resistant tuberculosis which fail to respond to previous therapy.

Adolescent↗

PubMed1995

The antiallergic activities of synthetic acrophylline and acrophyllidine.

The antiallergic activities of synthetic acrophylline [1] and acrophyllidine [2] have been demonstrated. Both compounds 1 and 2 at 30 mumol/kg reduced the plasma leakage in mouse ear in a passive cutaneous anaphylactic (PCA) reaction. In addition, compound 1 suppressed mast cell degranulation in a dose-dependent manner, while compound 2 at 100 microM produced no significant inhibition of the release of preformed inflammatory mediators. These results suggest that the antiallergic effect of compound 1 probably occurs through the suppression of mast cell degranulation, and that of compound 2 by protection of the vasculature against challenge by mediators of inflammation.

Alkaloids↗

PubMed1995

[Disseminated Strongyloides stercoralis infection mimicking pneumonia].

Strongyloides stercoralis is an intestinal nematode. In an immunocompetent host, Strongyloides infections usually produce only mild gastrointestinal symptoms. However, in an immunocompromised host, widespread dissemination of larvae to the extra-intestinal organs may occur. If unrecognized, the mortality rate is high. Here we report a case of disseminated strongyloidiasis in a chronic obstructive pulmonary disease (COPD) subject whose chest radiograph demonstrated multiple pneumonic patches and interstitial infiltrates. Strongyloides larvae were found in stool, sputum, and urine, and embryonated eggs were also found in sputum. The patient was treated successfully with mebendazole and alben albendazole. In conclusion, although high mortality rate is noted in disseminated strongyloidiasis, it is still a curable disease when early diagnosis and treatment could be made.

Animals↗

PubMed1994

Transcriptional activation of flanking sequences by Tn1000 insertion.

The carotenoid biosynthesis operon of Erwinia herbicola Eho13 consists of five genes, which are organized in the order crtE-crtX-crtY-crtI-crtB. These genes, with the exception of crtX, encode functions of beta-carotene biosynthesis and give an orange-coloured phenotype in Escherichia coli. Since crtX is not involved in the biosynthesis of beta-carotene, deletion of this gene does not alter the phenotype of pigmented cells. On the other hand, insertion of Tn1000 into crtX or into the upstream untranslated region of the operon resulted in a light-yellow, rather than an unpigmented phenotype, indicating that Tn1000 does not exert a strong polar effect when inserted in this operon. RNA analysis revealed that the sequence downstream from the insertion site was transcribed at a low level. Primer extension showed that the "-35"-like sequence in the terminal inverted repeats was not responsible for the transcription of the downstream sequence. Furthermore, primer extension and polymerase chain reaction (PCR) studies revealed that RNA transcribed from the promoters inside of Tn1000 was extended through the terminal inverted repeats into the adjacent sequences. In addition Tn1000, in either orientation, was able to generate fusion transcripts when placed upstream of a promoter-less tetracycline-resistance gene and resulted in cells resistant to the drug. These results showed that Tn1000 insertion transcriptionally activates the DNA sequences adjacent to the transposon.

Base Sequence↗

PubMed1994

The Pem homeobox gene is X-linked and exclusively expressed in extraembryonic tissues during early murine development.

