Biomedical subjects

Y Kawakami

Publications and source records attributed to Y Kawakami.

At least 127 records · Page 7Linked to original sources

PubMed2000

kappa-Opioid inhibits catecholamine biosynthesis in PC12 rat pheochromocytoma cell.

It was reported that nicotine-induced dopamine release in the rat pheochromocytoma cell line, PC12 cells, was inhibited by kappa-opioid. However, it is not known whether inhibition of catecholamine biosynthesis is involved in the inhibitory mechanisms of kappa-opioids in PC12 cells. U-69593 (a kappa-opioid agonist: >/=100 nM) significantly inhibited the nicotine-induced increase of tyrosine hydroxylase (TH, a rate-limiting enzyme in biosynthesis of catecholamine) enzyme activity and TH mRNA levels. These inhibitory effects were completely reversed by naloxone and nor-binaltorphimine dihydrochloride (nor-BNI), a specific kappa-antagonist, whereas pertussis toxin (PTX) only partially reversed this inhibitory effect. Also, U-69593 (>/=100 nM) significantly inhibited the nicotine-induced increase of cAMP production. This inhibitory effect was completely reversed by naloxone and nor-BNI, whilst only partially reversed by PTX. Moreover, U-69593 (>/=100 nM) significantly inhibited the nicotine-induced increase of both the TH protein level and intracellular catecholamine levels. These results indicate that the anti-cholinergic actions of kappa-opioid can be explained partially by its inhibition of both TH enzyme activity and TH synthesis, through suppression of the cAMP/protein kinase A pathway. It would also appear that the PTX-sensitive G-protein mediates the inhibitory effect of this pathway, at least in part.

Animals↗

PubMed2000

Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a regulator of tumor growth. Although positive and negative effects of MIF on tumor cell growth have been reported, to the authors' knowledge the precise role of MIF in tumorigenesis remains unclear. In the current study the authors assessed expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient prognosis. METHODS: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 74 patients with primary lung adenocarcinoma (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In addition, expression of MIF mRNA in the cancerous tissue was investigated using in situ hybridization. Patient prognosis was evaluated with regard to MIF expression levels and its distribution was analyzed with the Kaplan-Meier method. RESULTS: MIF mRNA and MIF protein were observed in the bronchial epithelium, alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF mRNA and protein were observed at much higher levels than in the normal alveolar epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in all tumor specimens examined. MIF protein also was observed in the nuclei of tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei of tumor cells from 15 patients (20.3%). The patients without nuclear MIF expression had a worse prognosis compared with those patients with MIF expression in the nuclei (P = 0.04). CONCLUSIONS: The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung.

Adenocarcinoma↗

PubMed2000

TCR/CD3-Induced activation and binding of Emt/Itk to linker of activated T cell complexes: requirement for the Src homology 2 domain.

Expressed in mast and T cells/inducible T cell tyrosine kinase (Emt/Itk), a Tec family protein tyrosine kinase, is critical for the development and activation of T lymphocytes. The mechanism through which Emt/Itk mediates its effector functions is poorly understood. In this study, we show that the Emt/Itk Src homology 2 (SH2) domain is critical for the transphosphorylation and activation of Emt/Itk catalytic activity that is mediated by TCR/CD3 engagement. Furthermore, we find that the Emt/Itk SH2 domain is essential for the formation of TCR/CD3-inducible Emt/Itk-LAT complexes, whereas the SH3 domain and catalytic activity are not required. The Emt/Itk-linker of activated T cells (LAT) complexes are biologically important because Jurkat T cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Confocal microscopy reveals that in activated cells, LAT complexes colocalize with TCR/CD3. The present data suggest that upon TCR/CD3 engagement, the Emt/Itk SH2 domain mediates the formation of a molecular complex containing Emt/Itk, LAT, and TCR/CD3; this complex is essential for Emt/Itk activation and function.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk and Syk.

