PubMed Health⌕ Search

Biomedical subjects

H H Lin

Publications and source records attributed to H H Lin.

At least 37 records · Page 2Linked to original sources

Human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 3 is a new member of the EGF-TM7 family that recognizes a ligand on human macrophages and activated neutrophils.

The epidermal growth factor (EGF)-TM7 subgroup of G-protein-coupled receptors is composed predominantly of leukocyte-restricted glycoproteins defined by their unique hybrid structure, in which extracellular EGF-like domains are coupled to a seven-span transmembrane moiety via a mucin-like stalk. The EGF-TM7 group comprises mouse F4/80, human EGF module-containing mucin-like hormone receptor (EMR) 1, human EMR2, and human and mouse CD97, the genes for which map to human chromosome 19p13 and the syntenic regions of the mouse genome. In this study we describe the cloning and characterization of EMR3, a novel human EGF-TM7 molecule, and show the existence of its cellular ligand. The EMR3 gene maps closely to the existing members of the EGF-TM7 family on human chromosome 19p13.1 and, in common with other EGF-TM7 genes, is capable of generating different protein isoforms through alternative splicing. Two alternative splice forms have been isolated: one encoding a 652-amino acid cell surface protein consisting of two EGF-like domains, a mucin stalk, and a putative G-protein-coupled receptor domain and the other encoding a truncated soluble form containing only two EGF-like domains. As with other members of the EGF-TM7 family, EMR3 mRNA displays a predominantly leukocyte-restricted expression pattern, with highest levels in neutrophils, monocytes, and macrophages. Through the use of soluble EMR3 multivalent probes we have shown the presence of a ligand at the surface of monocyte-derived macrophages and activated human neutrophils. These interactions suggest a potential role for EMR3 in myeloid-myeloid interactions during immune and inflammatory responses.

Alternative Splicing↗

Importance of urodynamic study before radical hysterectomy for cervical cancer.

OBJECTIVES: The aim of this study was to characterize the urodynamic findings in patients with cervical cancer before radical hysterectomy and to correlate the results with age, parity, menopausal status, and cancer stage. METHODS: All patients with cervical cancer before radical hysterectomy who underwent urodynamic study (UDS) from January 1996 through December 1998 were enrolled. Detailed history, physical examination, and multichannel UDS data including uroflowmetry, filling and voiding cystometry, stress urethral pressure profile, and 20-min pad test were obtained for each patient. The urodynamic findings of each patient were analyzed and correlated with age, parity, menopausal status, and cancer stage. RESULTS: A total of 210 patients with cervical cancer were included in the study. The mean age was 48.9 +/- 10.5 years with a mean parity of 3.3 +/- 1.7. Forty-two percent (n = 88) of patients were menopausal, and 88% (n = 184) belonged to stage IB while 10% (n = 20) were stage IIA and 2% (n = 6) stage IIB. Urodynamic study showed that only 17% (n = 37) of the 210 patients were normal, 10% (n = 21) had voiding dysfunction, 45% (n = 94) had storing dysfunction, and 28% (n = 58) had both voiding and storing dysfunctions. In addition, 51% (n = 106) had urinary incontinence and 37% (n = 78) had genuine stress incontinence (GSI), 8% (n = 16) detrusor instability (DI), and 6% (n = 12) GSI/DI. Age, parity, and cancer stage did not show any significant differences among these four groups. CONCLUSIONS: In this series, only 17% of patients with cervical cancer had normal urodynamic findings before radical hysterectomy.

Female↗

Clinical analysis and literature review of massive duodenal diverticular bleeding.

