Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 109 records · Page 6Linked to original sources

PubMed1999

Extragonadal germ cell tumor of the prostate associated with Klinefelter's syndrome.

PURPOSE: We report on a case of extragonadal germ cell tumor of the prostate associated with Klinefelter's syndrome. METHODS/RESULTS: The patient was a 33-year-old man. A transrectal prostate biopsy suggested combined germ cell tumor (yolk sac tumor + teratoma). Because there was no tumor except from the prostate, we considered this case to be a primary extragonadal germ cell tumor of the prostate. The prostate tumor responded to systemic chemotherapy with cisplatin, vinblastine and bleomycin and elevated lactate dehydrogenase and alpha-fetoprotein levels normalized. In addition to chemotherapy, the patient also underwent radiation therapy. CONCLUSION: The patient has survived for approximately 4 years since the diagnosis.

Adult↗

PubMed1999

Early monocytopenia after chemotherapy as a risk factor for neutropenia.

Neutropenia is a major adverse effect of cancer chemotherapy and sometimes causes life-threatening events. The present study was therefore conducted to identify risk factors for such neutropenia. Forty patients who had received chemotherapy at 3- or 4-week intervals for advanced lung cancer from May 1991 through February 1997 were analyzed retrospectively. Thirty-seven of the patients had received cisplatin-based chemotherapy. The mean neutrophil count on days 6 to 8 in 32 patients who developed grade 3 or 4 neutropenia during chemotherapy was not significantly different from that in eight patients who developed grade 1 or 2 neutropenia during chemotherapy. However, the mean leukocyte and monocyte counts on days 6 to 8 in the 32 patients with grade 3 or 4 neutropenia (5,181 +/- 1,830/microl and 87 +/- 84/microl, respectively) were significantly lower than those in the eight patients with grade 1 or 2 neutropenia (7175 +/- 1671/microl and 248 +/- 127/microl, respectively; p = 0.008 and p = 0.0001). Moreover, all 30 patients with a monocyte count of less than 150/microl on days 6 to 8 had grade 3 or 4 neutropenia and 8 of 10 patients with a monocyte count of 150/microl or higher on days 6 to 8 had grade 1 or 2 neutropenia, despite the absence of a correlation between the leukocyte count on days 6 to 8 and the neutrophil nadir. We conclude that a monocyte count of less than 150/microl on days 6 to 8 may be a predictor of grade 3 or 4 neutropenia during cancer chemotherapy at 3- or 4-week intervals (sensitivity 94%, specificity 100%).

Adult↗

PubMed1999

Phase II clinical study on the effects of recombinant human interleukin-3 on thrombocytopenia after chemotherapy for advanced ovarian cancer. SDZ ILE 964 [IL-3] Study Group.

The efficacy, safety, and optimum clinical dose of recombinant human interleukin-3 (rhIL-3) was examined in ovarian cancer patients with thrombocytopenia after cancer chemotherapy. In cases with a platelet count < 75,000/mm3 during the control observation period, rhIL-3 was administered subcutaneously at a dose of 5 or 10 micrograms/kg, once a day for 10 days starting from day 4 of the subsequent chemotherapy course. Comparison between the control observation period and the rhIL-3 administration period showed a significant improvement or a tendency toward improvement in increasing the nadir platelet count and the recovery of the platelet count. The major adverse reactions were pyrexia, fatigue, and headache, which were well controlled by the use of antipyretics, analgesics, and antiinflammatory agents. Adverse reactions were for the most part transient and disappeared quickly during or after rhIL-3 administration. Although severe adverse reactions were not observed, the incidence of grade 2 and 3 adverse reactions according to a World Health Organization (WHO) Toxicity Scale were slightly higher in the 10 micrograms/kg/d group. As a consequence, the 5 micrograms/kg/d dose was considered to have a slightly better safety profile than the 10 micrograms/kg/d dose. Although there was no significant difference in the efficacy (the platelet count) between the two doses, the safety profile of the 5 micrograms/kg/d dose was slightly better than the 10 micrograms/kg/d group. Therefore, the 5 micrograms/kg/d was considered to be the optimum clinical dose.

Adult↗

PubMed1999

High-risk types of human papillomavirus associated with the progression of cervical dysplasia to carcinoma.

