Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.

The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.     

Immunohistochemical and biochemical identification of pepsinogen isozymes in the hamster lungs: induction by polychlorinated biphenyls.

Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsinogen positive cells were observed mainly in the epithelia of the terminal bronchioles. They demonstrated morphological features of Clara cells. The pepsinogen isozyme pattern of lung tissue determined by polyacrylamide gel electrophoresis was similar to that of stomach mucosa. Treatment of hamsters with polychlorinated biphenyls at a dose of 500 mg/kg body weight ip caused a 2.8-fold increase in pepsinogen content (p less than 0.01) as well as increase in numbers of pepsinogen positive cells in the lung.     

Effects of Ageing on the Oral Absorption of d-Xylose in Rats: Analysis of Gastrointestinal Disposition

The effects of ageing on the oral (gastrointestinal) absorption of d -xylose were investigated by analysing the gastrointestinal disposition after oral administration to young (9 weeks) and old (53 weeks) rats. A linear model assuming first-order gastric emptying followed by first-order intestinal absorption was fitted to remaining fraction vs time profiles for the stomach and small intestine to estimate the gastric emptying rate constant (k_g) and the intestinal absorption rate constant (k_a). In young and old rats, k_g values were 0·087 ± 0·008 and 0·070 ± 0·007 min^?1, respectively, and k_a values were 0·020 ± 0·002 and 0·018 ± 0·002 min^?1 suggesting an insignificant effect on ageing on the rate of oral absorption. The average intestinal lumen volume (V_av) was unchanged with ageing, and so was the apparent intestinal membrane permeability clearance (CL_app) as the product of k_a and V_av. However, the small intestinal transit time (T_si) was suggested to be twice that in older rats (171 min) than in young rats (78 min) by the analysis of gastrointestinal disposition of inulin, a non-absorbable marker. It was also shown that our preceding finding of an increase in the fraction absorbed of D-xylose with ageing can be solely ascribable to the delay in intestinal transit. Thus, among various determinants of oral absorption, only T_si was found to be altered with ageing. The CL_a,app and k_a of passively absorbed drugs such as D-xylose may be generally unchanged, and the fraction absorbed may increase with ageing by the delay in intestinal transit.     

Differential Expression of Subspecies of Polyomavirus and Murine Leukemia Virus Enhancer Core Binding Protein, PEBP2, in Various Hematopoietic Cells

The core sequence of the enhancer of murine leukemia virus (MuLV) long terminal repeat is highly conserved in a large number of MuLV strains and appears to play an essential role when SL3-3 or Moloney strains induce T cell lymphoma in mice. We found by using the electrophoretic mobility shift assay that a polyomavirus enhancer core-binding protein, PEBP2, bound to this core motif of MuLV. We also noted that PEBP2 in several hematopoietic cell lines derived from B lymphocyte, macrophage and myelocyte lineages migrated significantly faster than the authentic PEBP2 detected in NIH3T3 (ibroblasts. Interestingly, PEBP2 detected in the cell lines of T lymphocyte lineage appeared to contain both types, which were indistinguishable in electrophoretic mobility from those of NIH3T3 and of B lymphocyte, macrophage and myelocyte lineages. The treatment of the nuclear extract containing PEBP2 with phosphatase generated PEBP3, which is a subcomponent of PEBP2 and retained the same DNA-binding specificity as PEBP2. The altered mobility of hematopoietic cell-derived or T lymphocyte-derived PEBP2 was found to be due to the alteration of the mobility of PEBP3. Based on the distinct mobility of PEBP2/3 of T lymphocytes from those of other hematopoietic cells, we discuss the implication of PEBP2 in MuLV-induced T cell leukemia and T cell-specific gene expression.     

