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Biomedical subjects

T T Chen

Publications and source records attributed to T T Chen.

At least 109 records · Page 6Linked to original sources

Transgenic fish.

A range of transgenic animal species have been generated using DNA microinjection, and application of this technique to fish is now showing some degree of success. Studies to optimize microinjection techniques specifically for use with fish, and to investigate possible alternative methods for mass culture, should lead to the commercial production of transgenic fish able to transmit desirable characteristics, such as enhanced growth or disease resistance, to their progeny.

Animals↗

Effects of cytokines on porcine granulosa cell steroidogenesis in vitro.

Recent evidence indicates that factors produced by immune cells (cytokines) may play a role in ovarian function. To explore this possibility, we examined the effects of conditioned medium obtained from cultures of either unstimulated splenocytes (splenocyte-conditioned medium; SCM) or concanavalin A-stimulated splenocytes (CAS) on estrogen and progesterone production by porcine granulosa cells. Granulosa cells were obtained from small (less than 3 mm) or large (greater than 7 mm) follicles and treated with increasing doses of SCM or CAS in the presence or absence of pFSH (100 ng/ml) for 24 h at 37 degrees C. In granulosa cells obtained from small follicles it was found that both SCM and CAS evoked a dose-dependent increase in estrogen but not progesterone production. Estrogen production was no further enhanced by the presence of FSH. Additionally, SCM was able to augment FSH-stimulated progesterone production by these cells, whereas CAS had no effect. Identical treatment of granulosa cells obtained from large follicles demonstrated that both SCM and CAS caused dose-dependent increases in estrogen as well as progesterone production. In response to CAS, FSH augmented progesterone production but exerted a biphasic on estrogen production (inhibiting at lower doses while stimulating at higher doses). In contrast, SCM had no effect on FSH-stimulated estrogen production. Additional controls indicated that the above results could not be attributed to either concanavalin A or serum. Taken together, these findings suggest that cytokines can exert significant effects over granulosa cell steroidogenesis and further imply that these factors may play an important role in the differentiation and developmental regulation of granulosa cell function.

Animals↗

Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family.

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.

Amino Acid Sequence↗

The opium wars revisited as US forces tobacco exports in Asia.

The tobacco industry has lobbied successfully to obtain the support of the United States government for opening Asian Markets to American tobacco products. This paper comments on two issues arising from these efforts: the development of an atmosphere of invasion and resistance to invasion in Asia; and the change in the image of the United States in Asian nations from that of a leader in health to that of an exporter of death. The threat of sanctions and the effects of the open market and United States tobacco company advertising in Japan, Taiwan, and South Korea are noted. Parallels are drawn between the opium wars a century and a half ago in China and the current threat of trade sanctions. Reacting to American policy, an Asia-Pacific Association for Control of Tobacco has been formed and linked with the US Coalition Against Smoking.

Asia, Southeastern↗

A review of methods for misclassified categorical data in epidemiology.

Misclassification introduces errors in categorical variables. This paper presents a review of methods for misclassified categorical data in epidemiology. Different sampling schemes for a 2 x 2 x 2 table and methods of analyses will be discussed first. A misclassification matrix is defined, and the usual misclassification models will be shown to be a subclass of log-linear models. Well-known results on a 2 x 2 table with misclassification and recent results on a 2 x 2 x 2 table are then reviewed. Finally two methods of adjusting for misclassification will be given. The first method assumes a known misclassification matrix, and the second method uses subsampling to estimate the misclassification matrix. The analysis is based on a recursive system of log-linear models: first determine a misclassification model, then select a model for the correctly classified variables. The methods are illustrated by data from traffic safety research on the effectiveness of seatbelt use in reducing injuries.

Biometry↗

Relative importance of newly synthesized and stored hormone to basal secretion by growth hormone and prolactin cells.

It is generally accepted that under basal conditions there is preferential release of newly synthesized hormone by a number of endocrine cell type, including those that secrete GH or PRL. However, the cellular basis for this phenomenon along with the relative contribution of stored hormone to basal secretion has yet to be clearly established. In the present study, we employed reverse hemolytic plaque assays to monitor basal and stimulated release of GH and PRL from individual cells in which de novo protein synthesis had been blocked. Monodispersed pituitaries from adult male rats were cultured for 21 h in the absence or presence of maximally effective doses of puromycin (100 microM) or cycloheximide (36 microM) and were then subjected to separate plaque assays for GH or PRL. Treatment with puromycin reduced the percentage of GH or PRL secretors (plaque formers) by about half. Coincubation with stimulatory secretagogues did not increase the percentages of GH or PRL secretors in control cultures, but returned the proportion in puromycin-treated cells to normal, demonstrating that cells which failed to secrete basally could still release hormone from their stored pools when stimulated. Very similar results were obtained when these experiments were repeated with cycloheximide. Taken together, these results demonstrate that only a fraction of the cells that release GH or PRL are dependent upon newly synthesized hormone for basal secretion; the remainder appear capable of mobilizing stored hormone for this purpose even in the absence of stimulation.