OBJECTIVES: In the past several years, much evidence has accumulated that strongly implicates human papillomavirus (HPV) as an etiological agent of cervical cancer. However, the natural history of HPV infection is not yet completely understood, and at present there is no good marker to predict progression to invasive cancer in individual patients with dysplasia. METHODS: Tissue specimens from 45 patients with cervical dysplasia were classified as showing progression to carcinoma (progression group; 26 women), spontaneous regression (regression group; 16 women), and persistence (persistence group; 3 women). The presence of HPV 16, 18, 33, and 52 DNA was examined in 90 formalin-fixed, paraffin-embedded surgical and biopsy specimens of dysplasia using the PCR method, and the relationship between the presence of HPV and cervical carcinogenesis was analyzed. The mean follow-up period was 25.8 months in the progressed group and 34.0 months in both the persistent and regressed groups. The mean ages were 46.4 in the progressed group and 46.8 in the persistent and regressed groups. RESULTS: HPV 16, 18, 33, and 52 DNA were detected in 19 of the 26 patients (73.1%) in the progressed group. All patients with HPV 16, 18, or 52 DNA showed progression to carcinoma. The HPV 33 DNA was detected in 5 of the 16 patients (31.3%) in the regressed group and in 2 of the 3 patients (66.7%) in the persistent group, while HPV 16, 18, and 52 DNA were not detected in the 19 patients that comprised the regressed and persistent groups. CONCLUSION: This retrospective study suggests that cervical dysplasia in patients with high-risk types of HPV possessed the potential to progress to carcinoma in situ and eventually to invasive carcinoma as well.

Adult↗

PubMed1999

Immunohistochemical studies concerning cathepsin D in endometrial carcinomas.

OBJECTIVES: To study the prognostic value of immunohistochemical detection of cathepsin D and laminin in endometrial carcinomas. METHODS: Immunohistochemical staining of cathepsin D was performed on paraffin sections of 111 endometrial carcinomas, and laminin deposition was studied in 65 endometrial carcinomas. RESULTS: Of 111 tissue specimens, 55 showed a positive reaction for cathepsin D. The incidence of cathepsin D-positive staining increased with the extension of the primary tumor (p < 0.01). Patients with vessel invasion and pelvic lymph-node metastasis had a higher incidence of cathepsin D-positive staining than patients without these findings (p < 0.05). A favorable prognosis was obtained in a negative case of cathepsin D in comparison with a positive case (p < 0.01). Of 9 patients in whom laminin was detected in the cytoplasm of cancer cells, 5 showed poor prognoses and died from a primary disease. CONCLUSION: Cathepsin D and laminin status might represent possible prognostic factors.

Adult↗

PubMed1999

[Bacteriological studies of traveller's diarrhoea (6). Analysis of enteropathogenic bacteria at Kansai Airport Quarantine Station from September 4th, 1994 through December 1996].

During the period of investigation from Sept. 4, 1994 to Dec, 1996, a total of 11,446,534 overseas travellers were quarantined at Kansai Airport Quarantine Station, and 22,187 voluntarily reported of episodes suffering from diarrhoea. Bacteriological examination of the stools a total of 9,299 individuals' was performed, and the following results were obtained. 1) Various enteropathogenic bacteria were isolated from 33.3% of the stools examined. Bacterial species isolated were as follows: Plesiomonas shigelloides, 2,066 cases (66.7%); Vibrio parahaemolyticus, 358 cases (11.6%); Aeromonas sobria, 360 cases (11.6%); Shigella spp., 291 cases (9.4%); Salmonella spp., 183 cases (5.9%); A. hydrophila, 126 cases (4.1%); and V. cholerae non-O1, 121 cases (3.9%). However, ETEC was not done with an object of test. 2) In 502 cases (16.2%), plural enteropathogenic bacteria were isolated from single patient, suggesting high frequency of a mixed infections. 3) From Feb. to Mar. 1995, thirteen cases cholera were found from patients who had travelled to Bali, Indonesia. Cases with enteropathogenic bacteria other than V. cholerae O1 were found without any seasonal variation. 4) The major regions where the travellers were infected with the pathogens are as follows: Vibrio spp., were from only Asia; Shigella, widely distributed but especially in India and Indonesia; P. shigelloides and Salmonella, widely distributed. 5) Among the Shigella strains, S. sonnei were isolated the most, followed by S. flexneri, S. boydii and S. dysenteriae. A strain of S. boydii provisional serovar E 16553 was isolated from a patient infected in India. 6) Among the Salmonella serovars, Salmonella Enteritidis was isolated the most frequently (49 cases, 25.7%). 7) 265 (89.2%) of 297 Shigella strains, 52 (27.2%) of 19] Salmonella strains, and 19 (95.0%) of 20 V. cholerae O1 were resistant to one or more drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). 8) All of the 20 V. cholerae O1 strains were Ogawa, E1 Tor. All of them were toxigenic strains. 9) The most frequently isolated serovar of V. parahaemolyticus was O3: K6. 89.8% of all V. parahaemolyticus strains were positive for thermostable direct hemolysin (TDH) gene, and 14.6% of them were positive for TDH-related hemolysin (TRH) gene by DNA-probe or PCR method.

