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Biomedical subjects

M Maeda

Publications and source records attributed to M Maeda.

At least 613 records · Page 34Linked to original sources

[Mitral valve replacement with homemade heterologous pericardial roll valve for mitral regurgitation after repair of complete atrioventricular septal defect].

Repair of using the double patch method was performed on a 6-month old child with Down's syndrome. However, at 1 year and 4 months (BW: 3.6 kg), the patient's resulting mitral regurgitation became severe and clinically unmanageable, necessitating further operation. At operation the anterior leaflet of the mitral valve was lifted up at the anterolateral side due to the patch attached to the interventricular septum, which restricted the valve from closing completely. Moreover, secondary severe hardening of the valve tissue made it difficult to reconstruct the valve. Since the diameter of the valve was only 13 mm after resection, making the impossible use of a standard prosthetic valve, we constructed a new roll valve out of a heterologous pericardium. Almost no regurgitation was observed and prognosis was favorable although a pattern of mitral stenosis was observed. The patient died 6 months later due to the worsening of respiratory infection before a reoperation could be performed. Post mortem examination revealed comparatively good valve function except mitral stenosis due to inadequate valve size. This technique has practical application for mitral valve replacement of small valve annuli of infants when other methods are not feasible.

Bioprosthesis↗

[An advanced invasive thymoma that responded remarkably to neoadjuvant chemotherapy with carboplatin, adriamycin, and etoposide].

A 23-year-old man was admitted to the hospital with hoarseness caused by recurrent nerve palsy. The chest X-ray film and CT scan on admission showed a large mass in the antero-superior part of the mediastinum and a small round mediastinal mass adjacent to right inferior pericardium. Examination of a specimen aspirated from the mediastinal mass revealed thymoma. The tumor was considered to be inoperable because of the pericardial dissemination, and the patient was treated with carboplatin, Adriamycin, and etoposide. After 4 courses of chemotherapy, remarkable regression of both tumors was observed on a chest X-ray film. The patient underwent surgery, and no remaining tumor was found. A combination of carboplatin, Adriamycin, and etoposide may be useful as neoadjuvant chemotherapy for advanced invasive thymoma.

Adult↗

[Mononeuropathy multiplex in a patient receiving interferon alpha therapy for chronic hepatitis C].

We report a case of mononeuropathy multiplex due to interferon alpha (IFN alpha) therapy for chronic hepatitis C. A 61-year-old man received IFN alpha (natural type 6 x 10(6) IU), every day for two weeks and three times a week for 22 weeks by intramuscular injection. Seventeen weeks after the initiation of IFN alpha therapy, he noticed painful dysesthesia, muscle weakness and muscular atrophy of the left lower extremity. Neurological examination revealed weakness of the left iliopsoas, quadriceps femoris and femoral adductor muscles, hypesthesia and dysesthesia. Electromyogram showed neuropathic change in the left vastus lateralis muscle. Muscle computed tomography showed muscular atrophy of the left lower extremity. Two months after discontinuation of the IFN alpha therapy, dysesthesia and muscle weakness of the left lower extremity improved spontaneously. He was diagnosed as mononeuropathy multiplex of the left femoral nerve and obturator nerve caused by IFN alpha therapy. Attention must be paid to dysesthesia, muscle weakness and muscular atrophy when IFN alpha therapy is initiated.

Chronic Disease↗

[A case of HLA-DR2, DQw1 negative post-traumatic narcolepsy].

