[A 2-year-old male patient with congenital sideroblastic anemia and long-term chelation therapy].
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Anemia, Sideroblastic↗
Biomedical subjects
C Schmid
Publications and source records attributed to C Schmid.
Production of carrier proteins for insulin-like growth factors (IGFs) by rat osteoblastic cells. Regulation by IGF I and cortisol.
A bone-derived rat cell line, PyMS, releases IGF I and IGF carrier proteins which are similar to those found in rat serum. Western blot analysis of culture media conditioned by hormone-treated cells shows that growth hormone and IGF I stimulate and cortisol inhibits production of IGF carrier proteins in vitro. A glycosylated carrier protein species of 49-42 kDa is closely related to the subunits of the growth hormone-dependent carrier protein complex found in rat serum. In addition, rhIGF I rapidly induces a 32 kDa, non-glycosylated IGF-binding protein whose accumulation is markedly increased by cortisol.
Alkaline Phosphatase↗
[Abdominal fibromatosis in a 58-year-old male patient].
We report on a 58 year-old male patient, in whom abdominal fibromatosis occurred 3 years after laparotomy and irradiation on account of rectal cancer. Abdominal fibromatosis are very rare tumour-like fibrous lesions of the anterior muscular abdominal wall, mainly affecting fertile females. Men, however, are only rarely affected and without age preponderance. A hereditary or mutant generalized defect of growth regulation of fibrous tissue is considered to be the cause of this disease; moreover, trauma, hormonal effects and pregnancies often play a role as cofactors. Interestingly, there is a high correlation between abdominal fibromatoses and osseous lesions of the femur, mandible and thoracic, as well as lumbar spine. In our case thoraco-lumbar Scheuermann's disease was detected.
Abdominal Muscles↗
Biosynthesis of tetrahydrobiopterin: a sensitive assay of 6-pyruvoyltetrahydropterin synthase using [2'-3H]dihydroneopterin 3'-triphosphate as substrate.
Pyruvoyltetrahydropterin synthase catalyzes the release of tritiated water from [2'-3H]dihydroneopterin 3'-triphosphate. The tritiated water formed during the enzymatic reaction is separated from substrate by adsorption of the latter to activated charcoal. The sensitivity and specificity of the assay allows the determination of the enzyme in crude cell extract.
Adsorption↗
Spindle cell and pleomorphic lipoma: an immunohistochemical study and histogenetic analysis.
Twenty-two spindle cell lipomas and seven pleomorphic lipomas were investigated immunohistochemically in order to study the differentiation of the non-adipocytic elements. In all cases, neither spindle cells nor pleomorphic cells reacted with antibodies to a monocyte/macrophage antigen (MAC-387), fibronectin, laminin or type IV collagen. The absence of demonstrable basement membrane material argues against the possible prelipoblastic nature of these cells. With the antibody to S-100 protein, spindle cells were immunonegative, whereas pleomorphic cells sometimes revealed an intracytoplasmic weak to moderate staining reaction. In the light of what is known about the development of adipose tissue, our results would support the hypothesis of Bolen and Thorning (Am J Surg Pathol 1981; 5: 435-441) that spindle cell lipoma is composed of adipocytes and non-fat storing immature mesenchymal cells. It would appear that pleomorphic lipoma is similarly derived but that in some cases adipocytic differentiation is also abnormal. The characteristic clinical distribution of these two types of tumour may be of relevance in determining the cause of these unusual benign patterns of differentiation.
Adult↗
Hamartoma of the spleen with haematological symptoms.
We report the case of a 29 year old male patient with a splenic hamartoma suffering from infections, anaemia and thrombocytopenia. Shortly after surgical removal of the tumour the blood cell count was within normal range. Hamartomas of the spleen are rare benign tumour-like lesions composed mainly of vascular elements. Most of them remain small in size and asymptomatic and are therefore incidental findings at laparotomy or autopsy. However, occasionally they present with symptoms, among which haematological disturbances appear in very few cases; only 16 cases of splenic hamartomas with haematological symptoms are described in the literature. The major symptoms were anaemia and/or thrombocytopenia as well as frequent infections. After removal of these lesions the symptoms disappeared.
Adult↗
Intraoperative sonographic measurements of the internal mammary artery as a coronary bypass conduit.
Intraoperative visualization of coronary artery anatomy and morphology is an innovative method to evaluate patients undergoing coronary bypass surgery. With the high frequency ultrasonic technique we were able to measure diameters of internal mammary arteries (IMA) before and after dilatation. Probe dilatation of the IMA led to an increase of the IMA diameter of 46% while balloon dilatation was more successful resulting in an enlargement of 66%. The measurement of the flow rates showed similar changes (95% vs. 275%). Furthermore we were able to reproduce coronary artery lesions by echocardiography which could not be demonstrated in the angiogram.
