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Biomedical subjects

M Lis

Publications and source records attributed to M Lis.

At least 19 recordsLinked to original sources
PubMed2002

Evidence for exercise-induced bone formation in premature infants.

We assessed the effect of a four weeks exercise training intervention on bone turnover markers in premature infants. Twenty-four very low birth weight premature infants were matched for gestational age, birth weight, gender, as well as for corrected age and weight at initiation of the study. Then the subjects were randomly divided into an exercise (n = 12) and a control group (n = 12). Exercise consisted of passive range of motion exercise with gentle compression of both the upper and lower extremities lasting 5 - 10 minutes each day, 5 days per week for 4 weeks. This protocol has been shown to increase bone mineral density in premature infants. Bone formation was assessed by measurements of circulating bone specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP). Bone resorption was determined by serum measurements of C- terminal cross-links telopeptide of type-I collagen (ICTP). Training led to a significant (P < 0.05) increase in weight gain (767 +/- 49 versus 586 +/- 24 gr in trained and control premature infants, respectively); and to a significant increase in BSAP (37.2 +/- 14.6 versus 4.1 +/- 8.4 % in trained and control premature infants, respectively). PICP increased also following exercise (34.6 +/- 18.9 versus 5.4 +/- 9.1 % in trained and control subjects, respectively), however, this increase was not statistically significant. Exercise led to a significant decrease in ICTP (-24.7 +/- 3.1 versus -5.5 +/- 5.4 % in trained and control subjects, respectively). A relatively brief exercise intervention was associated with a biochemical evidence of bone formation in very low birth weight premature infants.

Alkaline Phosphatase↗
PubMed2001

Measurements of bone turnover markers in premature infants.

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.

Aging↗
PubMed1999

Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir.

Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (-)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.

Animals↗
PubMed1997

Galactose oxidase-glucan binding domain fusion proteins as targeting inhibitors of dental plaque bacteria.

In order to inhibit the growth of bacteria present in the human oral cavity, a novel system which targets antimicrobial agents to dental plaque has been developed. This system involves a hybrid protein consisting of a peptide expressing the bactericidal properties of galactose oxidase (GAO) fused to the glucan binding domain (GBD) of the Streptococcus mutans glucosyltransferase-S enzyme. A gene encoding GAO from the fungus Fusarium sp. has been inserted into an Escherichia coli expression vector and fused to sequences encoding the GBD, which binds to the glucans synthesized by oral streptococci. Bacterial extracts expressing the hybrid protein were tested for their ability to target the GAO activity to an in vitro plaque model consisting of streptococcal cells bound to microtiter plate wells. The binding of the hybrid protein to the streptococcal cells through its GBD and the dependence of binding on the production of glucans by bacteria were demonstrated. Furthermore, killing of three different species of oral streptococci by bound hybrid protein in conjunction with the galactose-lactoperoxidase-iodide cytotoxic system has been demonstrated. These results suggest a novel strategy for controlling dental plaque formation as well as dental caries in humans.

Cariostatic Agents↗
PubMed1996

Amyloid precursor protein truncated at any of the gamma-secretase sites is not cleaved to beta-amyloid.

beta A4 secretion occurs upon processing of amyloid protein precursor (APP) by beta-secretase (N-terminus of beta A4) and gamma-secretase (C-terminus). To determine the sequence of these activities and the processing intermediate of beta A4, we expressed several truncated APP molecules in human HEK-293 cells. Immunofluorescence and biotinylation studies indicated that full-length APP or APP lacking the cytosolic domain both were located intracellularly, associated with the cell surface and secreted. APPs truncated after amino acid 40, 42, or 43 of beta A4 were not inserted into cell membranes, were found intracellularly but not on the cell surface, and were efficiently secreted into the culture medium. The secretion of APP truncated at amino acid 40 of beta A4 occurred without proteolytic processing. Neither beta A4 nor P3 (the product of the alpha-secretase) was secreted from any of the APP molecules truncated at the gamma-secretase sites. In sharp contrast to this, when the C-terminal 100 amino acids of APP were expressed (APP truncated at the N-terminus of beta A4), a robust beta A4 secretion was observed. Thus, the C-terminal fragment of APP produced by beta-secretase activity is likely to be the processing intermediate of beta A4.

Amino Acid Sequence↗
PubMed1995

Role of C-terminal direct repeating units of the Streptococcus mutans glucosyltransferase-S in glucan binding.

The C-terminal glucan-binding domain of the glucosyltransferase-S of Streptococcus mutans GS-5 contains five 65-amino-acid direct repeating units. A series of deletion derivatives of both the glucosyltransferase-S and its glucan-binding domain were constructed and analyzed. The results demonstrated that the four C-terminal direct repeating units constituted part of the minimum domain required for glucan binding.

