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Biomedical subjects

M Nasu

Publications and source records attributed to M Nasu.

At least 37 records · Page 2Linked to original sources

[Diffuse alveolar hemorrhage associated with idiopathic interstitial pneumonia syndrome after allogeneic bone marrow transplantation].

A 24-year-old male with myelodysplastic syndrome (refractory anemia) was treated with allogeneic bone marrow transplantation (BMT) from HLA-identical brother on September 9, 1994, after conditioning with busulfan and cyclophosphamide. From early in April 1995, the patient complained of cough and fever. Chest X-ray showed interstitial infiltrates involving hilar and lower lung fields. Although pulmonary infiltrates were resolved with methylprednisolone pulse therapy, on May 19, the patient rapidly deteriorated with dyspnea. Diffuse alveolar infiltrates appeared on chest X-ray and he died of respiratory failure. At autopsy, diffuse alveolar hemorrhage accompanied with thickening of the alveolar walls and interstitial infiltration of lymphocytes was demonstrated. There was no evidence of bleeding in other organs. This is a rare case of diffuse alveolar hemorrhage in the late stage of allogeneic BMT. This report should lead to an evaluation of this disease by the collection of similar cases.

Adult

[The case of left atrial myxoma originating from posterior leaflet of mitral valve].

We experienced the case of left atrial myxoma originating from posterior leaflet mitral valve. Mitral valve repair was performed in that case, because of the presence mitral leaflet defect due to removal of the myxoma. Transesophageal echocardiography was a useful tool for perioperative evaluation of the mitral valve and precise localization of the origin of the myxoma.

Adolescent

Hepatoid carcinoma of the lung with production of alpha-fetoprotein and abnormal prothrombin: an autopsy case report.

Alpha-fetoprotein (AFP) is a useful tumor marker for the diagnosis of hepatic and testicular tumors. Several cases of AFP-producing lung cancer have been reported. We present here a patient with AFP-producing primary lung carcinoma, which showed high values of serum AFP (100,000 ng/mL). The concanavalin A nonbinding fraction rate of AFP was 15%. Gross and microscopic features of the lung carcinoma bore a striking resemblance to those of hepatocellular carcinoma. According to the histologic classification of lung tumor, this case was large cell carcinoma with prominent hepatoid differentiation. Immunohistochemically, we detected AFP in the cytoplasm of the neoplastic cells. We also detected another useful tumor marker for the diagnosis of hepatocellular carcinoma, i.e., des-gamma-carboxy prothrombin (protein induced by vitamin K absence or the absence of antagonist-II [PIVKA-II]), in serum using an enzyme immunoassay and in tumor cells by immunohistochemical analysis.

Biomarkers

Sequential analyses of the mutations in the core upstream and precore regions of hepatitis B virus genome in anti-HBe positive-carriers developing acute exacerbation.

The nucleotide sequences of the core upstream and precore regions (371 nucleotide length, nt. 1604-1974) of hepatitis B virus (HBV) were analysed sequentially in three subjects who were positive serologically for anti-HBe and had acute clinical exacerbation after immunosuppressive treatment. These patients were asymptomatic HBV carriers before therapy. The results revealed that the mutant with an 8-bp deletion (nt. 1768-1775) located in the basic core promoter region was dominant in the asymptomatic HBV carrier phase in two of three subjects. After exacerbation, however, such mutant clones possessing 8-bp deletion disappeared or decreased in number and were replaced by the clones possessing a precore stop codon mutation G to A (nt. 1896) or by the clones possessing additional contiguous point mutations A to T (nt. 1762) and G to A (nt. 1764) and a new point mutation C to T (nt. 1653). Possible relationships between acute exacerbation of liver function accompanied by mutation and the transition of the dominant clones were discussed.

Acute Disease

Optical imaging of spatiotemporal patterns of glutamatergic excitation and GABAergic inhibition in the guinea-pig auditory cortex in vivo.

1. Glutamatergic excitation and gamma-aminobutyric acid (GABA)-ergic inhibition in layers II and III of the auditory cortex of anaesthetized guinea-pigs were recorded optically using a voltage-sensitive dye RH795 and a 12 x 12 photodiode array. 2. After contralateral ear stimulation with pure tones, transient excitatory responses followed by inhibitory responses were observed in fields A (primary) and DC of the auditory cortex. The area of the excitatory responses was sandwiched or surrounded by the areas of the inhibitory responses. 3. Optically recorded excitatory responses to pure tones had two components: a component sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, and a component sensitive to 2-amino-5-phosphono-valerate (APV), an NMDA receptor antagonist. Application of CNQX (5 microM) to the auditory cortex suppressed an early, but not a late, phase of the excitation; application of APV (100 microM) had the opposite effect. Concomitant application of CNQX and bicuculline methiodide (BMI, 4 microM), a GABAA receptor antagonist, increased the amplitude of the late phase 4-fold. This enhanced response was suppressed by APV. 4. These results indicate that (i) auditory cortical excitatory responses are mediated by both non-NMDA and NMDA receptors, (ii) inhibition is mediated by GABAA receptors, (ii) the excitatory bands are sandwiched or surrounded by GABAA receptor-mediated inhibitory areas and (iv) GABAA receptors effectively inhibit the NMDA, but not the non-NMDA, receptor-mediated excitation.