A duodenal diverticulum (DD) appears in 2.5% of upper gastrointestinal (UGI) examinations and up to 22% of endoscopic retrograde cholangiopancreaticographies (ERCP) and autopsies. Most of these patients are asymptomatic, but the lesion is occasionally associated with bleeding, inflammation, perforation, obstruction of the duodenum or biliary-pancreatic duct (or both), fistula formation in the bile duct, and bezoar formation inside the diverticulum. A total of 816 patients have undergone ERCP examination at our institution since January 1987, and 100 (12.25%) of them have DD. Seven (7%) patients presented with bloody or tarry stools from massive UGI bleeding followed by shock. Only two could be diagnosed by UGI endoscopy preoperatively. The lesions were demonstrated in angiographic studies in another four cases. However, only one was correctly interpreted and one required reoperation after a correct repeat endoscopic finding. The lesions in the other two patients were identified by thorough exploration during laparotomy. The remaining case was diagnosed by intraoperative endoscopy via pyloroduodenotomy. Six underwent surgical intervention, and one was successfully treated by expectant treatment. Three (50%) had leakage from the duodenotomy but recovered uneventfully with conservative treatment. In conclusion, we believe that DD bleeding is more frequent than usually thought. A high index of suspicion should be raised in cases of UGI bleeding when more obvious and common causes have been excluded by routine endoscopy. Aggressive but careful endoscopic examination combined with accurate angiography can help us diagnose most of the cases preoperatively. Diverticulectomy is an effective surgical procedure, though it is associated with a considerable leakage rate. The morbidity is minimal if we can identify the lesion earlier and evacuate the lesion without delay.

Angiography↗

Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases.

PURPOSE: To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. SUBJECTS AND METHODS: We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails (Ampullarium canaliculatus), as well as an environmental surveillance of larvae in snails. RESULTS: We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. CONCLUSION: Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

Adult↗

Variations within hepatitis C virus E2 protein and response to interferon treatment.

To determine whether the hepatitis C virus (HCV) E2 PePHD sequence (aa 659-670; PKR-eIF2alpha phosphorylation homology domain) is the determinant for the response of interferon treatment, we have analyzed PePHD sequences in HCV-infected patients who had received interferon-alfa treatment. The PePHD sequence from all (6/6) of the patients, who are non- or partial responders to the interferon treatment, is the wild-type sequence (RSELSPLLL-TT, consensus sequence of HCV-1a and HCV-1b). However, there are sequence variations from more than half (5/9) of the patients, who are complete responders to the treatment. We have also analyzed the NS5A ISDR sequence (aa 2209-2248, interferon sensitivity-determining region) variation in HCV-1b-infected patients. No such correlation has been observed. Thus, our data suggest that HCV E2 should play a more important role than NS5A in determining the interferon responses.

Adult↗

The colon cancer burden of genetically defined hereditary nonpolyposis colon cancer.

BACKGROUND & AIMS: Estimates of the frequency of hereditary nonpolyposis colon cancer (HNPCC) based on clinical criteria have varied widely. Recent studies of germline mismatch repair gene mutations have suggested that HNPCC accounts for close to 3% of all colon cancer, but this estimate may have been inflated by inclusion of founder effects peculiar to Finland. We therefore determined by genetic criteria the colon cancer burden associated with HNPCC in a population-based study of 1066 individuals from Utah and California. METHODS: The coding regions of mismatch repair genes hMSH2 and hMLH1 were sequenced from the germline of those individuals whose tumors exhibited microsatellite instability. RESULTS: Microsatellite instability was present in 16% (171/1066) of tumors. Pathogenic germline mismatch repair gene mutations were identified in 7 individuals, and missense amino acid changes of uncertain significance were identified in another 6 individuals. After adjusting for the availability of sufficient germline DNA for sequencing, the 7 clearly pathogenic mutations accounted for 0.86% of colon cancer at the population level. Individuals with these mutations were significantly younger, more likely to have a family history of colon and endometrial cancer, and more likely to have first-degree relatives with a young-age onset of colon cancer than individuals with unstable tumors but without germline mutations (P < 0.01). CONCLUSIONS: We conclude that genetically defined HNPCC accounts for a very small percentage of colon cancer at the population level, a percentage less than that estimated by most previous clinical studies.