Two protein-tyrosine kinases, Bruton's tyrosine kinase (Btk) and Syk, and members of the protein kinase C (PKC) subfamily of serine/threonine kinases play crucial roles in signal transduction through antigen receptors in B lymphocytes and high-affinity IgE receptors (FcepsilonRI) in mast cells. The present study provides genetic, biochemical, and pharmacological evidence that, on FcepsilonRI stimulation, Syk regulates Btk, and Btk selectively regulates the membrane translocation and enzymatic activity of PKCbetaI among the conventional PKC isoforms (alpha, betaI, and betaII) expressed in mast cells. Syk/Btk-mediated PKCbetaI regulation is involved in transcriptional activation of the IL-2 and tumor necrosis factor alpha genes through the JNK pathway induced by FcepsilonRI stimulation. Accordingly, FcepsilonRI-induced production of these cytokines is inhibited by specific inhibitors of Btk and Syk, as well as broad-specificity inhibitors of PKC and a selective inhibitor of PKCbeta. Specific regulation of PKCbetaI by Btk is consistent with the selective association of Btk with PKCbetaI. Components of this signaling pathway may represent an attractive set of potential targets of pharmaceutical interference for the treatment of allergic and other immunologic diseases.

Agammaglobulinaemia Tyrosine Kinase↗

PubMed2000

Angiotensin-II subtype 2 receptor agonist (CGP-42112) inhibits catecholamine biosynthesis in cultured porcine adrenal medullary chromaffin cells.

Angiotensin II subtype 2 receptor (AT(2)-R) is abundantly expressed in adrenal medullary chromaffin cells. However, the physiological roles of AT(2)-R in chromaffin cells remain to be clarified. Therefore, we investigated the effects of CGP42112 (AT(2)-R agonist) on catecholamine biosynthesis in cultured porcine adrenal medullary cells. We initially confirmed AT(2)-R was predominantly expressed in porcine adrenal medullary cells by [(125)I]-Ang II binding studies. CGP42112 (>==1 nM) significantly inhibited cGMP production from the basal value. Tyrosine hydroxylase (TH) is a rate-limiting enzyme in the biosynthesis of catecholamine, and its activity is regulated by both TH-enzyme activity and TH-synthesis. CGP42112 (>==1 nM) significantly inhibited TH-enzyme activity from the basal value. These inhibitory effects of CGP42112 on TH-enzyme activity and-cGMP production were abolished by PD123319 (AT(2)-R antagonist) while CV-11974 (AT(1)-R antagonist) was ineffective. We also tested whether decrease of cGMP is involved in the inhibitory effect of CGP42112 on TH-enzyme activity. Pretreatment of 8-Br-cGMP (membrane-permeable cGMP analogue) prevented the inhibitory effect of CGP 42112 on TH-enzyme activity. Similar to that of TH-enzyme activity, CGP42112 (>==1 nM) significantly reduced TH-mRNA and TH-protein level from the basal value, and these inhibitory effects were abolished by PD123319 but not CV-11974. These findings demonstrate that CGP 42112 reduces both TH-enzyme activity and TH-synthesis and that these inhibitory effects could be mediated by decrease of cGMP production.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Telomere reduction in human liver tissues with age and chronic inflammation.

Telomere shortening in human liver with aging and chronic inflammation was examined by hybridization protection assay using telomere and Alu probes. The reduction rate of telomere repeats in normal liver (23 samples from patients 17-81 years old) was 120 bp per year, which is in good agreement with the reported reduction rate in fibroblasts of 50-150 bp at each cell division and replacement rate of human liver cells, once a year. Mean telomere repeat length shortened to about 10 kbp in normal livers from 80-year-old individuals. The number of telomere repeats in chronic hepatitis (26 samples) and liver cirrhosis (11 samples) was significantly lower than that in normal liver of the same age (P < 0. 01). Telomere length in all these chronic liver disease samples, other than two exceptions, was not reduced shorter than 5 kbp, which was assumed to give a limit of proliferation (Hayflick's limit) to untransformed cells.

Adolescent↗

PubMed2000

Detection of alternatively spliced variant messages of Fas gene and mutational screening of Fas and Fas ligand coding regions in peripheral blood mononuclear cells derived from silicosis patients.

