Role of raising the upper limb of the non-rising side when performing rising movements from bed.

Rising movements from bed comprise an important aspect of recovery from the bedridden state; however, they have not been sufficiently investigated using motion analysis studies. In particular, the effect of using the upper limb of the non-rising side before waist flexion on rising movements remains to be analyzed; this study aimed to clarify this effect. Accordingly, motion analyses were performed on rising movements under two constraint conditions, namely raising the upper limb of the non-rising side (upper limb use-condition) and keeping it in contact with the pelvis (upper limb non-use-condition); subsequently, the kinematics and kinematics parameters were compared. In comparison with the upper limb use-condition, in the upper limb non-use-condition, the distance traveled by the center of mass of the body (CoM trajectory, p < 0.01) increased while switching from the half-side-lying to on-hand postures, horizontal body movement (movement speed (Normalized time/total time), p < 0.01 and weight of center of body mass (CoM momentum in horizontal plane), p < 0.05) during the same period increased, and the half-side-lying time approached the peak value of the waist flexion angular velocity (Time lag between from half-side-lying to waist angler peak velocity, p < 0.05). The compensatory movement that occurred due to the upper limb non-use-condition denoted an increase in body momentum in the horizontal direction, rather than in the sagittal plane. Therefore, the upper limb on the non-rising side contributed to the smooth movement of the body in the horizontal direction. Moreover, this study demonstrated that asymmetrical rising movement in the diagonal direction is a characteristic movement wherein the horizontal movement of the body constitutes the main movement.

Usefulness of Muscle Synergy Analysis in Individuals With Knee Osteoarthritis During Gait.

OBJECTIVE: To clarify whether there are any muscle synergy changes in individuals with knee osteoarthritis, and to determine whether muscle synergy analysis could be applied to other musculoskeletal diseases. METHODS: Subjects in this study included 11 young controls (YC), 10 elderly controls (EC), and 10 knee osteoarthritis patients (KOA). Gait was assessed on a split-belt treadmill at 3 km/h. A non-negative matrix factorization (NNMF) was applied to the electromyogram data matrix to extract muscle synergies. To assess the similarity of each module, we performed the NNMF analysis assuming four modules for all of the participants. Further, we calculated joint angles to compare the kinematic data between the module groups. RESULTS: The number of muscle modules was significantly lower in the EC (2-3) and KOA (2-3) groups than in the YC group (3-4), which reflects the merging of late swing and early stance modules. The EC and KOA groups also showed greater knee flexion angles in the early stance phase. Contrarily, by focusing on the module structure, we found that the merging of early and late stance modules is characteristic in KOA. CONCLUSION: The lower number of modules in the EC and KOA groups was due to the muscle co-contraction with increased knee flexion angle. Contrarily, the merging of early and late stance modules are modular structures specific to KOA and may be biomarkers for detecting KOA. SIGNIFICANCE: Describing the changes in multiple muscle control associated with musculoskeletal degeneration can serve as a fundamental biomarker in joint disease.

Predictors of disease course in patients with acute myocarditis.

BACKGROUND: Clinical manifestations of acute myocarditis, with distinct onset, vary from asymptomatic to fatal. The predictors of the course of the disease in patients with acute myocarditis at initial presentation have not yet been established. In this study, we examined the predictive values of various parameters in the disease course of patients with myocarditis. METHODS AND RESULTS: Twenty-one consecutive patients who had been diagnosed as having acute myocarditis by histological examinations were analyzed. The patients with myocarditis were divided into the survival group (n=13) and the fatal group (n=8). We examined the parameters of the clinical state, hemodynamic variables, required therapies, biochemical laboratory data, and cytokines. The control groups were composed of 23 patients with old myocardial infarction and 20 healthy volunteers. The fatal group had lower blood pressure and higher pulmonary capillary wedge pressure compared with those values in the survival group. Mechanical ventilation support was more frequently required in the fatal group. Serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) were significantly higher in the myocarditis group than in the 2 control groups. Furthermore, levels were significantly higher in the fatal group than in the survival group for sFas (13.93+/-4.77 versus 3.77+/-0.52 ng/mL, respectively; P:<0.001) and sFasL (611.4+/-127.7 versus 269.5+/-37.3 pg/mL, respectively; P:<0.05). Other clinical states, hemodynamic variables, required therapies, and biochemical laboratory parameters were not different between the 2 groups. CONCLUSIONS: Elevation of sFas and sFasL levels at initial presentation appear to be a good serological marker to predict the prognosis of acute myocarditis.

