Pancreatic response to mild non-insulin-induced hypoglycemia does not involve extrinsic neural input.

Mild non-insulin-induced hypoglycemia achieved by administration of a glycogen phosphorylase inhibitor results in increased glucagon and decreased insulin secretion in conscious dogs. Our aim was to determine whether the response of the endocrine pancreas to this mild hypoglycemia can occur in the absence of neural input to the pancreas. Seven dogs underwent surgical pancreatic denervation (PDN [study group]), and seven dogs underwent sham denervation (control [CON] group). Each study consisted of a 100-min equilibration period, a 40-min control period, and a 180-min test period. At the start of the test period, Bay R3401 (10 mg/kg), a glycogen phosphorylase inhibitor, was administered orally. Arterial plasma glucose (mmol/l) fell to a similar minimum in CON (5.0 +/- 0.1) and PDN (4.9 +/- 0.3). Arterial plasma insulin also fell to similar minima in both groups (CON, 20 +/- 6 pmol/l; PDN, 14 +/- 5 pmol/l). Arterial plasma glucagon rose to a similar maximum in CON (73 +/- 8 ng/l) and PDN (72 +/- 9 ng/l). Insulin and glucagon secretion data support these plasma hormone results, and there were no significant differences in the responses in CON and PDN for any parameter. Pancreatic norepinephrine content in PDN was only 4% of that in CON, confirming successful sympathetic denervation. Pancreatic polypeptide levels tended to increase in CON and decrease in PDN in response to mild hypoglycemia, indicative of parasympathetic denervation. It thus can be concluded that the responses of alpha- and beta-cells to mild non-insulin-induced hypoglycemia can occur in the absence of extrinsic neural input.

In the absence of counterregulatory hormones, the increase in hepatic glucose production during insulin-induced hypoglycemia in the dog is initiated in the liver rather than the brain.

We have previously demonstrated that the liver can release glucose in response to insulin-induced hypoglycemia, despite the absence of glucagon, epinephrine, cortisol, and growth hormone. The aim of this study was to determine whether this is activated by liver or brain hypoglycemia. We assessed the response to insulin-induced hypoglycemia in the absence of counterregulatory hormones in overnight-fasted conscious adrenalectomized dogs that were given somatostatin and intraportal insulin (30 pmol x kg(-1) x min(-1)) for 360 min. Glucose was infused to maintain euglycemia for 3 h and then to allow limited peripheral hypoglycemia for the next 3 h. During peripheral hypoglycemia, five dogs received glucose via both carotid and vertebral arteries to maintain cerebral euglycemia (H-EU group) concurrently with peripheral hypoglycemia, while six dogs received saline in these vessels to allow simultaneous cerebral and peripheral hypoglycemia (H-HY group). Throughout the study, arterial insulin was 1,675 +/- 295 and 1,440 +/- 310 pmol/l in the H-HY and H-EU groups, respectively. Glucose fell from 6.2 +/- 0.3 to 2.1 +/- 0.0 mmol/l and from 5.8 +/- 0.3 to 1.9 +/- 0.1 mmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both). Norepinephrine rose from 1.12 +/- 0.35 to 2.44 +/- 0.69 nmol/l and from 1.09 +/- 0.07 to 1.74 +/- 0.16 nmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both; no difference between groups). Glucagon, epinephrine, and cortisol were below the limits of detection. The liver switched from uptake to output of glucose during peripheral hypoglycemia in both the H-HY (-7.1 +/- 2.1 to 5.4 +/- 3.1 micromol x kg(-1) x min(-1)) and H-EU (-7.9 +/- 3.5 to 3.4 +/- 1.7 micromol x kg(-1) x min(-1)) groups (P < 0.05 for both; no difference between groups). Alanine levels and net hepatic alanine uptake fell similarly in both groups. There were increases (P < 0.05) in glycerol (12 +/- 3 to 258 +/- 47 micromol/l) and nonesterified fatty acid (194 +/- 10 to 540 +/- 80 micromol/l) levels and in total ketone production (0.4 +/- 0.1 to 1.1 +/- 0.2 micromol x kg(-1) x min(-1)) in the H-HY group, but these parameters did not change in the H-EU group. These data clearly indicate that the lipolytic and hepatic responses to hypoglycemia are driven by differential sensing mechanisms. Thus, during insulin-induced hypoglycemia, when counterregulatory hormones are absent, liver hypoglycemia triggers the increase in hepatic glucose production, whereas cerebral hypoglycemia causes the increases in lipolysis and ketogenesis.

Quality control for the board of directors.

At the Metropolitan General Hospital in Windsor, Ontario, a 69-point methodology has been developed and implemented to evaluate whether the board is discharging its principal responsibilities effectively. This process has received an initial positive assessment by the board, and its benefits to the board include clearer expectations about performance and improved information. This article describes the development and assessment of the evaluation methodology.

