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Biomedical subjects

D H Shin

Publications and source records attributed to D H Shin.

At least 91 records · Page 5Linked to original sources

p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women.

A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.

Alleles↗

Mammary gland tumor in transgenic mice expressing targeted beta-casein/HPV16E6 fusion gene.

The human papillomaviruses (HPV)-16 and HPV-18 referred to as high-risk HPVs are strongly associated with anogenital malignancies as well as benign epithelial cysts. It has been demonstrated that transgenic mice carrying HPV-16 E6-E7 under the control of the MMTV LTR developed malignant tumors including salivary gland carcinoma, lymphoma, skin histiocytomas and testicular tumors in a non-mammary gland specific manner. Another regulatory unit of rat beta-casein gene can confer the expression of fusion gene preferentially in the mammary glands of transgenic mice in a developmentally regulated manner. In order to generate mammary tumor formation in transgenic mice directing HPV16E6 gene alone into the mammary gland, this regulatory unit was fused to the E6 gene of HPV-16 type to constructing fusion gene. By screening 51 newborn founder transgenic mice, three mice carrying transgenes were identified. One line termed TG32 developed in a mammary gland tumor with large subcutaneous mass in the left rib region at 17 months of age. The levels of E6 transcript in the mass-tumor of TG32 line were lower than those in non-tumor mammary gland of identical TG32 and of TG250. In each tissue of TG32 line, high expression of E6 transcript was detected both in the mammary gland and brain. Histological analysis showed that cells from mammary gland tumor of the TG32 line had also hyperplasia appearance, with irregular or increased total number of mitotic rate. These observations suggest that developing phenotype and the level of E6 transcripts in the process of malignant transformation may have different mechanisms involving the capacity to bind and destabilize p53, although for confirmation it is necessary to investigate many more transgenic mice.

Animals↗

Reactive astrocytes express p53 in the spinal cord of transgenic mice expressing a human Cu/Zn SOD mutation.

In a previous study, we reported increased NOS expression in the astrocytes in the spinal cord of SOD mutant transgenic mice that are used as ALS animal model. Recently, Messmer and Brune suggested that nitric oxide-induced apoptosis is intimately related with p53-dependent signaling pathway, and de la Monte et al. reported increased p53-immunoreactivity in the spinal cord of ALS patients. In the present study, we performed immunocytochemical studies to investigate the changes of p53-immunoreactivity in the brains of the mutant transgenic mice expressing a human Cu/Zn SOD mutation. Immunocytochemistry showed intensely stained p53-IR glial cells with the appearance of astrocytes in all levels of the spinal cord of the mutant transgenic mice, but no p53-IR glial cells were observed in the spinal cord of the control mice. P53-IR astrocytes were also detected in the brain stem of the mutant transgenic mice. In the medulla, they were observed in the medullary reticular formation, hypoglossal nucleus, vestibular nucleus, dorsal motor nucleus of the vagus and nucleus ambiguus. In the pons, their presences were noted in the pontine reticular formation, and trigeminal and facial nuclei. In the midbrain, astrocytes were detected in the mesencephalic reticular formation, red nucleus and periaqueductal gray matter. In the cerebellum, intensely stained p53-IR astrocytes were detected in the intracerebellar nuclei. In contrast to the mutant transgenic mice, no p53-IR astrocytes were detected in the brain stem and spinal cord of the control mice. Further multidisciplinary investigations involving p53-mediated cellular damage and pathogenesis of ALS are needed to clarify the importance of these results.

Animals↗

In situ localization of neuronal nitric oxide synthase (nNOS) mRNA in the rat retina.