Asia, Southeastern↗

PubMed1999

Relation between coronary thrombus and angiographic no-flow during primary angioplasty in patients with acute myocardial infarction.

No flow is an unsolved issue in primary percutaneous transluminal coronary angioplasty (PTCA) for patients with acute myocardial infarction (AMI), and the pathophysiology of no-flow is undetermined. To evaluate the potential participation of coronary thromboembolism in no-flow during primary PTCA, the present study reviewed cinefilms of 256 consecutive patients who underwent primary PTCA for AMI within 24h after the onset of chest pain between January 1992 and June 1998, focusing on the thrombus size. Angiographic no-flow was defined as the cessation of flow into the distal coronary circulation of the treated vessel with a to-and-fro contrast movement, not attributable to high-grade stenosis or spasm of the original target lesion. The coronary thrombus size was determined by using the 2-cm balloon catheter as a reference after crossing the infarct-related occluded artery with a guide wire. Angiographic no-flow was observed in 37 patients (37/256, 14%): 14 of 29 cases (48%) with a large thrombus (> or =2cm) versus 23 of 227 cases (9%) with a small thrombus (<2cm, 14/29 vs 23/227, p<0.01). Among 37 patients who experienced angiographic no-flow, overt distal emboli were observed in 14 patients. A thrombolytic agent was used through a guiding catheter in 102 cases prior to or after balloon dilatation to prevent or attenuate distal embolism, particularly in all those cases with a large thrombus (29/29 100%), and angiographic no-flow was seen in 27 cases of this subgroup (27/102, 26%). It is suggested that distal thromboembolism plays an important role in the mechanism of angiographic no-flow during primary PTCA performed for AMI.

Aged↗

PubMed1999

Percutaneous transluminal coronary angioplasty, alone or in combination with urokinase therapy, during acute myocardial infarction.

To investigate the effect of pre-treatment of a thrombus with a low dose of urokinase on establishing patency in a persistent infarct-related artery (IRA) during direct percutaneous coronary angioplasty (PTCA), the frequency of acute restenosis during direct PTCA, alone, or in combination with the intracoronary administration of urokinase, was examined in a consecutive nonrandomized series of patients with acute myocardial infarction (AMI). Two hundred and seventy-two successful PTCA patients (residual stenosis <50%) were divided into 2 groups: 88 patients received pre-treatment with intracoronary urokinase following PTCA (combination group); 184 received only direct PTCA without thrombolytic therapy (PTCA group). In the present study, after achievement of a residual stenosis of less than 50%, IRA was visualized every 15 min to assess the frequency of acute restenosis, which was defined as an acute progression of IRA with more than 75% restenosis after initially successful PTCA. In the patients with a large coronary thrombus, the frequency (times) of acute restenosis was significantly lower in the combination group than in the PTCA group (0.98+/-0.19 vs 2.92+/-0.32, p<0.0001). On the other hand, in the patients with a small coronary thrombus, the frequency of acute restenosis showed no difference in either group. The present study indicates that in patients with AMI, PTCA combined with pre-treatment of a low dose of urokinase is much more effective than PTCA alone, especially for those patients who have a large coronary thrombus.

Angioplasty, Balloon, Coronary↗

PubMed1999

[A 96-year-old man with consciousness disturbance, convulsion, and left hemiplegia of acute onset].

