PubMed HealthSearch

Biomedical subjects

J Thomson

Publications and source records attributed to J Thomson.

At least 19 recordsLinked to original sources

Treatment of postmenopausal osteoporosis with calcitriol or calcium.

BACKGROUND AND METHODS: Osteoporosis is a common problem whose management is controversial. To evaluate the efficacy and safety of calcitriol (1,25-dihydroxyvitamin D3) in the treatment of postmenopausal osteoporosis, we conducted a three-year prospective, multicenter, single-blind study in 622 women who had one or more vertebral compression fractures. The women were randomly assigned to receive treatment with calcitriol (0.25 micrograms twice a day) or supplemental calcium (1 g of elemental calcium daily) for three years. New vertebral fractures were detected by means of lateral roentgenography of the spine each year, and calcium absorption was measured in 392 of the women. RESULTS: The women who received calcitriol had a significant reduction in the rate of new vertebral fractures during the second and third years of treatment, as compared with the women who received calcium (second year, 9.3 vs. 25.0 fractures per 100 patient-years; third year, 9.9 vs. 31.5 fractures per 100 patient-years; P less than 0.001). This effect was evident only in women who had had five or fewer vertebral fractures at base line (second year, 5.2 vs. 25.3 fractures per 100 patient-years; third year, 4.2 vs. 31.0 fractures per 100 patient-years; P less than 0.0001). The groups also differed significantly in the number of peripheral fractures; 11 such fractures occurred in 11 women in the calcitriol group, whereas 24 occurred in 22 women in the calcium group (P less than 0.05). There was no significant difference between the groups in the incidence of side effects requiring withdrawal of treatment (8.6 percent in the calcitriol group vs. 6.5 percent in the calcium group). CONCLUSIONS: Continuous treatment of postmenopausal osteoporosis with calcitriol for three years is safe and significantly reduces the rate of new vertebral fractures in women with this disorder.

Aged

The inhibition of the oxidation of low density lipoprotein by (+)-catechin, a naturally occurring flavonoid.

(+)-Catechin inhibited the copper-catalysed oxidation of human low density lipoprotein (LDL) in a dose-dependent manner with complete inhibition at 20 micrograms/mL. The flavonoid at a concentration of 50 micrograms/mL also inhibited oxidation of LDL induced by the mouse transformed macrophage J774, human monocyte-derived macrophages and vascular endothelial cells isolated from human umbilical cords. LDL modified by copper-catalysed or cell-induced oxidation was endocytosed and degraded by human macrophages at a much greater rate than native LDL. LDL reisolated from copper or cell incubations in the presence of (+)-catechin was endocytosed and degraded at rates similar to native LDL. (+)-Catechin appeared to inhibit the uptake and degradation by macrophages of cell-modified LDL. The actions of (+)-catechin on cell-induced oxidation of LDL are consistent with the ability of flavonoids of similar structure to inhibit lipoxygenases and with a role for lipoxygenases in cell-induced modification of LDL in vivo.

Animals

Purification and adhesion receptor phenotype of ovine bone marrow-derived haemopoietic colony-forming cells.

Ovine haemopoietic progenitor cells that form colonies (CFC) in soft agar cultures were compared to more mature bone marrow cells for their level of expression of the adhesion receptor molecules ovine (ov) CD44, ov CD11a (LFA-1) and ov CD58 (LFA-3) as well as the 175-antigen using specific monoclonal antibodies. Ov CD44, ov CD11a and ov CD58 were expressed on all CFC of the myeloid (non-erythroid) series, whereas ov CD44 and ov CD11a expression was very low or absent from a small number of blast and erythroid series CFC. Within the mature non-erythroid population of myeloid cells, neutrophils retained a low level of expression of ov CD11a. Most CFC representing all lineages strongly expressed the ov CD44 antigen. In contrast, the majority of CFC lacked the 175-antigen, as did bone marrow lymphocytes, basophils and mast cells. This property of CFC was exploited in a negative selection technique using panning and immunomagnetic beads to select CFC from other bone marrow cells with a 116-125-fold enrichment, 12-14% purity and 29-40% yield. These results demonstrate that ovine CFC express some of the molecules necessary to allow adhesion to haemapoietic stromal cells and vascular endothelium in the tissues. Future studies will concentrate on the function of the adhesion receptor molecules in medullary and extra-medullary haemopoiesis and inflammatory cell development in sheep.

