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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 361 records · Page 20Linked to original sources

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗

[Pulmonary tuberculosis with diabetes mellitus, presenting multiple nodular shadows].

An asymptomatic 52-year-old male, who was diagnosed as poorly controlled diabetes mellitus (DM), was referred to our hospital because of abnormal shadows on chest X-rays. Physical examinations and laboratory data showed no abnormal findings except increased values of blood sugar and HbA1c (12.1%). Chest X-ray and CT scan revealed multiple nodular shadows in both lung fields. The specimens from transbronchial biopsy showed epithelioid granuloma, and Mycobacterium tuberculosis was confirmed with bronchial wash fluid. The patient was then treated with antimycobacterial drugs and sulfonylurea along with diet therapy. The multiple nodular shadows gradually disappeared. It seemed that impaired host defense mechanisms caused by poorly controlled DM is responsible for the bronchogenic dissemination of M. tuberculosis, resulting in the extension into the multiple nodular shadows. Thus, a good control of DM is important for the prevention of an onset and excerbation of tuberculosis in patients with DM.

Diabetes Complications↗

Fosfomycin reduces CD15s-related antigen expression of Streptococcus pyogenes.

We have previously shown the immunological mimicry of human sialyl-Lewis(x) (CD15s) by a surface antigen of Streptococcus pyogenes. This mimicking surface antigen may act as a ligand to the selectin family and may induce antibody production against CD15s on host cells, suggesting a possible role in the pathogenesis of S. pyogenes. In this study, the effects of antibiotics on the CD15s-related antigen expression of S. pyogenes were examined at a concentration below the MIC (sub-MIC). The amounts of CD15s on the surfaces of S. pyogenes cells and on the surfaces of S. pyogenes biofilms were determined by a whole-cell enzyme-linked immunosorbent assay and by laser scanning fluorescence microscopy, respectively, by using an anti-CD15s monoclonal antibody. At the sub-MICs, fosfomycin (1R,2S-1,2-epoxypropyl phosphonic acid), its enantiomer (1S,2R-1,2-epoxypropyl phosphonic acid), and benzylpenicillin significantly inhibited the CD15s expression of all strains studied. The effects of fosfomycin and its enantiomer on biofilms were also observed by scanning electron microscopy. Incubation of S. pyogenes with the sub-MIC of fosfomycin or its enantiomer, which has no antibacterial activity, reduced the amount of CD15s on the biofilm surface and made it smooth. These results suggest that fosfomycin or its enantiomer might be useful for preventing S. pyogenes adherence to human CD15s receptors and the resulting immunological pathogenicity.

Anti-Bacterial Agents↗

Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist.

Involvement of bradykinin generation in bacterial invasion was examined by using a gram-negative bacillus, Vibrio vulnificus, which is known to invade the blood circulatory system and cause septicemia. V. vulnificus was injected intraperitoneally (i.p.) into mice with or without bradykinin or a bradykinin (B2 receptor) antagonist. Dissemination of V. vulnificus from peritoneal septic foci to the circulating blood was assessed by counting of viable bacteria in venous blood by use of the colony-forming assay. Intravascular dissemination of V. vulnificus in mice was significantly potentiated by simultaneous injection with bradykinin but was markedly reduced by coadministration with the B2 antagonist D-Arg,[Hyp3, Thi(5,8), D-Phe7]-bradykinin. Furthermore, V. vulnificus lethality was significantly increased when bradykinin was administered simultaneously with the bacillus, whereas it was definitely suppressed by treatment with D-Arg,[Hyp3, Thi(5,8), D-Phe7]-bradykinin. Similarly, ovomacroglobulin, a potent inhibitor of the V. vulnificus protease, showed a strong suppressive effect on the V. vulnificus septicemia. We also confirmed appreciable bradykinin production in the primary septic foci in the mouse peritoneal cavity after i.p. inoculation with V. vulnificus. It is thus concluded that bradykinin generation in infectious foci is critically involved in facilitation of intravascular dissemination of V. vulnificus.

Animals↗

Physiological control of a total artificial heart: conductance- and arterial pressure-based control.

To obtain a physiological response by a total artificial heart (TAH), while eliminating the hemodynamic abnormalities commonly observed with its use, we proposed the use of a conductance- and arterial pressure-based method (1/R control) to determine TAH cardiac output. In this study, we endeavored to make use of a variable more closely tied to central nervous system (CNS) efferents, systemic conductance, to provide the CNS with more direct control over the output of the TAH. The control equation that calculates the target cardiac output of the TAH was constructed on the basis of measurement of blood pressures and TAH flow. The 1/R control method was tested in TAH-recipient goats with an automatic method by using a microcomputer. In 1/R control animals, the typical TAH pathologies, such as mild arterial hypertension and substantial systemic venous hypertension, did not occur. Cardiac output varied according to daily activity level and exercise in a manner similar to that observed in natural heart goats. These results indicate that we have determined a control method for the TAH that avoids hemodynamic abnormalities exhibited by other TAH control systems and that exhibits physiological responses to exercise and daily activities under the conditions tested. The stability of the control and the complete lack of inappropriate excursions in cardiac output is suggestive of CNS involvement in stabilizing the system.

Animals↗

Gustatory and multimodal neuronal responses in the amygdala during licking and discrimination of sensory stimuli in awake rats.