Bacterial Adhesion↗
PubMed1995

Analysis of glucan synthesis by Streptococcus mutans.

Glucan synthesis by Streptococcus mutans GS-5 has been analyzed by examining the regulation of expression and structure-function relationships of the glucosyltransferases. Primer extension analysis of the gtf genes has identified the putative promoter sequences for these genes and indicated that the -10 sequences are similar to the Escherichia coli consensus sequence. Site-directed mutagenesis as well as deletion analysis of the enzymes have identified amino acid residues as well as functional domains which play important roles in glucan synthesis.

Adhesins, Bacterial↗
PubMed1992

Molecular genetic analysis of the catalytic site of Streptococcus mutans glucosyltransferases.

In the present communication molecular genetic approaches have been utilized to confirm the nature of the catalytic site of Streptococcus mutans glucosyltransferases (GTF)s. Site-directed mutagenesis was used to convert the putative sucrose binding Asp-451 of the GTF-I enzyme from S. mutans GS5 to Glu, Asn, and Thr. All three of the resulting mutated enzymes displayed no detectable sucrase or GTF activities. By contrast, mutation of nearby Asp residues did not markedly reduce enzymatic activity. The inactive enzymes also appear to bind acceptor dextrans as well as the parental enzyme. These results confirm the essential role of Asp-451 of the GTF-I from strain GS5 and analogous Asp residues in other related GTFs in enzymatic activity.

Amino Acid Sequence↗
PubMed1990

The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma.

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.

Adenocarcinoma↗
PubMed1985

Presence of high affinity dopamine receptors in estrone-induced, prolactin-secreting rat pituitary adenomas: a model for human prolactinomas.

Adenomatous cells obtained from a pituitary tumor induced in Fisher 344/Lis rats by the subcutaneous implantation of estrone (E1) were found to secrete large amounts of prolactin (PRL). The secretion of PRL was stimulated by thyrotropin-releasing hormone (TRH) and low concentrations of dopamine (DA), while micromolar concentrations of DA were inhibitory. High affinity binding sites for 3H-spiroperidol (3H-SPIR) were found to be present on the cells and to conform to the criteria of dopaminergic receptors. An adenylate cyclase (AC) present in the cells could be activated by a guanyl nucleotide and was inhibited by DA in the presence of guanosine 5'-triphosphate (GTP). Fractionation of the adenomatous cells by Percoll gradients identified two groups of cells capable of secreting PRL and bearing 3H-SPIR binding sites. These data indicate that this rat pituitary adenoma may be a model for human prolactinomas that might be utilized for the study of the mechanism of action of dopaminergic drugs.

Adenoma↗
PubMed1985

Effects of chronic bromocriptine treatment of an estrone-induced, prolactin-secreting rat pituitary adenoma.

Bromocriptine (BROM), a dopamine (DA) agonist, is commonly and successfully used for long-term treatment of human prolactinomas. We have studied the effects of chronic BROM administration to female 344 Fisher/Lis rats bearing an estrone-induced, prolactin (PRL)-secreting pituitary tumor recently characterized as a model for human prolactinoma. The animals were injected twice daily with BROM (2.5 mg/kg) or with diluent. After 1 month of treatment, the animals were sacrificed, and plasma collected and stored at -20 degrees C for PRL radioimmunoassay. The pituitary tumors were removed and tumoral mammotrophs dispersed enzymatically for studies of DA receptor binding and PRL release in vitro. BROM treatment significantly reduced tumor weight, cell size, rough endoplasmic reticulum, Golgi complexes and plasma PRL levels. [3H]-spiroperidol binding to tumoral mammotrophs was also evaluated. BROM induced a significant decrease in the number of DA binding sites without any changes in affinity. These results indicate that chronic BROM treatment of an animal model of prolactinoma induces tumor involution, reduction of PRL release and probably synthesis, and down regulation of dopaminergic binding sites.

Adenoma↗
PubMed1984

Estrone-induced, prolactin-secreting and dopamine-sensitive rat pituitary tumor.

Prolactin (PRL)-secreting rat pituitary tumors were induced in female Fisher 344/Lis rats by s.c. implants of estrone (E1) pellets. Tumor growth was relatively fast and reached about 100 mg within 2 months. Ovariectomy at the time of E1 implants seemed to accelerate the growth of the tumors. Tumor cells in primary culture produced mainly PRL, while growth hormone (GH) release was about 2% of PRL production and the release of some other pituitary hormones did not exceed 1% of PRL values. Tumor cells were found to have high-affinity dopamine (DA) receptors. The addition of DA in vitro at 10(-10) M concentration stimulated PRL release, while at 10(-6) M concentration it inhibited the release of the hormone by more than 50% of control values. Histological, immunohistochemical and electron microscopical studies demonstrated the tumor to be composed mainly of maximally stimulated mammotrophs.

