[A case of nutcracker esophagus complicated with angina pectoris].
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Angina Pectoris↗
Biomedical subjects
K Mizuno
Publications and source records attributed to K Mizuno.
[Cofilin phosphorylation and regulation of actin cytoskeletal reorganization by LIM-kinase].
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Actin Depolymerizing Factors↗
[The long-term result of implant arthroplasty for hallux valgus deformity in rheumatoid arthritis].
We have reviewed the results of reconstruction of the forefoot in rheumatoid patients with arthroplasty using a Swanson flexible hinge toe implant for the great toe and with resection arthroplasty for the lateral four toes. The follow-up averaged 8 years (range, 5-11 years). All patients were female and an average age was 52 (range, 31-72 years). Preoperative and postoperative hallux valgus angle (HVA), the angles between the axes of the first and second metatarsal shafts (M1-M2) and the first and fifth metatarsal shafts (M1-M5) were measured radiographically. Breakage of the implant and radiolucencies around the implant on X-ray were evaluated. Preoperative average HVA, M1-M2 and M1-M5 were 31, 10, and 30 respectively. Postoperative average HVA, M1-M2, and M1-M5 were 17, 10, and 28 respectively. Breakage of the implant was present in 77% of the feet and the radiolucencies around the implant was present in 63% of the feet. Although only one foot was performed revision surgery for severe pain and breakage of the implant, more than 95% of the feet obtained pain relief. We found that this type of operation was very effective in relieving pain in rheumatoid patients.
Adult↗
Danazol effects on human endometrial cells in vitro.
Although danazol has been reported to inhibit endometrial cell growth in vitro, it is difficult to accept that this is through direct inhibition of danazol on endometrial cells. This is because local danazol therapy improves endometriotic signs and symptoms without any disturbance in ovulation or the menstrual cycle. We have re-evaluated the effects of danazol on human endometrial cells by using normal human endometrial stromal cells and two cell lines derived from highly-differentiated endometrial adenocarcinomas. Danazol is difficult to dissolve in aqueous solutions, and undissolved danazol significantly inhibited endometrial cell growth even at less than 100 ng/ml. At 500 ng/ml of fully dissolved danazol, which is the therapeutic dose, danazol solution inhibited leukemic cell growth but not endometrial cell growth. Therefore, the action of danazol may be not an inhibitory effect but rather a regulatory function of endometrial cell growth.
Cell Division↗
Cutaneous sarcoidosis with cardiac involvement.
Despite the clinical importance of cardiac involvement in the prognosis of sarcoidosis, it is often overlooked because of the subclinical disease progression and difficulty in diagnosis. We report here five patients with cutaneous sarcoidosis lesions where cardiac involvement was detected with the appearance of mild cardiac symptoms on a careful examination of the heart after cutaneous sarcoidosis was diagnosed. In four of the five cases, the patients had annular lesions while the fifth case showed a nodular eruption on the face. Three of the five patients showed complete AV block while one showed complete right bundle block and left bundle anterior branch block. All four patients with conduction disturbances underwent a permanent pacemaker implantation with prednisolone tapering therapy. The remaining patient had congestive heart failure and was treated with prednisolone alone. The present findings support the belief that sarcoidosis patients with cutaneous lesions, especially facial annular lesions, should be carefully examined and monitored for cardiac involvement, even in cases without apparent cardiac symptoms.
Aged↗
In vitro decidualization activity assay of human endometrial stromal cells.
To address the need for a simple and reliable system for evaluating the effects of bioactive substances on decidualization of endometrial stromal cells, we designed and tested an assay for measuring decidualization activity. With our assay, it is easy to examine the effects of various bioactive substances on endometrial stromal decidualization. For example, as shown in this study, it is now clear that neither RANTES nor gonadotropin releasing hormone agonist has any effect on endometrial stromal decidualization. Our simple assay has also made it possible to evaluate individual stromal decidualization activities and the regulation of decidualization.
Biological Assay↗
Peroneus longus can not be fully activated during ankle complex exercises by uninjured subjects.