We previously reported the isolation of a cDNA clone for a homeobox-containing gene designated Pem, shown by Northern analysis of Day 7 through Day 16 mouse embryos to be expressed in extraembryonic tissues. In this study, Pem gene expression was further examined using in situ hybridization and immunocytochemistry to determine the spatial distribution of Pem transcripts and protein in peri-implantation embryos and in embryoid bodies (EBs). Low amounts of Pem mRNA were detected in undifferentiated EBs. When EBs were induced to differentiate, the outer cell layer of visceral or parietal endoderm expressed both Pem mRNA and protein. In developing embryos, no Pem protein was detectable in the uncompacted morula; 12% of the nuclei in compacted morulae were Pem positive, while 25% of the blastocyst trophectoderm and 15% of inner cell mass cells expressed Pem protein. Shortly after implantation, in 5.5 and 6.5 d.p.c. embryos, Pem expression was limited to extraembryonic tissues and was present in distal and proximal visceral endoderm, parietal endoderm, and ectoplacental cone. By 7.5-8.5 d.p.c. neither Pem RNA nor protein was found in the distal squamous visceral endoderm, which surrounds the embryonic region of the egg cylinder, nor in the parietal endoderm. Expression was retained in the proximal columnar epithelium of the visceral endoderm. Prominent Pem expression was observed in the chorion, in trophoblast-derived cells of the ectoplacental cone, and in secondary giant cells, localized in the nuclear compartment. Pem was localized to the X chromosome and found to be expressed in cell lineages where only the maternal X chromosome is active. The data indicate a possible role for Pem in regulating genes involved in the differentiation of extraembryonic tissues.

Animals↗

PubMed1994

Analysis of the gene cluster encoding carotenoid biosynthesis in Erwinia herbicola Eho13.

Erwinia herbicola is known to synthesize carotenoids and gives an orange-coloured phenotype. These carotenoids play a role in the protection of the cells from the damage caused by near-UV irradiation in nature. The genes encoding these carotenoids in E. herbicola Eho13 are clustered in a 7 kb DNA fragment. The complete sequence of this fragment has been determined. DNA sequence analysis revealed that the entire sequence contains at least five genes, which are transcribed in the same direction. These five genes are organized in the order crtE-crtX-crtY-crtI-crtB. A gene fusion study showed that two different regions in this 7 kb gene cluster contain promoter activity. Primer-extension analysis identified two transcription start sites, located 147 bp upstream from the first gene of the cluster, crtE, and within the last gene of the cluster, crtB. An RNA-PCR study suggested that the five crt genes were organized in an operon and were transcribed from the promoter upstream from crtE.

Alkyl and Aryl Transferases↗

PubMed1994

Current role of surgery in the management of pleuropulmonary tuberculosis.

This article reviews the recent surgical treatment of patients with pleuropulmonary tuberculosis in the northern Taiwan area. With the advent of effective chemotherapeutic agents and fewer failed medical treatments, the need for surgery has decreased. During the period 1985 to 1991, a total of 62 patients in the northern Taiwan area received surgical treatment for lesions or complications associated with pleuropulmonary tuberculosis. In the majority of cases, patients underwent operations for undiagnosed tumors. Other indications for surgery included tuberculosis cavity with aspergilloma, localized cavity or anatomic residue with a positive acid fast bacilli smear, complications with altered anatomy secondary to tuberculosis and chronic tuberculous empyema. The appropriate selection of patients for surgical intervention should ensure satisfactory surgical results. Surgery continues to play a vital role in the management of certain patients with pleuropulmonary tuberculosis.

Adult↗

PubMed1992

Role of endocrine, autocrine, and paracrine interactions in the development of mammary hyperplasia in Wnt-1 transgenic mice.

The Wnt-1 proto-oncogene is transcriptionally activated by mouse mammary tumor virus in mouse mammary tumor virus-induced tumors. Previous studies using transgenic mice showed that Wnt-1 expression in mammary gland causes alveolar hyperplasias which resemble mammary glands of pregnant mice. To understand the role of mammogenic hormones in the genesis of these hyperplasias, we examined the development of these glands before puberty in young transgenic mice and the effects of ovariectomy and adrenalectomy on the growth and morphology of Wnt-1 mammary hyperplasia. Mammary glands of Wnt-1 transgenic females showed hyperplastic morphology as early as 1 week after birth. The normal structure of the uterus of the adult Wnt-1 virgin mouse indicated that the circulating levels of ovarian hormones were not elevated. Ovariectomy and adrenalectomy had no obvious effect on the morphology of these mammary hyperplasias. To assess possible paracrine stimulation of mammary epithelial cells (MEC) by stromal cells, we transplanted MEC from normal BALB/c mice into gland-free fat pads of Wnt-1 transgenic mice and found that normal MEC maintained their normal ductal structure in Wnt-1 fat pads without alveolar development. Further, we did not detect Wnt-1 mRNA expression in the gland-free fat pads of these transgenic mice. When Wnt-1 MEC were transplanted into the fat pads of nude mice and allowed to grow towards existing normal MEC, the morphology of the existing normal MEC remained normal. We concluded that the development of mammary hyperplasia in Wnt-1 transgenic mice is solely dependent on Wnt-1 expression in MEC. We speculate that Wnt-1 may be a growth factor for mammary gland that only acts locally on the cells that produce it.

