Rheumatoid arthritis in patients aged above 75 years old at onset]

Elderly onset rheumatoid arthritis (RA) is difficult to diagnose definitively when the patients note their first symptoms of arthritis above the age of 75 years old. In this report, we reviewed the clinical features of elderly onset RA and its diagnosis. The subjects included 4 females, aged 78, 83, 84 and 93 years, respectively. The onsets were abrupt in 2 cases and more slowly arriving in the other 2. Shoulder joints and wrist joints were involved in all cases. Knee joints, finger joints and foot joints were involved in 3 cases and the elbow was involved in one case. Anti-RA treatment quickly attenuated the acute and severe arthritis and brought down the high CRP level associated with vivid inflammatory activity of RA. The RAPA value was very high in all but one of the cases. Severe destructive findings in radiography was undetectable in the major joints (e.g. shoulder, hip and knee joints). Radiographic findings in wrist and finger joints were also very difficult to differentiate from arthrosis and osteoporosis. On the other hand, RA involvement in the cervical spine was certain in the radiographs; 1 case had anterior atlantoaxial subluxation and 2 cases had subaxial intervertebral erosion. Pathological radiographic findings in the cervical spine are useful for the diagnosis of elderly onset RA.     

Living-Donor Liver Transplantation for Hepatoblastoma

Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pre-treatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.     

Changes in pulmonary circulation during the early postoperative period following single lung transplantation

This study examines the pulmonary hemodynamics during reimplantation and rejection following unilateral lung transplantation in dogs. Nineteen mongrel dogs were divided into three groups according to the method of treatment used: group 1 (n = 6) underwent modified autotransplantation of the left lung; group 2 (n = 6), allotransplantation without immunosuppression; and group 3 (n = 7), allotransplantation with immunosuppression. The pulmonary arterial blood flow and ventilation scores, assessed by chest X-rays, were measured for 2 weeks postoperatively. Pulmonary blood flow to the transplanted lung decreased slightly in group 1, whereas in group 2, it decreased sharply from the 3rd postoperative day (POD) and was almost completely absent by the 14th POD. In group 3, it decreased by 28% on the 1st POD but recovered gradually to 37% by the 14th POD. Ventilation scores were the same among the three groups on the 1st POD but in group 2, they decreased rapidly from the 3rd POD. This change correlated well with that of the pulmonary arterial (PA) flow, although the ventilation score changed after the PA flow did. In conclusion, rejection was reflected earlier and more distinctly by the changes in PA flow than by chest X-rays.     

The effect of hyperoxia on the lungs of rats deficient in essential fatty acids

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.(Murakami R, Obara H, Momota T et al.: The effect of hyperoxia on the lungs of rats deficient in essential fatty acids. J Anesth 3: 149–154, 1989)     

A new liver metastatic and peritoneal dissemination model established from the same human pancreatic cancer cell line: analysis using cDNA macroarray

To elucidate the mechanisms of metastasis, we established two sublines HPC-1H5 with a highly liver metastatic cell line and HPC-1P5a with a highly peritoneal disseminating cell line, which were sequentially selected from the parental pancreatic cancer cell line HPC-1. Using these three cell lines, we investigated several biological properties and mRNA levels of differentially-expressed genes involved in cancer metastasis by cDNA macroarray. Microscopic findings for the three cell lines were the same. The tumorigenicity, in vitro growth ability, motile activity, adhesive activity and the production of IL-8 of metastatic sublines were higher than those of parental HPC-1 cells. Particularly, HPC-1H5 cells showed clearly higher levels of IL-8 expression and tumors of HPC-1H5 cells grew faster and bigger than those of HPC-1P5a cells. In cDNA macroarray analysis of HPC-1H5 cells, 22 genes were up-regulated and 44 genes were down-regulated compared with parental HPC-1 cells. In HPC-1P5a cells, 9 genes were up-regulated and 28 genes were down-regulated compared with parental HPC-1 cells. This study provides a demonstration of global gene expression analysis of pancreatic cancer cells with liver metastasis and peritoneal dissemination. Furthermore, our results provide a new insight into the study of liver metastasis and peritoneal dissemination of human pancreatic cancer. This revised version was published online in July 2006 with corrections to the Cover Date.     