Protection against autoimmune myocarditis by gene transfer of interleukin-10 by electroporation.

BACKGROUND: Although immunosuppressive therapy for myocarditis has attracted a great deal of attention, its effectiveness is controversial. Interleukin (IL)-10 has a variety of immunomodulatory properties. Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe. METHODS AND RESULTS: We examined the applicability of murine IL-10 (mIL-10) gene transfer to the treatment of rats with experimental autoimmune myocarditis. Nine-week-old Lewis rats were inoculated with pig myosin (day 0). A plasmid vector expressing mIL-10 cDNA (800 microgram per rat) was transferred into the tibialis anterior muscles by electroporation 3 times (5 days before immunization and at days 4 and 13); control rats received empty plasmid. Electroporation increased the serum mIL-10 levels to >250 pg/mL. The 21-day survival rate in rats treated with mIL-10 cDNA was higher (15 of 15; 100%) than that of the control group (9 of 15; 60%). Furthermore, mIL-10 treatment significantly attenuated myocardial lesions and improved hemodynamic parameters. CONCLUSIONS: These findings showed that gene transfer into muscle by electroporation in vivo is an effective means of delivery of IL-10 for the treatment of autoimmune myocarditis.

Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis.

OBJECTIVES: Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated. BACKGROUND: The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated. METHODS: Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured. RESULTS: The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups. CONCLUSIONS: Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.

Abnormality of c-kit oncoprotein in certain patients with chronic myelogenous leukemia--potential clinical significance.

Chronic myelogenous leukemia (CML) is characterized by the Philadelphia (Ph) chromosome and bcr/abl gene rearrangement which occurs in pluripotent hematopoietic progenitor cells expressing the c-kit receptor tyrosine kinase (KIT). To elucidate the biological properties of KIT in CML leukemogenesis, we performed analysis of alterations of the c-kit gene and functional analysis of altered KIT proteins. Gene alterations in the c-kit juxtamembrane domain of 80 CML cases were analyzed by reverse transcriptase and polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP). One case had an abnormality at codon 564 (AAT --> AAG, Asn --> Lys), and six cases had the same base abnormality at codon 541 (ATG --> CTG, Met --> Leu) in the juxtamembrane domain. Because the change from Met to Leu at codon 541 was a conservative one which was also observed in the normal population and normal tissues of CML patients, it probably represents a polymorphic variation. Although samples of hair roots and leukemic cells from the chronic phase of one CML patient showed no abnormality, an abnormality at codon 541 (ATG --> CTG, Met --> Leu) was found only at blastic crisis (BC) of this case. In the case with the abnormality at codon 564, the mutation was detected only in a sample of leukemic cells collected at BC. To examine the biological consequence and biological significance of these abnormalities, murine KIT(L540) and KIT(K563) expression vectors were introduced into interleukin-3 (IL-3)-dependent murine Ba/F3 cells to study their state of tyrosine phosphorylation and their growth rate. Ba/F3 cells expressing KIT(WT), KIT(L540) and KIT(K563) showed dose-dependent tyrosine phosphorylation after treatment with increasing concentrations of recombinant mouse stem cell factor (rmSCF). The cells expressing KIT(L540) and KIT(K563) were found to have greater tyrosine phosphorylation than cells expressing KIT(WT) at 0.1 and 1.0 ng/ml of rmSCF. The Ba/F3 cells expressing KIT(K563) proliferated in response to 0.1 and 1.0 ng/ml of rmSCF as well as IL-3. The Ba/F3 cells expressing KIT(L540)showed a relatively higher proliferative response to 0.1 ng/ml of rmSCF than the response of cells expressing KIT(WT). These mutations and in vitro functional analyses raise the possibility that the KIT abnormalities influence the white blood cell counts (P < 0.05) and survival (P < 0.04) of CML patients.

