Insulinoma in a patient with non-insulin-dependent diabetes mellitus

Insulinoma in a patient with pre-existing diabetes is exceedingly rare. Only a small number of well-documented cases have been reported in the world during the last 40 years. We describe a case with non-insulin-dependent diabetes mellitus who after seven years of sulfonylurea treatment experienced recurrent episodes of hypoglycemia. Endogenous hyperinsulinism was found and radiographical examination and transhepatic venous sampling confirmed an insulin secreting pancreatic tumor. After surgical excision of the tumor, patient was relieved from hypoglycemic attacks but required to initiate insulin injection for the treatment of hyperglycemia.     

Miscoding properties of model estrogen-DNA adducts in reactions catalyzed by mammalian and Escherichia coli DNA polymerases

The miscoding properties of the model estrogen-derived DNA adducts, N2-[3-methoxyestra-1,3,5(10)-trien-6-yl]-2'-deoxyguanosine (dG-N2-3MeE) and N6-[3-methoxyestra-1,3,5(10)-trien-6-yl]-2'- deoxyadenosine (dA-N6-3MeE), have been explored, using an in vitro experimental system to quantify base substitutions and deletions. Site-specifically modified oligodeoxynucleotides containing a single dG-N2-3MeE or dA-N6-3MeE were prepared postsynthetically and used as templates in primer extension reactions catalyzed by Escherichia coli and mammalian DNA polymerases. When the 3'-->5' exonuclease free (exo-) Klenow fragment of DNA polymerase I was used, dG-N2-3MeE promoted mostly one- and two-base deletions, along with small amounts of incorporation of dAMP, dGMP, and dCMP opposite the lesion. dA-N6-3MeE promoted the incorporation of dTMP opposite the lesion as well as two-base deletions, accompanied by the incorporation of dAMP. Using pol alpha, primer extension reactions were blocked at dG-N2-3MeE; however, dA-N6-3MeE promoted preferential incorporation of dTMP opposite the lesion with small amounts of incorporation of dCMP and deletions. Primer extension reactions catalyzed by pol delta were blocked at these lesions. When pol beta was used, dG-N2-3MeE produced small amounts of incorporation of dAMP and deletions. dA-N6-3MeE promoted preferential incorporation of dTMP, along with incorporation of dCMP and two-base deletions. The miscoding specificities and frequencies varied depending on the DNA polymerase used. These results indicate that estrogen-DNA adducts have miscoding potential.     

Purification of four forms of the beta gamma subunit complex of G proteins containing different gamma subunits

To investigate the physiological significance of the diversity of gamma subunits of G proteins, we purified four forms of beta gamma of G proteins from bovine brain (beta gamma-B1, beta gamma-B2, beta gamma-B3), and spleen (beta gamma-S1) by the sequential chromatography on columns of DEAE-Sephacel, Ultrogel AcA 34, heptylamine-Sepharose, phenyl-5PW, and DEAE-5PW. Electrophoretic analyses showed that each beta gamma mainly contained the 36-kDa beta and a distinct but homogeneous gamma. These beta gamma complexes were subjected directly to proteolytic digestion and subsequent amino acid sequence analyses of their fragments. It was revealed that beta gamma-B1, -B2, and -B3 were identical to beta 1 gamma 7 (with a low level of beta 2 gamma 7), beta 1 gamma 2 and beta 1 gamma 3, respectively, while beta gamma-S1 was composed of beta 1 and an unidentified form of gamma. Then we examined the functional differences among these beta gamma complexes and the beta gamma of transducin (beta gamma-T, beta 1 gamma 1). Few differences were observed among all beta gamma complexes to enhance pertussis toxin-catalyzed ADP-ribosylation of the alpha subunits of G(o) and Gt. The four forms of beta gamma complexes purified from brain and spleen showed indistinguishable inhibitory effects on the release of GDP from G(o) alpha, but beta gamma-T was much less effective. Brain and spleen beta gamma complexes were equally effective in inhibiting calmodulin-stimulated adenylyl-cyclase activity, but beta gamma-T had a very weak inhibitory effect. Five forms of beta gamma facilitated metarhodopsin II-catalyzed binding of GTP gamma S to Gt alpha in a concentration-dependent manner with the following rank order of effectiveness: beta gamma-S1 > beta gamma-T > beta gamma-B1 > beta gamma-B2 > beta gamma-B3. Because the beta gamma complexes used in this study mostly contained the same beta subunit, the functional differences must be dependent on the gamma subunits. Thus, it seems likely that the receptor, the alpha subunits, and the effector are able to distinguish between the various gamma subunits.     

