Glucagon binding and lipolytic response in isolated adipocytes from streptozotocin-diabetic rats

Evidence for pre-receptor, receptor and post-receptor glucagon defects was investigated in adipocytes from streptozotocin-diabetic rats. For this purpose male Wistar rats were injected by cardiac puncture with streptozotocin (65 mg/Kg body-weight) or saline solution and sacrificed after 7 and 15 days of drug administration. Increased glucagon levels and increased glucagon degradation in serum together with a decrease in glucagon binding were found in both groups of diabetic rats. The decrease in glucagon binding was related to a decrease in the number of glucagon receptors/cell rather than to a change in receptor affinity. The lipolytic response of glucagon was increased. However, the ability of glucagon to increase basal or theophylline-stimulated cAMP accumulation in the incubation medium of adipocytes from diabetic rats was decreased. Such alterations could represent a counter-regulatory mechanism of the hyperglucagonemia detected in streptozotocin-diabetic rats.     

Increased insulin receptor binding in erythrocytes from growth hormone-deficient children

Erythrocytes from growth hormone-deficient children (GHd-children) (n=10) showed a statistically significant increase in insulin binding at low unlabeled insulin concentrations, together with a threefold decrease in apparent receptor affinity, as compared to control children (C) (n=11). Scatchard analysis of the binding data using the two-site model revealed that both the receptor concentration R₁ [GHd-children 0.10±0.01 ng/ml and C 0.03±0.002 ng/ml] and the dissociation constant K_D1 [GHd-children (0.48±0.05)×10^–9M and C (0.19±0.01)×10^–9M] for high affinitylow capacity sites were significantly increased in erythrocytes from GHd-children, while neither receptor concentrations (R₂) nor the dissociation constant (K_D2) for low affinity-high capacity sites proved to be altered. These events were accompanied by a normal sensitivity to insulin as well as glucose tolerance in the GHd-group. The meaning of the increased insulin binding with normal insulin sensitivity in GH-deficiency is discussed.     

Persistence of Cajal-Retzius cells in the adult human cerebral cortex. An immunohistochemical study

The presence of Cajal-Retzius cells in the adult human prefrontal and visual cortices has been demonstrated with calcium binding protein immunocytochemistry and NADPH-diaphorase histochemistry. These cells expressed parvalbumin, calbindin and calretinin calcium binding proteins and displayed NADPH-diaphorase enzyme activity. The three basic morphological profiles-horizontal, pyriform and multipolar-were observed. The morphologies of labelled cells resembled those of neurons observed in Golgi studies of the human cerebral cortex. The presence of calcium binding proteins and NADPH-diaphorase in these cells suggests a possible inhibitory role as GABAergic neurons. The persistence of Cajal-Retzius cells in the adult cerebral cortex supports the idea that they undergo developmental dilution rather than postnatal degeneration.     

Successful treatment of suspected erysipelas septicemia in a beluga whale (Delphinapterus leucas)

A 20-year-old male beluga whale (Delphinapterus leucas) was diagnosed with suspected acute septicemic erysipelas. Physical examination was unremarkable and no skin lesions were evident. Hematologic and serum biochemical abnormalities included mild anemia, a marked leukocytosis, an increase in the erythrocyte sedimentation rate, and moderate elevations of total protein, gamma globulins, blood urea nitrogen, and creatinine. Microtitration agglutination testing for Erysipelothrix rhusiopathiae antibodies revealed seroconversion and elevated antibody titers associated with the clinical illness, presumptive evidence of an active E. rhusiopathiae infection. Treatment consisted of oral fluids, cimetidine, and a 25-day course of ciprofloxacin hydrochloride. The whale made a rapid and uneventful recovery. None of the three female beluga whales that shared the pool with the ill male, nor male and female beluga whales maintained in a separate pool, became ill or showed serologic evidence of E. rhusiopathiae exposure. © 1993 Wiley-Liss, Inc.     

