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Biomedical subjects

M Kassem

Publications and source records attributed to M Kassem.

70 records · Page 4Linked to original sources
PubMed1992

Fetal antigen 2 (FA2) in human fetal osteoblasts, cultured osteoblasts and osteogenic osteosarcoma cells.

Immunohistochemical staining techniques used on an 11-week-old fetus showed that fetal antigen 2 (FA2) was present intracellularly in endochondral and perichondral osteoblasts, and the immunoreaction was extended into the adjacent bone matrix. Osteoclasts and chondroblasts were found to be FA2 negative. A granular perinuclear intracytoplasmic FA2 immunoreaction was found in cultured osteoblasts and osteogenic osteosarcoma cells, and immunoelectron-microscopical examination revealed a granular immunoreaction product in the rough endoplasmic reticulum. These findings indicate that FA2 is synthesized by osteoblasts and osteogenic osteosarcoma cells. A reaction of immunological identity was found between FA2 purified from second trimester amniotic fluid and serum-free supernatants of cultured osteogenic osteosarcoma cells. This shows that an antigen recognized by the anti FA2 antibody is secreted by these malignant cells. Thus, FA2 may represent a marker for altered bone metabolism, and have a potential in the classification of osteogenic osteosarcoma/chondrosarcoma.

Bone and Bones↗
PubMed1992

Quantification of fetal antigen 2 (FA2) in supernatants of cultured osteoblasts, normal human serum, and serum from patients with chronic renal failure.

Fetal antigen 2 (FA2) was found within the cytoplasm of osteoblasts and in osteoid material, in a bone biopsy with morphological changes of renal osteodystrophy. An ELISA technique for FA2 quantification was developed, and the specificity confirmed by comparison with electroimmunoassay. The intra- and interassay coefficient of variations (%) were 8.3 and 9.7 respectively, and the detection limit 0.0004 arbitrary units FA2/1 using second-trimester human amniotic fluid as reference (1 AU FA2/1). FA2 was detected in serum-free supernatants from osteoblast cultures. Following size chromatography, the FA2 distribution (two peaks eluted corresponding to Mw 30 kDa and 100 kDa) in serum from a patient with chronic renal failure complicated with secondary hyperparathyroidism and in human amniotic fluid were identical. Probably due to the detection limit, only one peak fraction (30 kDa) was seen in normal human serum. Significantly greater FA2 concentrations were found in sera (n = 14) from patients with chronic renal failure (median: 11.9 mAU FA2/1; range: 5.2-49.0 mAU FA2/1) compared to normal healthy individuals (n = 23) (median: 4.1 mAU FA2/1; range 2.4-9.4 mAU FA2/1) (P less than 0.00001). A close correlation was found between serum FA2 and alkaline phosphatase (R(s) = 0.761; P = 0.006), c-terminal fraction of PTH (R(s) = 0.872; P = 0.003) and intact PTH(1-84) (R(s) = 0.904; P = 0.011) in the haemodialysis patients. These data indicate that FA2 is synthesized by osteoblasts and may represent a new marker for metabolic bone changes.

Cells, Cultured↗
PubMed1992

Ultrastructure of human osteoblasts and associated matrix in culture.

The ultrastructure, as visualized by transmission electron microscopy, of cells obtained from human bone explants and subsequently cultured is described along with the electron microscopic appearance of the associated intercellular matrix. The cells were characterized as osteoblasts on the basis of immunohistochemical, enzymatic, and functional criteria. Although the osteoblasts could be cultured in standard culture media and always appeared singly, not forming syncytia, the cultures were eventually confluent and formed multilayers. The cells were fusiform or cuboidal with diameters ranging between 10-15 microns. The cytoplasm was characterized by numerous large mitochondria, and especially by a very prominent RER. The intercellular matrix was woven with collagen fibres surrounding large numbers of matrix vesicles. In areas with matrix vesicles, evidence for osteoblast activity, i.e. mineralization related to matrix vesicles, could be observed after incubation with beta-glycerophosphate. In conclusion, we provide evidence that human osteoblasts cultured in vitro synthesize collagen and produce a matrix with vesicles capable of initiating mineralization processes.

Calcification, Physiologic↗
PubMed1992

Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Adult↗
PubMed1991

Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals.

Suppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid-induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25-(OH)2D3 or prednisone. However, the two steroids have opposing effects: 1,25-(OH)2D3 increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25-(OH)2D3 can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 micrograms 1,25-(OH)2D3 and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 micrograms 1,25-(OH)2D3 + placebo in a crossover study. Seven normal subjects aged 23-36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25-(OH)2D3 serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p less than 0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p less than 0.01). The course of serum OC after administration of 1,25-(OH)2D3 + prednisone almost paralleled the course after placebo. We conclude that 1,25-(OH)2D3 and prednisone have opposing effects on serum OC.