Calcitonin inhibits proton extrusion in resorbing rat osteoclasts via protein kinase A

Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H(+) transport. In this study, we examined the effects of calcitonin on H(+) extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2'7'-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H(+) extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H(+)-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A(1)-sensitive and an amiloride-sensitive system [H(+) extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na(+)/H(+) exchanger (NHE), respectively]. Calcitonin inhibited both H(+) extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H(+) extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H(+) transport by calcitonin are important for the regulation of bone resorption.     

Polymer conformation and NMR chemical shifts, 9. Poly(α-methylene-γ-butyrolactone)

The conformational energies of poly(α-methylene-γ-butyrolactone) are calculated and compared with those of poly(methyl methacrylate). In spite of the structural resemblance of these two polymers, the patterns of the energy contour maps are clearly distinguishable from each other; the energy barriers between rotational isomeric states are appreciably higher in the former than in the latter polymer. The calculation indicates large non-bonded interactions between the protons in one lactone ring and those in the adjacent lactone rings. The broad NMR spectrum of poly(α-methylene-γ-butyrolactone) apparently reflects its rigid conformational structure. ¹H and ¹³C NMR chemical shifts are calculated by theoretical shielding calculations based on conformational analysis. Much lower magnetic field resonances of the O? CH₂ and α-CH₂ carbons in poly(α-methylene-γ-butyrolactone) as compared with those of the O? CH₃ and α-CH₃ carbons in poly(methyl methacrylate) are well reproduced by the calculation. The shift to lower magnetic field is mainly attributed to paramagnetic shielding derived from the interaction between O? CH₂ carbon and α-CH₂ carbon. Tacticity- and conformation-dependent ¹H and ¹³C NMR chemical shifts of poly(α-methylene-γ-butyrolactone) are well interpreted on the basis of the conformational analysis.     

Ramp rate of blood pressure changes does not affect aortic afferent sensitivity in anesthetized rats

To investigate whether the rate of change in blood pressure affects the sensitivity of the aortic baroreceptor afferent response, the change in aortic nerve activity (ANA) to two different rates of ramp increase in mean blood pressure (MBP), elicited by phenylephrine administration, was determined in the rat under urethane (1.5 g kg⁻¹) anesthesia. The sensitivity of the increase in ANA following a rapid (average ramp rate, 9.14 ± 0.60 mmHg s⁻¹, n = 11) or gradual (1.78 ± 0.24 mmHg s⁻¹, n = 11) increase in MBP was 2.03 ± 0.14% and 1.81 ± 0.20% of baseline mmHg⁻¹, respectively. These values were not significantly different from each other (P = 0.16). Furthermore, we found no correlation between the rate of ramp increase in MBP and the sensitivity of the increase in ANA (r = 0.24, P = 0.29, n = 22). These results suggest that, at least within the normal physiological range of MBP, the rate of the ramp change in blood pressure does not affect aortic baroreceptor afferent sensitivity in the anesthetized rat.     

Polymer conformation and NMR chemical shifts, 6. Alternating copolymer of α-methylene-γ-butyrolactone with styrene

In view of the structural resemblance of α-methylene-γ-butyrolactone to methyl methacrylate, conformation and NMR chemical shifts of poly(α-methylene-γ-butyrolactone-alt-styrene). are calculated and compared with those of poly(methyl methacrylate-alt-styrene). The conformational energy surfaces for the dyad sequence models of the both copolymers are analogous to each other, as is expected from the similarity in the constituting monomeric units. Agreement of calculation with observation is satisfactory with respect to the cotacticity-dependent splittings in the ¹³C NMR spectra and is improved by the fixation of a substituent in poly(α-methylene-γ-butyrolactone-alt-styrene). Calculation of ¹H chemical shifts gives an alignment of NMR signals which is in accordance with the observation.