The transplantation of tissue containing dopamine-producing cells into the mammalian central nervous system is an emerging treatment for Parkinson's disease, despite relatively poor survival of implanted tissue. Recent evidence has suggested that Cytodex microcarriers enhance the survival of dopaminergic rat chromaffin cells transplanted into the rat striatum in the absence of immunosuppression. The current study was undertaken to evaluate the survival of rat and human fetal ventral mesencephalic neurons (VM) implanted alone or after attachment to microcarriers in the striatum of rats without immunosuppression. Rat fetal VM neurons demonstrated enhanced survival in the rat striatum when transplanted on microcarriers, compared to their transplantation alone during the 3-mo period examined in the present study. Transplants of human fetal VM neurons on microcarriers also survived remarkably well in the rat striatum without systemic immunosuppression. In contrast, human fetal VM cells transplanted alone into the rat striatum did not survive without systemic immunosuppression. There was no evidence of TH fiber sprouting in the vicinity of any transplant site. These data indicated that Cytodex microcarriers provide enhanced survival of both rat allograft and human xenograft fetal mesencephalic cells in the rat striatum without the necessity of systemic immunosuppression, perhaps by inducing a unique neuron-glia environment.

Animals↗

PubMedDate not supplied

The Massachusetts experience.

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Charities↗

PubMedDate not supplied

Receptor depletion in diabetes mellitus: correction with therapy.

This report describes two patients with diabetes mellitus, presenting with insulin resistance and depression of erythrocyte insulin receptor binding to less than one-third of normal. Scatchard analysis of the data was consistent with a depletion in insulin receptors in these poorly controlled diabetic patients. Therapy with tolbutamide and reduced insulin administration resulted in restoration of erythrocyte receptor binding, clinical resolution of the insulin resistance, and amelioration of hyperglycemia. These data suggest a role for transient depletion and/or dysfunction of cellular receptors of insulin activity in the evolution of insulin resistance in diabetes.

Adult↗

PubMedDate not supplied

Men and women together.

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Civil Rights↗

PubMedDate not supplied

Identification of the urinary metabolites of tacrine in the rat.

Tacrine (THA) is a potent cholinesterase inhibitor being studied for the treatment of Alzheimer's disease. The metabolism and excretion of THA were studied in rats following a single oral dose of 20 mg/kg of THA. The results show THA was extensively metabolized in rats after oral administration. Three major urinary metabolites were isolated by HPLC on a semi-prep analytical phenyl column, and subsequent purification of the individual fractions on a semi-prep analytical cyano column. The major metabolic pathways involve the hydroxylation of the saturated ring at positions 1, 2, and 4. The structures of the metabolites 9-amino-1,2,3,4-tetrahydroacridin-1-ol (1-OH-THA), 9-amino-1,2,3,4-tetrahydroacridin-2-ol (2-OH-THA), and 9-amino-1,2,3,4-tetrahydroacridin-4-ol (4-OH-THA) were determined by electron impact mass spectrometry and/or 1H-NMR, and compared with synthetic references. The urinary excretion of THA and metabolites was quantitated by HPLC with UV detection. About 60% of the oral dose was eliminated as total THA, 1-OH-THA, 2-OH-THA, and 4-OH-THA over a 48-hr collection interval; and the non-conjugated THA and hydroxylated metabolites accounted for 45% of the dose.

Animals↗

PubMedDate not supplied

Polymerase chain reaction amplification products separated on rehydratable polyacrylamide gels and stained with silver.