Adaptor Proteins, Signal Transducing↗

Oxygen- and growth rate-dependent regulation of Escherichia coli fumarase (FumA, FumB, and FumC) activity.

Escherichia coli contains three biochemically distinct fumarases which catalyze the interconversion of fumarate to L-malate in the tricarboxylic acid cycle. Batch culture studies indicated that fumarase activities varied according to carbon substrate and cell doubling time. Growth rate control of fumarase activities in the wild type and mutants was demonstrated in continuous culture; FumA and FumC activities were induced four- to fivefold when the cell growth rate (k) was lowered from 1.2/h to 0.24/h at 1 and 21% O(2), respectively. There was a twofold induction of FumA and FumC activities when acetate was utilized instead of glucose as the sole carbon source. However, these fumarase activities were still shown to be under growth rate control. Thus, the activity of the fumarases is regulated by the cell growth rate and carbon source utilization independently. Further examination of FumA and FumC activities in a cya mutant suggested that growth rate control of FumA and FumC activities is cyclic AMP dependent. Although the total fumarase activity increased under aerobic conditions, the individual fumarase activities varied under different oxygen levels. While FumB activity was maximal during anaerobic growth (k = 0.6/h), FumA was the major enzyme under anaerobic cell growth, and the maximum activity was achieved when oxygen was elevated to 1 to 2%. Further increase in the oxygen level caused inactivation of FumA and FumB activities by the high oxidized state, but FumC activity increased simultaneously when the oxygen level was higher than 4%. The same regulation of the activities of fumarases in response to different oxygen levels was also found in mutants. Therefore, synthesis of the three fumarase enzymes is controlled in a hierarchical fashion depending on the environmental oxygen that the cell encounters.

Cell Division↗

Collagen gel overlay induces two phases of apoptosis in MDCK cells.

We previously demonstrated that collagen gel overlay induced cell remodeling to form lumen and apoptosis in Madin-Darby canine kidney cells. In the present study, we established that collagen gel overlay-induced apoptosis was initiated at areas exclusive of cell remodeling within 24 h (first phase) and extended into areas of cell remodeling within 48 h (second phase). Collagen gel overlay-induced apoptosis was accompanied by selective proteolysis of focal adhesion kinase (FAK), talin, p130(cas), and c-src. Upon collagen gel overlay, FAK was initially degraded into a 90-kDa product during the first phase and subsequently into a 80-kDa product during the second phase. Collagen gel overlay-induced apoptosis of focal adhesion complex proteins and apoptosis of the first phase could be blocked only by a protease inhibitor cocktail. In addition, we found that both DEVD-fmk and ZVAD-fmk inhibited secondary proteolysis of FAK, but only ZVAD-fmk blocked collagen gel overlay-induced apoptosis of the second phase. Finally, collagen gel overlay-induced apoptosis and proteolysis of focal adhesion complex proteins were completely inhibited by the combination of protease inhibitor cocktail and ZVAD-fmk. Taken together, collagen gel overlay induces two phases of apoptosis; the first phase is dependent on proteolysis of focal adhesion complex proteins, and the second phase on activation of caspases.

Actinin↗

Etk/Bmx activation modulates barrier function in epithelial cells.

Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O(2)) exposure, the TER and equivalent active ion transport rate (I(eq)) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I(eq) were maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of beta-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of beta-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.

Actins↗

An outbreak of meningitis caused by Angiostrongylus cantonensis in Kaohsiung.

Eight Thai laborers developed meningitis after eating raw snails (Ampullarium canaliculatus) during the period from September 27 to October 6, 1998. The diagnosis of Angiostrongylus cantonensis infection was established in all patients by serologic studies of serum and cerebral spinal fluid (CSF). Clinical manifestations included meningitis, radiculitis and cranial nerve palsy. Symptoms included fever, headache, orbital pain, gastrointestinal upset, hyperesthesia, muscle weakness, skin rash and diplopia. Laboratory abnormalities included peripheral eosinophilia, CSF eosinophilia, transient elevation of liver enzymes and creatinine phosphokinase, elevation of IgE. No space occupying lesions were detected by magnetic resonance imaging of the brain. None of the patients developed severe sequelae during the 6-month follow-up except for occasional headache in one patient. This report also provides evidence that third stage larvae were present in the intermediate host, A. canaliculatus, which the laborers had eaten.

