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Biomedical subjects

J Mackey

Publications and source records attributed to J Mackey.

24 records · Page 2Linked to original sources
PubMed1993

Use of random primer extension for concurrent amplification and nonradioactive labeling of nucleic acids.

A method for efficient nonradioactive labeling of DNA with biotin using random primer extension has been developed. Under the conditions described, a significant amount of DNA synthesis occurs during incorporation of the nonradioactive label, resulting in amplification of the original template DNA. The effect of primer size, substrate concentration, enzyme concentration, and ratio of biotinylated nucleotide to normal nucleotide on the amount of DNA synthesis was determined. Amplifications of 10- to > 300-fold were attained, depending on the starting template concentration. Template may be varied from 1 to 500 ng per reaction. The size of the resulting biotinylated probes is 100-1000 nucleotides with a significant proportion in the 100-300 nucleotide range. The biotinylated probes were used to detect single-copy genes on Southern blot hybridizations and to identify specific loci in metaphase chromosome spreads by in situ hybridization followed by fluorescent detection with streptavidin-fluorescein isothiocyanate. Random primer amplification and labeling provides a convenient method for preparation of biotinylated probes from small amounts of template DNA.

Biotin↗
PubMed1977

A multivariate, osteological approach to Towa culture history.

Eleven cranial measurements on 14 archeological populations from the American Southwest support the archeologically derived reconstruction of Towa population movements. The supposed (linguistic) relationship between Pecos and the Towa speaking villages is questioned.

Arizona↗
PubMedDate not supplied

Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial.

PURPOSE: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid alpha-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder. METHODS: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure-free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age. RESULTS: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient. CONCLUSIONS: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Age Factors↗
PubMedDate not supplied

Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial.

PURPOSE: Zoledronic acid, a new and more potent bisphosphonate, was compared with pamidronate, the current standard treatment for patients with osteolytic or mixed bone metastases/lesions. PATIENTS AND METHODS: A total of 1,648 patients with either Durie-Salmon stage III multiple myeloma or advanced breast cancer and at least one bone lesion were randomly assigned to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. The primary efficacy endpoint was the proportion of patients experiencing at least one skeletal-related event over 13 months. RESULTS: The proportion of patients with at least one skeletal-related event was similar in all treatment groups. Median time to the first skeletal-related eventwas approximately 1 year in each treatment group. The skeletal morbidity rate was slightly lower in patients treated with zoledronic acid than in those treated with pamidronate, and zoledronic acid (4 mg) significantly decreased the incidence and event rate for radiation therapy to bone, both overall and in breast cancer patients receiving hormonal therapy. Pain scores decreased in all treatment groups in the presence of stable or decreased analgesic use. Zoledronic acid (4 mg) and pamidronate were equally well tolerated; the most common adverse events were bone pain, nausea, fatigue, and fever and < 5% of serious adverse events were related to the study drug. The incidence of renal impairment among patients treated with 4 mg of zoledronic acid via 15-minute infusion was similar to that among patients treated with pamidronate. CONCLUSIONS: Zoledronic acid (4 mg) via 15-minute intravenous infusion was as effective and well tolerated as 90 mg of pamidronate in the treatment of osteolytic and mixed bone metastases/lesions in patients with advanced breast cancer or multiple myeloma. (Can-

Antineoplastic Agents↗