Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy.

AIMS: Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients. METHODS: The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole. RESULTS: The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006). CONCLUSION: Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate.

Dynamical structure of the hinge region of immunoglobulin G as studied by 13C nuclear magnetic resonance spectroscopy.

The segmental flexibility of the hinge region of immunoglobulin G (IgG) molecules has been considered to play important roles in the mediation between antigen recognition and effector functions. Here we report the result of a 13C nuclear magnetic resonance study of the dynamical structure of the hinge region of a mouse monoclonal IgG2a antibody. In the present work, a variety of IgG2a analogs selectively labeled with 13C at the carbonyl carbon atom were prepared. The flexibility of the hinge region was discussed on the basis of the linewidth data of 13C resonances obtained using a Carr-Purcell-Meiboom-Gill pulse train. It was concluded that the hinge region of the mouse IgG2a molecule has a mosaic structure with heterogeneous nature of flexibility with the rigid core part flanked by upper and lower hinges, which are highly flexible peptide segments. Cleavage of the inter-chain disulfide bridges led to homogeneous flexibility of the hinge region, except for the N-terminal side of the upper hinge. It was suggested that the rigidity in the N-terminal side of the upper hinge is due to the interaction with the CH1 domain. Biological significance of the mosaic structure of the hinge region was briefly discussed.

Molecular structural studies of effector functions of a mouse immunoglobulin G that lacks the entire CH1 domain: small-angle X-ray scattering, nanosecond fluorescence depolarization and stable isotope-aided NMR analyses.

Molecular structural studies are reported of a short-chain mouse IgG2a antibody that lacks the entire CH1 domain. We have recently shown that (1) this short-chain antibody comprises two components in which the inter light-chain disulfide bridge does and does not exist, and (2) these two components are different in the constitutive complement-activating activity [Mizutani et al. (1993) J. Immunol. 150, 131-138]. Structures were compared for these two components on the basis of small-angle X-ray scattering, nanosecond fluorescence depolarization and isotope-aided NMR data. It has been discussed how the presence and absence of the inter light-chain disulfide bridges affect the complement-activating activity of the two components of the short-chain antibody.

13C NMR study of the mode of interaction in solution of the B fragment of staphylococcal protein A and the Fc fragments of mouse immunoglobulin G.

The mode of interaction of the B domain (FB) of staphylococcal protein A and the Fc fragments of mouse immunoglobulin G (IgG) has been investigated by 13C NMR spectroscopy. Mouse IgG1, IgG2a, and IgG2b proteins have been selectively labeled with 13C at the carbonyl carbon of His, Met, Trp or Tyr residue and used to prepare the corresponding Fc fragments by limited proteolysis. Site-specific resonance assignments have been made for each of these Fc analogues. FB was reported to form two contacts (contact 1 and contact 2) with human Fc in the crystal [Biochemistry 20 (1981) 2361-2370]. Comparisons of the chemical shift data of the Fc fragments observed in the absence and presence of FB have led us to conclude that in solution contact 1 is responsible for the formation of the Fc-FB complexes.

Application of 13C NMR spectroscopy to paratope mapping for larger antigen-Fab complexes.

For the purpose of engineering the antibody combining site, mapping residues that are involved in antigen binding provide us with valuable information. By use of 13C NMR spectroscopy with selectively 13C-labeled Fv fragments, we have established a general strategy to identify the residues that are perturbed upon binding of small antigen (hapten) molecules [(1990) Biochemistry 30, 6604-6610]. In the present paper, we demonstrate that this strategy can be extended to molecular structural analyses of the complexes of an Fab fragment and a larger antigen molecule such as Pseudomonas aeruginosa exotoxin A with a molecular mass of 67 kDa.

Application of 13C nuclear magnetic resonance spectroscopy to molecular structural analyses of antibody molecules.

A 13C nuclear magnetic resonance study of a mouse anti-dansyl monoclonal antibody is reported. The antibody molecule was specifically labeled with [1-13C]methionine by growing hybridoma cells in serum-free medium. It was possible to observe all the carbonyl carbon resonances of the antibody. Fab and Fc fragments have been obtained from the antibody and used successfully for the assignment of each of the carbonyl resonances to either the Fab or Fc region. It has been shown that the spectrum of the intact antibody is simply those of Fab and Fc superimposed. It has also been shown that site specific assignments of carbonyl resonances can be made by means of a double labeling technique developed by Kainosho and coworkers.

Lingual factors enhance the increase of ornithine decarboxylase activity in rat jejunal mucosa after feeding.