Animals

Nutrient intake and weight/height of Saudi patients at King Faisal Specialist Hospital in Riyadh, Saudi Arabia.

Nutrition surveys in the past showed some mild and moderate degrees of malnutrition in young children below 10 years of age. Deficiency diseases like anaemia were also reported. This survey is part of a large study of 1005 patients and sitters to see the relationship of diet and disease. Seven hundred and fourteen patients were subsampled and became the subject of this report to find out if the nutritional status of the children surveyed 10 to 15 years ago had any major change. It also presented some new information about nutritional status of older groups up to 96 years of age. It was found that weight for height and height for age of children up 14 years (except the girls GT 10-LE 14 years) could now compare with the US NCHS standard. The adolescent girls' (up to age 18) weight for height were statistically lower than the standard. Later in life, with some influences from the other female members of the household, and because of their limited activity, the women's weights were even higher than the standard. The adolescent males' weights were within standard, but the adult males' from age 18 were statistically lower than NCHS. Height for age from age 14 years for all were statistically lower than standard and was attributed to poor nutritional states in the past. Energy intakes of the adult males and iron intakes of the infants below one year of age were significantly lower than standard. Low energy intakes of the adult males confirm low weight for height performance. The same problem with iron of milk-fed infants of 10 to 15 years ago was still encountered. This shows that some traditional practice of infant feeding still persists despite the improvement in the quality of life and standard of living of the Saudis due to the economic upheaval created by oil. This survey emphasizes the importance of follow-up reports to see the changes in the people's state of health after a period of transition from economic dependence to affluence.

Adolescent

Reactivity of the workshop monoclonal antibodies with ovine bone marrow cells and bone marrow-derived monocyte/macrophage and mast cell lines.

The workshop monoclonal antibodies were tested by flow cytometry for reactivity against: (1) ovine bone marrow cells, (2) cultured bone marrow-derived monocyte/macrophage cell lines and (3) cultured bone marrow-derived mast cell lines. Both single and two-colour immunofluorescence tests were performed. The results of these analyses are presented and discussed.

Animals

Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group.

The Radiation Therapy Oncology Group in 1985 began a study of IORT plus external beam radiation therapy for patients with locally unresected, non-metastatic pancreatic cancer. Patients were treated with a combination of 2000 cGy of IORT and postoperative external beam radiation therapy to 5040 cGy in combination with IV 5-FU (500 mg/m2/day on the first 3 days of the external beam treatment). As patients were registered on study prior to exploration, it was expected that a number of patients would be excluded from further analysis at the time of surgery. Eighty-six patients were entered on study through 6/1/88 and analyzed through 4/90. Fifty-one patients were fully analyzable. Median survival time of the 51 patients was 9 months with an 18-month actuarial survival rate of 9%. Local control could not be adequately evaluated in this multi-institutional study. Major postoperative complications were not excessive and occurred in 12% of patients. Two patients had major late morbidity leading to death, one from duodenal bleeding and the second from biliary obstruction. Although this study does demonstrate the feasibility of IORT in a multi-institutional setting, it does not demonstrate any advantage of IORT over conventional therapy for this disease.

Carcinoma, Intraductal, Noninfiltrating

Effect of production method on the systemic clearance rate of a human monoclonal antibody in the rat.