2-Amino-5-phosphonovalerate

Molecular typing of Helicobacter pylori: differences in pathogenicity among diverse strains.

Helicobacter pylori appears to be a species with strain diversity, according to studies carried out using various molecular biological techniques. Differences in pathogenicity caused by the strain diversity of H. pylori were therefore investigated. Two hundred and thirty strains were divided into four types by polymerase chain reaction-restriction fragment length polymorphism, and their relationship to endoscopic diagnosis, ammonia concentration of gastric juice, and urease activity were assessed. With regard to incidence by type, patients infected with type 1, type 2, and type 3 exhibited the highest incidences of gastric ulcer, duodenal ulcer, and gastritis, respectively. The urease activity of type 2 was significantly lower than that of types 1 and 3 (P < 0.05). These observations suggest differences in pathogenicity due to the strain diversity of H. pylori. However, the diversity of diseases related to H. pylori is also presumed to be caused by both the diversity of H. pylori strains and differences in the host immunological reaction. Future studies should be directed toward clarifying the entire pathogenic mechanism of H. pylori infection.

Bacterial Typing Techniques

Diverse inotropic effects of 5-hydroxytryptamine in heart muscles of various mammalian species.

The inotropic effects of 5-hydroxytryptamine (5-HT) on mammalian heart muscles were investigated. 5-HT (10(-8)-10(-3)M) produced increases in the contractile tension of atrial and ventricular muscles isolated from guinea pigs, Japanese monkeys, and humans, but not in rat heart preparations. The maximum percent increase of contraction was largest in guinea pig ventricular muscles (142.0 percent), followed by monkey atrium (86.3 percent), human atrium (71.7 percent), guinea pig atrium (48.7 percent), and monkey ventricle (30.1 percent). The sensitivity to 5-HT, measured as the negative logarithm of the half-maximal inotropic molar contractions of 5-HT, i.e., -logEC(50), was highest in the human atrium (6.65 +/- 0.20), followed by guinea pig atrium (5.53 +/- 0.36), monkey ventricle (4.83 +/- 0.28), guinea pig ventricle (4.56 +/- 0.11), and monkey atrium (4.46 +/- 0.16). The inotropic effects of 5-HT seen in the atrial and ventricular muscles of guinea pigs were abolished in the presence of the beta-receptor blocker, pindolol (8 mu M), while these effects in human atrial muscles and monkey atrial and ventricular muscles were abolished only in the presence of both pindolol (8 mu M) and of prazosin (1 mu M), an alpha(1)-receptor blocker. 5-HT increased the V(max) of the slow response recorded from guinea pig ventricular muscles exposed to high K+ (27 mM) media, whereas this agent did not alter the calcium current of isolated guinea pig ventricular myocytes devoid of sympathetic nerve terminals. In reserpinized guinea pig hearts, 5-HT exerted no inotropic effect on ventricular muscle, yet it had an inotropic effect in the atrial muscle, although the latter effect was considerably depressed, compared to that seen in non-reserpinized atrial muscles. We conclude that the positive inotropic effects of 5-HT observed in the ventricular muscle of the guinea pig and in the atrial and ventricular muscles of the Japanese monkey can be attributed to the release of noradrenaline from sympathetic nerve terminals (indirect effect). In contrast, in human atrial muscles, the positive inotropic effect of 5-HT was apparently the result of stimulation of a specific membrane receptor for 5-HT (direct effect). In guinea pig atrial muscles, both direct and indirect effects of 5-HT were involved in the positive inotropism. An explanation for the lack of sensitivity of rat atrial and ventricular muscles to 5-HT awaits further studies.

Adrenergic Fibers

Flow reserve capacity of left internal thoracic artery 23 years after Vineberg procedure.

Graft flow volume and flow reserve were assessed by Doppler echocardiography 23 years after Vineberg left internal thoracic artery implantation. Angiography showed good patency of the left internal thoracic artery, and the flow velocity profile was as biphasic as that of the coronary circulation. Drug-stressed test showed a physiologic reactivity of the Vineberg left internal thoracic artery but less response than that of a directly anastomosed left internal thoracic artery.

Blood Flow Velocity

Cloning and sequencing of the spore germination gene of Bacillus megaterium ATCC 12872: similarities to the NaH-antiporter gene of Enterococcus hirae.

