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Biomedical subjects

H H Lin

Publications and source records attributed to H H Lin.

At least 91 records · Page 5Linked to original sources

Riu's stain and the cytologic diagnosis of thyroid fine-needle aspiration: a single cancer center experience.

Riu's stain, a Romanowsky-type stain, has been in use in Taiwan over the past 40 years. In order to determine whether it is useful for the diagnosis of thyroid disease in thyroid fine-needle aspiration, we reviewed 254 of these aspirates obtained between April 1990 and June 1996 from patients seen in Koo Foundation Sun Yat-Sen Cancer Center in Taipei. Surgical follow-up was available for confirmation in 61 aspirations. The cytologic diagnosis was categorized into four groups: benign, 174; suspicious, 30; malignant, 41): and inadequate specimen, 9. There were two false-negative and no false-positive diagnoses. Our results showed a sensitivity of 93.5% and a specificity of 100% for the detection of malignancy. If suspicious cases were considered positive, the specificity decreased to 55%, while the sensitivity increased to 95%. We conclude that Riu's stain is a reliable quick stain in the diagnosis of thyroid malignancy. Compared to Papanicolaou stain, it shortens the time needed for a cytopathologist to reach a diagnosis. Papanicolaou stain can be reserved for confirmation.

Adult↗

Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis.

Serum hepatitis B virus (HBV) DNA from 4 infants with fulminant hepatitis B, 3 infants with acute self-limited hepatitis B, and 15 infants with chronic HBV infection were amplified by polymerase chain reaction followed by direct sequencing of the region of HBV genome encoding the major antigenic epitopes of hepatitis B surface antigen (HBsAg). All infants were born to carrier mothers and administered immunoprophylaxis from birth. Serum HBV DNA from 13 carrier children born to carrier mothers who did not receive immunoprophylaxis and had comparable length of infection were studied as controls. An S mutant (residue 126, Thr to Ala) initially found in an infant with fulminant hepatitis was replaced by another S mutant (residue 145, Gly to Arg) 4 days later. In a girl with chronic hepatitis B, Ala-126 variant and Arg-145 variant were found at 17 and 25 months of age, respectively. The Arg-145 variant persisted for 8 years in an asymptomatic male carrier and for 1 year in an infant with chronic hepatitis B. The Ala-126 variant persisted for 11 years in one child who had an early loss of hepatitis B e antigen. In the majority of the infants' mothers, corresponding mutations in HBsAg were not detected in serum by direct sequencing. The S mutants detected in three carrier infants were not found in their mothers' serum after cloning and sequencing of 10 DNA clones from each maternal sample. None of the 13 control patients had detectable S mutants. These results suggest that S variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. An S mutant (residue 129, Gln to Arg) found in one mother-infant pair suggested a direct maternal-infant transmission, resulting in immunoprophylaxis failure. None of the family members of children infected with Arg-145 variant had the same variant infection, implying this variant's low transmissability.

Alanine Transaminase↗

Comparison of endometrial changes among symptomatic tamoxifen-treated and nontreated premenopausal and postmenopausal breast cancer patients.

Breast cancer patients who received tamoxifen as adjuvant therapy have been reported to have more endometrial lesions such as polyps, hyperplasia, or carcinoma. We conducted a prospective study to elucidate the endometrial changes of premenopausal and postmenopausal breast cancer patients with tamoxifen. Sixty-seven symptomatic breast cancer patients who had been on tamoxifen treatment, including 34 premenopausal and 33 postmenopausal patients, and another group of 48 patients who had not been on tamoxifen, including 25 premenopausal and 23 postmenopausal patients, were recruited. Symptomatic patients were defined as having hypermenorrhea or abnormal vaginal bleeding among premenopausal patients or postmenopausal bleeding among postmenopausal patients. Endometrial thickness and uterine size determined by vaginal ultrasonography, histologic findings, and risk factors for endometrial cancer were compared. The mean endometrial thickness and uterine size showed no statistically significant difference in premenopausal patients with (n = 34) or without (n = 25) tamoxifen treatment, whereas there was a significant difference in the postmenopausal patients with (n = 33) or without (n = 23) tamoxifen treatment (12.11 +/- 12.38 mm vs 5.41 +/- 2.70 mm, P = 0.025; 234.71 +/- 76.36 cm3 vs 108.81 +/- 81.27 cm3, P = 0.0018, respectively). The frequency of endometrial histopathologic findings was 23.5% (8/34) in tamoxifen-treated women compared with 12.0% (3/25) in nontreated women (P = 0.269) in the premenopausal groups. In contrast, it was remarkably high with 66.7% (22/33) in tamoxifen-treated women compared with 30.4% (7/23) in the nontreated women in the postmenopausal groups (P = 0.025). There were four postmenopausal patients with tamoxifen, including three with atypical endometrial hyperplasia and one endometrial carcinoma, in contrast to no postmenopausal nontreated patients, although this difference did not reach statistical significance in this study (P = 0.096). There was a remarkably high prevalence of endometrial histopathologic findings in symptomatic tamoxifen-treated breast cancer patients, especially postmenopausal women. Tamoxifen might be associated with premalignant or malignant changes in postmenopausal endometrium. Thus timely, aggressive histologic assessment such as curettage or hysteroscope should be performed to detect the endometrial lesions when symptoms occur. Vaginal ultrasonography could be a useful tool to detect the endometrial lesions.

