Publications by authors named "Wierenga W"

Background: Self-monitoring of blood glucose (SMBG), including self-regulation, is an important tool to achieve good glycemic control. However, many patients measure their glucose concentrations less often than is recommended. This study investigates patients' perspectives of SMBG and all relevant aspects influencing SMBG in patients with type 1 and insulin-treated type 2 diabetes.

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Aims: To evaluate the effects of transient hypoglycaemia on the first day of life in 75 healthy term large for gestational age (LGA) infants, born to non-diabetic mothers, on their neurodevelopmental outcome at the age of 4 years.

Methods: Screening for hypoglycaemia was performed 1, 3, and 5 hours after birth, and continued if blood glucose levels were low. Treatment with intravenous glucose for hypoglycaemia was started if hypoglycaemia was severe or symptomatic.

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Sera were obtained from 50 individuals infected with human immunodeficiency virus type 1 or from HIV-1-uninfected individuals before or after vaccination with recombinant gp160. These sera were evaluated for activity antagonistic to the cell-killing activity of the chimeric Pseudomonas exotoxin hybrid protein, sCD4-PE40. For these studies, Chinese hamster ovary (CHO) cells were transfected with a chimeric plasmid encoding the tat, rev, and envelope genes of HIV-1 and a cell line was selected for stable expression of the envelope glycoproteins at the cell surface (CHO-env).

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The binding of the antitumor drug CC-1065 has been studied with nuclear magnetic resonance (NMR) spectroscopy. This study involves two parts, the elucidation of the covalent binding site of the drug to DNA and a detailed investigation of the noncovalent interactions of CC-1065 with a DNA fragment through analysis of 2D NOE (NOESY) experiments. A CC-1065-DNA adduct was prepared, and an adenine adduct was released upon heating.

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Interferons (IFNs) have established activities as antivirals and inhibitors of viral and transplantable tumors. To establish whether IFNs or their inducers can affect induction of carcinogenesis in vivo, the bladder-specific carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was administered in the diet at 0.11 or 0.

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The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency.

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This study was undertaken in an attempt to evaluate the structure-activity relationship of pyrimidinones. Of 20 pyrimidinones tested, only those with a monohalogen substitution at the ortho- or meta-position of the phenyl moiety of the 2-amino-5-halo-6-phenyl-4(3H)-pyrimidinone and ABPP showed statistically significant synergism with cyclophosphamide (CY) against P388 leukemia. Therefore, ABMFPP, AIMFPP, and ABPP were selected for detailed therapeutic evaluation.

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In an extensive analysis of the antiviral and interferon-induction structure-activity relationship of 6-arylpyrimidinones we found that modifications at positions 1-4 of the pyrimidine ring resulted in a loss of activity. However, we uncovered interesting hypotensive and antiinflammatory activity with a series of N-substituted analogues, the results of which we report herein.

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Pyrimidinones are low-molecular-weight compounds which are inducers of interferon in several animal species. They have established antiviral, immunomodulatory, and antitumor effects. Four pyrimidinones as well as another potent interferon inducer, polyriboinosinic-polyribocytidylic acid, and beta-interferon were tested for effects on growth of the transplantable mouse bladder tumor (MBT-2).

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We have studied the chemopreventive effectiveness of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) in 7,12-dimethylbenz(alpha)anthracene (DMBA) induced rat mammary tumors. ABPP is a biological response modifier and has various biological activities, including interferon induction, immunomodulation, and antiviral and antineoplastic properties, both in vitro and in vivo. Fifty-day-old female Sprague-Dawley rats were randomized into two groups and all received 20 mg DMBA by gastric gavage.

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Interferon induction and antiviral activity was discovered with 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone. An analogue study incorporating a series of 2-amino-5-substituted-6-arylpyrimidinones revealed that the most potent interferon inducers were mono- and difluorophenyl analogues. These same analogues were also potent antiviral agents against Semliki Forest virus and herpes simplex type 1.

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An unusual acid-mediated rearrangement of o-nitrostyrene oxide afforded 1-(hydroxymethyl)-2,1-benzisoxazol-3(1H)-one which exhibited broad-spectrum antimicrobial and cytotoxic activity. A number of analogues were prepared by employing a modified zinc-reduction procedure on o-nitrobenzoate. Several of these analogues exhibited interesting antipseudomonal activity in agar and broth but were ineffective in vivo.

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CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. The drug binds covalently through N-3 of adenine and lies within the minor groove of DNA. Previous studies indicated that CC-1065 reacted with adenine in DNA to yield a thermally labile product that could be used to reveal its sequence specificity.

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N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated a time- and concentration-dependent release of granule associated beta-glucuronidase and lysozyme but not cytoplasmic lactate dehydrogenase from human neutrophils. Maximum discharge of lysome activity released is insignificant when cells are not preincubated with cytochalasin B prior to being exposed to FMLP (10(-10)-10(-7) M); although 11.2 +/- 1.

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Sequential treatment of the protected beta-D-arabinofuran[1',2':4,5]-2-aminooxazoline (2) with methyl isocyanate and diimidazole carbonyl afforded the 2,2'-anhydro-beta-D-arabinofuranosyl nucleoside, 6. Deprotection and hydrolysis yielded the corresponding arabinoside. Although the anhydronucleoside exhibited in vitro antiviral activity against herpes simplex type 1, it exacerbated the infection in vivo.

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