Luminal nutrients are the main factors that stimulate ornithine decarboxylase (ODC) activity in rat intestinal mucosa following feeding. The aim of the present study was to determine whether lingual (oral) factors are related to the increase in jejunal ODC activity after feeding. ODC activity in the jejunum and liver was measured 3 hours after refeeding of 48-hour fasted rats. In the first experiment, rats were refed with a regular pellet, powder, or liquid diet. In the second experiment, rats were infused with the liquid diet through a gastric infusion tube following 48 hours' fasting. In the third experiment, the experimental rats had a gastric fistula that allowed free drainage from the stomach of all ingested liquid diet. In the fourth experiment, a truncal vagotomy was performed 1 week before the experiment. The increase of ODC activity in the jejunum of rats fed with the liquid diet was less than that of rats fed with the pellet diet or powder diet. The increase of ODC activity in the jejunal mucosa of rats infused through the gastric tube was less than that of rats fed per os, and the increase of ODC activity in the liver did not differ between these experimental groups. ODC activity did not increase in rats with a gastric fistula. Vagotomy did not affect the increase of jejunal ODC activity after feeding. In conclusion, the increase of ODC activity after feeding was attenuated in rats in which the diet was given by bypassing the mouth. This indicates that lingual factors enhance the increase of ODC activity in the jejunal mucosa after feeding, but the lingual factors alone do not increase ODC activity in the jejunum.

Cardiac autonomic dysfunction in rotogravure printers exposed to toluene in relation to peripheral nerve conduction.

The autonomic nervous effects of toluene remain less clear. To clarify this neurotoxicity, ten rotogravure printers and the same number of age-matched unexposed controls were examined, by using the coefficient of variation in electrocardiographic R-R intervals (CVRR), the distribution of nerve conduction velocities (DCV) and the maximal motor and sensory nerve conduction velocities (MCV and SCV) in the median nerve. Also, the C-CVHF and C-CVLF (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) were computed from component spectral powers using autoregressive spectral and component analyses. These printers had been exposed to toluene (estimated exposure levels of toluene at 83 ppm) for 1-36 years. The CVRR and C-CVHF were significantly lower in the printers than in the controls. No significant difference between the printers and the controls was found in either any DCV parameters or the SCV in the forearm, except the MCV and the SCV in the palm. In the light of previous work on the brainstem/hippocampus damages due to toluene, these data suggest that toluene causes potential damages in the central autonomic nervous system, mainly parasympathetic hypoactivity.

A 13C NMR study of the hinge region of a mouse monoclonal antibody.

A 13C NMR study is reported of the hinge region of an intact mouse monoclonal antibody with a molecular weight of 150 K. Cys, Ile, and Pro analogs of the antibody labeled with 13C at the carbonyl carbon were prepared by growing hybridoma cells in the serum-free media. Resonance assignments have been performed as described previously [Kato, K., Matsunaga, C., Igarashi, T., Kim, H., Odaka, A., Shimada, I. and Arata, Y. (1991) Biochemistry, 30, 270-278]. The spectral data obtained show that 13C NMR can give detailed information about the structure of the hinge region of the intact antibody molecule. Prospects for the future role of 13C NMR in the structural analyses of larger proteins are briefly discussed.

Comparative metabolic responses to prolonged cooling in precocial duck (Anas domestica) and altricial pigeon (Columba domestica) embryos.

1. Embryos and hatchlings of the duck and pigeon were exposed to a lowered temperature for 6 hr. The oxygen consumption (MO2) was measured before and after cooling and the ratio of the two was compared with that predicted for a temperature coefficient of 2 (Arrhenius value). 2. Late prenatal ducks kept the MO2 above the Arrhenius value at 28 degrees C, while the MO2 of pigeon hatchlings became the same as the Arrhenius value even at 32 degrees C. 3. Thus, incipient homeothermic ability appears in the duck during prenatal development, but it is not evident in the pigeon even after emergence from the shell. The precocial chicken and semi-precocial noddy previously studied are intermediate in their metabolic response between the duck and the pigeon.

Complete assignment of the methionyl carbonyl carbon resonances in switch variant anti-dansyl antibodies labeled with [1-13C]methionine.