Aged↗

Thyroid hormone upregulates Na,K-ATPase alpha and beta mRNA in primary cultures of proximal tubule cells.

In vivo studies have demonstrated that thyroid hormone regulates the activity of Na,K-ATPase in the mammalian kidney. However, it is still unclear whether upregulation of Na,K-ATPase by thyroid hormone is mediated through the direct action on renal tubule cells or through other mediators, such as an increase in glomerular filtration rate. Using primary cultures of rabbit renal proximal tubule cells, studies were undertaken to elucidate this problem. We found that Na,K-ATPase activity was increased by 26 +/- 8%, 30 +/- 9%, 39 +/- 9% after 24-h treatment with T3 of 10(-11), 10(-9), 10(-7) M, respectively. We further demonstrated that 24-h incubation of T3 (10(-7) M) enhanced alpha- and beta-protein abundance by 44 +/- 29% and 31 +/- 16%, and alpha- and beta-mRNA levels by 84 +/- 27% and 65 +/- 11%, respectively. The time course studies revealed that the significant increase in Na,K-ATPase activity, alpha- and beta-protein and mRNA abundance didn't appear until 24-h of T3 treatment. Our data indicate that thyroid hormone directly upregulates Na,K-ATPase in proximal tubule cells via a pretranslational mechanism.

Animals↗

Evolution of hepatitis C virus quasispecies in mothers and infants infected through mother-to-infant transmission.

BACKGROUND/AIMS: Two mother-infant pairs (Pair H and P) were studied to determine the evolution of hepatitis C virus (HCV) quasispecies. METHODS: Eight clones of the hypervariable region of HCV cDNA from the infants' sera sampled at the age of 3 months, 1, 2, and 3 years and the time-corresponding maternal sample were also sequenced. The sequences were analyzed by the nucleotide diversity, substitution rate, and phylogenetic studies. RESULTS: HCV quasispecies of the infants were more homogeneous than those of their mothers, particularly at the age of 3 months (nucleotide diversity, pi = 0.18 x 10(-2)/site in infant H, and 0.22 x 10(-2)/site in infant P). The nucleotide substitution rate in infants also increased as they aged, from 1.2 x 10(-2) to 4.46 x 10(-2)/site/year in infant H, and from 0.21 x 10(-2) to 4.88 x 10(-2)/site/year in infant P respectively. The nucleotide sequence differences between infants and mothers increased from 2.63 x 10(-2) to 9.06 x 10(-2)/site in Pair H, and from 1.85 x 10(-2) to 5.33 x 10(-2)/site in Pair P within 3 years. Phylogenetic studies suggest the infants' initial quasispecies were closely related to their mothers', while they evolved differently. HCV RNA titer was stable during follow-up and the infants' titer was similar to their mothers'. The fluctuations in titer did not correlate with nucleotide diversity. CONCLUSIONS: HCV quasispecies evolved differently in each individual, even though they were genetically linked. The sequence in infants was not a complex as in their mothers.

Adult↗

Breast mass due to alveolar soft part sarcoma of the pectoris major muscle.

We present a case of alveolar soft part sarcoma (ASPS) of the pectoris major muscle in a 20-year-old female. She felt a mass in her right side breast for 7 years. The lesion was almost the same size with occasional throbbing pain and tenderness. Fine needle aspiration of the tumor was performed in the OPD and suspicious abnormal cells were reported. Ultrasound (US) examination of the breast revealed a large heterogeneously hypoechoic lesion contiguous to the pectoris major muscle. Profound color flow signals were evident in both central and peripheral regions of the mass. Spectral Doppler US showed high flow velocity in the tumor vessels with resistivity index of 0.73. Surgical intervention was performed and the histological examination yielded a diagnosis of ASPS.