This study characterized, for the first time, the extent to which the peroneus longus muscle can be voluntarily activated by uninjured subjects during common ankle rehabilitative exercises. Ten healthy subjects performed isometric maximum voluntary contractions (MVCs) of eversion and plantarflexion on a dynamometer and against manual resistance, and performed dynamic whole-body activities that place large loads on the ankle complex (vertical jumps and side-cuts). During these activities, surface EMG signals were collected from the peroneus longus and expressed as a percentage of the maximum motor responses elicited by electric stimulation. Voluntary activation levels of the peroneus longus during isometric MVCs performed on the dynamometer and performed against manual resistance were not significantly different. Side-cuts produced significantly larger activation levels than those maximum vertical jumps and the isometric exercises. Nevertheless, the activation levels were substantially lower than those reported for other lower extremity muscles. These results serve as the basis for further questions related to whether voluntary peroneus longus activation level can be affected by specific rehabilitative efforts, whether activation levels are influenced by acute and chronic ankle complex injuries and, if so, whether this effect influences the functional outcome of rehabilitation efforts following ankle injuries.
Adult↗
Effects of subthreshold transcranial magnetic stimulation on choice reaction time and correlation with motor cortical activation.
To study the effect of subthreshold transcranial magnetic stimulation (TMS), we measured choice reaction time (RT), with or without TMS, in 7 healthy participants. TMS over the hand motor area was randomly delivered at variable delays after the imperative signal, while participants performed right or left abduction of the thumb. Lateralized movement-related potentials (MRPs) were recorded in a separate session to link the TMS effect with the motor cortical circuitry. For the right hand, the coexistence of a motor specific and non-specific effects of TMS was clearly evidenced, by the RT shortening at delays of 0 and 150 ms. The response dependency of the specific TMS effect was also demonstrated through the response-locked analysis, showing a maximal shortening at 120-ms bin before EMG onset. Furthermore, the lateralized MRP commenced at about 80 ms before EMG onset, indicating that TMS influences the cortical motor circuitry around 30-40 ms before the activation of the primary motor cortex. In contrast, for the left hand, we were faced with some uncertain concepts as human handedness and hemisphere asymmetries in both measures of RT and MRP, and thus it was not possible to substantiate about the motor specific effect of subthreshold TMS.
Action Potentials↗
Three-dimensional collagen gel culture promotes osteoblastic phenotype in bone marrow derived cells.
When calvarial cells or osteogenic cell lines were cultured in type I collagen gel, calcification was observed early and diffusely compared to monolayer culture. Bone marrow derived cells were cultured in three-dimensional type I collagen gel to investigate whether the cells can differentiate into osteogenic cells. In terms of efficient induction of osteogenic differentiation, we compared collagen gel culture to type I collagen coated dish culture and collagen-free plastic dish culture by morphology, alkaline phosphatase activity, and mRNA expression for type I collagen and osteopontin. Bone marrow derived primary cells formed colonies consisting of fibroblastic cells positively expressing alkaline phosphatase activity. Mineral deposition was observed in both primary and the 3rd passaged cells cultured in collagen gel, whereas the 3rd passaged cells on plastic dishes failed to be mineralized. Cells in collagen gel showed higher alkaline phosphatase activity than those in the other two methods suggesting that three-dimensional collagen network stimulated osteoblastic differentiation effectively. The expression level for type I collagen mRNA of the cells in collagen gel was three times higher in the 3rd passaged cells, and was slightly decreased in primary cells compared to the other two methods. The osteopontin mRNA expression of the cells in collagen gel was four times higher in the 3rd passaged cell culture but lower in primary cell cultures. These results suggested that collagen gel culture might be a useful environment for osteogenic induction of passaged cells derived from bone marrow.
Alkaline Phosphatase↗
[Clinical studies conducted in the U.S].
There are many things that we can learn from the clinical trials conducted in the U.S. They move ahead based on explicit basic principles regarding various matters such as the method for setting up the clinical trial system, selection of CRO, selection of investigators, monitoring activities that are mainly based on their direct access to source documents and sponsor's action when a lack of compliance with GCP occurs. The matters newly introduced in the Japanese new GCP have already been put into practice in the U.S. It is evident that compliance with these standards is ensured in the U.S. by the activities of study coordinators who take greater part in the clinical studies themselves. In order to expedite introduction of the study coordinator system in Japan even just a little, sponsors should consider providing medical institutions with relevant information as well as a chance to educate and train their study coordinators to optimize the function.
Clinical Trials as Topic↗
Stage-specific expression of testis-specific protein kinase 1 (TESK1) in rat spermatogenic cells.
