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Biomedical subjects

M Tahara

Publications and source records attributed to M Tahara.

At least 37 records · Page 2Linked to original sources

Tyrosine phosphorylation of STAT3 by leptin through leptin receptor in mouse metaphase 2 stage oocyte.

Leptin is the product of the obese gene (ob), and is secreted in plasma from mature adipocytes. It has been recently reported that leptin is synthesized in granulosa and cumulus cells within the follicle of the ovary, and is present in mature human oocytes, suggesting possible roles of leptin in several aspects of pre- and post-ovulatory follicular development. On the other hand, STAT (Signal Transducer and Activator of Transcription) transcription factors are involved in leptin-associated signal transduction. In this report, we studied the expression of leptin receptor and STAT3 activation by leptin in metaphase 2 stage (M2) oocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting showed that mRNA and protein of leptin receptor were expressed in M2 stage oocyte. Leptin at 15 ng/ml, the concentration observed in follicular fluid, caused tyrosine phosphorylation of STAT3 in mouse M2 stage oocytes. These results suggest possible roles of leptin in several aspects during oocyte maturation by activating the STAT signal transduction pathway.

Adipocytes↗

Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats.

A fatty liver is characterized by the hyperaccumulation of lipids within hepatocytes and is often caused by excessive alcohol intake. Rats fed ethanol-containing diets for 37 days showed remarkable increase in hepatic lipids and lipid droplet accumulation in the hepatocytes, indicating the onset of alcoholic fatty liver. Administration of hepatocyte growth factor (HGF) for the last seven days of ethanol treatment markedly decreased hepatic lipids to a level lower than that seen before HGF treatment. In contrast, serum levels of lipids and lipoproteins increased with HGF administration. Primary cultured hepatocytes prepared from the fatty liver retained lipid droplets during a 48-hour culture. However, when cultured in the presence of HGF, intracellular lipid concentrations decreased and lipid secretion was enhanced. Consistent with these events, HGF stimulated the rate of protein synthesis of apolipoprotein B (apoB) and enhanced subsequent mobilization of lipids into the medium. These results indicate that HGF administration induced recovery from the fatty liver, at least in part, by enhancing apoB synthesis and the subsequent mobilization of lipids from hepatocytes with fatty change. The possibility that HGF can be therapeutic for subjects with an alcohol-related fatty liver warrants further attention.

Animals↗

Analgesic efficacy and pharmacokinetics of ketoprofen administered into a surgical site.

A series of three clinical trials in the oral surgery model evaluated the analgesic efficacy and pharmacokinetics of ketoprofen administered locally as a strategy for decreasing systemic exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A gel formulation was administered directly into extraction sites 1 hour following oral surgery, and pain intensity was evaluated for 6 hours. Significantly less pain was seen following peripheral administration of both 10 and 30 mg ketoprofen in comparison to the placebo. In a second study, peripheral administration of the 1 mg dose resulted in greater analgesia than oral administration of the same dose formulation or the placebo. The third study demonstrated lower plasma drug levels following the peripheral route of administration in comparison to oral administration of the same dose or ingestion of a 25 mg oral capsule. These data indicate that administration of an NSAID to a peripheral site of tissue injury results in greater analgesia than oral administration and suggests the potential for less drug toxicity through lower circulating drug levels.

Administration, Oral↗

[A case of metachronous lung cancer in which tumor developed within the different ipsilateral lobe over a short period of time and completion pneumonectomy was required].

A 51-year-old man underwent a middle-lower lobectomy for squamous cell carcinoma on February 8, 1996. In July, 1997, a computed tomography revealed a mass shadow in the right upper lung field. Completion pneumonectomy was performed. Histopathological examination showed poorly differentiated adenocarcinoma. This case was the shortest time to occurrence of second tumor in our metachronous lung cancer cases. We must always give attention to exist second primary lung cancer and double primary lung cancer after resection of primary lung cancer.

Adenocarcinoma↗

[A case of superior mediastinal neurinoma resected from the supra-clavicular area].

We report a case of superior mediastinal neurinoma that was resected from the supra-clavicular area. An abnormal shadow on the chest X-ray film was pointed out in a 53-year-old male. A left supra-clavicular mass was subsequently also discovered. We underwent extirpation of the tumor through supra-clavicular approach and confirmed to be a neurinoma histologically. We consider supra-clavicular approach which allows a good view might be useful.

Humans↗

Biochemical and functional studies of cortical vesicle fusion: the SNARE complex and Ca2+ sensitivity.