Adolescent↗

Mature teratoma arising from an intra-abdominal undescended testis presenting as a fetal abdominal mass.

Teratoma of the intra-abdominal testis is a rare finding in infants. We describe the case of a full-term newborn treated for a calcified abdominal mass which was observed unexpectedly on prenatal sonography. An undescended right testis was also noted. During laparotomy, a twisted retroperitoneal tumor was found just above the right deep inguinal ring. Histological analysis revealed a mature teratoma of the intra-abdominal right testis. The tumor was removed and there was no recurrence at follow-up 1 year later. A teratoma should be considered in cases of fetal abdominal mass, especially when the testes cannot be detected in the scrotum by the 8th month. Prenatal sonographic diagnosis might be possible.

Adult↗

Role of benzathine penicillin G in prophylaxis for recurrent streptococcal cellulitis of the lower legs.

Cellulitis of the lower leg is an infection caused by streptococci or, less commonly, Staphylococcus aureus and other gram-negative rods. Recurrence of cellulitis is a common problem. In the present study, we evaluated the use of monthly intramuscular injections of benzathine penicillin G to prevent recurrences of cellulitis. A total of 115 patients with definite or presumptive cases of streptococcal cellulitis were enrolled in this study. Eighty-four of these patients who declined follow-up or received incomplete prophylaxis were considered controls. Recurrence occurred in four (12.9%) of 31 cases who received prophylaxis and 16 (19%) of the 84 cases who did not receive prophylaxis. The difference was not statistically significant. Predisposing factors for cellulitis were found in 57 (49.6%) of the 115 enrolled cases and were mostly related to the impairment of local circulation. Administration of prophylaxis successfully reduced the recurrence rate to zero among patients without predisposing factors but failed to prevent recurrence in those with predisposing factors (20%). We conclude that monthly benzathine penicillin G prophylaxis benefits only patients without predisposing factors for cellulitis.

Cellulitis↗

Adenomyosis in the broad ligament and tamoxifen: report of a case.

Adenomyosis confined to the broad ligament is extremely rare. Herein we present a case of adenomyosis in the broad ligament with unusual gross features. This 41-year-old woman had been on tamoxifen therapy for 3 years due to breast cancer. Ten months after discontinuing tamoxifen, she underwent exploratory laparotomy for a right adnexal mass suspected as ovarian malignancy. At laparotomy, the mass was located in the right broad ligament with a fibrous stalk connecting to the uterus. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathologic examination revealed adenomyosis with cyst formation and an unusual thick capsule. The possible effects of tamoxifen upon the uterus are discussed in this article, in view of reports of tamoxifen associated with endometrial carcinoma and endometriosis.

Adnexal Diseases↗

The potential of serum levels of soluble tumour necrosis factor receptor I as a biochemical marker in cervical cancer.

OBJECTIVES: To investigate the significance of serum levels of soluble tumour necrosis factor receptor I (sTNF-RI) as a potential biochemical marker in women with cervical cancer. DESIGN: A prospective, case-controlled study. PARTICIPANTS: Seventy-one women with cervical cancer and 33 women with myoma were enrolled in this study. METHODS: Pre-operative serum levels of sTNF-RI were measured with a standard enzyme-linked immunosorbent assay utilising murine monoclonal antibody against sTNF-RI. MAIN OUTCOME MEASURES: All data in both groups were evaluated and correlated with the pre-operative serum levels of sTNF-RI. Data analysis was carried out using ANOVA with multiple comparison and linear regression. RESULTS: The mean serum level of sTNF-RI in the cervical cancer group was significantly lower than that in the myoma group (P < 0.001). The sTNF-RI levels decreased sequentially with disease progression from Stage Ia to IIb in women with cervical cancer. The mean serum level of sTNF-RI was also significantly lower in women with positive lymph node (P < 0.05) or recurrent cancer (P < 0.001). A negative correlation was observed between serum levels of sTNF-RI and tumour size (r = -0.622, P < 0.0001). CONCLUSIONS: Decreased pre-operative serum levels of sTNF-RI are observed in women with cervical cancer. The results do not support that the use of sTNF-RI as a biochemical marker for cervical cancer.

Adult↗

Inducible expression of bcl-2 by the lac operator/repressor system in MDCK cells.