A 13C NMR study is reported of switch variant anti-dansyl antibodies developed by Dangl et al. [(1982) Cytometry 2, 395-401], who had used the fluorescence-activated cell sorter to select and clone these variants. These switch variant antibodies possess the identical VH, VL, and CL domains in conjunction with different heavy chain constant regions. In the present study, switch variant antibodies of IgG1, IgG2a, and IgG2b subclasses were used along with a short-chain IgG2a antibody, in which the entire CH1 domain is deleted. The switch variant antibodies were specifically labeled with [1-13C]methionine by growing hybridoma cells in serum-free medium. Assignments of all the methionyl carbonyl carbon resonances have been completed by using the intact antibodies along with their fragments and recombined proteins in which either heavy or light chain is labeled. A double labeling method [Kainosho, M., & Tsuji, T. (1982) Biochemistry 21, 6273-6279] has played a crucial role in the process of the spectral assignments. The strategy used for the assignments has been described in detail. In incorporating 15N-labeled amino acids into the antibodies for the double labeling, isotope dilution caused a serious problem except in the cases of [alpha-15N]lysine and [15N]threonine, both of which cannot become the substrate of transaminases. It was found that beta-chloro-L-alanine is most effective in suppressing the isotope scrambling. So far, spectral assignments by the double labeling method have been possible with 15N-labeled Ala, His, Ile, Lys, Met, Ser, Thr, Tyr, and Val.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon-13 NMR study of switch variant anti-dansyl antibodies: antigen binding and domain-domain interactions.

A 13C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical VH, VL, and CL domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of these antibodies has been selectively labeled with 13C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by following the procedure described previously for the switch variant antibodies labeled with [1-13C]Met [Kato, K., Matsunaga, C., Igarashi, T., Kim, H., Odaka, A., Shimada, I., & Arata, Y. (1991) Biochemistry 30, 270-278]. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, we discuss how 13C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule.

Multinuclear NMR study of the structure of the Fv fragment of anti-dansyl mouse IgG2a antibody.

A multinuclear NMR study is reported of Fv, which is a minimum antigen-binding unit of immunoglobulin. Fv has been prepared by clostripain digestion of a mouse anti-dansyl IgG2a monoclonal antibody that lacks the entire CH1 domain [Takahashi, H., Igarashi, T., Shimada, I., & Arata, Y. (1991) Biochemistry 30, 2840-2847]. A variety of Fv analogues labeled with 2H in the aromatic rings and with 13C and/or 15N in the peptide bonds have been prepared and used for multinuclear NMR analyses of Fv in the absence and presence of epsilon-dansyl-L-lysine (DNS-Lys). It has been shown that 1H-15N shift correlation spectra of Fv sensitively reflect the antigen binding and can be used along with 1H and 13C spectral data for the structural analyses of antigen-antibody interactions. Hydrogen-deuterium exchange of the amide protons has been followed in the absence and presence of DNS-Lys by using the 1H-15N shift correlation spectra. Use of the beta-shift observed for the carbonyl carbon resonances has also been helpful in following the hydrogen-deuterium exchange. On the basis of the NMR data obtained, the static and dynamic structure of the Fv fragment in the absence and presence of DNS-Lys has been discussed.

A human T-cell lymphotropic virus type I carrier with temporal arteritis terminating in acute myelogenous leukemia.

A human T-cell lymphotropic virus type I (HTLV-I) carrier with temporal arteritis (TA) in whom acute myelogenous leukemia (AML) developed 1 year after successful treatment of the autoimmune disease is described. This case suggested that the induction of immunodeficiency by infection with HTLV-I may be related to the development of the autoimmune disease and malignancy.

Effects of occupational use of vibrating tools in the autonomic, central and peripheral nervous system.

OBJECTIVES: The objective of this study was to clarify the autonomic, central and peripheral nervous effects of vibrating-tool operation. METHODS: The ECG R-R interval variability (CVRR), including the C-CVHF, C-CVLF (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) and the power spectral densities (PSDHF and PSDLF) after autoregressive analysis, short-latency somatosensory evoked potentials (SSEP), distribution of nerve conduction velocities (DCV), and median and radial nerve conduction velocities (NCVs) were measured in 17 vibrating-tool operators and the same number of age-matched control subjects. Some of the operators complained of white finger even in summer as soon as they arrived at the cold workplace. DESIGN: The significance of the differences in neurophysiological data between the exposed and unexposed groups and the associations between these data in the former were investigated. RESULTS: The CVRR, C-CVHF and PSDHF were significantly lower in the vibrating-tool operators than in the matched controls. The N9-N13 interpeak latency of the SSEP, i.e., conduction time of the cervico-spinobulbar pathway, in the operators was significantly prolonged as compared with the controls; the faster velocities of the DCV and the NCVs were significantly slowed in the operators. The N9-N13 interpeak latency in the operators was significantly correlated with the C-CVHF. CONCLUSION: Complex stressors of local vibration, cold, noise and heavy work, seem to affect the cervico-spinobulbar, parasympathetic and peripheral nerve functions. Also, parasympathetic hypofunction may imply a consequence in brainstem pathology induced by cold exposure in addition to vibration.

