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Biomedical subjects

A Kaminski

Publications and source records attributed to A Kaminski.

13 recordsLinked to original sources
PubMed1995

In vitro cytokine profiles and their relevance to rejection following renal transplantation.

Graft rejection remains an important cause of renal allograft failure, despite improvements in immunosuppression and HLA typing. Although HLA matching is beneficial, ensuring an exact match it is often impractical. Thus, a reliable in vitro method for quantitating and qualitating alloreactivity is an important goal. In this study, we measured in vitro the cytokine secretion profiles of mononuclear cells from patients prior to renal transplantation by stimulating with anti-CD3 monoclonal antibody and suppressing with cyclosporine. Mononuclear cells from patients who subsequently developed acute cellular rejection secreted higher mean levels of interleukin (IL)-2 and gamma-interferon (IFN-gamma) than those from patients who had no rejection episodes. IFN-gamma secretion was significantly associated with rejection (P = 0.002), whereas IL-2 secretion did not quite reach statistical significance. There was no significant correlation between IL-4 levels and rejection. Although cyclosporine suppressed the secretion of both IL-2 and IFN-gamma, there was no difference in sensitivity to suppression between rejectors and nonrejectors. These results further emphasize the importance of the TH1 lymphocyte subset in renal allograft rejection. The IFN-gamma secretory capacity of alloreactive T cells may influence the outcome of a renal allograft by (1) activating graft infiltrating macrophages and/or (2) up-regulating HLA molecules on the graft.

Antibodies, Monoclonal↗
PubMed1995

Oligonucleotide-mediated modulation of mammalian gene expression.

The notion that oligonucleotides can modulate gene-specific expression was established more than a decade ago. Recent advances in molecular genetics have broadened the armamentarium used to manipulate gene expression in biological systems including triplex DNA, antisense RNA/DNA, and ribozymes (catalytic RNA). These oligonucleotides demonstrated important early application to the elucidation of cellular signaling pathways. More recently, studies with these agents have probed their utility as potential therapeutic agents, especially in the realm of cancer. With the implementation of gene therapy in early clinical trials, oligonucleotide-mediated suppression of gene expression has emerged as an important strategy for gene therapy. This review will discuss the current knowledge in this field, focusing on the biology of triplex DNA, antisense oligonucleotides, and ribozymes.

Animals↗
PubMed1995

gamma-interferon production in atopic dermatitis shows differential modification by phosphodiesterase and prostaglandin inhibition.

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear leucocytes (MNL) is reduced in atopic dermatitis (AD) patients. This may be related to abnormalities in second messenger systems, and increased prostaglandin E2 (PGE2) release from monocytes. We compared the effects of manipulating the second messenger activity using the phosphodiesterase (PDE) inhibitor Ro 20-1724, dibutyryl cyclic adenosine monophosphate (cAMP), and cyclooxygenase inhibition of PGE2, on IFN-gamma production by cultured MNL from AD patients (n = 9) and normal controls (n = 10). Ficoll-Hypaque-separated MNL were cultured for 48 h with OKT3 stimulation, and cAMP, Ro 20-1724, or indomethacin. Supernatants were analysed for IFN-gamma by ELISA. Basal IFN-gamma was lower in AD patients, and the increase in IFN-gamma production with OKT3 was 6.5-fold greater in control subjects than patients with AD. Culture with indomethacin significantly enhanced OKT3-stimulated IFN-gamma production in both groups, whereas OKT3-stimulated IFN-gamma production was abolished with dibutyryl cAMP. IFN-gamma production was significantly lower with Ro 20-1742 in AD than in normal controls. We have shown reduced IFN-gamma release from unstimulated and stimulated MNL in AD patients compared with normal controls. The addition of indomethacin increased IFN-gamma production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN-gamma release from AD MNL was more sensitive to the inhibitory effects of PDE, and this may be due to increased PDE activity, or the hyperdynamic cAMP system present in atopics.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Sensitivity of the mystacial vibrissae of harbour seals (Phoca vitulina) for size differences of actively touched objects.