The lac operator/repressor-inducible system was utilized to dissect the biological consequences of human bcl-2 gene expression in Madin-Darby canine kidney (MDCK) cells. Cells were made transgenic for a constitutively expressed lacI gene, encoding lac repressor, and the bcl-2 gene that had been inserted downstream of a simian virus 40 (SV40) promoter containing the lac operator sequence. The expression of the bcl-2 gene could therefore be repressed to basal level by binding of lac repressor to the lac operator sequence in proximity to this SV40 regulatory region and be specifically activated by administration of the lactose analog isopropyl-beta-D-thiogalactoside (IPTG). We showed that expression of bcl-2 gene could be induced by 0.01 mM IPTG, and the maximal induction was obtained at 1 mM. With the treatment of IPTG, the Bcl-2 protein could be induced within 6 h. Moreover, the IPTG-inducible expression of Bcl-2 protein is a reversible process. Finally, functional assays revealed that IPTG-induced expression of bcl-2 gene conferred partial or complete resistance to homeless cell death or confluent cell death, respectively. The inducible expression system should be particularly useful for dissecting the effect of bcl-2 in phenotypic or morphological changes of MDCK cells.

Animals↗

Regulation of salivary-gland-specific gene expression.

The results from in vivo transgenic and in vitro transfection studies designed to identify cis-element(s) and transfactor(s) governing the salivary proline-rich proteins (PRPs), amylase, and parotid secretory protein (PSP) gene expression are utilized as a paradigm to discuss the regulation of salivary-specific gene expression. Particular attention is given to the molecular mechanism(s) underlying the salivary PRP R15 gene regulation. In rodents, the PRPs are selectively expressed in the acinar cells of salivary glands, and are inducible by the beta-agonist isoproterenol and by dietary tannins. The results from a series of experiments using chimeric reporter constructs containing different lengths of the R15 distal enhancer region, their mutations, and various expressing constructs are analyzed and discussed. These data suggest that the inducible nuclear orphan receptor NGFI-B may participate in the regulation of salivary acinar-cell-specific and inducible expression of the rat R15 gene via three distinct distal NGFI-B sites. Taken together, a model for the induction of R15 gene expression by Ipr is proposed. However, the exact molecular basis of this NGFI-B-mediated transactivation of cAMP-regulated R15 expression remains to be established.

Amylases↗

Characterization and stability of various liposome-encapsulated enoxacin formulations.

The necessity for antibacterial agents with greater intracellular efficacy has led to the development of endocytosable drug carriers such as liposomes. Enoxacin was selected as a model drug incorporated in various liposome formulations as a therapeutic dosage form using the ethanol injection method and freeze-drying. Liposomal behavior after preparation and stability test was characterized by determining the physicochemical properties of enoxacin encapsulation percent, vesicle size and turbidity. The non-phospholipid formulation of stratum corneum liposomes showed the highest encapsulation efficiency after preparation among nine liposomal formulations. The addition of dissacharides in liposomes also enhanced the encapsulation of enoxacin due to the protection of phospholipid bilayers during the freeze-drying process. The liposomes with negatively charged component and dissacharides showed lower enoxacin leakage after five weeks of storage at 45 degrees C, suggesting these formulations have high stability in long-term storage. The negative liposomes showed a different behavior than others in their decrease of size and turbidity during storage, possibly due to high surface charges of the negative formulation. Cholesterol stabilized bilayers interacted with plasma and high density lipoprotein (HDL) retained enoxacin in the vesicles. Nevertheless, liposomes with cholesterol caused a hydrolysis problem after incubation with normal saline. The formulation with trehalose not only showed high stability in storage but also in plasma and HDL. This suggested trehalose was useful to incorporate with phospholipids to produce a highly encapsulated and stabilized liposomes of enoxacin. This study also demonstrated that thought is required in utilizing turbidity as a direct index of liposomal vesicle size.

Anti-Infective Agents↗

Involvement of nuclear orphan receptor NGFI-B in transcriptional activation of salivary-specific R15 gene by cAMP.