Pharmacologic studies of human immunoglobulins (IgM) in non-primate animal models, whether directed toward efficacy or toxicity, rely on pharmacokinetic parameters to achieve optimal doses and schedules. In rodents, human IgMs have an effective circulatory half-life of 11 h and a plasma clearance rate of 0.044 ml/min/kg. Studies of a new group of human monoclonal antibodies (hMAb) specific for Gram-negative bacteria and endotoxin revealed an IgM molecule, hMAb-10058, which, when purified from tissue culture medium, exhibited a suprisingly short circulatory lifetime in rodents. Investigations into possible explanations for this short circulatory half-life resulted in the development of a simple and efficient method for producing hMAbs in the immunodeficient NIH-3 mouse (bg x nu x XID). This method of production of hMAb-10058 had dramatic effects on its half-life. Whereas hMAb-10058 produced in serum-free, defined medium had a clearance rate of 14.4 ml/min/kg and an effective half-life of 0.12 h, the same hMAb-10058 raised in mouse ascites had a decreased clearance rate of 0.092 ml/min/kg and an increased effective half-life of 12 h. This 100-fold enhancement of the hMAb's half-life was not affected by the purification process. Some potential molecular structures involved in the circulatory half-life of this hMAb are discussed.

Animals

Phenotypic analysis of ovine bone marrow cells using monoclonal antibodies and lectins.

Three major subpopulations of ovine bone marrow cells were identified by flow cytometry on the basis of differences in forward (FSC) versus right angle (SSC) light scattering properties and binding of monoclonal antibodies. Region 1 (low FSC, low SSC) contained erythroid series cells and some small lymphocytes. Region 2 (high FSC, low SSC) contained monocytes, myeloid blast cells, medium-large lymphocytes and virtually all of the progenitor/stem cells capable of forming colonies in soft agar cultures. Region 3 (high SSC) contained granulocytes at various stages of development, predominantly (greater than 90%) neutrophils and eosinophils. Using this technique it was possible to identify several cell-surface antigens on bone marrow cells of different lineages using specific monoclonal antibodies and lectins. Amongst the haemopoietic stem/progenitor cell population, immature colony-forming cells were leucocyte common antigen (LCA) negative while more mature colony-forming cells expressed LCA. A proportion of progenitor cells were MHC class I positive. This analysis is an important first step in characterising ovine haemopoietic cells for future studies on: the development of inflammatory cells, the migration of stem/progenitor cells in vivo and the tropism of pathogens.

Analysis of Variance

High-resolution structure of a mutagenic lesion in DNA.

The self-complementary dodecanucleotide d[CGC(m6G)AATTTGCG]2 (where m6G is O6-methylguanine), which contains two m6G.T base pairs, has been analyzed by x-ray diffraction methods and the structure has been refined to a residual error of R = 0.185 at 2.0-A resolution. The m6G.T mispair closely resembles a Watson-Crick base pair and there are very few structural differences between the m6G.T duplex and the native analogue. The similarity between the m6G.T base pair and a normal G.C base pair explains the failure of mismatch repair enzymes to recognize and remove this mutagenic lesion. A series of ultraviolet melting studies over a wide pH range on a related dodecamer indicate that the m6G.C mispair can exist in two conformations; one is a wobble pair and the other is a protonated Watson-Crick pair. The former, which predominates at physiological pH, will be removed by normal proofreading and repair enzymes, whereas the latter is likely to escape detection. Hence, the occasional occurrence of the protonated m6G.C base pair may explain why the presence of m6G in genomic DNA does not always give rise to a mutation.

Base Composition

Dermatoses in five related female carriers of X-linked chronic granulomatous disease.

Eight female members of a family with X-linked chronic granulomatous disease were identified. Five were shown to be carriers of the disease gene. Each of these female carriers of the gene had a history of skin eruptions. The identification of the carrier state is important as genetic counselling should be offered and the prenatal diagnosis of this disorder is possible.

Adult

Novel variants of human papillomavirus type 2 in warts from immunocompromised individuals.

Twenty cutaneous warts from I8 renal transplant recipients (RTR) and a single wart sample from a patient suffering from Hodgkin's disease were screened for the presence of human papillomavirus (HPV) sequences by Southern blot analysis. Thirteen samples were shown to contain HPV DNA sequences, one was identified as HPV-3, two as HPV-4, six as HPV-2 and four were unidentifiable by restriction digest analysis. HPV-3 was identified in the wart sample from the patient suffering from Hodgkin's disease. In the six samples in which HPV-2 was found, the viral genome showed polymorphism for the PvuII and PstI sites. Two PvuII patterns and one PstI pattern are novel.

Blotting, Southern