We performed a comparative study on the distribution of neuronal nitric oxide synthase (nNOS) immunoreactivity and mRNA in a normal rat retina using immunocytochemistry and in situ hybridization technique. As in previous studies, we found NOS immunoreactive (NOS-IR) cells and fibers in inner and outer plexiform layers (IPL and OPL), inner nuclear layer (INL) and inner photoreceptor segment (IPS). However, very little nNOS-IR could be detected in groups of amacrine cells and ganglion cells localized in ganglion cell layer (GCL). However, in situ hybridization showed that intense NOS mRNA signals were mainly found in the GCL and INL while weak or no mRNA signals were detected in IPL, OPL, outer nuclear layer (ONL) and IPS. This difference suggests that nNOS proteins may be transported through axons into the terminals in the IPL and OPL after they were synthesized with nNOS mRNA templates in the INL. In the case of nNOS mRNA in GCL, synthesizing nNOS proteins may move outside the eyeball and carry out tasks in central nervous system. The difference of nNOS mRNA and nNOS IR means that the complete concurrence of nNOS IR and in situ hybridization results may not always occur in the rat retina.

Animals↗

In situ localization of p53, bcl-2 and bax mRNAs in rat ocular tissue.

We mapped p53, bcl-2 and bax mRNAs, which are known to have correlation with apoptotic cell death, in the rat ocular tissue. p53 mRNA signals were present in several layers of retina, optic nerve, corneal epithelium, ciliary process and posterior surface of the iris. While almost the same pattern as p53 was recognized in the case of bcl-2 mRNA, bax signals were not found in ocular tissue except for ganglion cell layer (GCL). These results suggest that in the normal ocular tissue, p53 and bcl-2 genes play opposing parts in the physiological control of cell survival and death. A p53 mediated tumor-suppressing action might occur through the induction of transcriptional targets other than bax because only in GCL were p53 and bax mRNA expression co-localized.

Animals↗

Isolation, characterization, and functional analysis of a novel cDNA clone encoding a small rubber particle protein from Hevea brasiliensis.

Biochemical evidence reported so far suggests that rubber synthesis takes place on the surface of rubber particles suspended in the latex of Hevea brasiliensis. We have isolated and characterized a cDNA clone that encodes a protein tightly bound on a small rubber particle. We named this protein small rubber particle protein (SRPP). Prior to this study, this protein was known as a latex allergen, and only its partial amino acid sequence was reported. Sequence analysis revealed that this protein is highly homologous to the rubber elongation factor and the Phaseolus vulgaris stress-related protein. Southern and Northern analyses indicate that the protein is encoded by a single gene and highly expressed in latex. An allergenicity test using the recombinant protein confirmed that the cloned cDNA encodes the known 24-kDa latex allergen. Neither ethylene stimulation nor wounding changed the transcript level of the SRPP gene in H. brasiliensis. An in vitro rubber assay showed that the protein plays a positive role in rubber biosynthesis. Therefore, it is likely that SRPP is a part of the rubber biosynthesis machinery, if not the rubber polymerase, along with the rubber elongation factor.

Allergens↗

Are substance P neurons of the paraventricular nucleus related to the osmotic regulation in the Mongolian gerbil?

In recent years, the gerbil has been used as an experimental animal for study osmotic regulation, because of its inherent high degree of water re-uptake in kidney. Many evidences to explain this characteristic accumulated on the kidney level, it do not, however, manifest what concerns on hypothalmo-hypophyseal level. In this study, we have focused on the difference between the colchicine treated gerbil and rat in distributions of substance P (SP), which is known to have antidiuretic property. Unlike rat, in which a few SP+ neuron is present, SP+ neurons were abundantly observed in the paraventricular nucleus (PVN) of the gerbil. Furthermore SP+ cells in PVN were manifested in dehydrated gerbils, in spite of non-colchicine treatment. Therefore, we suggest that the abundant SP+ neurons in PVN may be a clue to address the neuroendocrinal mechanism concerning the high degree of osmotic regulation in this animal.

Animals↗

Rat osteopontin antibody is cross-reactive to a novel myelin-associated protein in chick.

Osteopontin (OPN) was initially identified as glycosylated phosphoprotein in bones of vertebrates. Recently, OPN is reported to express in the primitive neuroepithelia of early chick embryonic hindbrain. We have demonstrated that rat OPN is immunohistochemically localized in the white matter of chick CNS. We have further confirmed the specificity of OPN cross-immunoreaction in myelin using demyelinated optic nerve induced by lysophosphatidylcholine (LPC), where the intensity of immunoreaction was closely related to the degree of demyelination. Immunoblot analyses showed that rat OPN antibody recognized a protein with molecular weights of approximately 47 kDa from chick CNS. Our data suggest that the antigen recognized by rat OPN is a previously undescribed myelin-associated protein in the chick CNS.