We report a 96-year-old Japanese man who developed a sudden onset of left hemiplegia and coma. He was found to have diabetes mellitus, hypertension, and atrial fibrillation since 1996 with occasional episodes of congestive heart failure. He was otherwise apparently well until July 5 of 1997 when he developed a sudden onset of unresponsiveness and convulsion involving his right hand and was admitted to our hospital. On admission, his BP was 210/120 mmHg, heart rate 76/min and irregular, BT 36.5 degrees C, and Cheyne-Stokes respiration. General medical examination was otherwise unremarkable. Neurologic examination revealed semicoma, conjugated deviation to the right, loss of oculocephalic response, left facial paresis of central type, flaccid left hemiplegia, and bilateral Babinski sign. Pertinent laboratory findings are as follows: BUN 47 mg/dl, creatinine 1.46 mg/dl, GPT 69 IU/l, LDH 1,142 IU/l, and CK 385 IU/l. A chest x-ray film revealed cardiac enlargement and EKG showed left ventricular hypertrophy and atrial fibrillation. Cranial CT scan revealed low density areas involving the right anterior cerebral and the right posterior cerebral artery territories. He was treated with an intravenous osmotic agent and short course of intramuscular steroid. He remained unconscious despite these treatment and developed sudden cardiopulmonary arrest three weeks after the admission. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had suffered from cerebral embolism of cardiac origin. The cause of the death was ascribed to acute subendocardial myocardial infarction. Most of the participants agreed with this conclusion. Postmortem examination revealed an old subendocardial myocardial infarction involving the posterior septal region and posterolateral wall of the left ventricle. Neuropathologic examination revealed hemorrhagic infarctions involving the territories of the right anterior cerebral, right middle cerebral, right posterior cerebral, and left anterior cerebral arteries. The left A1 portion of the anterior cerebral artery was hypoplastic, and the left pericallosal artery appeared to have been receiving blood supply from the right anterior cerebral artery through the anterior communicating artery. The large arteries in the base showed marked arteriosclerosis; particularly, the initial portion of the right posterior artery showed near complete arteriosclerotic occlusions. These characteristic arterial changes appeared to be the reason why this patient suffered from an extensive infarction from what appeared to have been a single episode of cerebral embolism probably initially involving the right internal carotid artery.

Aged↗

PubMed1999

Detection of K-ras mutations of bronchoalveolar lavage fluid cells aids the diagnosis of lung cancer in small pulmonary lesions.

An increased prevalence of K-ras oncogene mutation in lung adenocarcinoma has been shown by PCR-primer-introduced restriction with enrichment for mutation alleles (PCR-PIREMA) experiments. In the present study we investigated whether this method is useful for the diagnosis of lung cancer in small pulmonary lesions, which are difficult to diagnose cytologically as lung cancer by bronchoscopic examination. We examined bronchoalveolar lavage fluid (BALF) cells from 33 patients with single nodular pulmonary lesions of less than 2 cm in diameter (measured on chest computed tomography scans) for K-ras (codon 12) mutation, by PCR-PIREMA. Transbronchial fiberscopic examinations had not revealed lung cancer cytologically in any of the patients. The final diagnoses for the 33 lesions were 20 adenocarcinomas, 5 cases of focal fibrosis, 5 cases of pneumonia, 1 case of tuberculosis, 1 hamartoma, and 1 case of lymph node swelling. BALF cell lysates were amplified and digested with a restriction enzyme to detect the K-ras oncogene. Only the normal K-ras was observed after the first amplification and digestion for each of the 33 patients. Three amplifications and digestions were performed for each sample. We detected mutation of K-ras in BALF cells from 15 (75%) of 20 lung cancer patients and in cells from only 4 (31%) of 13 patients with nonmalignant lesions. The detection rate of the K-ras mutation in lung cancer was significantly greater than that in nonmalignant lesions (P = 0.012). Our results indicate that the detection of the codon 12 K-ras mutation in BALF cells by PCR-PIREMA aids the diagnosis of lung cancer in patients with small pulmonary lesions with negative cytological findings.

Aged↗

PubMed1999

[Pathophysiology of the renin-angiotensin system].

Angiotensin II is a potent vasoconstrictor as well as a growth stimulator. Angiotensin type 1 (AT1) and type 2 (AT2) receptors have been cloned, and molecular mechanisms by which angiotensin II stimulates cell growth have been also clarified by molecular biological techniques including gene targeting and transgenic animals. AT1 promotes hypertrophy and hyperplasia through G protein-associated pathway and G-protein-independent pathway consisted of tyrosine kinase, JAK/STAT, and growth hormone signal transduction. Function of AT2 is not fully understood, but recently has been reported to reverse the effect of AT1. This is a brief review on angiotensin II functions and its signal transduction, including the aspect of the constitutively active AT1 mutant receptor.

