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Biomedical subjects

M Haq

Publications and source records attributed to M Haq.

34 records · Page 2Linked to original sources
PubMed1993

Biosynthesis and processing of endogenous parathyroid hormone related peptide (PTHRP) by rat Leydig cell tumor H-500.

We have examined in vitro the biosynthesis and processing of endogenous PTHRP in cultured rat H-500 Leydig tumor cells. Cells were grown to confluence and pulse labeled with [3H]Ile, 50 microCi/mL, in Ile free culture medium for 2 min to 6 h. In some experiments incubations were carried out in culture medium alone in the presence of 0.3 mM cycloheximide or 20 micrograms/mL unlabeled Ile. Cell extracts and culture media were analyzed by affinity chromatography employing an antibody directed against the bioactive NH2-terminal region, PTHRP(1-34), followed by gel-permeation or reversed-phase high-performance liquid chromatography. Incorporation of [3H]Ile into PTHRP in cell extracts increased over 20 min during pulse labeling and then remained constant throughout the incubation period up to 6 h. In contrast, the release of [3H]PTHRP into culture medium increased progressively over 6 h. Addition of cycloheximide or unlabeled Ile almost completely blocked incorporation of [3H]Ile into newly synthesised PTHRP. Three molecular forms of PTHRP were seen which comigrated with PTHRP(1-36), PTHRP(1-86), and PTHRP(1-141) standards in both chromatographic systems employed. After 20 min these species comprised approximately 63%, 30%, and 7% of newly synthesized PTHRP, respectively. These three molecular forms of PTHRP were observed both intra- and extracellularly, and no further metabolism of these species was seen after release into conditioned medium. Pulse-chase studies demonstrated a rapid decrease of newly synthesized PTHRP forms within cells after 20 min; there was, however, a progressive increase in [3H]PTHRP in conditioned culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Evaluation of three assays for the determination of serum total sialic acid.

There is increasing clinical interest in the measurement of serum total sialic acid (TSA). There are a number of methods available but with little data suggesting the preferred technique. We evaluated three serum sialic acid assays: the Warren assay, the Svennerholm assay, and a commercially available enzymatic method. The analytical performances of the three assays were similar, except that the enzymatic assay had a greater analytical range than the other assays and better precision at low and high serum sialic acid concentrations. The enzymatic assay was readily automated for use on a Cobas Bio analyser but was substantially more expensive than the other two methods.

Chemistry, Clinical↗
PubMed1993

Serum sialic acid and acute-phase proteins in hypertriglyceridaemic patients showing the Frederickson's type IIB phenotype.

1. We have shown that serum total sialic acid is elevated in hypertriglyceridaemic patients showing the Frederickson's type IIB phenotype in comparison with normal subjects (2.30 +/- 0.34 versus 1.92 +/- 0.32 mmol/l, P < 0.02). Lipid-associated sialic acid was also elevated in the hypertriglyceridaemic group in comparison with the normal subjects (0.60 +/- 0.09 versus 0.35 +/- 0.04 mmol/l, P < 0.001). 2. We measured five serum acute-phase proteins in the hypertriglyceridaemic patients and the normal subjects, namely alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, C-reactive protein and haptoglobin. Serum alpha 2-macroglobulin was significantly elevated in the hypertriglyceridaemic patients compared with the normal subjects (2.1 +/- 1.0 versus 1.5 +/- 0.55 g/l, P < 0.05) as was serum C-reactive protein (5.9 +/- 3.5 versus 3.5 +/- 1.9 mg/l, P < 0.05). There were, however, no significant differences in the serum concentrations of alpha 1-antichymotrypsin, alpha 1-acid glycoprotein or haptoglobin between the two groups. 3. There was a significant correlation between serum total sialic acid and serum alpha 1-antichymotrypsin, alpha 1-acid glycoprotein and haptoglobin (Spearman correlation coefficients 0.74, 0.50 and 0.76, respectively) in the normal subjects, and there was a significant correlation between serum total sialic acid and serum alpha 1-antichymotrypsin and alpha 1-acid glycoprotein (Spearman correlation coefficients 0.72 and 0.84, respectively) in the hypertriglyceridaemic patients.

Acute-Phase Proteins↗
PubMed1993

A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo.