Adult↗
Acute induction of sustained ventricular tachycardia: a new porcine model.
In this study we evaluated the possibility of initiating long-lasting ventricular tachycardias acutely, using isolated porcine hearts and thus avoiding an open-chest operation model. This set-up was designed especially to investigate defibrillating or antitachycardiac pacing devices, which terminate these malignant arrhythmias if medical treatment fails. The experiments were performed on 42 pigs, weighing 20-25 kg. After thoracotomy their hearts were removed and adapted to a Langendorff perfusion system. Supplied with their own blood, beating hearts were manipulated in three different ways: direct current impulses (4.5 V, 750 ms) or programmed ventricular stimulation, creation of a small myocardial infarction, and application of antiarrhythmic drugs (ajmalin, lidocaine, sotalol). Out of all possibilities the combination of ajmalin (mean concentration 0.041 micrograms/ml) and a small anteroapical myocardial infarction (3-6 cm2) along with direct current impulses (4.5 V), led to sustained ventricular tachycardias in the highest proportion (93%) of trials (P less than 0.001). The heart rate was 251 beats per minute on average. Lidocaine trials were less successful (53%), while programmed ventricular stimulation and sotalol failed to induce ventricular tachycardias. This study supports the evidence that the combination of ajmalin and a small myocardial infarction with direct current impulses is a reliable model for sustained ventricular tachycardias in isolated pig hearts. Although it is a rather artificial organ model, tachycardias can be induced acutely without any long-term pretreatment. Animal models based on chronic myocardial infarctions will therefore be unnecessary for the investigation of defibrillating systems and antitachycardiac pacing devices.
Animals↗
Adaptation of aldosterone biosynthesis to sodium and potassium intake in the rat.
The steroidogenic response of rat adrenal zona glomerulosa to stimulators is variable and depends on the activity of biosynthetic steps involved in the conversion of deoxycorticosterone (DOC) to aldosterone (Aldo). Corticosterone methyl oxidations (CMO) 1 and 2 are stimulated by sodium restriction and suppressed by potassium restriction. These slow alterations are accompanied by the appearance or disappearance of a specific zona glomerulosa mitochondrial protein with a molecular weight of 49,000. Induction of CMO 1 and 2 activities and the appearance of the 49 K protein can also be elicited in vitro by culture of rat zone glomerulosa cells in a medium with a high potassium concentration. The 49 K protein crossreacts with a monoclonal antibody raised against purified bovine adrenal cytochrome P-450(11 beta). The same antibody stains a protein with a molecular weight of 51,000 in rat zona fasciculata mitochondria and in zone glomerulosa mitochondria of rats in which CMO 1 and 2 activities have been suppressed by potassium restriction and sodium loading. The 51 K crossreactive protein was purified to electrophoretic homogeneity by chromatography on octyl-sepharose. In a reconstituted enzyme system, it converted DOC to corticosterone (B) and to 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) but not to 18-hydroxycorticosterone (18-OH-B) or Aldo. A partially purified 49 K protein preparation from zona glomerulosa mitochondria of rats kept on a low-sodium, high-potassium regimen converted DOC to B, 18-OH-DOC, 18-OH-B and Aldo. According to these results, rat adrenal cytochrome P-450(11 beta) exists in two different forms, with both of them capable of hydroxylating DOC in either the 11 beta- of the 18-position, but with only the 49 K form capable of catalyzing CMO 1 and 2. The adaptation of aldosterone biosynthesis to sodium deficiency or potassium intake in rats is due to the appearance of the 49 K form of the enzyme in zona glomerulosa mitochondria.
Adrenocorticotropic Hormone↗
Evidence for a direct effect of estrogen on bone cells in vitro.
Although the beneficial effects of estrogen in the treatment of postmenopausal osteoporosis are well documented, such effects were difficult to demonstrate in in vitro models. However, recent improvements in bone cell culture models (better defined osteoblastic cell populations, omission of Phenol Red from culture media) enabled several investigators to show albeit small, but reproducible, direct effects of estradiol in various osteoblastic cell types. Such findings were supported by the identification of low numbers of high-affinity estrogen receptors in bone cells derived from different mammalian species. The likely physiological relevance of the in vitro results is indicated by the specificity for 17 beta-estradiol, and the requirement for nanomolar concentrations of the hormone, consistent with a Kd of 0.6 nM for estradiol binding to its receptor [56]. In bone in vitro, estradiol may have anticatabolic effects by decreasing parathyroid hormone responsiveness, and anabolic effects by stimulating matrix synthesis and cell proliferation. Insulin-like growth factor-I is likely to be an autocrine/paracrine mediator for the anabolic effects and may, when associated with its binding proteins, effectively act in the bone compartment.
