Hyperopia and choroidal neovascularization.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Steinmetz.
Explore the source record for details and available documents.
UNLABELLED: We previously reported that PRL production is significantly enhanced by a PRL-releasing/regulating factor derived from the posterior pituitary (PP). Specifically, the levels of PRL messenger RNA synthesis and release were dramatically increased in cocultures of GH3 and PP cells. The present objectives were to: 1) determine whether PP cells activate PRL gene transcription in a promoter- and cell-specific manner; 2) compare promoter activation by PP cells with that caused by selected substances that regulate the PRL gene; and 3) examine which region of the promoter (proximal and/or distal) mediates the action of the PP. In Exp 1, GH3 cells, transfected either with luciferase reporter plasmids containing a wild type PRL promoter, a GH promoter, or a glycoprotein alpha-subunit promoter, were cocultured with PP cells. Luciferase activity was used as an index for promoter activation. PP cells induced an 18-fold stimulation of the PRL promoter, as compared with a 2-fold stimulation of the GH promoter and no effect on the glycoprotein alpha-subunit promoter. In Exp 2, GH3 cells transfected with the wild type PRL promoter were cocultured with PP, anterior pituitary, uterine, or PC12 cells for 24 h. PP cells caused a 20-fold stimulation of the PRL promoter, whereas anterior pituitary cells showed a moderate 5-fold stimulation; uterine and PC12 cells caused minimal (< 2-fold) increases in luciferase activity. In Exp 3, GH3 cells were transfected with either the wild type PRL promoter (-2500 PRLluc) or with a truncated promoter (-425PRLluc) containing the proximal region only and were incubated with PP cells, TRH, vasoactive intestinal peptide (VIP), epidermal growth factor (EGF), or estradiol (E2) for 24 h. Compared with the induction of the wild type promoter, PP cells activated the truncated promoter by 30% only. Stimulation of the promoter by relatively high concentrations of TRH, VIP, EGF, or E2, either alone or in combination, was significantly less effective than that caused by PP cells. CONCLUSIONS: 1) PP cells stimulate PRL gene transcription in a tissue- and promoter-specific manner; 2) the magnitude of induction caused by PP cells far exceeds that caused by high concentrations of TRH, VIP, EGF, or E2; and 3) the distal enhancer region of the rat PRL gene is necessary for maximal responsiveness of the PRL promoter to PP cells.
BACKGROUND: There is increasing circumstantial evidence that the chemical composition of the deposits in Bruch's membrane influences the clinical outcome in age-related macular disease. In particular, it has been postulated that deposition of neutral lipids in Bruch's membrane may cause hydrophobicity and predispose to detachment of the retinal pigment epithelium and cause functional loss. METHODS: Analysis of the lipid extracted from Bruch's membrane of eye bank eyes from donors of different ages has been undertaken using thin layer and gas chromatography. No clinical information was available concerning any previous eye disease. RESULTS: It is shown that the lipid extracted increases with the age of the donor, and that the total quantity and ratio of neutral fats to phospholipids varies widely from one specimen to another from donors older than 60 years of age. The ratios of the different phospholipids imply that they are not derived from blood. CONCLUSION: The results are compatible with the concept of hydrophobicity developing with age in Bruch's membrane.
16 patients, presenting with squamous cell carcinoma in previously irradiated sections of the oesophagus, are described. Oesophagectomy could be performed in 2 patients, resulting in long-term disease-free survival (38 and 60 months after diagnosis). 14 patients were treated with palliative radiotherapy (external beam or intraluminal), oesophageal stenting, bougienage or chemotherapy. Although most patients previously received curative dosages of mediastinal irradiation, additional full courses of high-dose radiotherapy could be given on five occasions; no major complications were encountered and adequate palliation for up to 10 months was achieved. Similar results were observed after oesophageal stenting and/or bougienage. Relief of dysphagia following intraluminal radiotherapy or chemotherapy was only minimal (2 months or less). Median survival in the palliative treatment group was 6.5 months (range 2-27 months), which is in keeping with results observed in non-radiation-associated oesophageal carcinoma. We concluded that, in selected cases, both surgery and radiotherapy offer good prospects for patients with radiation-associated oesophageal cancer.