Animals↗

A cellular basis for growth hormone deficiency in the dwarf rat: analysis of growth hormone and prolactin release by reverse hemolytic plaque assay.

The purpose of this study was to elucidate the cellular basis for growth hormone deficiency in Lewis-derived dwarf rats. To this end, we used reverse hemolytic plaque assays to evaluate hormone release. This allowed us to determine the proportional abundance of GH- and PRL- secreting cells and estimate the relative amount of hormone secreted by individual pituitary cells from dwarf rats and their somatically normal counterparts. The percentage of all pituitary cells that released GH (formed plaques) in pituitary dispersions was substantially lower for dwarfs when compared with normals in the absence (3.8 +/- 2.2% vs. 43.4 +/- 2.2%) or presence (6.6 +/- 3.8% vs. 45.7 +/- 1.4%; n = 3) of GRF. In addition, GH secretors from dwarfs released less hormone (formed smaller plaques) than their normal counterparts under both basal and stimulated conditions. An analysis of the relative number of GH cells that formed plaques of various sizes was accomplished by constructing a frequency distribution. Dwarf GH secretors formed more small plaques and proportionately fewer larger plaques than normals under both basal and stimulated conditions. For comparison, we also quantified the proportions of PRL secretors and found that they were actually more abundant in dwarfs than normals in the absence (52.4 +/- 4.6% vs. 33.7 +/- 3.7%) or presence (53.4 +/- 4.9% vs. 33.8 +/- 4.1%; n = 4) of TRH. Treatment with this secretagogue consistently increased mean PRL-plaque area for both groups. Our findings demonstrate that dwarf rats are severely deficient in the proportion of GH secretors. In addition, the few GH secretors present in the dwarf pituitary were less responsive to GRF than normals. In contrast, PRL cells in dwarfs appear to be functionally similar to those of their normal counterparts. The reciprocal relationship in the proportions of GH and PRL secretors in dwarfs provides a rather unique model for investigating the functional relationship between these cell types.

Animals↗

Pituitaries transplanted under the renal capsule contain functional growth hormone (GH) secretors and suppress GH and prolactin release from individual eutopic pituitary cells.

The extent to which pituitary explants secrete GH requires clarification. In the present study GH release from ectopic pituitary tissue was assessed using the reverse hemolytic plaque assay. In addition, the effects of this tissue on eutopic GH and PRL release were simultaneously investigated. Anterior pituitary glands from adult female donor rats were grafted beneath the kidney capsule of adult male hosts. Four weeks later, this ectopic pituitary tissue and the eutopic pituitary glands of the host animals were removed, dispersed with trypsin, and subsequently assayed for GH and PRL release. Contrary to expectations, we found that 37% of the ectopic pituitary cells were GH secretors. Furthermore, these GH cells remained highly responsive to GRF (10(-7) M), which evoked a 7-fold increase (P less than 0.05) in mean GH plaque area. By comparison, only 28% of these ectopic cells secreted PRL, and this release was not consistently augmented by exposure to TRH (10(-7) M). In the second half of this study we found that the presence of ectopic pituitary tissue severely compromised the secretory capacity of the eutopic pituitary cells. More specifically, GH-releasing factor induced a 3-fold increase in GH secretion from the eutopic pituitary cells of sham-operated control animals, but it enhanced the release from cells of host animals by only 2-fold. Moreover, the response to TRH by the eutopic PRL cells from explant-bearing animals was curtailed to such an extent that it was not significantly greater (P greater than 0.05) than basal release in that group. We conclude that the potential of pituitary explant cells to release GH is far greater than previously believed and that this ectopic hormone production may inhibit hormone release from the eutopic pituitary cells.

Animals↗

Anterior ischemic optic neuropathy--recurrent attacks in one eye in a bilateral case.

Subsequent involvement of the fellow eye is common in anterior ischemic optic neuropathy, but recurrent episodes in one eye are extremely rare. Our hypertensive patient had one eye attacked nine years before and two episodes in the second eye within ten days of each other. Visual-field examination revealed progressing field loss, and fluorescein angiography demonstrated an enlarged disc hypofluorescence area.

Fluorescein Angiography↗

Molecular cloning and sequencing of coho salmon growth hormone cDNA.

A cDNA library was constructed using mRNA isolated from coho salmon pituitaries. By employing rainbow trout growth hormone cDNA as a probe, the coho salmon cDNA was isolated and the complete nucleotide (nt) sequence determined. The coding region contains 630 nt while the 5'- and 3'-untranslated regions are 64 and 489 nt in length, respectively. Comparison of the noncoding regions of coho and chum salmon cDNAs reveal identity at the 5' end but significant variation in the 3' end. Chum salmon and rainbow trout have identical amino acid (aa) sequences, but coho salmon growth hormone has a sequence that differs by 6 of the 188 predicted aa. Since salmonids are tetraploid, this difference may be the result of either divergence of the same growth hormone locus or of variation between different loci. Comparisons of the cDNA restriction maps of these three fish species suggest the former possibility.

Animals↗

Rainbow trout has two genes for growth hormone.