Erythroid involvement in CD36 deficiency.

OBJECTIVE: The CD36 molecule is expressed in platelets, monocytes, erythroblasts, and other different tissues. The two types of platelet CD36 deficiency, types I and II, are associated with the absence and presence of CD36 on monocytes, respectively. To clarify the involvement of the erythroid lineage in CD36 deficiency, we investigated the phenotype and RNA expression of CD36. MATERIALS AND METHODS: CD36 expression was examined in 296 patients with several cardiovascular diseases in our outpatient clinic. There were 12 patients with type I deficiency and 16 with type II CD36 deficiency. A bone marrow sample was examined in five type I and four type II patients. Expression of CD36 mRNA was examined in burst-forming unit-erythroid (BFU-E). The sequences of reverse transcriptase polymerase chain reaction (RT-PCR) products of the CD36 mRNA from monocytes were examined. RESULTS: As expected, CD36 was deficient in erythroblasts from all five patients with type I deficiency. CD36 was present in erythroblasts from three of the four with type II deficiency, suggesting that their abnormality is restricted to platelets (type IIa). CD36 was unexpectedly absent from erythroblasts of a single type II patient (type IIb). CD36-specific mRNA was identified in BFU-E from each of two normals, six type I, and six type II patients, including type IIb. The sequences of RT-PCR products of the CD36 mRNA in a patient with type IIa and another with type IIb showed homozygous wild alleles. CONCLUSION: The findings provide evidence for further heterogeneity among CD36-deficient individuals and the existence of a basic principle mechanism of type II, such as glycosylation abnormality.

Low dose carvedilol inhibits progression of heart failure in rats with dilated cardiomyopathy.

The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor blocking agent) were studied in a rat model of dilated cardiomyopathy induced by autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1) (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2 months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end-diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were measured. Values were compared with those for normal Lewis rats (Group-N, n=10). Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP, LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04, 305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04 g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2 mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

Novel analysis of minimal residual disease in leukemia with TCR beta rearrangement--detection of monoclonality by single strand conformation polymorphism and PCR using a clonotype primer of leukemic T cell receptor beta-chain RNA.

Several means of analyzing minimal residual disease (MRD) in leukemia involving the rearranged T cell receptor (TCR) gene have been described. We investigated MRD in leukemia with TCR beta rearrangement by examining TCR beta-chain RNA. A complementary DNA (cDNA) corresponding to the variable region of the TCR beta-chains originating from the peripheral blood or bone marrow from four patients was amplified. Single strand conformation polymorphism (SSCP) analysis of amplified cDNA showed that all four patients had monoclonal leukemia with TCR beta rearrangement; two patients had Vbeta2+ leukemia, another patient had Vbeta14+ leukemia and the other had Vbeta9+ leukemia. Flow cytometry supported this finding. Sequencing of the Vbeta2-complementarity determining region 3 (CDR3), Vbeta9-CDR3 and Vbeta14-CDR3 revealed monoclonality. To investigate MRD using TCR beta-chain RNA, cDNA from each patient was diluted with the cDNA of a healthy person and amplified using a specific CDR3 clonotype primer. A band in the ethidium bromide-stained agarose gel was detected from samples diluted 10,000-fold. SSCP analysis determined which V region gene was utilized in monoclonal leukemic cells. The leukemic cell specific TCR, determined in such a manner, may be a target for immunotherapy. Because the MRD of T cell malignancy can be easily examined once the CDR3 clonotype primer is made, this novel analysis is considered to be a useful method.