Silicosis is clinically characterized not only by respiratory disorders but by immunological abnormalities such as the appearance of autoantibodies and complications of autoimmune diseases. Dysregulation of apoptosis, particularly in the Fas/Fas ligand (FasL) pathway, has been considered to play a role in the pathogenesis of autoimmune diseases. It has been found that serum soluble Fas (sFas) levels are elevated in silicosis patients (SIL) and the sFas message is dominantly expressed in peripheral blood mononuclear cells (PBMC) derived from these individuals. In the present study, one tried to detect alternatively spliced variant messages including typical sFas message and found four that were highly and frequently expressed, and which possess a signal peptide domain, but not transmembrane and signal transducing domains, in PBMC derived from SIL. Functional mutations were not detected in Fas and FasL genes in silicosis PBMC. Still, alternative spliced variants of the Fas gene including typical sFas message appear to play an important role in the immunological dysregulation in SIL.

Aged↗

PubMed2000

Identification of chick frizzled-10 expressed in the developing limb and the central nervous system.

We have identified chick frizzled (Fz)-10, encoding a Wnt receptor, and examined the expression pattern during embryogenesis. Fz-10 is expressed in the region posterior to the Hensen's node at stage 6. Fz-10 expression is detected in the dorsal domain of the neural tube and the central nervous system of the developing embryo. In the developing limb, Fz-10 expression starts at stage 18 in the posterior-dorsal region of the distal mesenchyme, and gradually expands to the anterior-distal region. Fz-10 is also expressed in the feather bud and branchial arch. Implantation of Sonic hedgehog (Shh)-expressing cells into the anterior margin of the limb bud resulted in the induction of Fz-10 expression in anterior-dorsal mesenchyme.

Amino Acid Sequence↗

PubMed2000

Differential retinoblastoma and p16(INK4A) protein expression in neuroendocrine tumors of the lung.

BACKGROUND: Neuroendocrine neoplasms of the lung represent a wide spectrum of phenotypically and biologically distinct entities. Their histopathologic diagnosis, which carries therapeutic and prognostic significance, may sometimes be difficult because of their overlapping features. We previously demonstrated that large cell neuroendocrine carcinomas (LCNECs) and small cell lung carcinomas (SCLCs) failed to show positive nuclear staining of RB protein (RB-), whereas typical and atypical carcinoids (TCs and ACs) showed nuclear RB immunostaining (RB+). METHODS: In the current study, a series of 58 surgically resected lung tumors, of which 33 tumors were initially diagnosed as SCLCs and 25 as TCs or ACs, were studied for RB and p16 protein expression by immunohistochemistry. They were also reviewed for their pathologic diagnosis; the reviewers were blinded to the RB and p16 protein status. RESULTS: Nineteen tumors were diagnosed as TCs, 5 as ACs, 7 as LCNECs, and 27 as SCLCs. Three of seven LCNECs were RB+, whereas the other four were RB-. In contrast, all 19 TCs were RB+ and all 27 SCLCs were RB-. In addition, two of five ACs were RB+, whereas the other three were RB-. Interestingly, all 3 RB+ LCNECs and the 1 RB+ AC tested failed to show nuclear staining of p16 protein in any tumor cells (p16-), although some normal stromal cells showed nuclear staining of p16 protein (p16+) as positive internal controls, indicating loss of p16 function in these tumors. It is also noteworthy that the three RB+ LCNECs were initially diagnosed as SCLCs and one of the RB- ACs was initially considered a TC. With the exception of TCs, tumors were significantly more prevalent among heavy smokers with >20 pack-years compared with nonsmokers and light smokers with < or = 20 pack-years (P < 0.01). CONCLUSIONS: These findings suggest that all SCLCs and LCNECs have abnormalities in the p16:RB pathway, as do at least certain ACs, whereas the p16:RB pathway is normal in TCs.

Adult↗

PubMed2000

Precancerous hepatic nodules had significant levels of telomerase activity determined by sensitive quantitation using a hybridization protection assay.