We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production and on the development of hypercalcemia in Fischer rats implanted with the Leydig cell tumor H-500. Leydig cell tumors were implanted subcutaneously into male Fischer rats, which received constant infusions intraperitoneally of either 1,25(OH)2D3 (50-200 pmol/24 h), EB1089 (50-400 pmol/24 h), or vehicle for up to 4 wk. A control group of animals received similar infusions without tumor implantation. Plasma calcium, plasma levels of immunoreactive iPTHRP, and tumor PTHRP mRNA levels were determined as well as tumor size, animal body weight, and animal survival time. Non-tumor-bearing animals receiving > 50 pmol/24 h of 1,25(OH)2D3 became hypercalcemic, whereas no significant change in plasma calcium was observed in animals receiving < or = 200 pmol/24 h of EB1089. Tumor-bearing animals receiving vehicle alone or > 50 pmol/24 h of 1,25(OH)2D3 became severely hypercalcemic within 15 d. However, animals treated with low dose 1,25(OH)2D3 and all doses of EB1089 maintained near-normal or normal levels of plasma calcium for up to 4 wk. Additionally, reduced levels of tumor PTHRP mRNA and of plasma iPTHRP were observed compared with controls in both vitamin D- and EB1089-treated rats. Infusion of 50 pmol/24 h of 1,25(OH)2D3 and 200 pmol/24 h of EB1089 significantly reduced tumor volume by the end of experiment. The analogue but not 1,25(OH)2D3 substantially prolonged survival time in tumor-bearing animals with longer survival achieved at the highest dose, 400 pmol/24 h, of EB1089. These studies demonstrate that 1,25(OH)2D3 and a low calcemic vitamin D analogue are potent inhibitors of PTHRP production in vivo. Low calcemic analogues may therefore represent important alternative therapy for malignancy-associated hypercalcemia.

Animals↗
PubMed1993

Serum total sialic acid and lipid-associated sialic acid in normal individuals and patients with myocardial infarction, and their relationship to acute phase proteins.

Serum total sialic acid (TSA) has gained medical interest, particularly as a cardiovascular risk factor and it has been hypothesized that serum levels relate to serum acute phase proteins, some of which are sialylated. We assayed serum TSA and also lipid associated sialic acid (LASA) in 50 normal individuals (24 male) and 15 subjects (12 male) who had experienced a myocardial infarct. The mean serum TSA in the normal individuals was 2.05 SD 0.38 mmol/L (range 1.16-2.74) and the mean serum LASA was 0.70 SD 0.19 mmol/L (range 0.23-1.03). We also measured five serum acute phase proteins and found a good correlation between these and serum TSA: C-reactive protein, r = 0.52, P < 0.001, alpha-1-antichymotrypsin, r = 0.79, P < 0.0001, alpha-2-macroglobulin, r = 0.38, P < 0.01 and alpha-1-acid glycoprotein, r = 0.32, P < 0.05. A significant correlation between plasma TSA and plasma C-reactive protein (r = 0.47, P < 0.04) and also fibrinogen (r = 0.53, P < 0.04) was noted on day one following the myocardial infarction, whereas a significant correlation between plasma TSA and plasma alpha-1-antichymotrypsin (r = 0.51, P < 0.03) and also plasma alpha-1-acid glycoprotein (r = 0.64, P < 0.05) was found on day two following the infarction. Thus it would seem that serum TSA is at least in part related to some of the acute phase proteins in both healthy individuals and those having had a myocardial infarction.

Acute-Phase Proteins↗
PubMed1992

Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells.

Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host-tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through the sequential inoculation of bone marrow-derived carcinoma cells into the left ventricle and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells was significantly higher than the adhesion to other bone-derived cells, including nonendothelial bone marrow stromal cells (3.5x) and osteoblasts (1.7x). It was also significantly higher than the adhesion to rat fibroblasts (7x) and to hepatic endothelial cells (7.5x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone.

Adenocarcinoma↗
PubMed1992

Structural requirements for the growth factor activity of the amino-terminal domain of urokinase.

High molecular weight urokinase-type plasminogen activator (uPA) in which proteolytic activity was inactivated (diisopropyl fluorophosphate (DFP)-uPA), its amino-terminal fragment (ATF, amino acids (aa) 1-143), and fucosylated and defucosylated growth factor domains (GFD, aa 4-43) were tested for growth-promoting effects and binding in human SaOS-2 osteosarcoma cells and U-937 lymphoma cells. DFP-uPA, ATF, and both the fucosylated and defucosylated GFD were capable of competing with 125I-ATF for binding to both SaOS-2 and U-937 cells. DFP-uPA, ATF, and fucosylated GFD were also mitogenic in SaOS-2 cells and increased cell numbers. However, defucosylated GFD was nonmitogenic in SaOS-2 cells and did not stimulate cell proliferation, even though it bound to these cells in a manner equivalent to the fucosylated GFD. A nonglycosylated high molecular weight uPA expressed and purified from Escherichia coli inhibited 125I-ATF binding to SaOS-2 cells but was also nonmitogenic. No mitogenic activity was observed in U-937 cells treated with the uPA forms capable of eliciting a mitogenic response in SaOS-2 cells. Proteolytically prepared kringle domain (aa 47-135) and low molecular weight uPA (aa 144-411) did not compete for 125I-ATF binding and did not elicit any mitogenic response in either of the cell lines tested. In addition, tissue plasminogen activator (tPA), which has been shown to be homologous to uPA in its growth factor domain and is also fucosylated, did not inhibit 125I-ATF binding nor elicit any mitogenic response. These results demonstrate that the GFD, implicated in binding to the uPA receptor, is also responsible for growth factor like activity in SaOS-2 cells and that the fucosylation at Thr18 within this domain may serve as a molecular trigger in eliciting this response.