Cortical vesicles (CV) possess components critical to the mechanism of exocytosis. The homotypic fusion of CV centrifuged or settled into contact has a sigmoidal Ca2+ activity curve comparable to exocytosis (CV-PM fusion). Here we show that Sr2+ and Ba2+ also trigger CV-CV fusion, and agents affecting different steps of exocytotic fusion block Ca2+, Sr2+, and Ba2+-triggered CV-CV fusion. The maximal number of active fusion complexes per vesicle, Max, was quantified by NEM inhibition of fusion, showing that CV-CV fusion satisfies many criteria of a mathematical analysis developed for exocytosis. Both Max and the Ca2+ sensitivity of fusion complex activation were comparable to that determined for CV-PM fusion. Using Ca2+-induced SNARE complex disruption, we have analyzed the relationship between membrane fusion (CV-CV and CV-PM) and the SNARE complex. Fusion and complex disruption have different sensitivities to Ca2+, Sr2+, and Ba2+, the complex remains Ca2+- sensitive on fusion-incompetent CV, and disruption does not correlate with the quantified activation of fusion complexes. Under conditions which disrupt the SNARE complex, CV on the PM remain docked and fusion competent, and isolated CV still dock and fuse, but with a markedly reduced Ca2+ sensitivity. Thus, in this system, neither the formation, presence, nor disruption of the SNARE complex is essential to the Ca2+-triggered fusion of exocytotic membranes. Therefore the SNARE complex alone cannot be the universal minimal fusion machine for intracellular fusion. We suggest that this complex modulates the Ca2+ sensitivity of fusion.

Animals↗

Calcium can disrupt the SNARE protein complex on sea urchin egg secretory vesicles without irreversibly blocking fusion.

The homotypic fusion of sea urchin egg cortical vesicles (CV) is a system in which to correlate the biochemistry and physiology of membrane fusion. Homologues of vesicle-associated membrane protein (VAMP), syntaxin, and SNAP-25 were identified in CV membranes. A VAMP and syntaxin immunoreactive band at a higher apparent molecular mass (approximately 70 kDa) was detected; extraction and analysis confirmed that the band contained VAMP, SNAP-25, and syntaxin. This complex was also identified by immunoprecipitation and by sucrose gradient analysis. VAMP in the complex was insensitive to proteolysis by tetanus toxin. All criteria identify the SNARE complex as that described in other secretory systems. Complexes exist pre-formed on individual CV membranes and form between contacting CV. Most notably, CV SNARE complexes are disrupted in response to [Ca2+]free that trigger maximal fusion. N-Ethylmaleimide, which blocks fusion at or before the Ca2+-triggering step, blocks complex disruption by Ca2+. However, disruption is not blocked by lysophosphatidylcholine, which transiently arrests a late stage of fusion. Since removal of lysophosphatidylcholine from Ca2+-treated CV is known to allow fusion, complex disruption occurs independently from the membrane fusion step. As Ca2+ disrupts rather than stabilizes the complex, the presumably coiled-coil SNARE interactions are not needed at the time of fusion. These findings rule out models of fusion in which SNARE complex formation goes to completion ("zippers-up") after Ca2+ binding removes a "fusion-clamp."

Animals↗

A serial echocardiographic observation of acute heart injury associated with pheochromocytoma crisis.

There are no previous reports of serial echocardiographic findings in patients with pheochromocytoma. We report a 50-year-old woman with pheochromocytoma who developed acute heart injury. Echocardiography revealed that the acute myocardial injury started early in the base and subsequently extended to the mid-portion of the heart. The injury persisted longer in the base than in the mid-portion.

Adrenal Gland Neoplasms↗

A new criterion combining ST/HR slope and deltaST/deltaHR index for detection of coronary artery disease in patients on digoxin therapy.

We evaluated the clinical value of a new index combining deltaST/delta heart rate (HR) index and ST/HR slope for diagnosing coronary artery disease (CAD) in patients on digoxin therapy. Exercise treadmill tests were performed by 72 patients on digoxin therapy. Simple HR-adjusted indexes of ST-segment depression during exercise (deltaST/deltaHR index) and the decline calculated from the final 12 data points relating ST-segment depression to HR (ST/HR slope) were determined. A new index was obtained by subtracting the deltaST/deltaHR index from the ST/HR slope. On thallium scintigraphy, 37 of the 72 patients showed reversible perfusion defects related to the diseased coronary artery. The new index derived from this ST-HR relation was 4.1 +/- 3.6 microV/beats/min in the ischemic group and 1.3 +/- 1.0 microV/beats/min in the group of patients without ischemia (p <0.0001). An ST-HR relation > or = 1.5 was found in 33 of the 37 patients in the ischemic group, and in 7 of the 35 patients without ischemia (p <0.0001). The sensitivity of this criterion for prediction of myocardial ischemia was 89%, the specificity was 80%, and the predictive accuracy was 85%. Thus, this new ST-HR index is useful for detecting CAD in patients on digoxin therapy.