Adult↗
PubMed1991

Diurnal rhythm in serum osteocalcin: relation with sleep, growth hormone, and PTH(1-84).

We examined the role of sleep, growth hormone (GH), and parathyroid hormone [PTH(1-84)] as regulators of the diurnal rhythm of the osteoblastic bone marker, serum osteocalcin (OC). Nine normal subjects were followed with hourly blood sampling during one 24-hour period with normal sleep pattern, and one 24-hour period with absolute sleep deprivation. We found that the rhythm in serum OC did not exhibit significant changes (P greater than 0.50). Serum OC (mean +/- SE) was 30.9 +/- 2.5 micrograms/liter during sleep (2330-0730 hours) versus 29.9 +/- 4.9 micrograms/liter during sleep deprivation (not significantly different). The serum GH rhythm was significantly different on the two occasions (P less than 0.01). A maximum GH peak (mean +/- SE) of 10.3 +/- 2.4 micrograms/liter occurred at 0136 hours +/- 6 minutes during sleep compared with a maximal peak of 7.6 +/- 1.2 micrograms/liter (P less than 0.01) at 0245 hours +/- 20 minutes (P less than 0.01) during sleep deprivation. During sleep (2330-0730 hours), mean serum GH was 3.61 +/- 0.60 micrograms/liter compared with 2.39 +/- 0.40 micrograms/liter during sleep deprivation (P less than 0.005). Small insignificant changes occurred in serum PTH (1-84) and serum ionized calcium during the two occasions. We conclude that sleep and GH are not acute controlling factors of the diurnal rhythm in serum OC and the role of serum PTH(1-84) remains unsettled.

Adult↗
PubMed1991

Antacid-induced osteomalacia: a case report with a histomorphometric analysis.

The case of a 75-year-old woman with severe osteomalacia secondary to ingestion of large amounts of an aluminum-containing antacid is reported. Biochemical analysis revealed signs of phosphate malabsorption and increased levels of bone markers (S-alkaline phosphatase and U-hydroxyproline). A 99mTc-bone scan revealed multiple areas of increased uptake. The patient was normocalcaemic, with normal serum levels of intact parathyroid hormone and 25-hydroxyvitamin D. Serum 1,25-dihydroxyvitamin D was high normal. A transiliac bone biopsy from the patient showed severe osteomalacia. Symptoms, biochemical parameters, bone scan and bone morphology were all normalized 1 year after stoppage of antacid ingestion and treatment with vitamin D2. calcium phosphate and sodium fluoride because of severe osteopeni. The characteristics of this condition and the role of phosphate depletion and aluminum in the pathogenesis of bone lesions are discussed.

Aged↗
PubMed1991

Formation of osteoclasts and osteoblast-like cells in long-term human bone marrow cultures.

A culture system for human osteoclasts is described. It is based on incubation of mononuclear marrow cells for three weeks in the presence of 1,25 dihydroxyvitamin D3. The resulting cells exhibited all the classic characteristics of osteoclasts. They formed a true syncytium with up to 25 nuclei per cell. The cells revealed a strong positive reaction for tartrate-resistant acid phosphatase and a ruffled border. When these cells were cultured on 100 microns thick human dentine slices for three weeks, typical resorption pits were formed. In the culture, alkaline phosphatase-positive osteoblast-like cells were formed in the vicinity of osteoclasts. This culture system permits studies of human osteoclasts and their interaction with osteoblast cell precursors in the human bone marrow.

Acid Phosphatase↗
PubMed1991

Formation of osteoblast-like cells from human mononuclear bone marrow cultures.

Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.

Adult↗
PubMed1991

[Familial hypercalciuric hypercalcemia].

Familial hypocalciuric hypercalcemia (FHH) or familial benign hypercalcemia is an autosomal dominant inherited disorder of calcium metabolism. It is characterized by lifelong asymptomatic hypercalcemia associated with a relative hypocalciuria and a tendency to hypermagnesemia. The biochemical features of this disorder are difficult to distinguish from mild primary hyperparathyroidism. Several patients have therefore been operated upon for hyperparathyroidism with no effect on calcium levels. The most important diagnostic criterion of FHH in a single individual is the demonstration of asymptomatic hypercalcemia in other family members including children. The pathophysiology of the disorder is unknown. A genetic defect of cellular calcium transport leading to a disturbed regulation of extracellular calcium by parathyroid glands and kidneys has been suggested. The hypercalcemia in this disorder is asymptomatic, usually without complications and does not require treatment. Partial parathyroidectomy has no effect on the hypercalcemia. However, it is important to diagnose this condition in order to avoid unnecessary neck explorations. Two complications have been described in some families: pancreatitis and neonatal primary hyperparathyroidism. The recommended management of these complications is total parathyroidectomy.

Adult↗
PubMed1989

[Volumetric analysis of the principal subdivisions of the brain of Gobioidei (Teleosts, Perciformes)].