TESK1 (testis-specific protein kinase 1) is a serine/threonine kinase, with a unique structure composed of an N-terminal protein kinase domain and a C-terminal proline-rich domain. Northern blot analysis revealed that TESK1 mRNA is predominantly expressed in testicular germ cells. We present here evidence that expression of TESK1 mRNA and protein in the rat testes is developmentally regulated and increases after 20-22 postnatal days. To identify cells which express TESK1 mRNA and protein during male germ cell differentiation, in situ hybridization and immunohistochemistry were done using frozen sections of adult rat testes. Prominent expression of TESK1 mRNA and protein was detected in testicular germ cells at stages of late pachytene spermatocytes to round spermatids, but not in somatic cells such as Sertoli and Leydig cells. Expression of TESK1 mRNA and protein at specific stages of testicular germ cells suggests a role for this kinase in spermatogenesis, particularly at stages of meiosis and/or early spermiogenesis.
Animals↗
Hybridization-AT-tailing (HybrAT) method for sensitive and strand-specific detection of DNA and RNA.
delta Tth DNA polymerase catalyzed polymerization of dATP and dTTP into a high-molecular-weight d(A-T) copolymer using oligo-d(A-T) as the template/primer (Hanaki et al., Biochem. Biophys. Res. Commun. 244, 210-219). Taking advantage of this reaction, we developed a highly sensitive method for strand-specific detection of DNA or RNA. The probe consisted of a 40- to 50-base-long complementary sequence on the 5' side and 10 repeats of AT on the 3' side. After hybridization using the 5' side, the 3' side AT repeat region was elongated by delta Tth DNA polymerase in the presence of the dATP, dTTP, and digoxigenin (dig)-11-dUTP. The elongation condition was 52-62 degrees C for 3 h. The method named HybrAT (hybridization-AT-tailing) was at least 100-fold more sensitive than the conventional hybridization with 5' end dig-11-dUTP labeled probe.
Adenine↗
Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization.
Rac is a small GTPase of the Rho family that mediates stimulus-induced actin cytoskeletal reorganization to generate lamellipodia. Little is known about the signalling pathways that link Rac activation to changes in actin filament dynamics. Cofilin is known to be a potent regulator of actin filament dynamics, and its ability to bind and depolymerize actin is abolished by phosphorylation of serine residue at 3; however, the kinases responsible for this phosphorylation have not been identified. Here we show that LIM-kinase 1 (LIMK-1), a serine/threonine kinase containing LIM and PDZ domains, phosphorylates cofilin at Ser 3, both in vitro and in vivo. When expressed in cultured cells, LIMK-1 induces actin reorganization and reverses cofilin-induced actin depolymerization. Expression of an inactive form of LIMK-1 suppresses lamellipodium formation induced by Rac or insulin. Furthermore, insulin and an active form of Rac increase the activity of LIMK-1. Taken together, our results indicate that LIMK-1 participates in Rac-mediated actin cytoskeletal reorganization, probably by phosphorylating cofilin.
Actin Depolymerizing Factors↗
Cytoplasmic localization of LIM-kinase 1 is directed by a short sequence within the PDZ domain.
LIM-containing protein kinase 1 (LIMK1) is a serine/threonine kinase with a structure composed of two LIM domains, a PDZ domain, and a protein kinase domain. We examined the subcellular localization of LIMK1 and its variously deleted mutants in HeLa cells by transfection with these cDNAs. Immunofluorescence analysis revealed that the full-length LIMK1 and its mutants deleted with LIM domain or protein kinase domain preferentially localized in the cytoplasm, while the mutants deleted with the PDZ domain or a 52 amino acid region (B region) within the PDZ domain localized mainly in the nucleus. When the normally nuclear cyclin A was fused with the PDZ domain or the B region of LIMK1, it was localized in the cytoplasm of transfected cells. The corresponding region of the PDZ domain of postsynaptic density protein (PSD)-95 had no such function. Additionally, the PDZ domain of LIMK1 had no potential to bind to the C-terminal S/TXV peptides, to which the PSD-95 PDZ domain can bind. Taken together these results suggest that the PDZ domain, particularly the B region, of LIMK1 has a specific function to localize the protein in the cytoplasm. When glutathione S-transferase (GST) fused with the PDZ domain of LIMK1 (GST-PDZ) or GST-PDZ deleted with the B region (GST-PDZ delta B) was microinjected into the nucleus of COS cells, GST-PDZ was almost completely excluded from the nucleus within 30 min, whereas GST-PDZ delta B remained in the nucleus. These findings suggest that the B region of LIMK1 probably has nuclear export signal activity.
