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D Small

Publications and source records attributed to D Small.

At least 73 records · Page 4Linked to original sources

Intranasal aerosolized insulin. Mixed-meal studies and long-term use in type I diabetes.

We assessed the efficacy of intranasal aerosolized insulin containing laureth-9 as a surfactant in patients with Type I diabetes by fasting studies in 8 patients, mixed-meal studies in 15, and long-term home use in 8. The intranasal insulin (1 U per kilogram of body weight in 1 per cent laureth-9) was rapidly absorbed (in 15 minutes); it lowered the plasma glucose level by 50 per cent in 45 minutes in fasting normal controls and by 50 per cent in 120 minutes in fasting diabetics. The glucose-lowering potency depended on the insulin dose and surfactant concentration. Nasal irritation was proportional to surfactant concentration, with great variability among subjects. After intranasal insulin used before meals (1 U per kilogram in 1 per cent laureth-9), the two-hour postprandial glucose level increased above before-meal levels by 38 mg per deciliter, as compared with 191 mg per deciliter after intranasal placebo in patients with Type I diabetes (P less than 0.05). An outpatient feasibility study examining three months of use of intranasal aerosolized insulin before meals as a supplement to Ultralente insulin revealed that the aerosol was well tolerated, with glycemic control (as indicated by the percentage of glycohemoglobin, home glucose measurements, and hypoglycemic reactions) comparable to that during a subsequent three-month period of conventional subcutaneous insulin treatment. The results suggest that intranasal insulin has potential as an adjunct to subcutaneous insulin in the therapy of Type I diabetes.

Absorption↗

The association of transcribed genes with the nuclear matrix of Drosophila cells during heat shock.

Using the transcriptional modulation afforded by heat shock, we found that the association of active genes with the nuclear matrix was not dependent on their level of transcription. Heat shock genes were matrix associated both before heat shock (when transcription was relatively low), and during heat shock (when transcription was greatly increased). Conversely, the cytoplasmic actin gene was matrix associated during normal growth conditions (when transcription was high) and during heat shock (when transcription was greatly decreased). Removal of greater than 99.7% of nascent RNA during preparation of the matrices did not affect these findings. Detailed examination of the cytoplasmic actin gene revealed that its matrix association was apparently mediated by multiple interactions near the 5' end of the gene.

Actins↗

Comparison by nuclear angiography of resting left ventricular function in insulin-dependent diabetic patients and normal subjects and the effect of diabetic control.

Resting left ventricular ejection fraction (LVEF) was measured by nuclear angiography in 28 type 1 (insulin-dependent) diabetic patients and 31 control subjects. None had any clinical evidence of cardiac disease. The influence of age, duration of diabetes, plasma glucose (PG) and glycosylated haemoglobin (HbA1) levels at the time of testing was also assessed in a larger group of 52 type 1 diabetic patients. Resting LVEF was significantly lower in the diabetic patients, 0.46 +/- 0.11 (mean +/- SD), compared with the control subjects, 0.53 +/- 0.07 (p = 0.02). No significant correlation was found between resting LVEF and age, duration of diabetes, PG or HbA1 levels. While LV function may be abnormal in diabetic patients the causes are still unclear.

Adolescent↗

The association of transcriptionally active genes with the nuclear matrix of the chicken oviduct.

Eucaryotic DNA is organized into a series of supercoiled loops that are anchored to the nuclear matrix. When these DNA loops are cleaved by endonucleases, the DNA sequences which remain associated with the nuclear matrix can be recovered and analyzed for their content of specific genes. Using restriction endonucleases to cleave the loops, we demonstrate that ovalbumin and conalbumin gene sequences are preferentially associated with the nuclear matrix of hen oviduct cells but not with the nuclear matrix of hen brain cells. Furthermore, we determined that several regions of the ovalbumin gene were independently attached to the nuclear matrix of hen oviduct cells. This included sequences located 3.8 kb downstream from the 3' end of the ovalbumin gene transcription unit. To determine whether the nuclear matrix association of the ovalbumin gene was regulated by hormones, we examined the oviduct cells of chicks that underwent primary estrogen stimulation, estrogen withdrawal and secondary estrogen stimulation. Ovalbumin gene sequences selectively dissociated from the chick oviduct nuclear matrix during estrogen withdrawal and reassociated with the nuclear matrix following restimulation.

Animals↗

Nonrandom distribution of repeated DNA sequences with respect to supercoiled loops and the nuclear matrix.

The DNA in a eukaryotic nucleus is arranged into a series of supercoiled loops that are anchored at their bases to the nuclear matrix. We have analyzed the DNA sequences that are closest to the matrix attachment points for their relative content of specific repeated sequences. Sequences were enriched (mouse satellite, human Alu family) or depleted (mouse EcoRI repeat, monkey alpha component), depending on the specific sequence and species examined. These results can be understood in terms of a nonrandom arrangement of DNA sequences with respect to nuclear DNA loops.

Animals↗

Variability in generation of anti-sheep erythrocyte plaque-forming cells from cultures of human peripheral blood. Influence of monocytes.

We have encountered two types of variability in the numbers of cells making antibodies in vitro to sheep erythrocytes (PFC) in pokeweed-stimulated human peripheral blood mononuclear lymphocytes (PBM). One is a variation in number of PFC generated by the PBM of one individual compared -o that of another, which is probably an in vitro counterpart to the well known individual variation in in vivo antibody responsiveness and presumed to be T cell controlled. The other variability is in numbers of PFC found in replicate tubes from a given individual. This variation is not T cell controlled, but rather is releated to the relative number of monocytes in the system. Enhancement by monocytes of the numbers of PFC generated is also demonstrated.

Animals↗

Erythropoietin: isolation by affinity chromatography with lectin-agarose derivatives.

Affinity chromatography using agarose-bound lectins was used to isolate erythropoietin from crude preparations of sheep plasma and human urinary erythropoietin. On the basis of previous estimates of the sugar content of the hormone, six lectins (wheat germ agglutinin, phytohemagglutinin, Ricinus communis 120, soybean agglutinin, concanavalin A, and limulin) were chosen for study. Only wheat germ agglutinin-agarose and phytohemagglutinin-agarose derivatives had significant affinity for erythropoietin. By use of wheat germ aggutinin-agarose columns, erythropoietin could be separated from over 95% of the initial starting protein, resulting in an 8-to 100-fold purification and a recovery of at least 40% depending on the source of the hormone. Affinity chromatography with agarose-bound lectins provides a simple rapid method for isolating erythropoietin from crude preparations of the hormone.

Animals↗