We reported a case of a 24-year-old man who had frequent sleep attacks beginning 4 years after a head trauma. He showed frequent episodes of excessive daytime sleepiness and cataplexy which were triggered by emotional excitement. He also complained of sleep paralysis and hypnagogic hallucination. An overnight polysomnography revealed the sleep onset REM stage as typically observed in narcoleptic patients. The HLA typing was negative for DR2 and DQw1. He was diagnosed as having HLA-DR2 and DQw1 negative-post-traumatic narcolepsy. Peroral pemoline suppressed excessive daytime sleepiness, sleep paralysis and hypnagogic hallucination with dramatic relief of cataplectic attacks by the addition of imipramine. It has been reported that more than 90% of narcoleptic patients are HLA-DR2 and-DQw1 positive. About 10% of the narcolepsy patients were regarded as symptomatic due to brain tumors, cerebrovascular disorders, head trauma, multiple sclerosis, encephalitis and so on, which mainly affect the brainstem or diencephalon. Thus far, narcolepsy is considered to develop depending on both the genetic background including HLA types, and exogenous factors. According to reported cases with narcolepsy, sporadic cases were HLA-DR2 positive even more frequently than familial cases. To date, however, there have been only three previous reports of a symptomatic narcolepsy patient without association of HLA-DR2 and DQw1. In conclusion, the present report suggests that typical symptomatic narcolepsy could be HLA-DR2 or DQw1 negative.

Adult↗

Design and synthesis of new cross-linking agents.

We have previously synthesized 6-vinylated guanosine derivatives by new Pd(0)-catalyzed cross-coupling reaction using guanosine 6-O-tosylate and vinyltributyl-stannane. Its potentials as a cross-linking agent have been demonstrated by adduct formation with guanosine and cytidine. But these 6-vinylated derivatives could not be incorporated to oligonucleotide because of chemical instability. In this paper, we report new deoxyguanosine derivatives with substituted olefin (2 and 3), which were designed to control the reactivity of vinyl functional group. Although either 2 or 3 did not formed the adducts with nucleobases, these compounds reacted with hydroxylamine hydrochloride in the presence of acid catalyst. The reactivity was in the order of 1 > 2 > 3. These results suggest that new guaosine derivatives (2 and 3) have moderate reactivity toward nucleophiles and are expected to be stable in incorporating into oligonucleotides as a cross-linking agent.

Cross-Linking Reagents↗

Analysis of polymerase chain reaction-product by capillary electrophoresis with laser-induced fluorescence detection and its application to the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency.

Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) has been developed to detect polymerase chain reaction (PCR) amplified samples. LIF detection was performed using Thiazole Orange as the fluorescent intercalating dye. This method was ca. 100x as sensitive as that with UV detection. The highly sensitive CGE-LIF was applied to the detection of the most prevalent mutation (lysine329-to-glutamic acid substitution) in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The disorder, which shows an autosomal recessive inheritance, is known to be highly prevalent among Caucasian population and often mimics as Reye-like syndrome or sudden infant death. A DNA fragment containing the mutation site was PCR-amplified with two sets of allele specific oligonucleotide primers, followed by CGE-LIF. The mutant allele produced a 175-base pairs DNA fragment, which the normal allele generated a 202-base pairs DNA fragment. CGE-LIF clearly distinguished these PCR products, facilitating rapid diagnosis of MCAD deficiency.

Acyl-CoA Dehydrogenase↗

N-ethylmaleimide-sensitive mutant (beta Val-153-->Cys) Escherichia coli F1-ATPase: cross-linking of the mutant beta subunit with the alpha subunit.

A beta subunit mutation, beta Val-153-->Cys, in the glycine-rich sequence (phosphate-binding loop) of Escherichia coli F1 was constructed. Like vacuolar-type ATPase, the mutant enzyme was inhibited by N-ethylmaleimide (NEM) and labeled with [14C]NEM. The inhibition and labeling were prevented by ATP. m-Maleimidobenzoyl-N-hydroxysuccinimide (MBS) (3 microM) almost completely inhibited the mutant enzyme, and cross-linked one pair of alpha and beta subunits. These results suggest that the interaction of the domain near beta Val-153 with the alpha subunit is essential for catalytic cooperativity of the enzyme and that beta Val-153 is within 10 A of the alpha subunit.

Adenosine Triphosphate↗

Brain blood flow regulation of the brainstem.