Angiotensin II↗

PubMed1999

[Angiotensin receptor in the lung].

In situ hybridization of angiotensin receptor mRNA and ligand-binding assay showed that main subtype of angiotensin receptor in the lung was type 1(AT1) in pulmonary vessel, whereas type 2(AT2) was not detectable. AT1 induces the pulmonary artery contraction through inositol phosphate-protein kinase C pathway, therefore the non-peptide AT1 antagonist was applied to animal model of pulmonary hypertension (PH). AT1 antagonist improved pulmonary arterial remodeling and right ventricular hypertrophy in rat hypoxia-induced PH but not in rat monocrotaline-induced PH. Less effectiveness of AT1 antagonist for PH might be no AT2 stimualtion under increased angiotensin II level in blood and lung tissue response to AT1 antagonist treatment.

Animals↗

PubMed1999

Evaluation of new 4 French catheters by comparison to 6 French coronary artery images.

The use of 4 Fr catheters for diagnostic coronary arteriography improves patient comfort and could potentially reduce costs by decreasing arterial complications and encouraging outpatient examination. We examined the performance of recently developed 4 Fr catheters (100 cm long, 0.042 inch internal diameter) through in vitro flow rate patterns and in vivo image quality. Flow patterns (flow rate calculated from pressure with the Hagen Poiseuille relation) were obtained by hand (10 ml volume; maximal effort, one-handed full injection) and power injection (10 ml volume; 5 ml/sec) in the 4 Fr catheters were compared to 5 Fr (0.047 inch) and 6 Fr (0.057 inch) catheters. In 20 patients, coronary arteriograms were obtained from 4 Fr hand injection (4 HI), 4 Fr power injection (4 PI), 6 Fr hand injection (6 HI ), and 6 Fr power injection (6 PI) were compared after being scored into 5 grades. Coronary diameter was assessed at two sites for all injections in the same group of patients. In power injections, peak flow rates were consistently 5.5 ml/sec in all catheters. Hand injections were much more variable; peak flow rate ranges for 5 different physicians were 3.5-6.0 ml/sec. in 6 Fr, 1.8-3.0 ml/sec. in 5 Fr and 1.4-2.0 ml/sec in 4 Fr catheters. Mean image scores of left arteriograms were significantly higher for 4 PI versus 4 HI and for 6 Fr images compared to 4 PI (p < 0.001). In right arteriograms, 4 HI scored significantly lower than other methods (4 PI, 6 HI and 6 PI; p < 0.001). In 4 HI left coronary arteriograms, the frequency of grade > 2 was 96% and > 3 was 82%. Power injection improved 4 Fr imaging to 99% greater than grade 2 and 93% greater than grade 3. There were no differences in the frequency of images above grade 3 in right coronary arteriograms. Measured coronary artery diameters at 40 normal and 17 stenotic sites by QCA analysis (Acom, Siemens AZ, Erlangen, Germany) did not influence the study data. We concluded that coronary arteriograms by hand injection with 4 Fr catheters were inferior compared to 6 Fr images. Power injection and/or larger catheters may be necessary to ensure the highest quality images are obtained.

Blood Flow Velocity↗

PubMed1998

Auditory evoked off-response: its source distribution is different from that of on-response.

Offset auditory responses were investigated by electroencephalography mainly in the 1970s, but since then no particular attention has been paid to them. Among the studies using magnetoencephalography (MEG) devices there are, to our knowledge, only three studies of the auditory off-response, and no significant variance has ever been observed between the source locations of on- and off-responses elicited from pure tones. We measured auditory evoked magnetic fields (AEFs) to various frequency pure tone stimulation in 5 healthy subjects with a 122-channel helmet-shaped magnetometer, and compared the distributions of the source locations of auditory N100m-Off (magnetic off-response around 100 ms) with those of N100m-On. Their spatial distributions were quite close to each other, and yet they were significantly different.

Acoustic Stimulation↗

PubMed1998

Design of a compact synchrotron light source for medical applications at NIRS.