Effects of various drugs on bladder function in conscious restrained-denervated rats placed in a restraining cage and produced by transection of the hypogastric nerve

We evaluated the effects of various intravenously administered drugs, which had been shown to influence bladder function in anesthetized and/or conscious rats, on the cystometrogram in conscious restrained-denervated rats (produced by transection of the hypogastric nerve) placed in a restraining cage in comparison to those in conscious restrained-intact rats (with the hypogastric nerve intact) placed in a restraining cage. The bladder capacity in the restrained-denervated rats was smaller than that in restrained-intact rats and did not change when they were transferred to a wide cage, but the bladder capacity of the restrained-intact rats decreased following transfer to the wide cage. Therefore, the activity of the hypogastric nerve in conscious rats appears to be stimulated by restraint. Atropine suppressed the amplitude of the micturition contraction (time to micturition in the cystometrogram). In the restrained-denervated rats, thiopental and indomethacin increased the bladder capacity at almost the same doses as those in restrained-intact rats, but it took a higher dose of morphine to increase the bladder capacity than in restrained-intact rats. These findings suggest that cystometrography in restrained-denervated rats is a useful method for evaluating the effect of a newly developed agent on bladder function without any influence from the hypogastric nerve.     

Influence of Osteoarthritis on Serum Marker Levels of Bone Formation and Resorption in Patients with Benign Prostatic Hypertrophy

Background :
The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH).
Methods :
Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminaltelopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p.
Results :
Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis.
Conclusion :
The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.     

Rapidly enhancing hepatic hemangiomas at MRI: Distinction from malignancies with T2-weighted images

The purpose of this study is to describe a subset of atypical hepatic hemangiomas that enhance rapidly and diffusely and to determine whether heavily T2-weighted images could distinguish between atypically enhancing liver hemangiomas and hypervascular malignancies. A retrospective search of MR records identified seven patients with liver hemangiomas that demonstrated diffuse early enhancement and 23 patients with biopsy-proven malignant liver lesions that were hypervascular on dynamic gadolinium-enhanced MR images. Quantitative analysis of signal intensity measurements was performed on the T2-weighted images, heavily T2-weighted (TE < 140), and dynamic gadolinium-enhanced images. Blinded reader comparison of the T2-weighted images and gadolinium-enhanced images was performed. Hypervascular hemangiomas enhanced to a greater degree than hypervascular malignant liver lesions on the early phase gadolinium-enhanced images. Perilesional parenchymal enhancement was demonstrated in five cases of rapidly enhancing hemangiomas. Signal intensity and contrast-to-noise ratios on the heavily T2-weighted images of the hemangiomas were significantly greater than that of the hypervascular malignant lesions (P < .05). Hemangiomas were differentiated from the hypervascular malignant liver lesions with high accuracy (97–100%) by three blinded readers based on the T2-weighted images. A subset of hemangiomas have atypical rapid diffuse enhancement on dynamic gadolinium-enhanced images. These atypical hemangiomas can be distinguished from hypervascular malignant liver lesions on T2-weighted MR images.     

Cerebrovascular reserve capacity in ischemia due to occlusion of a major arterial trunk: studies by Xe-CT and the acetazolamide test.

Classifications based on clinical and radiographic criteria have proved to be inadequate predictors of the course of cerebral ischemia or its response to therapy. In this study the cerebrovascular reserve capacity (CRC) of 46 patients with symptomatic cerebrovascular ischemia was studied by stable xenon-enhanced CT (Xe-CT) combined with the acetazolamide test. Fifteen patients had internal carotid artery (ICA) occlusion, 10 had ICA stenosis, 10 had middle cerebral artery (MCA) occlusion, and 11 had MCA stenosis. In the patients with chronic cerebral ischemia due to occlusive lesions of the ICA and MCA, the CRC was reduced most in those with MCA occlusion, followed, in descending order, by those with ICA stenosis, MCA stenosis, and ICA occlusion. Our results indicate that measurement of the CRC elucidates cerebral hemodynamic factors that cannot be detected by angiography in patients with chronic cerebral ischemia and that Xe-CT combined with the acetazolamide test is useful for this purpose.