Adrenalectomy↗

PubMed1992

Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice.

The Wnt-1 and int-2 proto-oncogenes are transcriptionally activated by mouse mammary tumor virus insertion mutations in virus-induced tumors and encode secretory glycoproteins. To determine whether these two genes can cooperate during carcinogenesis, we have crossed two previously characterized lines of transgenic mice to obtain bitransgenic animals carrying both Wnt-1 and int-2 transgenes under the control of the mouse mammary tumor virus long terminal repeat. Mammary carcinomas appear earlier and with higher frequency in the bitransgenic animals, especially the males, than in either parental line. Nearly all bitransgenic males develop mammary neoplasms within 8 months of birth, whereas only 15% of Wnt-1 transgenic males and none of the int-2 transgenic males have tumors. In virgin bitransgenic females, tumors occur approximately 2 months earlier than in their Wnt-1 transgenic siblings; int-2 transgenic females rarely exhibit tumors. Preneoplastic glands from the bitransgenic animals of either sex demonstrate pronounced epithelial hyperplasia similar to that seen in Wnt-1 transgenic virgin females and males, and both transgenes are expressed in the hyperplastic glands and mammary tumors. RNA from the int-2 transgene is more abundant in mammary glands from bitransgenic animals than from int-2 transgenic animals; the increase is associated with high levels of RNA specific for keratin genes 14 and 18, suggesting that Wnt-1-induced epithelial hyperplasia is responsible for the observed increase in expression of the int-2 transgene.

Animals↗

PubMed1991

Effects of antioxidants and reduced oxygen tension on rat mammary epithelial cells in culture.

Free radical damage has the potential to significantly affect the behavior of cells in culture. In this study the effects of antioxidants (superoxide dismutase, catalase, and vitamin E) and lowered oxygen tension (1% oxygen) on primary culture of rat mammary epithelial cells were examined. Rat mammary epithelial cells were dissociated in collagenase with or without the addition of antioxidants and low oxygen tension, then cultured for 10 d in rat-tail collagen gel matrix and fed with Dulbecco's modified Eagle's F12 medium supplemented with various hormones and growth factors. Growth potential of the mammary cells was enhanced when antioxidants and low oxygen tension were used, alone or in combination, during the cell dissociation period. Using antioxidants and low oxygen tension during the culture period failed to improve growth potential regardless whether cells were dissociated in standard conditions or with antioxidants and low oxygen tension. The use of antioxidants and low oxygen tension during the cell dissociation period also reduced the degree of keratinization of the cells after 10 d of culture. Using antioxidants and low oxygen tension during the cell culture period did not further reduce keratinization if antioxidants and low oxygen tension were used during the dissociation period, but were effective in reducing keratinization if cells were dissociated in standard condition. In this system, antioxidants and low oxygen tension reduced lipid peroxidation during the cell dissociation period. An iron chelator, desferal, can also reduce lipid peroxidation and enhance growth when used during cell dissociation, suggesting the enhanced growth potential by the addition of antioxidants and low oxygen to be due to the reduction of lipid peroxidation.

Animals↗