Animals↗

Risk factors for early filtration failure requiring suture release after primary glaucoma triple procedure with adjunctive mitomycin.

PURPOSE: Postoperative release of scleral flap closure suture is useful in trabeculectomy combined with cataract surgery. We determined risk factors for early filtration failure requiring suture release during the first month after primary glaucoma triple procedure. METHODS: The medical records of 71 consecutive patients with primary open-angle glaucoma who underwent a primary glaucoma triple procedure (primary trabeculectomy, phacoemulsification, and posterior chamber intraocular lens implantation) were reviewed. Suture release had been performed in 24 of the patients for early filtration failure with postoperative intraocular pressure greater than the target value during the first postoperative month. The long-term filtration failure was defined according to 2 criteria based on medical dependency and requirement of additional surgical procedure for intraocular pressure control. Cox proportional hazards multivariate analysis was performed to identify independent risk factors. RESULTS: African American race (P = .02), more than 2 preoperative glaucoma drugs (P = .02), and intraocular pressure greater than 14 mm Hg during the first postoperative week (P = .006) were identified as significant independent risk factors requiring suture release for filtration failure during the first postoperative month. Their significance was further confirmed by Kaplan-Meier survival analysis with Mantel-Cox log-rank test (P = .03, P = .02, and P = .001, respectively). CONCLUSIONS: African American race, more than 2 preoperative medications, and intraocular pressure greater than 14 mm Hg in the first postoperative week are major independent risk factors for initial filtration failure requiring suture release during the first month after primary glaucoma triple procedure. Presence of the risk factors may warrant a more aggressive antiproliferative regimen and/or earlier suture release.

Aged↗

Cytotoxic constituents from the roots of Anthriscus sylvestris.

Activity-guided fractionation of the roots of Anthriscus sylvestris resulted in the isolation and characterization of five cytotoxic compounds, deoxypodophyllotoxin (1), falcarindiol (2), and angeloyl podophyllotoxin (5) from the hexane soluble fraction and morelensin (3), bursehernin (4) from the chloroform soluble fraction. It is the first report of the occurrence of compound 5 in nature.

Antineoplastic Agents, Phytogenic↗

Spatial and temporal expression of UDP-galactose: ceramide galactosyl transferase mRNA during rat brain development.

We studied the expression of UDP-galactose: ceramide galactosyl transferase (CGT) mRNA in postnatal rat brains using an in situ hybridization technique. From P0 to P16, there was a defined temporal and spatial pattern to the earliest acquisition of CGT mRNA expression. In the forebrain, CGT mRNA-expressing (CGT+) cells were first detected in regions outside the subventricular zone around the lateral ventricle at P2. Cells in the external capsule, internal capsule and corpus callosum were later found to be CGT-positive. At P8 to P16, CGT+ cells were found in the thalamus, striatum, occipital and frontal cortex. In the case of midbrain and hindbrain, the first CGT+ signals were detected in the medullary raphe of the medulla oblongata at P0. CGT+ cells were subsequently located in the cerebellum, midbrain and pons from P4 to P16. That is, in regions closer to the areas in which CGT+ cells were first found, CGT mRNA expression was observed much earlier. These findings support the notion that there are at least two discrete waves of CGT mRNA signal expression in the forebrain and hindbrain.

Animals↗

Foldable posterior chamber intraocular lens implantation in the absence of capsular and zonular support.

