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A Windebank

Publications and source records attributed to A Windebank.

5 recordsLinked to original sources

Insulin-like growth factor-II as a paracrine growth factor in human neuroblastoma cells.

The human neuroblastoma line, SK-N-SH, has been subcloned into SH-SY5Y, a neuroblast N cell line, and SH-EP, an epithelial Schwann S cell line. We have previously shown that SH-SY5Y neuroblastoma cells produce insulin-like growth factor II (IGF-II), which acts by an autocrine mechanism to stimulate cell growth. In the current study, we examined the effect of IGF-II on SH-EP neuroblastoma cells. Northern blot and reverse transcriptase-polymerase chain reaction analyses indicate that SH-EP cells do not produce IGF-I or IGF-II but express the type I and type II IGF receptors (IGF-IR and IGF-IIR). Cell surface expression of IGF-IR, assessed by fluorescence-activated sorting, was lower in SH-EP cells than in SH-SY5Y cells. Immunoprecipitation of IGF-IR, followed by anti-phosphotyrosine or anti-IGF-IR immunoblotting, demonstrated functional expression of these receptors in both cell types and confirmed the lower level of IGF-IR expression in SH-EP cells. IGF-II promoted SH-EP cell growth in the presence of low concentrations of calf serum (0.1-0.3%) or 10 ng/ml epidermal growth factor (EGF). IGF-II stimulation of SH-EP growth was eliminated by the IGF-IR blocking antibody (alpha IR-3) but not by an IGF-IIR blocking antibody. Stimulation of cell growth via this receptor was also indicated by the ligand specificity for IGF analogs and insulin (IGF-II approximately IGF-I approximately des(1-3)IGF-I >> insulin). These results indicate that in the presence of a permissive factor such as calf serum or EGF, IGF-II stimulates SH-EP cell growth via the IGF-IR. Collectively, these data suggest that within primary neuroblastomas, IGF-II may act as a paracrine factor to contribute to the promotion of S cell growth.

Base Sequence↗

Diabetic neuropathy.

The incidence and prevalence of diabetic neuropathies in Insulin Dependent (IDDM) and Non-Insulin Dependent (NIDDM) Diabetes Mellitus is not known because in previous studies the heterogeneity of diabetes and of the neuropathies was not taken into account, criteria for diagnosis and surveillance for neuropathy were variable, and studies were not prospective or population based. We have begun such prospective epidemiologic studies using a uniform algorithm for the classification of the diabetic disorders and uniform and validated approaches for the assessment of symptoms, neurologic deficits and various quantitative end-points of neural dysfunction. As regards cause, a key question which we are trying to answer is whether hyperglycemia and associated metabolic alterations affect neural tissue directly or whether there is an intervening tissue alteration between metabolic derangement and tissue change. Improved control of hyperglycemia does not appear to be associated with rapid neurologic improvement, possibly arguing for an intervening tissue alteration. The recently observed decrease in nerve oxygen tension and blood flow in streptozotocin diabetes suggests that an alteration of the nerve microenvironment may relate importantly to the cause of diabetic neuropathy.

Diabetes Mellitus, Type 1↗

Capillary number and percentage closed in human diabetic sural nerve.

The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei per capillary section, and percentage of capillaries closed were evaluated in transverse sections of fascicles of 45 control and 36 diabetic sural nerves. All controls and patients were prospectively studied to ascertain their diabetic and neuropathic status. An index of pathology was introduced and it was found to provide a sensitive and reliable measurement of the presence and severity of neuropathy. The number of capillaries and minimum intercapillary distance of diabetic nerves were not significantly different from those of controls (P greater than 0.05). Diabetic nerves exhibited a small but statistically significant increase in the number of endothelial nuclei per capillary that was positively correlated with the severity of neuropathy. The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls. Among diabetics, this percentage increased with the severity of neuropathy (P = 0.008). The two capillary abnormalities that have been demonstrated may play a role in the development of diabetic polyneuropathy.

Adult↗

Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.

We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption. Four were severely disabled; all improved after withdrawal. Weakness was not a feature of this condition, and the central nervous system was clinically spared. Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin.

Adult↗

The Mayo Clinic experience with plasma exchange in chronic inflammatory-demyelinating polyneuropathy (CIDP).

Fourteen patients with static or progressive CIDP with a neurologic disability score (NDS) greater than or equal to 50 were entered into a double-blind, stratified, 3-week trial of twice-weekly plasma exchange or sham plasma exchange. The end-points evaluated included the NDS, computer assisted sensory examination of the foot, and various attributes of nerve conduction of motor and sensory fibers of limb nerves. Of the 7 patients receiving plasma exchange, 4 improved by more than 10 points on the NDS (45, 32, 11, and 24 points) while 3 remained unchanged (2, -2, and -3 points). One patient, who did not appear to respond to either sham or plasma exchange, improved (100 points) with a 3 month alternate day course of prednisone. Of the 7 patients on sham exchange, 3 improved by more than 10 points (26, 15, and 16), 3 remained unchanged (-5, 4, and 8) and 1 was not able to complete the study due to cardiac tamponade. This preliminary trial will end with acquisition of 30 patients. It is too early to draw any conclusion from these studies other than that the double-blind study employed here is feasible and should provide information on the efficacy of plasma exchange in CIDP if its effect is prompt and large. The improvement which may be seen in the sham group appears to suggest that studies of efficacy require a double-blind design.

Adult↗