In anesthetized, paralyzed and artificially ventilated rats, the nucleus tractus solitarii (NTS), caudal ventrolateral medullary depressor area (VLDA), and rostral ventrolateral medullary pressor area (VLPA) were chemically stimulated. The roles of these areas on cerebral and spinal cord circulation, the receptor type of the NTS to control cerebral circulation, and the interaction between the VLDA and the VLPA were investigated. The NTS, VLDA, and VLPA have vasoconstrictor effects on the cerebral circulation, respectively. The VLPA has a vasoconstrictor effect on spinal cord circulation. The greater petrosal nerve (GPN) cell group, which is a subgroup of the superior salivatory nucleus, may constitute a parasympathetic cerebrovasodilator center. The NMDA receptors in the NTS may be involved in the control of cerebral circulation. The vasoconstrictive pathway to control cerebral vessels from the VLDA is mediated via the VLPA and the cervical sympathetic nerves. The present results also suggest that there may be a sympathoexcitatory pathway from the VLDA to the VLPA for controlling cerebral vessels and a sympathoinhibitory pathway from the VLDA to the VLPA for controlling systemic vessels. These different roles of the pathways from the VLDA to the VLPA for the different organs may explain the regional differences of the sympathetic nerves activities.

Animals↗

Catalysis and energy coupling of H(+)-ATPase (ATP synthase): molecular biological approaches.

The molecular biological approach has provided important information for understanding the F0F1 H(+)-ATPase. This article focuses on our recent results on the catalytic site in the beta subunit, and the roles of alpha/beta subunit interaction and amino/carboxyl terminal interaction of the gamma subunit in energy coupling. Extensive mutagenesis of the beta subunit revealed that beta Lys-155, beta Thr-156, beta Glu-181 and beta Arg-182 are essential catalytic residues. beta Glu-185 is not absolutely essential, but a carboxyl residue may be necessary at this position. A pseudo-revertant analysis positioned beta Gly-172, beta Ser-174, beta Glu-192 and beta Val-198 in the proximity of beta Gly-149. The finding of the roles of beta Gly-149, beta Lys-155, and beta Thr-156 emphasized the importance of the glycine-rich sequence (Gly-X-X-X-X-Gly-Lys-Thr/Ser, E. coli beta residues between beta Gly-149 and beta Thr-156) conserved in many nucleotide binding proteins. The A subunits of vacuolar type ATPases may have a similar catalytic mechanism because they have conserved glycine-rich and Gly-Glu-Arg (corresponding to beta Gly-180-beta Arg-182) sequences. The results of these mutational studies are consistent with the labeling of beta Lys-155 and beta Lys-201 with AP3-PL, and of beta Glu-192 with DCCD [15]. The DCCD-binding residue of a thermophilic Bacillus corresponds to beta Glu-181, an essential catalytic residue discussed above. The defective coupling of the beta Ser-174-->Phe mutant was suppressed by the second mutation alpha Arg-296-->Cys, indicating the importance of alpha/beta interaction in energy coupling. The gamma subunit, especially its amino/carboxyl interaction, seems to be essential for energy coupling between catalysis and transport judging from studies on gamma Met-23-->Lys or Arg mutation and second-site mutations which suppressed the gamma Lys-23 mutation. Thus the conserved gamma Met-23 is not absolutely essential but is located in the important region for amino/carboxyl interaction for energy coupling.

Amino Acid Sequence↗

Endogenous tumor necrosis factor functions as a resistant factor against adriamycin.