A frequency domain hypothesis for human postural controlcharacteristics [visual feedback]

Experiments performed to determine the effect of filtered visual feedback information in the frequency domain on human body sway during quiet standing is described. The three-dimensional visor display system (3D-VD) was used to filter the visual feedback information. A hypothesis is proposed to explain the test subject's postural control characteristics and to estimate the different roles of the visual information used for postural stability in the low and high frequency domains. It is concluded that the hypothesis based on the spatial map in the brain is useful to explain the different roles of the visual feedback information in the frequency domain     

Strength improvement and fusion splicing for carbon-coated opticalfiber

Problems associated with the use of carbon coating on silica fibers, including the initial strength and fusion splicing, were examined. A carbon-coated fiber with 6.2-kgf failure strength and excellent hydrogen resistance was obtained by suppressing strength degradation due to carbon coating. A scanning microscope utilized to estimate the carbon surface roughness and a smooth surface was found to be essential to obtain high strength. These results show that no significant technical problems remain for carbon-coated fiber and that it is now ready for practical application     

Continuous monitoring of autonomic nerve information for the control of an artificial heart

To drive an artificial heart system optimally, information from the autonomic nervous system may be needed; however, it is very difficult to monitor autonomic nerve discharges continuously. In this study, we propose a new automatic control algorithm for a total artificial heart (TAH) using fluctuations in the circulatory system. It was reported that fluctuations in hemodynamics reflect ongoing information from the autonomic nervous system. A Mayer wave at 0.1 Hz was reported to reflect sympathetic information. We observed fluctuations in vascular resistance, which can be measured during use of an artificial heart. Four adult goats were used for the experiments. Through a left thoracotomy, hemodynamic parameters were measured during chronic animal experiments. All time series data were recorded on magnetic tape. Quantitative analysis, statistics, and spectral analysis were carried out on a computer through an analog-digital (AD) converter. A Mayer wave peak was clearly recognized in all goats in the spectrum of vascular resistance. A band pass filter was used to convert this information to automatic control. Time series curves of the Mayer wave of vascular resistance were provided, and compared with the time series curve of the cardiac output. After a change in the Mayer wave, increase in cardiac output was observed. This phenomenon may be interpreted as sympathetic nervous control of changes in cardiac output. These results suggest that an artificial heart may be controlled by the measurement of the Mayer wave of vascular resistance, making it possible to control an artificial heart with neural information.     

Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice

Recently we found that a single administration of T-2 toxin (T-2), a trichothecene mycotoxin, into mice induced DNA fragmentation, a biochemical hallmark of apoptosis, in the thymus. In this study, we investigated the effective chemical structure(s) of T-2-derived metabolites capable of inducing thymic apoptosis in vivo in mice. Metabolic conversion of T-2 to 3'-hydroxy-T-2 toxin (3'-OH-T-2) did not diminish the apoptosis-inducing activity, since essentially the same level of fragmented DNA was detected in the thymus taken from mice injected with either T-2 or 3'-OH-T-2. In contrast, hydrolysis of T-2 and 3'-OH-T-2 at the carbon-4 (C-4) position to HT-2 toxin (HT-2) and 3'-hydroxy-HT-2 toxin (3'-OH-HT-2), respectively, greatly decreased the level of DNA fragmentation. Similarly, hydrolysis of T-2 at the carbon-8 (C-8) position to neosolaniol strongly diminished its ability to induce DNA fragmentation. T-2 tetraol, having no ester groups, was unable to induce apoptosis. Based on the data presented in this study, we concluded that both the acetyl group at the C-4 position and the isovaleryl or 3'-hydroxyisovaleryl group at the C-8 position of the T-2 molecule are important for inducing cell death through apoptosis in the thymus.     

Real-time cardiac output estimation of the circulatory system underleft ventricular assistance

A method for indirect and real-time estimation of the cardiac output of the circulatory system supported by the left ventricular assist device (LVAD) is proposed. This method has low invasiveness and is useful for clinical applications of the LVAD since it needs only two measurements: the rate of blood outflow from the LVAD and the aortic pressure. The method is based on a system identification technique for the time-series model of the cardiovascular system and requires less computational time than other methods with similar estimation accuracy. Hence, the method could be implemented in a personal computer system and realize online, real-time estimation of the instantaneous outflow rate of the natural heart. Results obtained in vitro using a mock circulatory system and in vivo using an adult goat show that the method can yield a fairly high correlation coefficient between the true stroke volume of the natural heart and its estimate of more than 0.99 (in vitro) or 0.95 (in vivo). The estimation method thus appears suitable for clinical use