Aged↗

Expression of Rab3A in the cortical region in mouse metaphase II eggs.

Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in regulated exocytosis at presynapses. At fertilization, sperm-egg fusion induces cytosolic calcium mobilization and cortical granule (CG) exocytosis in the egg. However, it is not yet clear whether Rab3A is involved in this process. We previously reported that Rabphilin-3A functions in calcium-dependent CG exocytosis. Rabphilin-3A is known to bind with Rab3A, Rab3B, and Rab3C. In this study, we clarified which member of the Rab3 was expressed in mouse metaphase II eggs. Messenger RNA encoding Rab3A but not Rab3B or Rab3C, was detected in unfertilized metaphase II eggs by RT-PCR. Rab3A protein was also detected in unfertilized metaphase II eggs by immunoblot analysis. Next the expression and the localization of Rab3A in eggs at various stages of development were determined by immunofluorescence analysis using confocal laser scanning microscopy. Rab3A protein was specifically distributed in the cortical region in eggs from before fertilization to the two-cell stage. However, it was not detected at the three- or four-cell stage 40 hr after fertilization. These results suggest that Rab3A may function with Rabphilin-3A in CG exocytosis.

Animals↗

Predicting the effects on patients with dilated cardiomyopathy of beta-blocker therapy, by using iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy.

We examined whether the iodine-123 15-(p-iodophenyl)-3- R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy was useful for predicting the treatment response to beta-blocker in patients with dilated cardiomyopathy (DCM). Sixteen patients with DCM were studied. BMIPP single photon emission computed tomography (SPECT) was performed before beta-blocker therapy. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated. Several measurements including the BMIPP H/M ratio before the administration of metoprorol were retrospectively compared among the 10 "good responders" (showing improvement by at least one NYHA class or an increase in the ejection fraction of > or = 0.10, 6 months after the start of the drug therapy) and the 6 "poor responders." The bull's eye map of BMIPP was divided into 17 areas. Each segmental score was analyzed quantitatively by means of a two-point scoring system (good uptake > or = 67%, poor uptake < 67%). The total score was regarded as the uptake score. The H/M ratio was significantly higher in the good responders than in the poor responders (2.41 +/- 0.24 vs. 1.86 +/- 0.17 p < 0.01). There were no significant differences between the two groups in any other variable data at entry. The uptake score was also a good index for predicting the therapeutic effect. When a relative uptake of 67% or higher was scored as 1, uptake scores of 9 to 17 corresponded to good responses (sensitivity = 100%, specificity = 100%, accuracy = 100%, positive and negative predictive value = 100%). Although the number of patients studied is small, our results suggests that BMIPP myocardial scintigraphy can predict the response to a beta-blocker in patients with DCM.

Adrenergic beta-Antagonists↗

SNAP-25 is essential for cortical granule exocytosis in mouse eggs.

Synaptosome-associated protein of 25 kDa (SNAP-25) has been shown to play an important role in Ca2+-dependent exocytosis in neurons and endocrine cells. During fertilization, sperm-egg fusion induces cytosolic Ca2+ mobilization and subsequently Ca2+-dependent cortical granule (CG) exocytosis in eggs. However, it is not yet clear whether SNAP-25 is involved in this process. In this study, we determined the expression and function of SNAP-25 in mouse eggs. mRNA and SNAP-25 were detected in metaphase II (MII) mouse eggs by RT-PCR and immunoblot analysis, respectively. Next, to determine the function of SNAP-25, we evaluated the change in CG exocytosis with a membrane dye, tetramethylammonium-1,6-diphenyl-1,3,5-hexatriene, after microinjection of a botulinum neurotoxin A (BoNT/A), which selectively cleaves SNAP-25 in MII eggs. Sperm-induced CG exocytosis was significantly inhibited in the BoNT/A-treated eggs. The inhibition was attenuated by coinjection of SNAP-25. These results suggest that SNAP-25 may be involved in Ca2+-dependent CG exocytosis during fertilization in mouse eggs.

Animals↗

[Resection of asymptomatic infected bulla associated with pulmonary tuberculosis].

The patient was a 49-year-old man. A physical examination in 1995 had disclosed the presence of a bulla in his left lung. Chest x-ray films taken in February 1997 disclosed niveau formation as an abnormal shadow in contact with the bulla. The patient was given a diagnosis of an infected bulla, and underwent an operation for partial resection of the S 6 portion of the left lung. The intracystic fluid was serous and no general bacteria or mycobacteria were detected. However, histopathological examination found granulation tissue associated with caseous necrosis and containing mycobacteria. The patient is currently receiving tuberculostatic agents on an outpatient basis.