Separation of polymerase chain reaction (PCR) amplification of specific fragment length polymorphisms was carried out on rehydratable polyacrylamide gels on a horizontal flat slab system. A discontinuous sulfate-borate buffer system was employed on 5-8% T gels crosslinked with 3.5% C. Samples were diluted in leading sulfate ion buffer at 1/10 the ionic strength of the separating gel buffer and placed directly onto the surface of the rehydrated gels in 0.5-10 microliters volumes. The trailing ion and counterion were contained in a gel plug and placed directly onto the anodal and cathodal ends of the gel, and the electrodes placed directly onto the surface of the gel plugs. Filter paper wicks, soaked in diluted leading ion buffer, were placed along each side to lower the ionic strength of the edges, thereby increasing mobility at the edge and thus preventing smile effects. The gel-gel contact of the plug and separating gel prevent the production of a junction potential which occurs between dissimilar materials such as a paper wick and the gel. Ten- to 20-cm separations were carried out from 2-5 h, respectively, and resolution in the 20 cm system was 1.6-4 bp (base pairs) between 100 and 500 bp, 4-7 bp between 500 and 1000 bp, 12-20 bp between 1000 and 2000 bp and about 50 bp between 2000 and 3000 bp. Between 3000 and 4000 bp, resolution fell off to +/- 100 bp. Sensitivity, using a silver stain, indicated that one could readily distinguish less than 10 pg of DNA per mm width on the gels.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotechnology↗

PubMedDate not supplied

Maternal autoantibodies and fetal disease.

We have examined the relationships between maternal connective tissue disease (CTD), fetal and neonatal health, and the presence of specific autoantibodies: antinuclear antibodies (ANA), anti-Ro, antiLa, anti-Sm, anti-RNP, anti-DNA, and anticardiolipin (ACL) in 27 mothers with CTD (Group A), and 10 asymptomatic mothers of babies with complete congenital heart block (CCHB), or cardiac arrhythmias (Group B). Compared to 100 normal pregnant controls, autoantibodies were significantly more common in both Group A (96.3%, p less than 0.0005) and Group B (70%, p less than 0.0005), although the prevalence of autoantibodies in the Group A mothers having abnormal babies compared with those who had normal babies did not differ. Anti-La was present only in mothers with abnormal babies (7 of 17 compared to 0 of 10, p less than 0.025). Anti-La did not occur without anti-Ro, but anti-Ro occurred in 9 mothers without anti-La. Anti-Ro was present in the serum of all mothers of infants with CCHB and occurred alone in 3 of 4 instances. Titers of anti-Ro did not differ between abnormal and normal infants or their mothers. ACL occurred alone in the serum of 10 of 38 mothers, and was present in 7 mothers who had infants with cardiac abnormalities other than CCHB.

Antibodies, Antinuclear↗

PubMedDate not supplied

"Normal" insulin secretion: the goal of artificial insulin delivery systems?

Prehepatic insulin production can be determined from analysis of connecting-peptide behavior in the plasma. In the present study, we have determined prehepatic insulin production in six normal men throughout a day that included three typical 750-cal meals. Total insulin secretion for the 24 h was 45.4 U, secreted as 10.6 U with breakfast, 13.4 U with lunch, and 13.8 U with dinner. The remaining 7.6 U was secreted during the 9 h night at a rate of 0.85 U/h. At least 50% of the newly secreted insulin is known to be extracted by the liver during the initial transhepatic passage, so that total peripheral delivery can be estimated as approximately 22 U/day. Consequently, portal vein insulin levels are in excess of those seen in peripheral blood by at least 20 +/- 8 microU/ml in the fasted state, and by as much as 115 +/- 15 microU/ml in the 2-h postabsorptive state. The data suggest that insulinization of the liver, without peripheral hyperinsulinemia, may be a goal of artificial insulin delivery.

Artificial Organs↗

PubMedDate not supplied

An improved method for concurrent isolation of human granulocytes and lymphocytes. Its application in isoelectric focusing electrophoresis.

A modified method of Boyum's technique to isolate granulocytes and lymphocytes from human blood is described. The granulocytes and the lymphocytes separated by this isolation procedure are highly pure, viable, and in sufficient number for subsequent isoelectric focusing studies. Different proteins have been separated by isoelectric focusing. This technique can be useful in the investigation of granulocytic and lymphocytic disorders.

Cell Separation↗