Effect of long-term nickel ingestion on insulin binding and antilipolytic response in rat adipocytes

Male Wistar rats of the third generation of rats drinking 200 micrograms Ni2+/mL as NiCl2 in their drinking water were studied. Basal plasma glucose and insulin levels were unchanged. Epididymal adipocytes from Ni2(+)-fed rats showed an increased insulin binding with a slight increase in apparent insulin affinity (ED50: Ni2(+)-fed rats 2.8 x 10(-9) M and controls 5 x 10(-9) M) with no change in insulin receptor numbers (Ni2(+)-fed rats 143,000 +/- 12,000 (6) receptors/cell and controls 126,000 +/- 13,000 (5]. Moreover, a decreased sensitivity to the antilipolytic response of insulin was also observed in adipocytes from Ni2(+)-fed rats. These events could represent actions of Ni2+ both at the receptor and post-receptor insulin levels. Several possible mechanisms involved in the process are suggested.     

Chronic and endogenous regulation of insulin receptors by catecholamines in adipocytes from patients with a phaeochromocytoma

Insulin binding in adipocytes from patients with a phaeochromocytoma (PH) approached that of the controls (C) at low and higher concentrations of unlabeled insulin. The apparent receptor affinity was unchanged (ED50: PH 0.50×10^–9M and C0.60×10^–9M). Scatchard analysis of the binding data using the negative cooperative model revealed a 46% decrease in the total number of receptors together with no changes in both K^–e (PH 0.55×10⁹M^–1 and C 0.36×10⁹M^–1) and K^–f (PH 0.13×10⁹ M^–1 and C 0.07×10⁹ M^–1). According to the two site model, an altered proportion in the two classes of insulin binding sites was detected. This was accompanied by a catecholamine-desensitization of the adipocytes to the antilipolytic action of insulin. These events could represent a final situation of a chronic and endogeneous regulation by high levels of catecholamines of insulin receptors in human adipose tissue.     

Viral and bacterial serology of six free-ranging bearded seals Erignathus barbatus

Serum or heparinized plasma samples were obtained from 3 male (2 adult and 1 weaned calf) and 3 adult female free-ranging bearded seals Erignathus barbatus in May of 1994, 1995, or 1996. Blood samples were obtained from animals taken in subsistence hunts near St. Lawrence Island, Alaska and screened for antibodies to a suite of bacteria and viruses potentially pathogenic for pinnipeds and/or humans. No samples had detectable antibodies to Brucella spp., Phocine distemper virus, influenza A virus or caliciviruses (San Miguel sea lion virus strains 1, 2, and 4 to 13, vesicular exanthema of swine serotypes A48, B51, C52, D53, E54, F55, G55, H54, 155, J56, K54, 1934B, and Tillamook and Walrus calicivirus). One seal had a low titer of 100 to Leptospira interrogans serovar     

Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels

Preeclampsia is a common ( approximately 7% of all pregnancies) disorder of human pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the concentration of coenzyme Q10 in normal pregnancy and preeclampsia. Pregnant women (n = 18), women with preeclampsia (n = 12), and nonpregnant normotensive women (n = 22) were included. Plasma levels of coenzyme Q10 were measured by high-performance liquid chromatography. Plasma coenzyme Q10 levels were significantly higher in normal pregnant women (mean = 1.08, SEM = 0.08 umol/l; p <.005) in comparison to nonpregnant women (mean = 0.86, SEM = 0.16 umol/l) and women with preeclampsia (mean = 0.7, SEM = 0.03 umol/l; p <.0001). These results demonstrated that during preeclampsia there is a significant decrease in plasma levels of coenzyme Q10 compared to normal pregnant women, and compared to those who are not pregnant.     

The crystal structure of the fab fragment of the monoclonal antibody MAK33. Implications for folding and interaction with the chaperone bip

The Fab fragment of the murine monoclonal antibody, MAK33, directed against human creatine kinase of the muscle-type, was crystallized and the three-dimensional structure was determined to 2.9 A. The antigen-binding surface of MAK33 shows a convex overall shape typical for immunoglobulins binding large antigens. The structure allows us to analyze the environment of cis-prolyl-peptide bonds whose isomerization is of key importance in the folding process. These residues seem to be involved with not only domain stability but also seem to play a role in the association of heavy and light chains, reinforcing the importance of beta-strand recognition in antibody assembly. The structure also allows the localization of segments of primary sequence postulated to represent binding sites for the ER-specific chaperone BiP within the context of the entire Fab fragment. These sequences are found primarily in beta-strands that are necessary for interactions between the individual domains.