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Biomedical subjects

F Kelly

Publications and source records attributed to F Kelly.

At least 19 recordsLinked to original sources

Induction of hepatic and pulmonary caeruloplasmin gene expression in developing guinea pigs following premature delivery.

We have previously shown that mRNA for caeruloplasmin, the serum copper-binding protein, is not expressed in guinea-pig liver prior to birth and expression increases rapidly following parturition. To further study the regulation of caeruloplasmin in neonatal animals we have used 3-day preterm guinea pigs, delivered by caesarean section, to investigate mRNA expression in liver and lung. Within 12 h of premature birth, hepatic caeruloplasmin mRNA levels are significantly increased and remain elevated by 72 h. This induction of expression is accompanied by an increase in circulating levels of holoprotein. Even greater induction of caeruloplasmin mRNA was observed in premature animals maintained in 95% oxygen for 72 h, confirming an acute-phase response in prematurity. Studies of lung RNA showed that caeruloplasmin mRNA is expressed throughout development, with highest levels observed in adult lung. In the premature animals levels were significantly elevated 12 h after delivery, but then fell by 72 h to below those seen in normal term lung. Hyperoxia did not influence the pulmonary mRNA levels.

Age Factors

Basic fibroblast growth factor stimulates myelopoiesis in long-term human bone marrow cultures.

We previously showed that basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow (BM) stromal cells and significantly delays their senescence. In the present study, we demonstrated that low concentrations of bFGF (0.2 to 2 ng/mL) enhance myelopoiesis in long-term human BM culture. Addition of bFGF to long-term BM cultures resulted in an increase in (a) the number of nonadherent cells (sixfold), particularly those of the neutrophil granulocyte series; (b) the number of nonadherent granulocyte colony-stimulating factor (G-CSF)- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive progenitor cells; (c) the number of adherent foci of hematopoietic cells (10-fold); and (d) the number of progenitor cells in the adherent stromal cell layer. These effects were not noted with higher concentrations of bFGF (20 ng/mL). Thus, low concentrations of bFGF effectively augment myelopoiesis in human long-term BM cultures, and bFGF may therefore be a regulator of the hematopoietic system in vitro and in vivo.

Bone Marrow Cells

The prevalence of dementia in a total population: a comparison of two screening instruments.

Two short screening tests for dementia, the Information/Orientation (IO) sub-test of the Clifton Assessment Scale (CAPE) and the Mini-Mental State Examination (MMSE) were included in a survey of 1579 elderly people of a large general practice. All those scoring 21 and under on the MMSE, a one in two sample of those scoring 22, 23 and a one in ten sample of the remainder were investigated further using the Cambridge Examination for Mental Disorders of the elderly (CAMDEX). The prevalences of moderate to severe dementia and mild to severe dementia determined from the CAMDEX interview were 4.8% and 14.2%, respectively. For detection of moderate to severe dementia, a cut-point of 21/22 on the MMSE gave a sensitivity of 100%, specificity of 85% and an overall prevalence of 19.7%; mild to severe dementia was best detected by a cut-point of 23/24 giving a sensitivity of 89%, specificity of 81% and prevalence of 28.5%. A cut-point of 7/8 on the IO sub-test gave a sensitivity and specificity for detecting moderate to severe dementia of 87% and 97%, respectively, with a prevalence of 7.3%; for mild to severe dementia a cut-point of 10/11 gave a sensitivity of 67%, specificity of 94% and prevalence of 14.7%.

Aged

Zopiclone.

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Azabicyclo Compounds

Bacterial chemotaxis. Cell flux model, parameter measurement, population dynamics, and genetic manipulation.

In this paper, we summarized our recent efforts toward accomplishing four key goals important for control of microbial population dynamics in nonmixed systems: (1) derivation of a cell population flux model based on individual cell properties; (2) measurement of the population random motility and chemotaxis parameters appearing in this model using a simple experimental assay; (3) quantitative understanding of the effects of cell motility and chemotaxis properties on microbial population dynamics; and (4) manipulation of chemotactic responses by genetic modification.

Bacteria

Immortalization of early embryonic cell derivatives after the transfer of the early region of simian virus 40 into F9 teratocarcinoma cells.