Animals↗
PubMed1984

Effect of steroids on ACTH release from cultured pituitary cells of the rat.

Using a primary cell culture of rat anterior pituitary and corticotropin (ACTH) RIA, the effects of various steroids have been investigated. Dexamethasone inhibited the ACTH release stimulated by alpha-melanotropin and Pitressin (posterior pituitary extract), but did not influence the non-stimulated release. The effect of all the investigated steroids was significant; aldosterone exhibited a more marked inhibition than spironolactone. Simultaneous administration of aldosterone and spironolactone resulted predominantly in the manifestation of spironolactone action. A new effect of spironolactone has been demonstrated in vitro; the evaluation of its pharmacological importance requires studies in vivo.

Adrenocorticotropic Hormone↗
PubMed1983

N-terminal peptide of pro-opiomelanocortin in human amniotic fluid.

N-terminal peptide of pro-opiomelanocortin (N-POMC) was measured in the human amniotic fluid. At the gestational age of 16 to 20 weeks, the radioimmunoassay with three different antibodies demonstrated the respective values of 2.39 +/- 0.78, 4.69 +/- 2.27, and 5.92 +/- 2.66 ng/ml. These values are approximately 10 times higher than the measurements in the plasma of women at the corresponding gestational period. The amniotic fluid collected during the delivery had significantly lower concentrations of N-POMC than the amniotic fluid at 16 to 20 weeks' gestation. However, the plasma values of N-POMC had increased approximately three times when measured at delivery and compared with the plasma values at 16 to 20 weeks' gestation. Adrenocorticotropic hormone, measured simultaneously with N-POMC in some of the samples, showed changes similar to those in N-POMC. The N-POMC immunoreactivity from the amniotic fluid has the same retention time on reversed-phase high-performance liquid chromatographic separation as the peptide purified from the human pituitary gland, thus indicating the identity of both peptides.

Adrenocorticotropic Hormone↗
PubMed1983

Inhibition of corticotropin release in vitro by dexamethasone, aldosterone and spironolactone.

Dexamethasone, aldosterone and spironolactone inhibited the release of immunoreactive corticotropin (ACTH) from primary culture of the rat anterior pituitary cells. The steroids inhibited only the ACTH release stimulated by Pitressin and not the basal ACTH release by non-stimulated cells. On a molar basis, aldosterone appears to be the most efficient inhibitor of ACTH release while the effect of spironolactone is similar to the effect of dexamethasone. Simultaneous incubation with aldosterone and spironolactone inhibited the ACTH release to the same extent as spironolactone alone. This indicates that aldosterone's effect on ACTH release is also inhibited by spironolactone at the pituitary level.

Adrenocorticotropic Hormone↗
PubMed1983

Response of human aldosteronoma cells in culture to the N-terminal glycopeptide of pro-opiomelanocortin and gamma 3-MSH.

Cells were isolated from one of two adenomas from the adrenal cortex of a hypertensive patient with primary hyperaldosteronism. A primary culture of these cells responded with increased aldosterone secretion to gamma 3-MSH and human (residues 1-76) and porcine (residues 1-80) N-terminal peptides of pro-opiomelanocortin (POMC). EC50 was lowest for gamma 3-MSH, while maximal response was greater for both N-terminal peptides of POMC. We conclude that gamma 3-MSH derived from the N-terminal segment of POMC contains the active core of the aldosterone-stimulating activity of the N-terminal on these adrenal cells.

Adenoma↗
PubMed1982

Concomitant changes of ACTH, beta-endorphin and N-terminal portion of pro-opiomelanocortin in rats.

Radioimmunoassay developed to measure N-terminal peptide of pro-opiomelanocortin isolated from porcine pituitaries was used to measure changes in the concentration of immunoreactive material in rat plasma. The N-terminal peptide immunoreactive material decreased in plasma after hypophysectomy of both female and male rats below the level of detectability and substantially increased after adrenalectomy as compared to normal control rats. The same changes were observed when beta-endorphin and ACTH like immunoreactive material was measured. The primary culture of rat anterior pituitary cells released ACTH and N-terminal peptide-like immunoreactive material into the incubation medium. The results seem to indicate that the N-terminal immunoreactive material is a secretory product produced by the pituitary gland.

Adrenalectomy↗