Adult↗

Clinical characteristics of emphysematous pyelonephritis.

A total of 21 patients (20 women and one man) with emphysematous pyelonephritis (EPN), treated in the Kaohsiung Veterans General Hospital during the period from 1991 through 1999 were included in this study. All of the patients were diabetic. The most common symptoms or signs were fever/chills (80%) and costovertebral angle knocking pain (71%). Diagnosis was confirmed by the presence of gas in the parenchyma or paranephric space on plain X-ray of the abdomen or computed tomography. The left kidney (11 cases, 52%) was more frequently affected than the right one (nine cases, 43%), and both kidneys were involved in one case. Obstruction of the corresponding renoureteral unit was found in 19% of the patients, and renal or ureteral stone was found in 23% of the patients. One third of the patients had type I EPN, and two-thirds had type II EPN. Escherichia coli was the most commonly isolated organism, accounting for 61%, 76%, and 47% of isolates from blood, urine, and aspirated pus culture respectively. Prompt control of blood sugar was begun and intravenous antibiotics were given. Drainage was performed in 71% of the patients, and two persons required nephrectomy because of poor control of the infection or complications. Overall survival was 72%. Emphysematous pyelonephritis is a rare, life-threatening, suppurative infection of the renal parenchyma and perirenaL tissues. For successful management of EPN, appropriate medical treatment should be initiated, and immediate nephrectomy or drainage should not be delayed.

Adult↗

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Acyclovir↗

Legionnaires' disease in an immunocompetent young adult.

Infection with Legionella pneumophila (LP) is a rare cause of pneumonia in previously healthy young adults. Pleural effusion is relatively common in Legionnaires' disease but is usually clinically insignificant. Herein we describe an immunocompetent, 19-year-old female with LP respiratory infection that presented with pleural effusion and mild interstitial infiltrates in the lower lungs. She received 3 weeks' treatment with erythromycin and rifampin and recovered completely. Diagnosis was based on serology testing with a four-fold rise of the antibody titer in the acute and convalescent phase. Legionnaires' disease should be considered in the differential diagnosis of culture-negative pleural effusion in immunocompetent young adults.

Adult↗

Pneumocystis carinii pneumonia in systemic lupus erythematosus: a report of two cases.

Patients with systemic lupus erythematosus (SLE) have increased susceptibility to infection by Pneumocystis carinii, but this condition has rarely been reported in Taiwan. Here, we describe two cases of patients with SLE who developed Pneumocystis carinii pneumonia (PCP). The first patient was a 39-year-old woman presenting with fever and dyspnea that had lasted 2 weeks. Chest roentgenography disclosed bilateral interstitial and alveolar infiltrates. The second patient was a 22-year-old woman presenting with a 4-day history of malaise, cough, dyspnea, and fever. She had concomitant Mycobacterium tuberculosis infection. Both patients had been treated with varying doses of corticosteroids and/or cytotoxic drugs within 4 months before presentation. Diagnosis was established based on the findings of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB). Both patients received trimethoprim-sulfamethoxazole (20 mg.kg-1.d-1 trimethoprim), but finally died of nosocomial septicemia (Acinetobacter baumanni and Pseudomonas aeruginosa bacteremia in one, P. aeruginosa bacteremia in the other). These two cases demonstrate that PCP should be included in the differential diagnosis of patients with SLE presenting with pneumonic processes. In addition, a second opportunistic pathogen should be suspected. Bronchoscopic examination should be performed if the diagnosis is not clear and should include TBLB and BAL.

Adult↗

Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97.