BACKGROUND: Telomeric repeat amplification protocol using internal telomerase assay standard (ITAS) (conventional TRAP) has detected telomerase activity in various malignant tumors. With conventional TRAP, it is difficult to differentiate quantitatively low levels of telomerase activity between well-differentiated hepatocellular carcinomas (HCCs) and dysplastic nodules because of quantitative limitation. To apply a telomerase assay for differential diagnosis, we used a hybridization protection assay combined with TRAP (TRAP/HPA). This combination had better sensitivity and wider linearity than conventional TRAP. METHODS: TRAP/HPA was applied for quantitative measurement of telomerase activity in various hepatic tissues. Telomerase activity was evaluated in 10 precancerous hepatic nodules, 17 well-differentiated HCCs, 19 moderately differentiated HCCs, 5 poorly differentiated HCCs, 22 nontumorous chronic hepatic disease samples, and 2 normal liver tissues. RESULTS: Telomerase activity in HCCs tended to increase according to the malignant transformation. The average relative telomerase activity in 0.6 microg protein, which was expressed as cell equivalent activity of MKN-1, a gastric carcinoma cell line, was 8.5 in precancerous hepatic nodules, 87 in well-differentiated HCCs, 265 in moderately differentiated HCCs, 447 in poorly differentiated HCCs, and 0.4 in nontumorous hepatic tissues, including chronic liver diseases. CONCLUSIONS: TRAP/HPA was sensitive enough to distinguish the telomerase activity in precancerous hepatic nodules from that in other lesions. Telomerase activity in precancerous hepatic nodules was higher than that in nontumorous hepatic tissues. However, the activity in precancerous hepatic nodules was lower than that in well-differentiated HCCs, although statistically not significant. The authors suggest that precancerous hepatic nodules with telomerase activity above the diagnostic cutoff level (twice the highest activity in nontumorous hepatic tissues, or the 2 cell equivalent activity of MKN-1) should be treated as malignancy.

DNA Primers↗

PubMed2000

T cells that are autoreactive to beta2-glycoprotein I in patients with antiphospholipid syndrome and healthy individuals.

OBJECTIVE: To identify the T cells responsive to beta2-glycoprotein I (beta2GPI) that mediate antiphospholipid antibody production in patients with antiphospholipid syndrome (APS). METHODS: In vitro proliferative responses and anti-beta2GPI antibody production induced by beta2GPI were examined in peripheral blood mononuclear cell (PBMC) cultures from 12 APS patients, 13 systemic lupus erythematosus patients without APS, and 12 healthy donors. RESULTS: Peripheral blood T cells from all subjects failed to respond to beta2GPI in its native form. In contrast, reduced beta2GPI was able to stimulate T cells not only from all 12 patients with anti-beta2GPI antibodies, but also from 10 of 25 individuals without anti-beta2GPI antibodies. The specificity of the responses to beta2GPI was confirmed by activation of the reduced beta2GPI-primed T cells by recombinant beta2GPI in secondary cultures. Characterization of the T cell response induced by beta2GPI revealed that the response was associated with the presence of the DR53-associated alleles, the responding T cells were CD4+ and restricted by HLA class II, and antigenic peptides were located in domains IV and/or V. Anti-beta2GPI antibody production was induced specifically in anti-beta2GPI antibody-positive patients, in PBMC cultures with reduced beta2GPI. Anti-beta2GPI antibodies produced in vitro recognized beta2GPI immobilized with cardiolipin or beta2GPI coated on "high-binding" polystyrene plates. CONCLUSION: These results strongly suggest that CD4+ and HLA class II-restricted T cells responsive to beta2GPI are involved in the production of antiphospholipid antibodies in APS patients.

Adult↗

PubMed2000

Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis.

OBJECTIVE: To examine serial changes in serum anti-topoisomerase I (anti-topo I) antibody levels in patients with systemic sclerosis (SSc), as well as associations with clinical features and the in vivo activation status of circulating topo I-reactive T and B cells. METHODS: Serum anti-topo I antibody levels were serially measured at different time points in 28 SSc patients who were positive for anti-topo I antibody at their first visit (range of followup 6-29 years). The patients were subgrouped according to the disappearance (group 1) or persistence (group 2) of anti-topo I antibody. Clinical findings as well as T and B cell responses to topo I were compared between these 2 groups. RESULTS: Serum anti-topo I antibody disappeared during the period of followup in 6 patients (group 1), but persisted in 22 patients (group 2). Loss of anti-topo I antibody occurred within 10 years after the first visit and independently of treatment. Group 1 patients had less extensive skin and lung involvement and better survival rates than did group 2 patients. Complete loss of anti-topo I antibody followed a reduction in isotype expression and epitope reactivities. The kinetics of in vitro T cell proliferation induced by topo I were delayed and circulating topo I-reactive T cells were less frequently detected in group 1 versus group 2 patients, suggesting that the disappearance of anti-topo I antibody was due to loss of activation of topo I-reactive T cells. In vitro production of anti-topo I antibody in peripheral blood mononuclear cell cultures in response to antigenic stimulation in both group 1 and group 2 patients indicated persistence of anti-topo I antibody-producing "memory" B cells even after the loss of serum anti-topo I antibody. CONCLUSION: Our results indicate that there is a distinct subset of anti-topo I-positive SSc patients who lose anti-topo I antibody during the disease course and have a favorable outcome. In vivo production of anti-topo I autoantibody may require antigenic stimulation that activates topo I-reactive T and B cells.