Animals↗
Phenol red mimics biological actions of estradiol: enhancement of osteoblast proliferation in vitro and of type I collagen gene expression in bone and uterus of rats in vivo.
Since osteoblasts are direct targets for estradiol in vitro, and Phenol Red has been reported to bear estrogen-like bioactivity, we investigated whether the pH indicator also mimicked the biological effects of estradiol on bone cells in vitro. We then asked whether estrogenic effects of Phenol Red could be observed in vivo, firstly on the uterus, and if so, whether Phenol Red could also effect bone in vivo. The proliferation of calvarial osteoblasts was stimulated by commercially available preparations of Phenol Red in a dose-dependent manner at 1.5-50 microM. This effect was not abolished in the presence of an antibody against insulin-like growth factor I. In addition, Phenol Red increased alpha 1 (I) collagen mRNA levels of osteoblasts in vitro. 17 beta-estradiol (1.5 micrograms) or Phenol Red (10 mg) administration to immature female rats (45-50 g) resulted in a weight gain of the uterus, and alpha 1(I) procollagen transcripts were more abundant in RNA prepared from uterus of drug-treated rats than observed in the control rats. Similarly, higher procollagen mRNA steady-state levels were observed in RNA prepared from parietal bones of Phenol Red or estradiol-treated rats compared to RNA from control rats. The data extend previous findings in vitro by demonstrating that Phenol Red also exerts estrogen-like effects in vivo. Moreover, we show that Phenol Red stimulates bone cells and, therefore, is likely to interfere at least in experiments designed to investigate estrogen effects on osteoblasts.
Animals↗
Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypophysectomized and diabetic rats.
The physiology of the specific serum binding proteins which constitute the main storage pool for insulin-like growth factors (IGFs) in mammals is still incompletely understood. We have, therefore, investigated the regulation of these proteins in (i) hypophysectomized (hypox) rats infused with recombinant human growth hormone (rhGH) or recombinant human IGF 1 (rhIGF I) and (ii) streptozotocin-diabetic rats infused with insulin or rhIGF I. The main carrier protein, a GH-dependent complex of apparent molecular mass 200 kDa, contains N-glycosylated IGF-binding subunits (42, 45, and 49 kDa) that differ in their glycosyl but not in their protein moiety. These subunits are lacking in hypox and diabetic rats. They are induced by GH and insulin, respectively, and appear in the 200-kDa complex. Infusion of rhIGF I induces the subunits in both states; however, only in diabetic, not in hypox, rats do they form the 200-kDa complex. Glycosylated carrier protein subunits do not appear before 8 hr of rhIGF I infusion. During that period, hypox rats may become severely hypoglycemic. After 16 hr, glycosylated subunits are clearly induced, and blood sugar values are normal. We conclude: (i) The N-glycosylated subunits of the 200-kDa complex reflect the IGF I status. (ii) IGF I may mediate the induction of these subunits by GH. (iii) Significant association to the 200-kDa complex occurs only in the presence of GH. It is likely that GH, but not IGF I, induces a component, which itself does not bind IGF, but associates with the glycosylated IGF-binding subunits. (iv) The glycosylated subunits protect against IGF-induced hypoglycemia and may be involved in tissue-specific targeting of IGFs.
Animals↗
Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects.
Insulin-like growth factor I (IGF-I) is an important mediator of growth hormone (GH) action and it appeared tempting to evaluate possible clinical applications. Recombinant IGF-I was infused s.c. at a dose of 20 micrograms/kg of body weight per hour during 6 days in two healthy adult subjects. Blood glucose and fasting insulin levels remained within normal limits and IGF-II levels were suppressed. In contrast to insulin, fasting C peptide levels were decreased. GH secretion was also suppressed by IGF-I. Our preliminary data allow us to distinguish between the effects of GH per se and those of IGF-I: GH causes hyperinsulinism, whereas IGF-I leads to decreased insulin secretion. Glomerular filtration rate, as estimated by creatinine clearance, increased to 130% of preinfusion values during the IGF-I infusion. Total creatinine and urea excretion remained unchanged. We conclude that IGF-I influences kidney function and, in contrast to GH, exerts an insulin-sparing effect. It may be speculated that the therapeutic spectrum of IGF-I is quite different from that of GH.
Adult↗
Extramedullary haematopoiesis in the thyroid gland.
The case of an 82-year-old female patient with extramedullary haematopoiesis in the thyroid gland due to agnogenic myeloid metaplasia is reported.