F9 embryonal carcinoma (EC) cells were transformed using a recombinant plasmid carrying simian virus 40 (SV40) early genes linked to the promoter-enhancer region of the early transcription unit 1A (E1A) of adenovirus type 5. One clone of transformed cells, F9-K4B2, contained several integrated copies of the plasmid and expressed SV40 early genes (T antigens) only when it was induced to differentiate in vitro by the addition of retinoic acid and dibutyryl-cAMP. From the cell population positive for T antigen, it is possible to isolate permanent cell lines with high efficiency. Most of these cells exhibit stable traits that are characteristic of parietal endoderm. We also obtained another cell type which did not express the specific markers of either undifferentiated EC cells or endoderm cells; this type might represent a different stage of commitment in the differentiation of F9 cells. All clones are tumorigenic when injected into irradiated syngeneic mice, and they maintain their phenotype after successive passages in vivo as well as in vitro. The introduction of SV40 early genes into other EC cell lines and early mouse embryos appears to be a promising approach for the immortalization of early embryonic cells.

Animals

Karyologically identified homozygous tw18 embryos: extrauterine growth properties and transformation by SV40.

A method for identifying individual embryos from crosses segregating homozygous t lethals using the marker chromosome Rb7 is described and applied to the tw18 haplotype. In contrast to wild-type and heterozygous littermates, homozygous tw18/tw18 6 and 8 day embryos have very limited growth potentialities in vitro. When transplanted under the testis capsule, homozygous tw18 embryos (3, 6 and 7 day) produce teratomas at a much lower efficiency than heterozygous and wild-type embryos, and the rare teratomas thus obtained have limited growth potentialities when cultured in vitro. Upon transformation with SV40, however, permanent lines of cells of mesodermal origin, capable of myoblastic or adipocytic differentiation, have been obtained. This shows that the effect of the mutation on cell growth can be overcome by SV40 transformation.

Animals

The association of HLA with juvenile diabetes mellitus in Newfoundland.

In view of the reported variation in the association between HLA antigens and Juvenile Diabetes Mellitus (J.D.M.) among different Caucasian populations, we have undertaken a study of these antigens among 44 Caucasian Newfoundlanders and 135 matched controls. We have also studied the allotypic markers for Immunoglobulin G (Gm) and variants of C3 among 36 of these patients. We found that both HLA--B8 and B15 were increased among the patient group, resulting in a relative risk of 3.9 and 4.4 respectively. While these values are the highest to be described for J.D.M. among Caucasians, and fell outside the 95% confidence intervals for the combined relative risk calculated from published series, it is still possible that they can be accounted for by sampling. The combination of the two antigens increased the relative risk for J.D.M. in an additive fashion. Additionally, we also found that the combination of HLA B8 and B18, but not B15 and B18, also appear to act in an additive manner. The incidence of Gm allotypes and variants of C3 were not different in the J.D.M. group from those observed among controls.

Adolescent

Prolonged survival after immunotherapy (irradiated cancer autografts) or mammary cancers, assessed by a measure of therapeutic deficiency.

Sixteen women, twelve with stage 2 and four with stage 3 mammary cancers, were given autografts of irradiated cancer cells immediately after simple mastectomy and before postoperative radiotherapy, as a pilot trial with entry limited for ethical and operational reasons. Entry was based upon the presence of the poor prognostic features of tumor diameter exceeding 4 cm, fixation to skin or fascia or presence of axillary lymph nodal metastases. Actuarial survival curves for a period of six years show significant (p less than 0.01) prolongation of survival of the small autografted group (63% at six years) compared to that (30% at six years) of 139 ungrafted stage 2 mammary cancer patients treated by mastectomy and postoperative radiotherapy. The concept of deficiency of a treatment based upon person-years lived is introduced and used to analyze the data. The observations and analyses support the theoretical concept that irradiated autografts of cancers may sensitise residual cancer to subsequent conventional radiotherapy and in the process can activate systemic immunological restraints.

Adult

Preclinical warning of recrudescent mammary cancers by pregnancy-associated alpha-macroglobulin.

Nine of 30 mammary cancer patients developed metastases during 13-94 months after mastectomy. All 9 patients had elevated blood levels of pregnancy-associated alpha-macroglobulin (PAM) 1-21 months before conventional detection of metastases. Seven of the clinically well patients had PAM rises exceeding 90 per cent above the baseline and in 4 of these the PAM later fell to lower levels. PAM appears to have potential as an indicator of the growth of micrometastases.

Adult