Antibody Formation↗

PubMed2000

Modulatory roles of RANTES in IL-4 production by human blood CD4(+)T cells.

An increase in serum IgE levels has been reported in several thrombotic cardiovascular diseases. Since such diseases are associated with the activation of platelets, we hypothesized that platelets are implicated in a mechanism leading to heightened IgE synthesis. To this end, we performed an in vitro investigation of the effects on IL-4 production caused by several bioactive substances potentially released from platelets. Human blood CD4(+)T cells from blood donors were stimulated with anti-CD3 antibody and costimulatory signals delivered via CD58 and CD80 in the presence or absence of IL-4. One of the following test substances was also included in the culture: platelet factor-4, beta-thromboglobulin, platelet-derived growth factor, serotonin, platelet activating factor, or RANTES. The cells were restimulated in the absence of IL-4 and test substances. Among the six substances, RANTES alone exhibited significant effects on IL-4 production. RANTES enhanced IL-4 production in the presence of IL-4, whereas it suppressed IL-4 production in the absence of IL-4. The enhancing effect of RANTES was positively correlated with plasma IgE levels in the donors. We concluded that RANTES may induce IgE synthesis by increasing IL-4 production in individuals predisposed to high IgE responses. Our observations indicate a link between platelets and immune phenomena associated with increased IgE responses.

Adult↗

PubMed2000

Phantom study of fusion image of CT and SPECT with body-contour generated from external Compton scatter sources.

PURPOSE: A phantom study was conducted to evaluate the feasibility of body contour definition with Compton scatter photons from external sources of technetium-99m pertechnetate (Tc-99m) to create a fusion image of CT and SPECT images. METHODS: External sources of 1 mCi (37 MBq) Tc-99m were placed on each collimator, and body-contour SPECT images were obtained with an energy window of 100 keV +/- 25% for detecting 90 degrees and 180 degrees Compton scatter photons of Tc-99m from the body surface in water-filled cylindrical and hexagonal phantoms, and in a chest phantom with a Tc-99m-avid simulated lung nodule and multimethod surface markers. In the chest phantom, each transaxial SPECT slices was registered with the corresponding CT slice by using image-matching soft ware. A summation of the registered images yielded a three-dimensional (3-D) fusion image of this phantom. RESULTS: This method clearly visualized the body contour on all the SPECT slices in all the phantoms except for the complex hexagonal phantom. There was no significant difference between the known and SPECT-measured diameters of the cylindrical phantom. The fit of CT and SPECT images of the chest phantom was achieved with a mean alignment error of 5% in visual inspection, which was improved to 0.2% after correction of the magnification of the SPECT images according to the resultant dimensional differences. The 3-D fusion image of this phantom effectively visualized the anatomic location of the lung nodule and surface markers. CONCLUSION: This simple method effectively provided boundary information on the cold phantoms. Although further improvements in the registration technique with CT images are desirable, the body-contour SPECT image obtained by this method has the potential for accurately creating a 3-D fusion image with CT images, and is a feasible way of anticipating the anatomical localization of a target tissue.

Humans↗

PubMed2000

Changes in the elastic properties of tendon structures following 20 days bed-rest in humans.