Binding, Competitive↗
PubMed1985

Evaluation of silicone elastomer catheters for long-term intravenous chemotherapy.

We evaluated the efficacy and the complications of 65 silicone elastomer catheters inserted percutaneously for long-term venous access for administration of chemotherapy, antibiotics, and blood products in patients with metastatic cancer. Treatments were administered either in the hospital or in the outpatient clinic, using a portable infusion pump. The median indwelling time of catheters was 238 days (range, two to 521). The projected duration of catheter function, when the electively removed catheters were censured, was 310 days. Twenty-three catheters were removed because of malfunction, while the remaining either were discontinued electively (20) or were functioning at the conclusion of the study (22). The problems necessitating removal of 23 catheters were inadvertent dislodgement from loose sutures (eight), mechanical damage to the catheters (four), sepsis (four), phlebitis (four), intraluminal blockage with a clot (two), and cellulitis (one). We conclude that silicone elastomer catheters are safe and reliable for extended venous access for cancer chemotherapy. They are easy to insert and remove and can be replaced with a guide wire without requiring surgical intervention.

Antineoplastic Agents↗
PubMed1984

In vitro suppression of DNA synthesis by a remission induction agent and its correlation with response in adult acute leukemia.

Fifty-three adult patients who presented with previously untreated acute leukemia had leukemic cells incubated in vitro with five doses of cytosine arabinoside (0.001-0.1 microgram/ml) and adriamycin (0.1-10 microgram/ml). Thymidine incorporation was measured in treated and untreated cells. Greater than 80% suppression of pretreatment thymidine incorporation after treatment with 0.004 micrograms/ml of cytosine arabinoside correlated with complete remission (CR) of the patient. A Mahalanobis' D2 score, which provides an index of the deviation of patient's in vitro drug response from the mean profile of responders, was calculated for each drug. Patients who had D2 values greater than 10 for Ara-C were less likely to respond to therapy. Patients with low D2s had rates of CR higher than predicted by the prognostic model employed at U.T.M. D. Anderson Hospital. However, unlike in our previous report, responders and non-responders were not clearly separable on the basis of the D2 value.

Adolescent↗
PubMed1970

Study of the effects of progesterone therapy on the stilboestrol-induced sensitivity of isolated uteri of hypophysectomized rats.

1. In intact rats progesterone (50 mg/kg) antagonized the effect of stilboestrol (100 mug/kg) on the vaginal smears and the uterine sensitivity. The uterine sensitivity to acetylcholine, oxytocin and 5-hydroxytryptamine was decreased by 6.8, 64 and 14.8 times, respectively, as compared with uteri removed after stilboestrol injections.2. Progesterone therapy in hypophysectomized rats also antagonized the effect of stilboestrol on the vaginal mucosa and on the uterine sensitivity to drugs. The sensitivity to acetylcholine, oxytocin and 5-hydroxytryptamine was decreased by 6.2, 50 and 14.5 times, respectively. Similar results were obtained on uteri removed from sham-hypophysectomized rats.3. On the basis of these results it is suggested that the hypophysis does not play any part in the desensitization of the myometrium to the oxytocic drugs and in the changes found in the vaginal mucosa after progesterone therapy.

Acetylcholine↗
PubMedDate not supplied

Ehrlichiosis infection in a 5-year-old boy with neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly.

Ehrlichiosis should be considered in the differential diagnosis of any patient with recent fever, pancytopenia, hepatosplenomegaly, and history of tick exposure. We present a previously healthy 5-year-old boy who was referred to the Hematology-Oncology Clinic to consider a bone marrow etiologic process after his pediatrician discovered progressive neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly accompanied by 2 days of fever. Bone marrow aspirate and biopsy were nonrevealing. Because of the history of a recent tick bite, a diagnosis of ehrlichiosis infection was considered and ultimately confirmed by IgG-specific serum testing. The patient's fever was treated symptomatically with acetaminophen, and symptoms resolved on their own without intervention. Ehrlichiosis is a tick-borne infection that occurs throughout the spring and summer, often causing findings that mimic a malignancy or serious hematologic disorder. The diagnosis should be considered in any person living in tick-infested areas and can be confirmed by polymerase chain reaction or serum antibody titers. Treatment with doxycycline can lead to rapid clinical improvement if the diagnosis is made early.

Anemia↗