The epidermal growth factor (EGF)-TM7 proteins [EMR1, (EGF-like molecule containing mucin-like hormone receptor 1) F4/80, and CD97] constitute a recently defined class B GPCR subfamily and are predominantly expressed on leukocytes. These molecules possess N-terminal EGF-like domains coupled to a seven-span transmembrane (7TM) moiety via a mucin-like spacer domain. Genomic mapping analysis has suggested a possible EGF-TM7 gene family on the human chromosome 19p13 region. In this study, a new member of the EGF-TM7 family, EMR2, which shares strikingly similar molecular characteristics with CD97, is described. In addition to mapping closely to CD97 on human chromosome 19p13.1, EMR2 contains a total of five tandem EGF-like domains and expresses similar protein isoforms consisting of various numbers of EGF-like domains as a result of alternative RNA splicing. Furthermore, EMR2 and CD97 exhibit highly homologous EGF-like domains and share identical gene organization, indicating that both genes are the products of a recent gene duplication event. The homologous EGF-like domains enable the identification of both EMR2 and CD97 by monoclonal antibodies (mAbs) raised against the first EGF-like domain of CD97, whereas mAbs directed against the extracellular spacer domain of CD97 are able to differentiate these two proteins. Both EMR2 and CD97 are highly expressed in immune tissues; however, unlike CD97, which is ubiquitously expressed in most cell types, EMR2 expression is restricted to monocytes/M&phi; and granulocytes. EMR2 fails to interact with CD55, the cellular ligand for CD97, suggesting the possibility of a different cellular ligand(s). EMR2 may therefore have a unique function in cells of monocyte/M&phi; and granulocyte lineages.

Alternative Splicing↗

LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors.

A number of unusual seven-transmembrane molecules have recently been characterized that have significant amino acid sequence similarity within the membrane-spanning hydrophobic regions and intervening loops to members of G-protein-coupled receptor family B. However, in contrast to the family-B G-protein-coupled receptors, these molecules have unusually large N-terminal extracellular domains that contain a number of well- characterized protein modules. The range of cell types expressing these complex molecules and their potential roles in cell adhesion and signalling have become a major focus of research in a number of biological systems.

Amino Acid Sequence↗

Effectiveness of second- and third-generation immunoassays for the detection of hepatitis C virus infection in pregnant women.

OBJECTIVE: To compare the sensitivity and specificity of a third-generation anti-hepatitis C virus (anti-HCV) assay (HCV 3.0) with second-generation one (HCV 2.0), and correlate with HCV-RNA positivity by reverse-transcription polymerase chain reaction (RT-PCR). METHODS: We enrolled 197 pregnant women without screening for alanine aminotransferase (ALT) (Group A) and 324 pregnant women with elevated ALT activity (> 45 IU/l) (Group B). Each serum sample was tested by second- and third-generation tests, and anti-HCV titer was determined by serial dilutions. Anti-HCV-positive samples were subjected to HCV-RNA assays. RESULTS: Three (1.5%) and 4 (2.0%) of the 197 group A subjects were anti-HCV-positive by the second- and third-generation methods, respectively, while 17 (5.3%) and 21 (6.5%) of group B were positive, respectively. Three (1.5%) in group A and 8 (2.5%) in group B were HCV 2.0-negative, but positive for HCV 3.0. The sensitivity, specificity, positive and negative predictive values of HCV 2.0 and HVC 3.0 for positive HCV-RNA in both groups were 67 vs 100%, 30 vs 75%, 67 vs 92%, and 30 vs 100%, respectively. The anti-HCV-positive samples with optical density (O.D.) < 1.0 either by second- or third-generation test were negative for HCV-RNA, whereas samples with O.D. > or = 1.0 were all HCV-RNA-positive. CONCLUSIONS: The performance of HCV 3.0 is better than that of HCV 2.0, and anti-HCV-positive samples with O.D. < 1.0 are negative for HCV-RNA.

Adult↗