The purpose of this study was to investigate the effects of 20 days bed-rest on the elastic properties of tendon structures of the human knee extensor muscles in vivo. Six healthy men carried out a 6 degrees head-down bed-rest for 20 days. Muscle volume and maximal voluntary contraction (MVC) torque of the quadriceps femoris muscle significantly decreased by an average of 7.8 (SD 2.7)% and 14.9 (SD 6.9)%, respectively. Before and after bed-rest, the elongation (l) of the tendon and aponeurosis of vastus lateralis muscle was measured directly by ultrasonography, while the subjects performed ramp isometric knee extension up to MVC. The extent of l tended to be greater after bed-rest. The l above 110 N was significantly greater after bed-rest. Furthermore, the mean stiffness after bed-rest [35.5 (SD 7.8) N x mm(-1)] was significantly lower than that before bed-rest [52.6 (SD 19.2) N x mm(-1)]. The rate of torque development significantly reduced after bed-rest by an average of 47%, and the bed-rest induced a lengthening in the electromechanical delay (mean 21%). These results suggest that bed-rest results in a decrease in the stiffness of tendon structures with a reduction of muscle strength and volume. These adaptations of the tendon structures to bed-rest would bring about the changes in electromechanical delay and rate of torque development.

Adult↗

PubMed2000

Elastic properties of muscle-tendon complex in long-distance runners.

The purpose of this study was to investigate the elastic properties of muscle-tendon complex (MTC) in knee extensor muscles and the capacity for elastic energy utilization in long-distance runners (LDR) by comparing with data obtained from untrained individuals (CON). The elongation (L) of the tendon and aponeurosis of vastus lateralis muscle during isometric knee extension was determined by real-time brightness mode ultrasonography, while the subjects developed a gradually increasing torque from 0 (relaxed) to maximal effort (MVC) within 7 s. In addition, performances in two kinds of maximal vertical jumps, i.e. squatting (SJ) and counter-movement jumps (CMJ), were measured. The relationship between L muscle and force (F) was curvilinear and consisted of an initial region (toe region), characterized by a large increase in L with increasing F, immediately followed by a linear region. The slope of the regression equation for the L-F relationship in the range 50%-100% of MVC was defined as an index of MTC compliance, where the rate of the changes in L to that in muscle F at every 10% of MVC became almost constant. The maximal L (Lmax) and MTC compliance were significantly lower in LDR than in CON: 29.9 (SD 3.9) mm in LDR compared to 33.3 (SD 5.5) mm in CON for Lmax and 1.55 (SD 0.25) x 10(-2) mm.N-1 in LDR compared to 1.88 (SD 0.82) x 10(-2) mm.N-1 in CON for MTC compliance. Also, LDR showed significantly less elastic energy absorption (Ee) than CON, defined as the area below the L-F relationship curve from 0 to 100% of MVC. Not only jump heights but also the differences between the heights in SJ and CMJ, expressed as the percentage of the height in SJ, were significantly lower in LDR than in CON. The augmentation with counter-movement was significantly correlated to either MTC compliance (r = 0.554, P < 0.05) or Ee (r = 0.563, P < 0.05). Thus, the present results would indicate that MTC of vastus lateralis muscle is less compliant and its potential for energy storage during MTS lengthening is lower in LDR than untrained individuals. These elastic profiles of vastus lateralis muscle in LDR may be associated with their lower performances during CMJ.

Adult↗

PubMed2000

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia.

Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports.

Aged↗

PubMed2000

Interaction between series compliance and sarcomere kinetics determines internal sarcomere shortening during fixed-end contraction.

The interaction between contractile force and in-series compliance was investigated for the intact skeletal muscle-tendon unit (MTU) of Rana pipiens semitendinosus muscles during fixed-end contraction. It was hypothesized that internal sarcomere shortening is a function of the length-force characteristics of contractile and series elastic components. The MTUs (n=18) were dissected, and, while submerged in Ringer's solution, muscles were activated at nine muscle lengths (-2 to +6 mm relative to optimal length in 1 mm intervals), while measuring muscle force and sarcomere length (SL) by laser diffraction. The MTU was clamped either at the bone (n=6), or at the proximal and distal ends of the aponeuroses (n=6). Muscle fibers were also trimmed along with aponeuroses down to 5-20 fibers and identical measurements were performed (n=6). The magnitude of shortening decreased as MTU length increased. The magnitude of shortening ranged from -0.08 to 0.3 microm, and there was no significant difference between delta SL as a function of clamp location. When aponeuroses were trimmed, sarcomere shortening was not observed at L(0) and longer. These results suggest that the aponeurosis is the major contributor to in-series compliance. Results also support our hypothesis but there also appear to be other factors affecting internal sarcomere shortening. The functional consequence of internal sarcomere shortening as a function of sarcomere length was to skew the muscle length-tension relationship to longer sarcomere lengths.

Animals↗