Blister↗

[A case of mediastinal cavernous hemangioma resected through thoracoscope].

A case of mediastinal cavernous hemangioma was reported. An abnormal shadow on the chest X-ray film was pointed out in a 55-year-old male. CT scan and MRI revealed a right posterior mediastinal tumor but did not aid in the final diagnosis. We underwent extirpation of the tumor through thoracoscope and confirmed to be a cavernous hemangioma histologically. No major vascular connections between the tumor and major vessels were found. It was useful of thoracoscopic surgery in this case.

Endoscopy↗

A new predictor of restenosis after successful percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease.

With the goal of improving prediction of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for multivessel coronary artery disease (CAD), we evaluated the usefulness of serial exercise treadmill tests. We previously reported that an increase in the deltaST/delta heart rate (HR) index at follow-up over the value obtained several days after PTCA was useful for detecting restenosis following PTCA for 1-vessel CAD. In that report, comparison of the deltaST/deltaHR index was made based on measurements from the lead disclosing the greatest ST displacement before PTCA. This method was not applicable to patients with multivessel CAD. Seventy-eight patients with multivessel CAD before and several days after PTCA and just before follow-up performed exercise treadmill tests. Simple HR-adjusted indexes of ST-segment depression during exercise (deltaST/deltaHR index) and the sum of the deltaST/deltaHR index in leads II, III, aVF, V4, V5, and V6 (sigma deltaST/deltaHR index) were determined. We compared the predictive power of an increase in sigma deltaST/deltaHR index at follow-up with that of a positive exercise treadmill test and a positive thallium scintigram for restenosis. At follow-up, 37 of the 78 patients showed restenosis. The sigma deltaST/deltaHR index had increased in 30 of these 37 patients (81%), and in 12 of the 41 patients (29%) without restenosis. An increase in sigma deltaST/deltaHR index had a significantly higher sensitivity than the other methods and a significantly higher specificity than a positive exercise treadmill test.

Aged↗

Involvement of a sperm protein sensitive to sulfhydryl-depleting reagents in mouse sperm-egg fusion.

Effects of various sulfhydryl (SH)-depleting reagents on sperm-egg fusion were demonstrated. When sperm were treated with three plasma membrane-permeable SH-depleting reagents, N-ethyl-maleimide, sodium tetrathionate and 5,5'-dithiobis (2-nitro-benzoic acid), the rates of cleavage of eggs were significantly lower than those with control sperm. Neither the motility, penetration of the zona pellucida, acrosomal status of the sperm, nor sperm-egg binding was affected by the SH-depleting reagents. Fusion of sperm and zona-free egg was estimated by the sperm nuclear incorporation into the eggs, intracellular calcium mobilization, and cortical granule exocytosis in the eggs. Sperm-egg fusion was blocked dose-dependently when sperm were exposed to membrane-permeable SH-depleting reagents, but was not blocked by a membrane-impermeable SH-depleting reagent, eosin-5-maleimide. Blockage of fusion by sodium tetrathionate was completely reversed by an SH-reductant, dithiothreitol. These results suggest that a protein which is sensitive to SH-depleting reagents may play an important role in mouse sperm-egg fusion and that the functional SH region of the protein may be located at an intracellular site.

Acrosome↗

Relationship between specific binding of 125I-omega-conotoxin GVIA and GTP binding protein: effects of the GTP analogues, mastoparan and A1F4-.

We investigated whether the specific binding or labeling of 125I-omega-CgTX on crude membranes from chick whole brain was affected when endogenous GTP binding protein (G protein) was activated by GTP analogues, mastoparan (MP) and aluminum fluoride (AIF4-; AICl3 + NaF). Both GTPgammaS and Gpp(NH)p attenuated the inhibitory effect of selective N-type Ca channel inhibitors such as aminoglycoside antibiotics (AGs) or dynorphine (1-13)(Dyn) on specific 125I-omega-CgTX binding in a dose-dependent manner. On the other hand, the inhibitory effects of the divalent metal cations Cd2+, Co2+, Mg2+ and Mn2- on such binding were not attenuated by GTPgammaS. MP and AIF4- also attenuated the inhibitory effect of Neo on this binding similar to GTPgammaS. The attenuating effect of MP was enhanced by the presence of Mg2+ in a dose-dependent manner. However, GTP analogues, MP and AIF4-, did not affect binding or labeling without AGs or Dyn. GTPgammaS, MP and AIF4- also attenuated the specific labeling of a 215-kDa band in crude membranes with 125I-omega-CgTX using the cross-linker DSS (non-reduced condition) in the presence of Neo. These results indicate that there are direct or indirect relationships between N-type Ca channels and G proteins via binding sites for AGs or MP.

Aluminum Compounds↗