The germination mutant TM-31 of Bacillus megaterium ATCC 12872, was isolated by transposon Tn917 insertional mutagenesis. Glucose, L-proline, L-leucine and KNO3 germinated TM-31 poorly. The DNA in the region of the Tn917 insertion was cloned, and its nucleotide sequence determined. One major open reading frame was present on the cloned DNA. The hydrophobic protein encoded is presumably membrane-associated. A homology search revealed that the gene encoded in the region of the Tn917 insertion is homologous to napA of Enterococcus hirae. napA codes for the NaH-antiporter. It is hypothesized that transport of cations must play an important role in spore germination in B. megaterium ATCC 12872.

Amino Acid Sequence

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys.

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n = 5) infected with H. pylori and in control monkeys without H. pylori infection (n = 6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P < 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P < 0.01 and P < 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P < 0.025-0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P < 0.025-0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.

Acetic Acid

[Detection of DNA specific for Aspergillus species in serum samples from two patients with invasive pulmonary aspergillosis].

We investigated the possible presence of DNA specific for Aspergillus species in serum samples of two patients who were strongly suspected for invasive pulmonary aspergillosis (IPA) by a nested polymerase chain reaction (PCR) method. Both patients were diagnosed as having acute myelogenous leukemia and treated with induction chemotherapy. During chemotherapy-induced granulocytopenia, they complained of high fever, and the chest X-rays indicated infiltration shadows in their lungs. They were treated with antibiotics intravenously, but no clinical improvement was observed. As the results of the nested PCR were positive at the acute stage of infection, amphotericin B i.v. and granulocyte colony stimulating factor s.c. administrations were started in both cases. In case 1, the infectious disease improved and the nested PCR results turned negative after treatment. In case 2, in spite of the progression of the disease, the nested PCR results turned negative during treatment. Although we consider this method very useful for the diagnosis of IPA, further prospective evaluation with a large clinical population sample is required.

Aged

[Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF].

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.

Aged

Detection of specific bacterial cells with 2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate and fast red TR in situ hybridization.

An in situ hybridization technique with HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate) and Fast Red TR was used to detect specific bacterial cells at the single-cell level. By this technique, the fluorescent signals of target bacterial cells were up to eight times more intense than those of standard fluorescence in situ hybridization with mono-fluorescein isothiocyanate-labeled oligonucleotide probes. This novel HNPP-Fast Red TR whole-cell hybridization technique is available for the identification of small or low-rRNA-content bacterial cells in the natural environment.

Bacteria

PCR detection of DNA specific for Aspergillus species in serum of patients with invasive aspergillosis.

We investigated the possible presence of DNA specific for Aspergillus species in serum samples of patients with invasive aspergillosis (IA) by the nested PCR method. Fourteen strains of fungi including 5 strains of Aspergillus species and 10 strains of common bacteria were used for examination of specificity and sensitivity of the nested PCR. Two sets of oligonucleotide primers were derived from the sequence of the variable regions V7 to V9 of the 18S rRNA genes of Aspergillus fumigatus. The specific fragment was amplified from five strains of Aspergillus species in the single and nested PCR but not from other microorganisms. Target DNA was detected by the nested PCR with as little as 50 fg of the extracted DNA of A. fumigatus. We investigated the detection of DNA specific for Aspergillus species in serum samples of a murine model of aspergillosis and 20 patients with IA. The specific fragment was detected by the nested PCR in 71% of serum samples of infected mice and 70% of serum samples of patients with IA, while galactomannan antigen was detected in 43 and 60% of samples, respectively. The high sensitivity and specificity of the nested PCR indicate that the assay can provide early diagnosis with sufficient accuracy to be clinically useful for immunocompromised patients with IA.

Animals

In vitro susceptibility of Trichosporon beigelii to antifungal agents.

The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of amphotericin B, flucytosine, miconazole, fluconazole and itraconazole against 21 isolates of Trichosporon beigelii in RPMI-1640 medium were determined using National Committee for Clinical Laboratory Standards (NCCLS) methodology in microdilution method. Most isolates were sensitive to miconazole (MIC90 0.78 microgram/ml), fluconazole (MIC90 6.25 micrograms/ml), and itraconazole (MIC90 0.19 microgram/ml), with the former being the most active agent tested (MFC90 3.12 mu/ml). Although amphotericin B inhibited most strains (MIC range, 0.78-3.12 micrograms/ml), poor fungicidal activity was observed (MFC range, 1.56-12.5 micrograms/ml) showing a pattern of relative resistance in vitro. Flucytosine showed generally poor activity against most isolates tested. These in vitro findings confirm the resistance of T.beigelii to amphotericin B and suggest that azoles may be an alternative to the former for the treatment of disseminated trichosporonosis. However, in vivo studies would better validate these in vitro findings.

Amphotericin B