The coral reef Gobioidei have very small olfactory bulbs. Compared to other teleost fishes, Gobioidei are all microsmic. The forebrain shows little variation; its size is the same as that of other perciform fishes, giving a good idea of the phylogenetic level of the Gobioidei. The mesencephalic tectum is very important in Gobioidei but very small in Trypauchen vagina, which is a burrowing species that is almost blind. The cerebellar body is small as in all other benthic fishes. The cerebellar valvula is also always small, especially the reflex lamina. The medulla oblongata is very large; the size of the vagal and facial lobes is correlated with the gustatory sense, an important feature of most Gobioidei.

Animals↗
PubMed1987

Echocardiography of the pericardium in pregnancy.

Echocardiography is a simple, accurate, and noninvasive technique for the study of the pericardium. Twenty-one normal pregnant women in their third trimester were examined with the Smith-Kline Ekoline 20 Ultrasonoscope. Twelve (57.1%) had normal echocardiography, and nine (42.9%) had pericardial effusion: four mild, three moderate, and two large in amount. There was no correlation between the amount of pericardial effusion and the red blood cell and white blood cell counts, hemoglobin level, total serum protein, serum albumin level, or albumin/globulin ratio. One patient with moderate effusion was followed for 50 days after delivery, by which time the effusion had resolved completely.

Adult↗
PubMedDate not supplied

Age- and sex-related changes in iliac cortical bone mass and remodeling.

Iliac crest bone biopsies were obtained from 64 normal individuals (41 women and 23 men) aged 19-90 (mean 48.2) years. Thirty-four were double-labeled with tetracycline before biopsy. The following variables were measured in all biopsies: biopsy core width (C.Wi), absolute (A.Ct.Wi) and fractional (F.Ct.Wi) cortical width, absolute (A.Cn.Wi) and fractional (F.Cn.Wi) cancellous width, cortical porosity (Ct.Po), osteon diameter (On.Dm), Haversian canal diameter (Ha.Ca.Dm), and wall thickness (W.Th). In the tetracycline-labeled biopsies the typical cortical remodeling cycle was reconstructed and the activation frequency was estimated. A negative cortical bone balance with aging was found in both sexes. In females F.Ct.Wi decreased (p < 0.02) with aging because of marrow expansion (p < 0.05). Furthermore, Ct.Po increased (p < 0.001) because of a decrease in W.Th (p < 0.01) and an increase in H.Ca.Dm (p < 0.001). In males the negative cortical bone balance with aging was exclusively caused by an increase in Ct.Po (p < 0.001) partially explained by an expanding H.Ca.Dm (p < 0.01). The On.Dm increased with aging (p < 0.01), but surprisingly, no fall in W.Th was observed. Reconstruction of the remodeling cycle did not reveal any significant difference between younger women and men. However, the activation frequency rose from 0.5 per year in premenopausal to 1.0 per year in postmenopausal women (p < 0.001), giving rise to a high turnover state, an increase in the remodeling space, and thereby the porosity in the cortical bone immediately after menopause. The present study has shown a reduction in cortical bone mass in elderly people, compared with younger, which may be explained by an age-related remodeling imbalance. This reduction is further increased in women in the postmenopausal state because of a postmenopausal accelerated bone turnover.

Adult↗
PubMedDate not supplied

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis.

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, aged 23-58 years, mean = 36.5 years), and 5 type II disease (5 men, aged 20-48 years, mean = 29.8 years). The normal controls (aged 23-48 years, mean 34.1 years) were recruited from the medical staff. The biopsies were immediately divided. From each patients, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy. The osteoclasts were markedly reduced in number and size in Type I disease (0.2 +/- .7 cells vs. 2.9 +/- 1.0 cells per 2.7 mm2 of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces. In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 +/- 2.3 cells vs. 2.9 +/- 1.0. cells per 2.7 mm2 of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Growth hormone (GH) and adult bone remodeling: the potential use of GH in treatment of osteoporosis.

Decreased osteoblastic activity seems to be of major importance in the pathogenesis of postmenopausal and senile osteoporosis and several lines of evidence suggest that GH may become useful in treatment of osteoporosis. GH stimulates osteoblastic proliferation and differentiation in vitro and increases production of Insulin-like Growth Factor-I and II (IGF-I and IGF-II) which both have profound stimulatory effects on osteoblasts and are important local regulators of bone remodeling. GH affects several other osteotropic hormones in vivo and increases bone turnover while the effect on bone mass is less pronounced and depends on the skeletal compartment. The few published clinical studies on the use of GH in treatment of osteoporosis have been inconclusive and well controlled studies of adequate size are greatly needed. Future research should focus on intermittent use of GH in combination with other hormones stimulating IGF production or antiresorptive agents.

Bone Remodeling↗