Non-01 Vibrio cholerae bacteremia--complication of a LeVeen shunt.

Vibrio cholerae bacteremia occurred in a patient with cirrhosis after placement of a LeVeen shunt. At the time of bacteremia, cultures of peritoneal fluid were negative and fluid dynamics did not suggest spontaneous bacterial peritonitis. Despite apparent successful treatment of the bacteremia, relapse and death occurred with culture positivity of peritoneal fluid for V. cholerae. Simultaneously, blood cultures were positive for Klebsiella pneumoniae. Agglutination studies demonstrated the V. cholerae to be a non-01 strain. Insertion of a LeVeen shunt, which bypasses the hepatic clearance mechanisms, appeared to have allowed bacteremia to occur with this bacterium that is rarely isolated from blood. In patients with LeVeen shunts, bacteremia with noninvasive pathogens may occur, and in coastal areas, Vibrios should be considered when bacteremia occurs.

Heterogeneity of proteins resembling high-mobility-group protein HMG-T in trout testes nuclei.

Two proteins, HMG-T1 and HMG-T2, with electrophoretic mobilities and compositions similar to those of protein HMG-T, were isolated from trout testes nuclei. The isoelectric points of proteins HMG-T1, HMG-T2 and HMG-T differ. The first 20 residues of protein HMG-T2 have been sequenced and differ from protein HMG-T by only one residue.

The primary structure of a non-histone chromosomal protein.

The primary structure of the calf thymus non-histone chromosomal protein HMG-17 has been determined. The sequence was determined mainly from data provided by the peptides obtained by cleavage with staphylococcal protease. Additional information was obtained from peptides produced by cleavage with trypsin and alpha-protease (from Crotalus atrox venom) and by partial acid hydrolysis. The protein is 89 amino acid residues in length, and has molecular weight of 9247. The N-terminal two-thirds of the molecule is highly basic, 22 of the first 58 residues being lysine or arginine, whereas only seven residues are aspartic or glutamic acid residues. In contrast, the C-terminal region of the molecule has an overall negative charge, only four of the last 31 residues being basic, whereas seven aspartic and glutamic acid residues are present. The protein is also characterised by a region of high density of proline residues, there being six proline residues between residues 31 and 40. A region of 19 residues sequence similarity with the trout-specific histone, H6, is noted together with some smaller regions of sequence similarity with histones H1 and H5.

Leydig-cell tumor of the testis with gynecomastia and elevated estrogen levels.

A normally-virilized 24-year-old white man who had gynecomastia was found to have a Leydig-cell tumor of the testis, without demonstrable metastases. Hormonal evaluation revealed negative serum and urine tests for human chorionic gonadotropin, and normal steroid excretion. Prior to orchiectomy, serum estradiol was elevated and serum testosterone depressed; postoperatively these values reverted to normal. Attempts to quantitative the estradiol content of the tumor failed to show a significant increase over normal testicular tissue, however. Histologically, the tumor showed classic Reinke crystalloids, the nature of which remains undefined. Electron-microscopic studies showed these crystals to have a regular hexagonal pattern.

Spectroscopic evidence for the uneven distribution of adenine and uracil residues in ribosomal ribonucleic acid of Drosophila melanogaster and of Plasmodium knowlesi and its possible evolutionary significance.

RNA was isolated from subribosomal particles of the malaria parasite Plasmodium knowlesi. The nucleotide composition (mole fraction) of the principal species was obtained (S-rRNA, 0.295A, 0.36U, 0.25G, 0.105C: L-rRNA, 0.326A, 0.31U, 0.228G, 0.144C). Ribosomal RNA was also isolated from Drosophila melanogaster. Optical properties of these A + U-rich species were measured. In all four cases analysis of the hypochromic effect revealed that adenine and uracil residues tended to form clusters along the polynucleotide chain. A substantial fraction of residues was located in bihelical regions of approx. 50% G-C base pairs or in regions of approx. 30-35% G-C base pairs. The possible evolutionary significance of these results was considered on the basis of comparison with properties of rRNA from bacteria (Escherichia coli) and a mammal (rabbit reticulocyte).

The nucleic acids of Drosophila melanogaster.

1. Nucleic acids of whole Drosophila adults were prepared in good yield and substantially free from impurities by new modifications of the phenol method. 2. The average molar base compositions of the DNA (41% of guanine+cytosine) and transfer RNA (60% of guanine+cytosine) resemble those of mammalian nucleic acids; the ribosomal RNA has a DNA-like molar base composition (43% of guanine+cytosine), and it is considered that this is reflected in the lower stability of its secondary structure compared with mammalian ribosomal RNA. 3. The two main ribosomal forms were separated and average base compositions and sedimentation values determined.