We report the primary structures of two mRNA species (GH1 and GH2), each predicted from the cloned cDNA and genomic gene sequences, that encode growth hormone in rainbow trout (Salmo gairdneri). Both GH1 and GH2 mRNA contain open reading frames comprising 630 nucleotides and encode 210 amino acid residues, of which 11 are variant. The translated regions of mRNA are flanked by a short 5'-untranslated sequence, which is highly conserved, and a relatively long 3'-untranslated sequence, which is highly divergent. The differences at the 3'-untranslated regions suggest that the GH1 and GH2 mRNA originate from different loci. RNA blot analysis of trout pituitary RNA using an oligonucleotide probe specific for the GH2 sequence indicates that the cloned gene is expressed. The GH1 and GH2 mRNA likely are transcribed from two distinct loci, which were duplicated during tetraploidization of the salmonid genome between 50 and 100 million years ago.

Amino Acid Sequence↗

Modelling the liver function data in diabetes.

We have enrolled diabetic patients into a long-term follow-up study that entails visits to the eye clinic every six months at which time use of a classification scheme determines whether or not the patient is normal regarding liver function. Since the study is still in progress, not all patients have complete follow-up data. We fit models of complete symmetry to the multi-visit binary data with supplemental margins and also investigate the data as stationary Markov chains with testing for stationarity and determination of the order of chain. The final model, a synthesis of both approaches, has potential use in future clinical trials of new drugs for diabetic patients.

Diabetes Mellitus↗

Outcome of prophylactic and therapeutic cranial irradiation in disseminated small cell lung carcinoma: a Southwest Oncology Group Study.

The issue whether cranial radiotherapy (RT) should be used prophylactically (PCI) or therapeutically (TCI) in small cell lung carcinoma (SCLC) is considered controversial by some oncologists. Trying to clarify this issue we have performed a retrospective analysis of a Southwest Oncology Group (SWOG) protocol for disseminated SCLC. Three Hundred and seventy-seven cases had no evidence of metastases to the brain (MB). One hundred and forty four of those had PCI. Seventy one cases were diagnosed of MB, and 64 received TCI. We confirmed previous reports showing a low percentage of brain relapse with PCI (around 5%), with minimal immediate morbidity. We also confirmed a high percentage of objective response (90%) with TCI, (although we had no response information in 40% of them) with long duration of response of 33 weeks. Brain relapse after TCI was only 18%. Only long-term survivors had brain relapse as survival of relapsing patients was longer than those without brain relapse (45 weeks versus 33 weeks, p = 0.06). However, 20 (31%) of the 65 with initial MB died within 6 weeks of registration, some without completing RT to brain. In the majority, cause of death was considered related directly to brain damage, or indirectly as sepsis developed in patients whose poor performance status was considered to be caused by their brain symptoms. When comparing patients with and without MB, the former had (a) worse survival (24 versus 32 weeks, p = 0.02) and (b) higher proportion of patients with poor initial performance status (50% versus 34%, p = 0.04). Although the possibility of long-term morbidity with PCI is deterring some oncologists from recommending it, our data show that MB creates a real chance for immediate morbidity and this should not be ignored. The pros and cons of both approaches and some new recommendations for PCI are discussed.

Brain↗

Structure of a fish (rainbow trout) growth hormone gene and its evolutionary implications.

We have isolated and sequenced a clone from a rainbow trout (Salmo gairdneri) genomic library that carries a gene encoding a fish growth hormone (GH). This gene spans a region of approximately equal to 4 kilobases, nearly twice that of mammalian GH genes. The trout GH gene is comprised of six exons, in contrast with five exons in mammals. The additional intron in the fish gene interrupts translated regions that are analogous to the last exon of its mammalian counterpart. In addition, the alleged internally repeating sequence in mammalian GH, prolactin (Prl), or placental lactogen (PL) is not observed in the predicted polypeptide sequence of fish GH. Direct repeats that flank exons I, III, and V of the mammalian GH, Prl, and PL genes are absent in the fish GH gene. These findings indicate that the rainbow trout GH gene structure does not support the current hypothesis that internally repeated regions in GH, Prl, and PL arose from a small primordial gene.

Animals↗

Cataract and health status: a case-control study.

Data from 97 cataract patients and 105 normal controls with ages less than 67 years were collected with respect to sex, age, disease status, drug intake, and blood chemistries. The statistical method of fitting log-linear models was used to determine the association between the case-control indicator variable and the other variables. The following variables were shown to be important and to associate independently with the risk of developing cataracts: age, allergy, diabetes, hypotension, hypertension, use of analgesics and coronary disease.

Adult↗

Cataract epidemiological study: correlation of cataract morphology with health status.

Data on 288 cataract patients were collected with respect to sex, age, disease status, drug intake, and blood chemistry. Eight different types of lens opacities could be discriminated using slit-lamp examination, Scheimpflug photography of the anterior eye segment, and microdensitometric image analysis of the film negatives. The statistical method of fitting log linear models was used to investigate the association between cataract morphology and other variables. The following variables were shown to be important and to contribute independently to the differentiation of cataract types: cholelithiasis, pneumonia, heart insufficiency, allergy, and age.

Adult↗