A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus.

A polymorphic region flanking the human insulin gene on the short arm of chromosome 11, the insulin-gene-linked DNA polymorphism, can be described as a locus with at least three classes of alleles: a common small "class 1" allele averaging 570 base pairs, a rare intermediate "class 2" allele of about 1320 base pairs, and a large "class 3" allele averaging 2470 base pairs in size. We have determined the genotype at this locus of 393 unrelated diabetic and nondiabetic individuals. Differences were observed in the genotypic and allelic frequencies between groups of different races.

Reduced solubility of short-acting soluble insulins when mixed with longer-acting insulins.

Using insulins from three manufacturers, we examined the recovery by radioimmunoassay of short-acting soluble insulin when mixed with long-acting insulin as a function of the ratio of the mixture and the time of pre-mixing. In ratios of 1:2, 1:3, and 1:5 (short- to long-acting insulin), all Novo, Nordisk, and Lilly short-acting insulins tested showed a significant loss of solubility when mixed with the respective company's long-acting insulin either for less than 75 s or for 20 min before centrifugation. In ratios of 1:1, Novo's Actrapid (regular) with Monotard (lente) and Lilly's regular with lente showed no significant loss of solubility when pre-mixed for less than 75 s, and the regular insulin also showed no significant loss when pre-mixed for 20 min.

Evaluation of efficacy and safety of human insulin (Novo) in the treatment of insulin-dependent diabetes mellitus: a double-blind, multicenter clinical trial.

The safety and efficacy of human insulin (Novo) were evaluated in a double-blind, parallel, multicenter trial in which 47 insulin-dependent diabetic patients were randomly divided into two equal groups and treated with either purified pork or human insulin (Actrapid and Monotard, Novo) for 12 wk. Mean levels of fasting plasma glucose, glycohemoglobin, and daily insulin dosages showed no statistical differences between the two groups, and there was no significant difference in the incidence of hypoglycemic reactions. The results from this clinical trial indicate that human insulin, prepared by enzymatic transpeptidation of pork insulin, appears to be as safe and efficacious as purified pork insulin in the treatment of insulin-dependent diabetes mellitus.

Stimulatory effects of tolbutamide infusion on plasma glucagon in insulin-dependent diabetic subjects.

The effect of iv tolbutamide on endogenous glucagon levels was measured in nine insulin-dependent diabetic patients chosen because they evidenced no C-peptide response to beta-cell secretagogues. Basal glucagon levels were not suppressed by a sustained tolbutamide infusion; in fact, a slight stimulatory effect was observed at 5, 10, 30, and 45 min. In the absence of detectable insulin secretory capacity and suboptimal insulin replacement, tolbutamide appears to be a stimulus, not a suppressant, of glucagon secretion.

Properties of a polymorphic DNA segment in the 5' flanking region of the human insulin gene.

The 5' flanking region of the human insulin gene contains a section of variable as to length and sequence. This polymorphic region begins 363 bp from the 5' end of the gene and extends upstream for a variable distance. The restriction fragment length heterogeneity is generated by variation in the redundancy of a family of 14-15 bp GC-rich oligonucleotides.

Polymorphic DNA region adjacent to the 5' end of the human insulin gene.

The length of a segment of DNA associated with the human insulin gene, which has been localized to the short arm of chromosome 11, is heterozygous in 63% of 52 individuals analyzed. This polymorphic region is approximately 500 base pairs from the nucleotide encoding the 5' end of insulin mRNA. The polymorphism appears to be due to an insertion or deletion of DNA sequences so that DNA fragments of different length are generated when DNA from a heterozygous individual is digested with selected restriction endonucleases.

Translational regulation: identification of the site on bacteriophage T4 rIIB mRNA recognized by the regA gene function.

The bacteriophage T4 gene regA encodes a protein that diminishes the expression of many unlinked early T4 genes. Previous work demonstrated that regA-mediated repression occurs after transcription. We report here on the identification of the target site on one regA-sensitive mRNA, the message encoding the phage T4 rIIB protein.

Insulinopenic diabetes after rodenticide (Vacor) ingestion: a unique model of acquired diabetes in man.

A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction.

