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R P Boot-Handford

Publications and source records attributed to R P Boot-Handford.

45 records · Page 3Linked to original sources
PubMed1990

Effects of long-term diabetes and galactosaemia upon lens and retinal mRNA levels in the rat.

The levels of mRNAs encoding the alpha 1 chain of collagen IV and the B1 chain of laminin were assayed in the lenses and retinas of long-term (28-week) diabetic and galactosaemic rats in order to gain some insight into the effects on basement membrane (BM) synthesis in these tissues. mRNAs coding for beta-actin, glucose transporter protein and the alpha 2 catalytic subunit of Na+,K(+)-ATPase were also assayed to determine whether any effects on BM-coding mRNA levels were specific. Long-term diabetes had no significant effect on the levels of alpha 1 (IV) collagen mRNA but caused a significant reduction in the laminin B1 message in the lens. In the same samples, the level of the glucose transporter protein mRNA was found to be elevated significantly in the diabetic tissue, whereas the mRNAsen coding beta-actin and alpha 2 Na+,K(+)-ATPase were unaffected in comparison with age-matched controls. Long-term galactosaemia resulted in significant increases in the levels of all mRNAs assayed when expressed per micrograms total RNA used for each analysis. However, this effect appeared to be due to a specific loss of ribosomal RNA from these severely cataractous lenses. When related to the beta-actin mRNA internal control, the levels of mRNA in the galactosaemic lenses were very similar to that found in the diabetics. Laminin B1 mRNA levels were decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1990

Modulation of type X collagen gene expression by calcium beta-glycerophosphate and levamisole: implications for a possible role for type X collagen in endochondral bone formation.

Chondrocytes from the cephalic region of 18-day chick embryo sterna were cultured within type I collagen gels in the presence of increasing concentrations of calcium beta-glycerophosphate (Ca beta GP) (2.5 mM, 5 mM and 10 mM) or 2 mM levamisole. Addition of Ca beta GP produced an increase in type X collagen synthesis and when 10 mM Ca beta GP was used, mineral deposits were observed in the matrix elaborated by the chondrocytes. Measurement of mRNA levels of type II and type X collagen microgram-1 total RNA revealed that the level of alpha 1(II) mRNA decreased whereas the level of alpha 1(X) mRNA remained relatively constant in the presence of Ca beta GP. Thus, Ca beta GP appears to increase type X collagen synthesis by enhancing the rate of collagen type X mRNA translation. In levamisole-treated cultures the synthesis of type X collagen and its deposition within the matrix were inhibited. Measurement of mRNA levels micrograms-1 total RNA revealed that the level of alpha 1(II) mRNA increased whereas the level of alpha 1(X) mRNA was markedly decreased in the presence of levamisole. Consequently, it must be concluded that levamisole inhibits type X collagen synthesis by inhibiting type X collagen gene transcription. These results add support for type X collagen having an important role in the mineralization process and have demonstrated that type X collagen synthesis is probably regulated at the mRNA translational stage during chondrocyte hypertrophy.

Alkaline Phosphatase↗
PubMed1990

Streptozotocin-diabetes but not galactose-feeding increases the serum concentration of type IV collagen antigens in rats.

Serum concentrations of NC-1 (antigens related to the carboxy-terminal non-collagenous domain of type IV procollagen) were found to be increased significantly above normal in short-term (up to eight weeks duration) streptozotocin diabetic rats despite normal steady-state levels of the alpha 1 (IV) collagen mRNA previously reported in the kidneys of the same animals. The effect of long-term (11 and 28 weeks) diabetes on serum NC-1 was compared to the effects of galactose feeding (50% w/w) with and without aldose reductase inhibition (Statil). Serum concentrations in long-term diabetic animals remained significantly elevated above control levels at both time points. Normal NC-1 levels were found in galactosemic rats although this treatment is known to lead to capillary basement membrane thickening. Statil was proven to be effective in preventing polyol accumulation in sciatic nerve samples from diabetic rats but did not decrease the elevated serum NC-1 concentrations. These results suggest etiological heterogeneity in the development of different aspects of diabetic late complications and demonstrate no involvement of the polyol pathway in the events leading to increased serum NC-1 levels in diabetes.

Aging↗
PubMed1988

Increased steady-state levels of laminin B1 mRNA in kidneys of long-term streptozotocin-diabetic rats. No effect of an aldose reductase inhibitor.