PURPOSE: To implant foldable posterior chamber intraocular lenses in the absence of capsular and zonular support. METHODS: Case reports. In two patients, two eyes with aphakia, lack of capsular or zonular support, and contact lens intolerance underwent the implantation of a silicone and an acrylic foldable posterior chamber intraocular lens, respectively. RESULTS: In the two eyes, final visual acuity was 20/25 and 20/50, respectively. No intraoperative vitreal, retinal, or choroidal complications were noted. The postoperative recovery was rapid, and there was minimal induced astigmatism. CONCLUSIONS: The implantation of foldable posterior chamber intraocular lenses in aphakic eyes without capsular and zonular support may result in fewer intraoperative complications. It also allows for faster postoperative recovery and less postoperative astigmatism.

Acrylates↗

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy.

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.

Adrenergic alpha-Agonists↗

The additive effect of latanoprost to maximum-tolerated medications with low-dose, high-dose, or no pilocarpine therapy.

OBJECTIVE: To assess the efficacy of latanoprost additive therapy in patients with intraocular pressure (IOP) out of control while taking maximum-tolerated medications and to determine whether pilocarpine therapy has a dose-dependent adverse effect on the efficacy of latanoprost therapy. DESIGN: Noncomparative case series. PARTICIPANTS: Sixty-one eyes of 61 patients with chronic glaucoma with IOP out of control while receiving maximum-tolerated medications were treated with latanoprost additive therapy on a compassionate basis. MAIN OUTCOME MEASURES: Follow-up was up to 22 months with a mean of 13.9 +/- 5.7 months. Kaplan-Meier survival analysis with Mantel-Cox log-rank test was performed to determine the overall success of latanoprost additive therapy and to compare the success rates of high-dose pilocarpine, low-dose pilocarpine, and no pilocarpine therapies. The criterion for success was avoiding glaucoma surgery with IOP decrease of 20% or greater and final IOP less than 22 mmHg. The IOP change and its significance for patients satisfying and failing the criterion for success also were determined to assess the latanoprost additive therapy. In addition, a number of pretreatment variables, including pilocarpine therapy, were analyzed for a significant effect on the efficacy of latanoprost additive therapy using Cox proportional hazards regression analysis. RESULTS: Latanoprost additive therapy significantly lowered mean IOP by 3.9 +/- 5.5 mmHg at 3 months and by 3.5 +/- 5.8 mmHg at 12 months. The cumulative success rate of the latanoprost additive therapy was 70% at 1 month, 42% at 3 months, 40% at 6 months, and 30% at 12 months. Of the variables studied, only increased number of previous incisional glaucoma surgeries and IOP greater than 24 mmHg before latanoprost additive therapy were significant prognostic factors for failure of latanoprost additive therapy. Pilocarpine therapy in any dose had no significant effect. CONCLUSION: This study supports a trial of latanoprost additive therapy before glaucoma surgery in patients with IOP out of control while receiving maximum-tolerated medications irrespective of pilocarpine therapy and the pilocarpine dosage, especially when the number of previous incisional glaucoma surgery is less than three and the IOP is less than 25 mmHg.

Adult↗

Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.

OBJECTIVE: The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. INTERVENTION: Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. MAIN OUTCOME MEASURES: Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. RESULTS: The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). CONCLUSION: Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.

Aged↗

Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer.

Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 +/- 3.9 months vs 50.1 +/- 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 +/- 6.1 months vs 74.6 +/- 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor.

Adult↗

Endobronchial metastasis from stomach cancer.

A young woman presented with a dry cough present during the previous 4 weeks. A chest radiograph demonstrated diffuse interstitial infiltration in both lower lung fields. Fibreoptic bronchoscopic examination revealed multiple 2-3 mm elevated nodules on the bronchial surface and a mucosal biopsy showed extensive subepithelial infiltration of poorly differentiated adenocarcinoma without definite precancerous alteration in the overlying epithelium. Studies for the evaluation of primary tumour focus were performed. Oesophagogastroduodenoscopy showed advanced gastric cancer of Borrmann type III, and mucosal biopsy of the stomach showed poorly differentiated adenocarcinoma. The patient was treated three times with systemic chemotherapy, but her condition deteriorated. Three months after diagnosis, she died of complicated pneumonia. This is a rare case of endobronchial metastasis from stomach cancer. The stomach is an unusual site of endobronchial metastasis from extrathoracic primary malignancy.

Adenocarcinoma↗