Effect of polydextrose on absorption of triglyceride and cholesterol in mesenteric lymph-fistula rats.

In most experimental designs, the inhibitory effect of water-soluble dietary fibers on lipid absorption is evaluated by the decrease in plasma lipid concentration or the increase in fecal lipid output. The aim of this study was to evaluate the acute effect of a water-soluble polysaccharide, polydextrose, on lipid transport to the mesenteric lymph using lymph-fistula rats. The mesenteric lymph duct of rats was cannulated, and an infusion tube was introduced into the duodenum. After recovery, a lipid emulsion containing radioactive triolein and cholesteryl oleate was infused into the duodenum for 8 hr. The tested group was infused with the lipid emulsion containing 5% or 10% polydextrose as dietary fiber. Samples from the lymph-fistula were collected, and the luminal contents and mucosa were collected at the end of infusion. Lymph flow in the mesenteric lymph decreased in the polydextrose group after the infusion. The amounts of both triglyceride and cholesterol remaining in the lumen were greater in the polydextrose group, due to decreased transport of lipid into the lymph. These effects were dose dependent in the 5% and 10% polydextrose groups. The results of this study indicate that polydextrose retarded the transport of triolein and cholesterol into the mesenteric lymph.

Oxygen consumption of brown noddy (Anous stolidus) embryos in a quasiequilibrium state at lowered ambient temperatures.

1. The oxygen consumption (MO2) of the semi-precocial Brown Noddy embryos at different stages of development was measured at 36 degrees C and again after 5-hr exposure to lowered ambient temperatures (30 and 32 degrees C). 2. The MO2 measured in a quasiequilibrium state was equal to the value predicted by a temperature coefficient of 2. 3. In contrast to precocial chickens, the semi-precocial Noddy had no apparent metabolic response to cooling before hatching.

Effect of smoking on pleural thickening in asbestos workers.

It is well known that an interaction exists between smoking and exposure to asbestos in the occurrence of lung cancer, whereas occurrence of malignant mesothelioma has not been related to smoking. In the case of pleural thickening related to asbestos, there is a disagreement in previous studies as to the effect of smoking. This could be because the diagnosis of pleural changes has a subjective element. Taking this into account, in the present work the maximum width of the pleura was used as an index of pleural changes. Study subjects were 134 asbestos workers of a brake manufacturing company who had received medical checks in 1978 and in 1990. The maximum width of the pleura on the chest x ray films of the workers was measured by two examiners who did not know the year of examination or smoking state of the worker. A general linear model was applied to analyse the effects of smoking, the year of examination, age, and duration of exposure to asbestos. The difference between maximum widths measured in 1978 and 1990 suggested chronological progression. The increase in width during the 12 years, however, did not differ significantly between smokers and nonsmokers. This suggests that smoking does not significantly increase pleural thickening in asbestos workers.

Newly synthesized histamine accelerates ornithine decarboxylase activity in rat intestinal mucosa after ischemia-reperfusion.

We previously demonstrated that both histamine synthesis (histidine decarboxylase activity) and polyamine synthesis (ornithine decarboxylase activity) increased in the rat intestinal mucosa after ischemia-reperfusion, whereas the relationship between these two factors remains unclear. To elucidate this relationship, we performed the present study. The superior mesenteric artery was occluded for 15 min followed by reperfusion. After ischemia-reperfusion, histidine decarboxylase activity and ornithine decarboxylase activity in the rat jejunal mucosa were measured in a time-dependent manner. Histidine decarboxylase activity increased 1 hr after ischemia-reperfusion, although ornithine decarboxylase activity did not; however, its activity did increase 6 hr after. The increase of ornithine decarboxylase activity was attenuated when the increase of histamine synthesis was suppressed by the inhibition of histidine decarboxylase activity caused by pretreatment with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. Pretreatment with H1-receptor antagonist attenuated the increase of ornithine decarboxylase activity after ischemia-reperfusion. These results indicate that the newly synthesized histamine, as indicated by an increase of histidine decarboxylase activity, increases ornithine decarboxylase activity after ischemia-reperfusion of the rat intestinal mucosa.