We studied the capability of one male and one female harbour seal Phoca vitulina to discriminate diameter differences of circular discs by means of active touch with their mystacial vibrissae. To prevent the animals from perceiving visual information, they were blindfolded during trials. In a two-alternative forced-choice procedure, the seals were required to choose the larger of two Perspex discs. Weber fractions c (the ratio of the lowest diameter difference detected by the seals on 75% of occasions to the starting disc diameter D, delta D/D = c) were determined for three standard discs (diameters 1.12cm, 5.04cm and 8.74cm) by the psychophysical method of limits. While the seals achieved Weber fractions of 0.29 (male) and 0.26 (female) at the smallest standard disc, their performance improved with increasing disc size, resulting in an approximately constant Weber fraction of 0.13 (male) and 0.08 (female) for the two larger standard discs. The difference in performance between the two seals did not reflect a real difference in sensitivity, but may best be explained by a difference in choice behaviour. As a measure of tactile acuity, the Weber fractions obtained for the larger standard discs indicate that harbour seals can use their mystacial vibrissae as efficiently for active touch as monkeys use their hands.

Animals↗
PubMed1994

The RNA-binding properties of protein synthesis initiation factor eIF-2.

Protein synthesis initiation factor eIF-2 bound ATP in the presence or absence of Mg2+ ions. ATP impaired the binding of GTP or GDP to eIF-2. However, excess GTP did not significantly decrease the binding of ATP to eIF-2, suggesting eIF-2 has distinct ATP and GTP binding sites. Highly purified eIF-2 can bind mRNA, and this did not require the mRNA to be capped. mRNA binding was saturable, and maximal binding corresponded to about 0.4 mol mRNA bound per mol eIF-2. GTP, and, at lower concentrations, GDP, inhibited the binding of mRNA to eIF-2. In addition, ATP and other nucleoside triphosphates decreased mRNA binding. The implications of these findings for the structure and function of eIF-2 are discussed. Preparations of eIF-2 deficient in the beta-subunit showed reduced ability to bind mRNA, suggesting that while it is not essential for mRNA binding, this subunit is involved in the interaction. Consistent with this is the observation that ultraviolet crosslinking of mRNA to eIF-2 resulted primarily in labelling of the beta-subunit. Subsequent analysis revealed that mRNA was cross-linked to the C-terminal region of eIF-2b which contains a putative Zn-finger structure.

Adenosine Triphosphate↗
PubMed1992

Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs.

The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and -D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation.

Alkaline Phosphatase↗
PubMed1990

Initiation of encephalomyocarditis virus RNA translation: the authentic initiation site is not selected by a scanning mechanism.

The authentic initiation site on encephalomyocarditis virus (strain R) RNA is the 11th AUG codon (at nt. 834) from the 5' end of the viral RNA, the downstream of the two AUGs in the sequence....ACGAUGAUAAUAUGGCC... In order to assess the role of ribosome scanning in the selection of the correct initiation site, transcripts of a construct comprising the viral 5' noncoding sequence fused to a reporter gene were translated in vitro and the relative frequency of initiation at these two AUG codons, AUG-10 and AUG-11, was assayed. When deletions from the 5' end were made that retained less than 100 nucleotides of the viral 5'-noncoding sequence, initiation was highly cap-dependent and AUG-10 was utilized in preference to AUG-11, consistent with the scanning ribosome model. On the other hand, when the constructs included the entire 574 nt. segment of the 5' noncoding region situated between the poly(C) tract of the virion RNA and nt. 834, initiation was cap-independent and occurred exclusively at AUG-11, with negligible use of AUG-10. These results suggest that structural features of the 574 nucleotide segment cause initiating ribosomes to bind directly to AUG-11, without scanning the immediate upstream sequences that include AUG-10.

Base Sequence↗
PubMed1990

The novel mechanism of initiation of picornavirus RNA translation.

The initiation of translation of picornaviral RNAs takes place by an unusual mechanism whereby ribosomes bind directly to an internal site rather than scan the RNA from the 5'-end. This internal entry mechanism requires a 450-nucleotide segment of the picornavirus 5'-untranslated region. The ribosome binds initially to a site at the 3'-end of this segment, and then may scan the RNA to reach the authentic initiation site. This novel mechanism may be of relevance to the translation of some cellular mRNAs.

Base Sequence↗
PubMed1975

A vision care module within a prototype HMO.

The Health Maintenance Organization (HMO) concept is dedicated to the prevention of disease and disability. Organizations incorporating this concept must include vision care if complete service is to be offered. Described in this paper is one such HMO, Group Health Cooperative of Puget Sound, with details of the successful integration of optometric vision care into this medically oriented, multidisciplinary setting.

Health Maintenance Organizations↗