The steady-state levels of mRNAs coding for two components of basement membranes, the alpha 1 chain of type IV collagen and the B1 chain of laminin, were measured in the kidneys of male CDF rats following the induction of diabetes with streptozotocin for periods of between 2 days and 28 weeks. The concentration of mRNA for the alpha 1 chain of type IV collagen/microgram of RNA decreased markedly with age in control and diabetic rats. The diabetic level was significantly lower than control after 2 and 11 weeks of diabetes. After 28 weeks, however, there was no significant difference from the levels in control animals. Treatment of control and diabetic rats with the aldose reductase inhibitor Statil (350 mg/kg diet) did not affect the levels of the mRNA for the alpha 1 chain of type IV collagen. In contrast to the continuous decline in the concentration of mRNA for the alpha 1 chain of type IV collagen, the level of mRNA for the B1 chain of laminin increased two-fold between 11 and 28 weeks after induction of diabetes. This increase occurred as aging of control rats reduced the level of laminin B1 mRNA by approximately 50%. Treatment with Statil had no effect on laminin B1 mRNA levels. In control rats there was no change in the ratio of the levels of mRNAs for laminin B1: alpha 1 (IV) collagen with age. The mean ratio was 0.97 +/- 0.10 at 19 weeks and 1.0 +/- 0.10 at 36 weeks of age. In diabetic rats there was a marked increase in the ratio from 0.85 +/- 0.11 at 19 weeks to 3.2 +/- 1.2 at 36 weeks of age. The increased abundance of mRNA for laminin B1 raises the possibility that increased synthesis of laminin contributes to the thickening and abnormal function of renal basement membranes in streptozotocin-diabetic rats.

Aging↗
PubMed1987

Steady-state levels of mRNAs coding for the type IV collagen and laminin polypeptide chains of basement membranes exhibit marked tissue-specific stoichiometric variations in the rat.

Rat retina, lens, and kidney from 8-week-old animals were assayed for the steady-state levels of mRNAs for four basement membrane components: The alpha 1 chain of type IV collagen, the alpha 2 chain of type IV collagen, the B1 chain of laminin, and the B2 chain of laminin. Each tissue exhibited markedly different ratios of the four mRNAs. The mRNA ratio for the alpha 1 chain of type IV collagen to the B1 chain of laminin varied from a value of 0.7 in retina to a value of 17 in lens. Also, the mRNA ratio for the alpha 1 chain to the alpha 2 chain of type IV collagen varied from 1.6 in retina to 17 in lens, and the mRNA ratio for the B1 chain to the B2 chain of laminin varied from 0.6 in lens to 2.9 in kidney. The mRNA coding for the alpha 1 chain of type IV collagen decreased in all three tissues as the animals increased in age from 8 to 16 weeks, with the rate of decline being greater in retina than in lens of kidney. The levels of mRNA coding for the B1 and the B2 chains of laminin decreased in the kidney between 8 and 16 weeks but at different rates. Comparison of mRNAs from kidney of rats over this time period showed that the ratio of alpha 1 to B1 remained relatively constant with age, whereas the ratio of B1 to B2 increased. One possible explanation for the results is that each tissue has elaborate, tissue-specific controls for translation that provide synthesis of basement membrane components in the same proportion, in spite of the varying steady-state levels of the mRNAs. A more likely explanation is that different tissues synthesize type IV collagen and laminin at different rates, and that even the subunit compositions of the type IV collagen and laminin molecules vary from tissue to tissue and in an age-dependent manner.

Animals↗
PubMed1983

The effects of long-term treatment of streptozotocin-diabetic rats with an aldose reductase inhibitor.

To test the possible involvement of the sorbitol pathway in the pathogenesis of retinopathy in long-term experimentally-diabetic rats, streptozotocin-diabetic and normal rats were dosed orally (50 mg/kg body weight daily) for up to 373 days with an aldose reductase inhibitor (ICI 105552) or a placebo. Long-term treatment with ICI 105552 (1,(3,4-dichlorobenzyl)-3-methyl-1,2-dihydro-2-oxoquinol-4-ylaceti c acid; sodium salt) markedly reduced the normal accumulations of sorbitol and fructose in the sciatic nerves (86 and 69% reductions) and seminal vesicles with coagulating glands (75 and 49% reductions). Thus, by these criteria, the inhibitor was as effective after several months of dosing as after three weeks. There was no evidence that treatment with this aldose reductase inhibitor had any protective effect against the development of pathological changes in the retina and kidney of these rats.

Aldehyde Reductase↗
PubMed1981

The effect of dietary fructose and diabetes on the rat kidney.

To determine whether the fructose moiety of sucrose or the lack of some factor essential for the integrity of the microvascular system is responsible for the development of sucrose-induced glomerulosclerosis, a series of diets with or without such a factor and/or fructose was fed to rats over a 6-month period. Consumption of diets containing or yielding fructose caused a significant increase in kidney weight in comparison with glucose-yielding diets. Diabetic animals also exhibited an increased kidney weight. The incidence of diffuse glomerulosclerosis, tubular damage and lymphocyte infiltration was increased in the starch-diabetic, fructose- and sucrose-normal groups. Diabetic MRC 41B- and normal MRC 41B/fructose-, MRC 41B-, glucose- and starch-fed rats (with the exception of one animal in the latter group) did not develop these kidney lesions. Sucrose-, in comparison with starch-ingestion was found to produce significant increases in blood fructose and kidney fructose-1-phosphate concentration. The results are discussed in relation to blood-glucose concentration, renal-fructose metabolism and the development of glomerular and tubular damage.

Animals↗