Possible transforming activity of interferon regulatory factor 2 in tumorigenicity assay of NIH3T3 cells transfected with DNA from chronic myelogenous leukemia patients.

Little is known about the transforming gene identified in the genomic DNA of chronic myelogenous leukemia (CML) by the tumorigenicity assay. To detect a new transforming gene of CML, we re-investigated the transforming activity of interferon regulatory factor (IRF)-1 and -2 genes in the tumorigenicity assay of NIH3T3 cells transfected with genomic DNA of leukemic cells from 15 patients with CML (12 patients in the chronic phase, one in the blastic phase and two in both phases). We detected the functionally active IRF-2 gene only in the tumor DNA from two CML patients in the blastic phase. We did not detect integration of the IRF-1 gene in the DNA of any tumors derived from the CML patient samples, and also we detected no expression of human IRF-1 mRNA. Thus, NIH3T3 cells may have been transformed due to integration of the functionally active IRF-2 gene from CML patients in the blastic phase. We surmise that there is a possibility that the IRF-2 gene may be involved in the evolution of the blastic phase of CML.

A case of giant cell myocarditis with evidence of cardiac autoimmunity.

A 45-year-old-woman with giant cell myocarditis showing high titer of circulating antiheart antibodies is reported. She experienced two recurrences of myocarditis and repeatedly responded to immunosuppressive therapy using prednisolone. The titer of antiheart antibodies went up and down appropriately according to the clinical responses to immunosuppressive therapy. This case suggested that giant cell myocarditis might be related to autoimmunity.

Minimal residual disease in acute myelogenous leukemia with PML/RAR alpha or AML1/ETO mRNA and phenotypic analysis of possible T and natural killer cells in bone marrow.

Here we studied minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) who have PML/RAR alpha or AML1/ETO as well as the phenotypic analysis of lymphocyte subsets involved in antitumor immunity. Eight patients in long-term (LT; 3 to 15 years) and 15 patients in short-term (ST; up to 3 years) remission were studied. Using the reverse transcription-polymerase chain reaction (RT) assay, the limit of detection was 10(-5) to 10(-6) for PML/RAR alpha transcript and 10(-4) to 10(-5) for the AML1/ETO transcript. Simultaneously, T lymphocyte subsets and NK cells from the peripheral blood (PB) and bone marrow (BM) were investigated by flow cytometric analysis. Four of the eight patients in LT and 7 of the 15 patients in ST remission were MRD-positive. Although all MRD-positive patients in LT remission are still until now event-free, 3 of the 7 MRD-positive (MRD+) patients in ST remission soon relapsed. The total populations of CD4+, CD8+ and CD56+ [possible T-cell and natural killer (T/NK) populations] in the BM of ST patients and MRD+/LT patients were significantly (p < .01) low. The CD8+ CD28+ population showed the same tendency (p < .01-.02). The T/NK subsets in the BM of MRD-negative (MRD-) LT (MRD-/LT) patients showed similar numbers of cells as normal volunteers. Basically, the total percentage of the CD4+, CD8+ and CD56+ cell populations in the BM was increased and in the following order: MRD-/LT patients, normal volunteers, MRD+/LT patients and MRD+ or -/ST patients. The percentages of the T/NK-cell subsets in the PB were not significantly different among these groups. Thus, the difference of the possible T/NK-cell phenotype in the BM may strongly influence clinical and molecular remission. These results still remain to be confirmed by further studies of the functional anti-tumor immunity of T/NK cells of AML in remission.

Dual rearrangement of immunoglobulin and T-cell receptor genes in a case of splenic lymphoma with villous lymphocytes.