UNLABELLED: Recent evidence suggests that the posterior pituitary (PP), also called the neurointermediate lobe, regulates PRL release. We previously reported that cocultures of anterior pituitary and PP cells resulted in a 2- to 3-fold increase in PRL content and release. For this study we chose GH3 cells (a somatomammotroph tumor cell line) to determine whether coculturing GH3 with PP cells: 1) stimulates the release and cell content of PRL as compared with GH; 2) increases GH3 cell proliferation; and 3) affects PRL messenger RNA (mRNA) levels. Exp 1. GH3 cells (25,000 cells per well; 25K) were cocultured with PP cells (0K, 12.5K, or 25K) from male rats in serum-free media for 1, 2, 4, and 7 days; hormones were measured by RIA. Coculturing resulted in 5- to 10-fold increases in both media and cell PRL that were linear with time and dependent on the number of PP cells. In contrast, media GH increased only 1.5- to 2-fold, and GH cell content reduced by 75%. Exp 2. GH3, PP, and GH3 + PP cells were cultured for 1, 2, and 4 days and then incubated with [3H]thymidine for 5 h. The incorporation of [3H]thymidine in GH3 cells remained constant over time and showed a small, early increase in cocultures. In contrast, incubation of PP cells alone resulted in a 50- to 60-fold rise in [3H]thymidine incorporation from days 1-4 in culture. Exp 3. Cytoplasmic mRNA was determined by slot blot hybridization with 32P-labeled complementary DNA probes for PRL and GH. After coculturing 25K GH3 cells with 12.5K and 25K PP cells for 4 days, PRL mRNA levels increased 15- and 30-fold, respectively, whereas GH mRNA levels rose less than 2-fold. Neither PRL nor GH mRNA were detected in PP cells. CONCLUSIONS: 1) coculturing GH3 with PP cells dramatically stimulates PRL gene expression, synthesis, and release; 2) this response is specific for PRL, has little effect on GH, and is not due to increased GH3 cell proliferation; and 3) we speculate that a subpopulation of intermediate lobe cells, possibly with a proliferative capacity, is responsible for inducing these effects.
The refractive error of 186 eyes with choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD) was determined. It was found that the risk for the development of this form of ARMD increased with increasing degrees of hyperopia. The 96 patients afflicted with bilateral CNV were significantly older than the unilaterally affected patients (P = 0.027). Abnormal choroidal perfusion was identified in 66.4% of the fluorescein angiograms. These findings support the concept that hyperopic shortening in eyes afflicted with ARMD might cause secondary changes in the choroidal vasculature, predisposing them to choroidal neovascularization.
We examined the effect of foscarnet (Foscavir) in 15 AIDS patients with cytomegalovirus infection. Cytomegalovirus infection was presented as retinits (n = 8), colitis (n = 3), oral (n = 1) and perianal ulcers (n = 3) and pneumonitis (n = 1). Induction therapy with foscarnet showed a complete response in 9 and a partial response in 6 patients after a medium therapy of 3.5 weeks. Three patients showed progressive disease under ganciclovir and were treated subsequently with foscarnet. Main side effects were ulcers of the glans penis (n = 6) and a rise of creatinine (> 1.5 mg/dl; n = 4). Therapy was changed to ganciclovir because of renal toxicity in 1 patient receiving induction therapy with foscarnet. Within a period of foscarnet therapy between 5 and 9 months (median: 7 months) no clinical progression occurred. Medium survival after diagnosis of cytomegalovirus infection was 7.4 months. We describe our experience with foscarnet and compare treatment results of cytomegalovirus infection at certain locations.
Out of a total of 379 patients with ovarian carcinoma a rectosigmoid stenosis was detected in 44 (12%). A barium enema was available in 27 cases, which revealed a severe stenosis (less than 1/2 lumen open) in 23, with an average length of 17 cm (5-40 cm). Five characteristic types of stenosis were found: solitary stenosis (n = 6), large spherical impression (n = 6), multiple stenoses (n = 4), long narrow tract (n = 6) and a total obstruction (n = 5). Desmoplastic reaction with tethering and/or parallel folds (n = 16) or fixation and/or angulation (n = 18) were frequently found, but tumour invasion was rare (n = 3). A sigmoid resection (n = 1) or colostomy (n = 3) was seldom needed, due to beneficial response to combined therapy.
Explore the source record for details and available documents.
In a 15-year period at the Netherlands Cancer Institute, 27 patients were found with breast carcinoma metastatic to the stomach. Presenting symptoms were non-specific, mainly nausea, vomiting, dysphagia, epigastric pain, and melena. Endoscopy, performed in 22 of these patients, yielded a correct diagnosis in 13. Lobular rather than ductal breast carcinoma was the predominant source of gastric metastases in this series. Non-surgical treatment was rewarded by a favorable, palliative response in 32% of cases.
In a 15-year period at the Netherlands Cancer Institute, 17 patients were found with breast carcinoma metastatic to the colon or rectum or both. The presenting symptoms and signs were non-specific and included diarrhea, crampy pain, vomiting, and palpable tumor. Endoscopic examination, possible in only 10 of the 17 patients because of luminal obstruction, yielded a correct diagnosis in seven cases. Biopsy was confirmatory in five cases. Lesions metastatic to the colorectum originated predominantly in lobular carcinoma of the breast. Systemic hormonal or chemotherapy or x-irradiation, either alone or as an adjunct to surgery, produced a favorable response in over half the patients so treated.