Adenoma↗
Potassium-induced aldosterone biosynthesis in cultured rat zona glomerulosa cells.
Rat adrenal zona glomerulosa cells lost their ability to produce aldosterone from either endogenous precursors or added deoxycorticosterone within 2 days of primary monolayer culture in a medium with a potassium concentration of 6.3 mmol/l. The lost corticosterone methyl oxidase I and II activities were totally regenerated when the ambient potassium concentrations was raised to 31 mmol/l. The conversions of deoxycorticosterone to 18-hydroxycorticosterone and aldosterone were completely restored by culture in a high-potassium medium also in zona glomerulosa cells of rats in which aldosterone biosynthesis had been suppressed by potassium restriction and sodium loading. However, these conversions were not induced in zona fasciculata-reticularis cells. The induction of aldosterone biosynthesis was associated with the appearance of a mitochondrial 49,000 protein cross-reacting with an antibody raised against bovine adrenal cytochrome P-450(11) beta. Thus primary cultures of zona glomerulosa cells are promising models for studying in vitro the molecular mechanisms of long-term adaptation of aldosterone biosynthesis to sodium and potassium intake.
18-Hydroxycorticosterone↗
Detection of the early steps of cadmium nephropathy--comparison of light- and electron-microscopical patterns with the urinary enzymes excretion. An experimental study.
Few data are yet available comparing the histological patterns of cadmium nephropathy with the values of urinary enzyme excretions, useful indexes of renal tubular damage. 40 Wistar rats, divided into four groups (A-D), were intoxicated with cadmium chloride (CdCl2) at 16 ppm in drinking water for 4, 16, 40 and 60 weeks, respectively. At the end of each period all the intoxicated rats and 5 controls were assessed for creatinine clearance, fractional excretion of gamma-glutamyltransferase (UfrGGT) and alpha-glucosidase (UfrAGL), indexes of anatomical tubular damage, and for fractional clearance of lysozyme (CfrLys), index of functional tubular damage. Thereafter, the rats were sacrificed and their kidneys examined with light and electron microscopy. Control rats and group A and B rats did not show any histological impairment. A widespread vesiculation of proximal tubular cells with mitochondrial and lysosomal alterations was found in the group C rats and was more evident in group D. The brush border never showed any damage in all groups in accordance with the finding of a normal excretion pattern of UfrGGT, an enzyme situated in this structure. The UfrAGL was increased only in group D rats (p less than 0.025), who showed the most severe anatomical damages. The CfrLys, an index of tubular function, was elevated in group C and D rats (p less than 0.02 and p less than 0.002, respectively). It was possible to detect the initial renal tubular damage.
Animals↗
Insulin-like growth factor I regulates type I procollagen messenger ribonucleic acid steady state levels in bone of rats.
RNA extracted from parietal bones of rats was analyzed for the abundance of type I procollagen mRNA by a dot hybridization assay using specific cDNA probes. Hypophysectomized rats, deficient in IGF I, have 4.1-fold lower steady state levels of mRNA encoding the alpha 1 chain of type I collagen when compared to normal rats of the same weight (120 g). Administration of recombinant human insulin-like growth factor I (IGF I) for 6 days restores bone collagen mRNA levels to normal, and a single sc injection of 100 micrograms IGF I results in a 1.9-fold increase of both alpha 1(I) and alpha 2 (I)chain mRNAs after 8 h. Studies with calvaria cells in primary culture and with a bone-derived cell line, PyMS, yielded similar results: IGF I treatment of these osteoblast-like cells for 24 h increased steady state levels of type I procollagen mRNAs. Thus, IGF I appears to contribute to osteoblast mRNA expression for both chains of type I collagen.
Animals↗
Inhibition of insulin degradation by insulin-like growth factors I and II in human hepatoma (HepG2) cells.
IGF-I infused at pharmacological doses in healthy men markedly decreases C-peptide levels, whereas insulin levels remain within the normal range. One possible explanation is decreased insulin removal. As the liver is the major site of insulin degradation, we studied insulin degradation by HepG2 cells in the presence of IGF. We found that IGF-I at a concentration of 130 nmol/l inhibits insulin degradation by HepG2 cells when the initial insulin concentration is 0.34 nmol/l. The effect of IGF-I on insulin degradation is dose-dependent and the rate of insulin degradation is dependent on the insulin concentration. IGF-II is 6 to 10 times more potent than IGF-I in inhibiting 125I-insulin binding to HepG2 cells and in protecting insulin from being degraded. Thus, IGF-I and IGF-II inhibit insulin degradation most likely by competing for binding at insulin binding sites of liver cells.
Carcinoma, Hepatocellular↗