One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) and heat is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF and heat by inducing manganous superoxide dismutase (MnSOD) to scavenge the reactive oxygen molecules. Intracellular hydroxyl radical production is also involved in adriamycin-induced cytotoxicity. In this study, we therefore examined the possibility that enTNF may act as a protective protein against adriamycin-induced cytotoxicity in a manner similar to that in which it protects against exogenous TNF and heat. Adriamycin-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with an expression vector which directs the synthesis of non-secretory-type human TNF (enTNF). The stable transformants became resistant to adriamycin with increased levels of MnSOD. Conversely, when HeLa (human uterine cervical cancer) cells, which originally produce an appreciable amount of enTNF, were transfected with an anti-sense TNF mRNA expression vector to inhibit enTNF synthesis, their intracellular MnSOD activity was suppressed and adriamycin sensitivity was enhanced. However, no alterations in expression of multidrug-resistant gene products--P-170 glycoprotein, glutathione S-transferase pi (GST-pi) and the intracellular concentrations of glutathione (GSH)--were observed in these transfectants as compared to their parent cells. These results indicate that enTNF exerts its intracellular protective effect against adriamycin-induced cytotoxicity by the same mechanism as that against exogenous TNF and heat, namely scavenging reactive oxygen with induced MnSOD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency.

The IL-2R gamma-chain is an indispensable subunit for the functional IL-2R. Recently, mutations of the gamma-chain have been reported to be closely associated with X-linked severe combined immunodeficiency (XSCID). The present study reveals that three patients with XSCID have three different mutations in the gamma-chain; a point mutation, a two consecutive-base deletion, and lack of the second exon in mRNA. The point mutation that we have detected is C to T, which results in one amino acid substitution of valine for alanine in the extracellular domain of the IL-2R gamma-chain (named AV mutant). The two-base deletion detected causes a frame shift of the coding region in the SH2 subdomain in the cytoplasmic domain (named tSH mutant). Transfection studies performed with the mutant gamma-chains demonstrated that the AV mutant and tSH mutant failed to bind to IL-2 and to transduce growth signals, respectively. These findings indicate that the gamma-chain gene mutations that accompany XSCID induce loss of the gamma-chain function, possibly resulting in stagnation of the differentiation and development of T cells.

Base Sequence↗

Human papillomavirus not found in squamous and large cell lung carcinomas by polymerase chain reaction.

BACKGROUND: Human papillomavirus (HPV) has been identified not only in anogenital carcinomas, but also in malignancies of other organs, including bronchogenic carcinomas. Previous studies reporting detection of these viruses in lung cancers used mainly in situ hybridization. The authors applied the polymerase chain reaction (PCR) for investigating the occurrence of HPV in bronchial neoplasms. METHODS: Formalin fixed, paraffin embedded tissues of 40 squamous and 7 large cell lung cancers were examined. PCR was done with consensus primers, capable of detecting HPV 6, 11, 16, 18, 31, 33, 52b, and 58. RESULTS: None of the 47 samples contained any of the examined HPV types. CONCLUSIONS: Because the squamous and large cell cancer cases were found not to be associated with HPV infection, this study does not support the potential role of these viruses in the development of lung cancers.

Base Sequence↗

Endonuclease V from bacteriophage T4 interacts with its substrate in the minor groove.

The binding of bacteriophage T4 endonuclease V to its substrate has been studied using synthetic oligodeoxyribonucleotide duplexes containing a cis-syn thymine dimer. Substrate analogues containing a methylphosphonate linkage with a defined configuration at the thymine dimer site were prepared, and the binding of the enzyme to each diastereomer was analyzed by the filter-binding method. The duplex containing a methylphosphonate with the SP configuration formed a complex with the enzyme, although the dissociation constant for this substrate analogue was about 8 times larger than that for the 12-mer substrate containing a phosphodiester linkage at this site. In contrast, no binding was observed when a duplex containing the RP-methylphosphonate linkage was used. The glycosyl bond of the thymine dimer in the SP isomer was cleaved by the enzyme, while no incision was detected in the case of the RP isomer, even after alkali treatment. Another substrate analogue containing a sulfur atom in place of the 3'-oxygen of the 5'-component at the thymine dimer site showed a reduced affinity for the enzyme. These results suggest that T4 endonuclease V interacts with its substrate in the minor groove. This mode of binding was confirmed by methylation protection experiments.

Bacteriophage T4↗