A synchrotron light source dedicated to medical applications is required to be compact for installation in limited spaces at hospitals. The NIRS storage ring, with a circumference of 44.8 m, is designed to accelerate electrons up to 1.8 GeV and to store a beam of 400 mA. The ring is composed of superconducting bending magnets for downsizing. A beam of 300 MeV is injected into the ring from a microtron operated at an L-band RF frequency. There are two superconducting multipole wigglers with nine poles and a maximum field of 8 T, which can produce a photon flux of about 1.4 x 10(13) photons s(-1) mrad(-1) (0.1% bandwidth)(-1) at 33 keV used for coronary angiography.

Journal Article↗

PubMed1998

Effects of aging on numbers, sizes and conduction velocities of myelinated and unmyelinated fibers of the pelvic nerve in rats.

The effects of aging on the conduction velocities, numbers and sizes of the myelinated and unmyelinated fibers of the pelvic nerve in Wistar rats, aged 3-9 and 30-37 months were examined using electrophysiological and ultrastructural techniques. The myelinated fibers did not show significant age-related changes in the maximum conduction velocities (9.7 +/- 1.1 m/s in adult vs. 11.0 +/- 1.5 m/s in aged rats), the number of fibers (662 +/- 27 vs. 625 +/- 56) and distribution of fiber diameters. In aged rats, the unmyelinated fibers did not show a significant change in maximum conduction velocity (1.5 +/- 0.1 m/s vs. 1.5 +/- 0.1 m/s), but showed a significant decrease in the number of fibers (4133 +/- 114 vs. 3113 +/- 456), specifically of fibers smaller than 0.7 microm in diameter. It is concluded that myelinated fibers of the pelvic nerve in rats preserve their conduction ability and fiber population during aging, but unmyelinated fibers, particularly fibers with smaller diameters decrease in number. Unmyelinated fibers with larger diameters maintain their conduction ability and numbers with aging.

Aging↗

PubMed1998

Aberrant FHIT transcripts in squamous cell carcinoma of the uterine cervix.

The fragile histidine triad (FHIT) tumor suppressor gene at 3p14.2 has abnormalities in several types of human cancers. To investigate the potential role of FHIT in cervical cancer, which exhibits frequent loss of heterozygosity of 3p, we have examined primary cervical cancer samples from 28 patients for alterations of the FHIT gene. Abnormal FHIT transcripts were detected using reverse transcription-polymerase chain reaction (PCR) and subsequently by sequencing. Of 28 primary cervical carcinomas analyzed, 12 tumors (43%) showed abnormal FHIT transcripts, including deletion, insertion and point mutation. Loss of a FHIT transcript was observed in 2 cases (7%). Allelic loss of the FHIT gene was detected in 16 of 27 informative cases (59%). Oncogenic human papillomavirus (HPV) type 16, 18, 33, 35, 58 and 59 were not only present but were expressed in 24 of 28 cases (85%) by consensus PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis for the HPV E6 and E7 genes. Our data indicate that alteration of the FHIT gene is an important genetic event associated with cervical cancer and oncogenic

Acid Anhydride Hydrolases↗

PubMed1998

Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2.

MKN28-derived nonreceptor type of serine/threonine kinase/mixed lineage kinase 2 (MST/MLK2) directly phosphorylates and activates SEK1/MKK4/JNKK1/SKK1 in vitro, thereby acting as a mitogen-activated protein (MAP) kinase kinase kinase in the JNK/SAPK pathway (Hirai, S. -i., Katoh, M., Terada, M., Kyriakis, J. M., Zon, L. I., Rana, A., Avruch, J., and Ohno, S. (1997) J. Biol. Chem. 272, 15167-15173). The in vitro reconstitution system for the kinase cascade allowed us now to identify JNK/SAPK activators involved in the MST/MLK2-dependent activation of JNK/SAPK in vivo. We show that at least two distinct MST/MLK2-dependent JNK/SAPK activators are present in the fractionated COS-1 cell lysate, and that they appear to be SEK1/MKK4/JNKK1/SKK1 and MKK7/JNKK2/SKK4 by Western blot analysis. Notably, a majority of the MST/MLK2-dependent JNK/SAPK-activating activity is found in MKK7-containing fractions, whereas the MEKK1-dependent activity is comparably distributed in SEK1- and MKK7-containing fractions. Moreover, MST/MLK2 activates recombinant MKK7 more effectively than recombinant SEK1, whereas MEKK1 activates both to a similar extent. In addition, the deletion analysis on MST/MLK2 showed that the kinase domain is responsible for the determination of substrate specificity. These results provide a molecular aspect to the differential regulation of the two JNK activators by a variety of cellular stimuli.

Animals↗