G gamma and A gamma globin-chain biosynthesis by adult and umbilical cord blood erythropoietic bursts and reticulocytes.

We examined gamma-globin-chain biosynthesis by adult and umbilical cord blood or erythropoietic bursts in methylcellulose clonal culture and gamma-chain synthesis by cord blood reticulocytes. Globin chains were labeled with 14C-amino acids and guantitated by using autoradiography or fluorography. Alpha, beta, and G gamma and A gamma chains were separated by isoelectric focusing in polyacrylamide gels containing 8 M urea and 3% Nonidet P-40 (a nonionic detergent).

Endocrine responses to sugar ingestion in man. Advantages of fructose over sucrose and glucose.

Nine normal subjects ingested 100 gm. glucose, fructose, and sucrose on separate days after an overnight fast. Plasma glucose, fructose, insulin, glucagon, growth hormone, and triglyceride levels were then measured over the following 5 hr.

Pheochromocytoma of the broad ligament. Localization by computerized tomography and ultrasonography.

Computerized tomography (CT) and ultrasonography demonstrated a pheochromocytoma of the broad ligament of the uterus in a patient in whom arteriographic findings had been negative. We suggest that either or both of these techniques be used initially because, although they are not histologically specific, they are noninvasive and sensitive. An additional advantage of CT is its ability to evaluate sites of extra-adrenal pheochromocytomas above the diaphragm.

Biosynthesis of hemoglobin F Malta-I in culture by adult circulating erythropoietic precursors.

By using a methylcellulose clonal assay, we cultured peripheral blood erythropoietic precursors (BFU-E) from an adult couple whose child had HbF Malta-I(gamma 117 His leads to Arg), a G gamma variant, and measured the synthetic rates of HbA, HbF, and HbF Malta-I. Hemoglobin was labeled with 14C-amino acid in culture, separated by slab gel isoelectric focusing technique, and quantitated by autoradiographic or fluorographic method. Culture of BFU-E from both parents revealed significant HbF biosynthesis.

[Anesthesia of more than 8 hours in cardiac surgery for babies 10 kg or less (author's transl)].

25 cases of total correction of complex congenital heart disease operated from January 77 to May 79 at Laënnec Hospital in Professor J. Mathey's department of thoracic and cardiovascular surgery. All 25 cases were of small weight: to kg or less.

Increased growth hormone response to dopamine infusion in insulin-dependent diabetic subjects: indication of possible blood-brain barrier abnormality.

To test the hypothesis that cerebral capillaries, which share the embroyologic and morphologic characteristics of retinal capillaries, might have the same abnormal permeability in diabetic patients, we investigated the growth hormone response to a small amount of peripherally administered dopamine (1.5 microgram/kg.min).

Prolactin-secreting pituitary adenomas in multiple endocrine adenomatosis, type I.

In three unrelated families, four patients with multiple endocrine adenomatosis, type I, had confirmed or highly probable prolactin-secreting pituitary adenomas. In one patient, selective transsphenoidal tumor resection resulted in normal prolactin levels and resumption of menses. Heretofore, the majority of pituitary tumors in such patients had been thought to be nonsecreting chromophobe adenomas, but recent studies have shown that, in sporadic cases, as many as three fourths of "nonsecreting" pituitary tumors in fact secrete prolactin.

Phentolamine and the action of somatostatin in man.

The inhibition by somatostatin (SRIF) of basal and arginine-stimulated glucagon, insulin, and glucose levels was compared with that obtained when SRIF was preceded by alpha-adrenergic blockade with phentolamine. No noteworthy differences were observed, except that the characteristic rebound of insulin upon discontinuation of SRIF was significantly lower with phentolamine (P less than 0.01).

Hemoglobin biosynthesis in individual erythropoietic bursts in culture. Studies of adult peripheral blood.

By using a methylcellulose clonal assay, we cultured peripheral blood erythropoietic precursors from a patient with sickle cell anemia, a patient with sickle cell hemoglobin C disease, and a normal volunteer. We then analyzed the synthetic rates of adult and fetal hemoglobins (Hb) in individual erythropoietic bursts. Bb were labeled with 14C-amino acids in culture, separated by slab gel isoelectric focusing techniques, and quantitated by fluorographic methods.