Proline-rich proteins (PRPs) are selectively expressed in the acinar cells of the salivary glands and are inducible by beta-agonist isoproterenol and dietary tannins. In the previous studies of rat PRP gene, R15, the 5'-flanking region up to -1.7 kilobase pairs (kb), which was thought to contain the necessary proximal regulatory elements, failed to confer the catecholamine isoproterenol and dietary tannin inducibility to the transgene expression in the salivary glands of transgenic mice. Here we analyzed distal 5'-flanking region of R15 in order to understand the mechanisms of tissue-specific and inducible gene regulation. An upstream regulatory region located between -2.4 and -1.7 kb of the R15 5'-flanking region is demonstrated to be indispensable for the salivary-specific and inducible reporter gene expression in vivo, by transgenic approach. Element(s) within the 0.7-kb (-2.4 to -1.7) region that is able to cis-activate the expression of a heterologous reporter gene expression is further elucidated by transient transfection assays in vitro. Three distinct nuclear orphan receptor NGFI-B regulatory sequences are identified within a 184-base pair (bp) minimal control region extended from -1995 to -1812 nucleotides relative to the transcription start site. When reporter gene containing this 184-bp control region and heterologous promoter was cotransfected with the NGFI-B expression construct, a transactivation that mimics the effect of cAMP is observed in the parotid cells. Finally, mutations on all three identified NGFI-B binding sites and coexpression of a dominant negative mutant construct, pCMV-NGFI-B(Delta25-195), abolish this transactivation mediated by NGFI-B. In summary, these data suggest that the inducible nuclear orphan receptor NGFI-B may participate in the regulation of salivary acinar cell-specific and inducible expression of the rat R15 gene via three distinct distal NGFI-B sites.

Animals↗

Role of apoptosis in growth and differentiation of proximal tubule cells in primary cultures.

In this study, we assessed the profile of cell proliferation, Na,K-ATPase activity and apoptosis in primary cultures of proximal tubule cells. Freshly isolated proximal tubules exhibited apoptosis very early in culture: floated cells within 6 hr; attached tubule cells within 20 hr. The onset of apoptosis in either attached or floated proximal tubules was accompanied by a decline of Na,K-ATPase activity, indicating a close relationship between apoptosis and dedifferentiation. The ratio of apoptosis was highest at the lag phase and lowest at the rapid growth phase, reflecting an inverse relationship between mitogenesis and apoptosis. Our data indicate that apoptosis is involved in the growth and early downregulation of Na,K-ATPase activity in primary cultures of proximal tubule cells.

Animals↗

Functional analysis of the c-myb proto-oncogene.

Targeted mutagenesis studies were initiated to determine the normal biological function of the c-myb proto-oncogene. While heterozygous mice are phenotypically indistinguishable from their wild-type littermates, homozygous mutant fetuses die at approximately 15.5 days of gestation apparently due to anemia, which results from an inability to switch from embryonic yolk sac to fetal liver erythropoiesis. Studies are currently being done to determine the extent of hematopoietic abnormalities in the homozygous mutant fetuses. In vitro assays for hematopoietic colony-forming cells have been used to determine the frequency of both erythroid and myeloid progenitors in the fetal livers of wild-type, heterozygous, and homozygous mutant c-myb fetuses. The reduced number of erythroid progenitors was not unexpected considering the mutant fetus's pale color and reduced hematocrit. The dramatically reduced number of colonies derived from myeloid progenitors in the mutant fetuses in comparison to the number detected in phenotypically normal littermates suggests that expression of the c-myb proto-oncogene is critical for the proliferation and/or differentiation of early hematopoietic progenitors and possibly hematopoietic stem cells. Other possible explanations would include a hematopoietic progenitor migration problem from the yolk sac to the fetal liver or a defect in the microenvironment of the liver. Whether the lymphoid lineage is also adversely affected by the lack of c-myb expression remains to be determined. RT-PCR and Northern blot analyses were used in an attempt to identify downstream genes which may be directly or indirectly regulated by the Myb gene product. While the levels of expression of several genes involved in erythropoiesis (GATA-1, NF-E2, SCL, and EpoR) were reduced in the livers of homozygous mutant fetuses in comparison to phenotypically normal littermates and one gene, Kit ligand (KL), was expressed at higher levels in the mutant livers, these results must be viewed with caution. The livers of the mutant fetuses have been shown to be hypocellular in comparison to those of phenotypically normal littermates (35). It is possible that the Myb gene product is directly or indirectly modulating the expression of these genes. Conversely, the alteration in expression may be due to the reduced number or absence of specific hematopoietic lineages in the livers of the mutant fetuses. Differential display has also been used to identify putative novel genes that are involved in hematopoiesis. Preliminary studies suggest that this may be a powerful methodology to compare the expression pattern of genes in the fetal liver of wild-type, heterozygous, and homozygous mutant littermates at 14.5 days of gestation. To date nearly 60% of the partial cDNAs subcloned analyzed have been shown to be differentially expressed. More importantly, 75% of the differentially expressed cDNAs that have been sequenced appear to encode novel genes. Whether any of these novel genes are involved in the c-myb transcriptional cascade remains to be determined. Overall, analysis of the c-myb mutant fetuses have provided valuable insight into the biological function of this interesting proto-oncogene. The continued analysis of this resource will undoubtedly provide additional information concerning the role of the c-myb gene in hematopoiesis.

Animals↗