Amino Acid Sequence↗
Identification of testis-specific (Limk2t) and brain-specific (Limk2c) isoforms of mouse LIM-kinase 2 gene transcripts.
LIM-kinase 1 (LIMK1) and LIM-kinase 2 (LIMK2) are members of a novel serine/threonine kinase subfamily with structural features composed of N-terminal two LIM domains, an internal PDZ-like domain, and a C-terminal protein kinase domain. We recently identified and characterized the mouse Limk2 gene and two Limk2 transcripts (Limk2a and Limk2b) coding for proteins with distinct N-terminal LIM structures. Here we describe two additional transcripts of the mouse Limk2 gene. One is a 1.7-kb transcript, termed Limk2t, which is specifically expressed in the testis and codes for an N-terminally truncated form of LIMK2 consisting of only a part of a PDZ-like domain and a protein kinase domain. The other is a transcript, termed Limk2c, which is specifically expressed in the brain and codes for a protein with a 6-amino-acid insert within the protein kinase domain. Exons specific to the 5'-terminal extra sequence of Limk2t and the insert sequence of Limk2c locate between exons 5-6 and exons 8-9 in the mouse Limk2 gene, respectively. Testis- and brain-specific expression of Limk2t and Limk2c suggests specific roles in these tissues.
Alternative Splicing↗
gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes.
We have recently reported that mitogen activated protein kinase (MAP kinase) is activated by the stretch of the cultured cardiac myocytes in the angiotensin II deficient state in the angiotensinogen-deficient mice (Atg-/-), suggesting that factors other than the cardiac renin-angiotensin system are involved in the stretch-induced MAP kinase activation. We examined the contribution of cytokines using RX435, an anti-gp130 antibody. Leukemia inhibitory factor, which is one of the cytokines and has the common receptor subunit gp130, activated MAP kinase and the response was completely blocked by pretreatment of the Atg-/- cardiac myocytes with RX435. RX435 pretreatment greatly reduced stretch-induced activation of MAP kinase in Atg-/- cardiac myocytes. Interestingly, the same results were obtained in the cardiac myocytes of control mice. These results suggest that cytokine-gp130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardiac myocytes.
Angiotensinogen↗
Serial changes of sensory nerve conduction velocity and minimal F-wave latency in streptozotocin-induced diabetic rats.
We studied the serial changes of sensory nerve conduction velocity (SNCV) in the caudal nerve of streptozotocin (STZ)-induced diabetic rats using a new technical method. Minimal F-wave latency was also studied by stimulating the tibial nerve. The SNCV in the diabetic rats was slower than that in the normal rats 2 weeks after STZ injection, and minimal F-wave latency was prolonged compared to normal rats 4 weeks after STZ injection. Treatment of the diabetic rats with insulin for 14 days inhibited SNCV slowing and minimal F-wave latency prolongation. This new method to measure SNCV is useful for various studies, and improvement of diabetic neuropathy with insulin treatment is indicated by recovery from SNCV slowing and minimal F-wave latency prolongation.
Animals↗
Two different reactions involved in the primer/template-independent polymerization of dATP and dTTP by Taq DNA polymerase.
Taq and Tth DNA polymerases catalyzed polymerization of dATP and dTTP into poly d(A-T) without requiring added primer/template (Hanaki et al., Biochem. Biophys. Res. Commun. 238, 113-118), while the Stoffel fragment of Taq DNA polymerase and delta Tth DNA polymerase with respective deletions of ca. 290 and 250 N-terminal amino acids did not. The primer/template-independent polymerization appeared to proceed via two reactions, the slow process of formation of 16-19 nt long oligo d(A-T) without primer/template and the rapid process of elongation of the oligo d(A-T) by self-priming. As the former step was more sensitive to N-ethylmaleimide than the elongation reaction, probably the formation of the oligonucleotide preceded the elongation. But when the substrates were depleted, Taq DNA polymerase degraded the high molecular weigh d(A-T) polymer to the oligomers which were resistant to the further digestion by the 5'-->3' exonuclease activity of Taq DNA polymerase. Probably, the elongation and the degradation reactions proceeded simultaneously, the former process being faster than the latter in the presence of enough dATP and dTTP.
DNA↗