We report here a case of "splenic lymphoma with villous lymphocytes" (SLVL) which exhibited both B- and T-cell phenotypes and genotypes. The patient was a 73-year-old man. Physical examination revealed splenomegaly and lymphadenopathy. The white blood cell count was 55.2 x 10(9)/L with 70.5% atypical lymphocytes, having cytoplasmic villi, characteristic of SLVL. The atypical cells infiltrated both the red and white pulps. Immunological analysis of the peripheral leukocytes showed both B- and T-cell phenotypes (CD5,CD11c,CD19,CD20,HLA-DR, SmIgM and lambda positive). DNA analysis revealed a dual rearrangement of the immunoglobulin heavy chain gene and T-cell receptor beta gene. SLVL has been identified as a B-cell leukemia with a relatively benign clinical course. This case had both B- and T-cell pheno- and genotypes with a progressive course. To the best of our knowledge, no case of SLVL with dual genotypes has ever been reported.

Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency.

Long-chain fatty acids (LCFA) are one of the major cardiac energy substrates, so understanding LCFA metabolism may help in elucidating the mechanisms of various heart diseases. CD36 is a multifunctional membrane glycoprotein that acts not only as a receptor for thrombospondin, collagen and oxidized low density lipoprotein but also as a receptor for LCFA. We investigated the relationship between CD36 expression in myocardial capillary endothelial cells and myocardial LCFA uptake in patients with CD36 deficiency. We analyzed CD36 expression in blood cells from 250 patients with heart diseases by means of a flow cytometer. In 218 patients, myocardial LCFA scintigraphy was performed with 123I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP). In 5 patients, myocardial capillary endothelial cells were examined immunohistochemically for CD36 expression. Eleven patients (4%) showed signs of type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Twenty patients (8%) had type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 11 patients with type I CD36 deficiency, no BMIPP accumulation was observed in the heart, but in 13 patients with type II CD36 deficiency, BMIPP accumulation in the heart was focally reduced, but there were no patients without BMIPP accumulation in the heart. Although the myocardial capillary endothelial cells from two CD36-positive patients expressed CD36, those from two patients with type I CD36 deficiency did not. In a patient with type II CD36 deficiency, some capillary endothelial cells displayed patchy CD36 expression. CD36 deficiency was documented in 31 (12%) patients with heart diseases. Because CD36 was not expressed in the myocardial capillary endothelial cells in patients with type I CD36 deficiency, type I CD36 deficiency is closely related to lack of myocardial LCFA accumulation and metabolism in the myocardium.

[Clinical studies of effectiveness of ceftezole (Falomesin 'Chugai') on the infectious disease in infancy and childhood (author's transl)].

Clinical studies of the effectiveness of ceftezole (Falomesin 'Chugai') were performed on 50 cases of infants and children with infectious disease during November 1978 and February 1979. Effective results were obtained in 86% of subjects with remarkable effect especially in the group of acute upper respiratory disease. No side effect was detected in our study while elevated mean value of platelet count was observed after medication.

[Variations of clinical rest position in complete denture-wearing subjects].

With a view to proposing concrete grounds for the measurement of the rest vertical dimension on the face in the establishment of the vertical dimension of occlusion for edentulous patients, 20 complete denture-wearing subjects were made to take a clinical rest position by 4 different denture-wearing patterns, i.e. setting both dentures (UL), setting maxillary denture only (U), setting mandibular denture only (L) and completely edentulously (O), and were measured for the distance between 2 points on the face by slide calipers masking the reading part. The data were statistically analyzed and the following results were obtained. 1) Rest vertical dimension was largest for L, and significant differences were noted between UL, O, U and L, but not between UL and O, between UL and U and between O and U. 2) No significant difference in rest vertical dimension was noted between subjects of not more than 65 years and those of not less than 65 years. 3) No significant difference in rest vertical dimension was noted between the group of subjects of not more than 6 edentulous years and that of subjects of not less than 6 edentulous years. 4) The above results give suggestions to the measurement and evaluation of the vertical dimension between 2 points on the face when jaws are in the vertical relationship with the clinical rest position, in the establishment of the vertical dimension of occlusion.