The amygdala (AM) receives information from various sensory modalities via the neocortex and directly from the thalamus and brain stem and plays an important role in ingestive behaviors. In the present study, neuronal activity was recorded in the AM and amygdalostriatal transition area of rats during discrimination of conditioned sensory stimuli and ingestion of sapid solutions. Of the 420 responsive neurons, 227 responded exclusively to one sensory modality, 120 responded to two or more modalities, and the remaining 73 could not be classified. Among the responsive neurons, 108 responded to oral-sensory stimulation (oral-sensory neurons). In detailed analyses of 84 of these oral-sensory neurons, 24 were classified as taste responsive and were located mainly in the central nucleus of the AM. The other 60 oral-sensory neurons were classified as nontaste oral-sensory neurons and were distributed widely throughout the AM. Both the taste and nontaste oral-sensory neurons also responded to other sensory stimuli. Of the 24 taste neurons, 21 were tested at least with four standard taste solutions. On the basis of the magnitudes of their responses to these sapid stimuli, the taste neurons were classified as follows: seven sucrose-best, four NaCl-best, three citric acid-best, and six quinine HCl-best. The remaining cell responded significantly only to lysine HCl and monosodium glutamate. Multivariate analyses of these 21 taste neurons suggested that, in the AM, taste quality was processed based on palatability. Taken with previous lesion studies, the present results suggest that the AM plays a role in the evaluation of taste palatability and in the association of taste stimuli with other sensory stimuli.

Acoustic Stimulation↗

Modulation of the inspiratory-related activity of hypoglossal premotor neurons during ingestion and rejection in the decerebrate cat.

Single-unit activities of the bulbar reticular inspiratory neurons directly projecting to hypoglossal motoneurons were studied during fictive ingestion (e.g., swallowing) and rejection elicited by repetitive stimulation of the superior laryngeal nerve and by application of water to the pharynx in immobilized decerebrated cats. The single-unit activity was recorded during 113 episodes of fictive ingestion from 25 inspiratory neurons directly projecting to hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons directly projecting to both hypoglossal and phrenic motoneurons (dual projection neurons) in the regions ventrolateral to the nucleus tractus solitarii and dorsomedial to the nucleus ambiguus. All of single projection neurons ceased inspiratory-related rhythmical discharges coincidentally with the onset of repetitive stimulation of the superior laryngeal nerve. The majority of them (19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority (6/25, 24%, type B) kept silent until the end of repetitive stimulation of the superior laryngeal nerve. During fictive ingestion elicited by application of water to the pharynx, the type-A neurons showed a spike burst activity, whereas the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C) ceased inspiratory-related rhythmical discharges at the onset of repetitive stimulation of the superior laryngeal nerve and showed no activity during fictive ingestion. Likewise, the type-C neurons kept silent during fictive ingestion elicited by application of water to the pharynx. A spike burst was induced during 33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and 6 tested type-C neurons. It is concluded that the premotor neurons involved in the respiratory-related rhythmical activity of hypoglossal motoneurons is responsible for switching from respiration to ingestion and rejection.

Animals↗

Larva currens: the usefulness of the agar plate method.

Creeping eruption caused by Strongyloides stercoralis is called larva currens, while those caused by other parasites are called larva migrans. To detect the parasite, the direct smear method was used. However, this method is not very sensitive in detecting S. stercoralis. A 62-year-old male with polyarteritis nodosa cutanea had an erythematous creeping eruption in various regions, such as his lumbar region, abdomen and thigh. The diagnosis of larva currens was made by the clinical appearance and the detection of S. stercoralis in his feces using the direct smear method and the agar plate method. This is the first reported case of larva currens in Japan. The agar plate method was useful and more sensitive than the usual direct smear method for detecting the S. stercoralis in feces and for elucidating the effects of treatment with antiparasitic drugs.

Adult↗

Hypercalcemia in a patient with malignant melanoma arising in congenital giant pigmented nevus. A case of increased serum level of parathyroid hormone-related protein.

We describe a 43-year-old Japanese female who developed hypercalcemia associated with malignant melanoma. The patient underwent three resections of tumors on her groin and buttock secondary to a bathing trunk congenital nevus, and the histopathological findings showed benign congenital nevi. At the age of 42 years, she developed a malignant melanoma under the giant pigmented nevus in her groin. Fourteen months after the diagnosis of melanoma, she developed metastases to the lung, para-aortic lymph nodes and bones accompanied by hypercalcemia resulting from a remarkable increase in the serum level of parathyroid hormone-related protein (PTHrP). The patient died from acute renal and respiratory failure. In addition, we analyzed serum levels of calcium and PTHrP in 19 patients with advanced malignant melanoma. Seven patients had hypercalcemia, and 3 had increased serum levels of PTHrP.

Adult↗

Swallowing-related perihypoglossal neurons projecting to hypoglossal motoneurons in the cat.

Although previous studies have examined the functional role of the neurons in the area ventrolateral to the hypoglossal nucleus (perihypoglossal neurons) in the trigemino-hypoglossal reflex, no convincing evidence for the direct connection from the perihypoglossal neurons to the hypoglossal motoneurons has yet been provided. In addition, the role of the perihypoglossal neurons in swallowing has not been studied. The purpose of this study was to investigate (1) the input-output relationship of the perihypoglossal neurons and (2) whether the afferent feedback was essential for their swallowing-related activity in chloralose-anesthetized cats. Before and after the cats were paralyzed, single-unit activities were recorded extracellularly from 30 perihypoglossal neurons during swallowing elicited by electrical stimulation of the superior laryngeal nerve. These perihypoglossal neurons responded with spike potentials after short latencies to stimulation of the inferior alveolar and hypoglossal nerves. The neurons also responded with spike potentials to single shocks applied to the superior laryngeal nerve, but were activated transiently at the initial phase of repetitive stimulation of the nerve and kept silent until the occurrence of swallowing before and after the animal was paralyzed. They showed burst activities in coincidence with swallowing. Averaging of intracellular potentials of a hypoglossal motoneuron by simultaneously recorded extracellular spikes of a perihypoglossal neuron revealed monosynaptic inhibitory post-synaptic potentials. We conclude that, in the region ventrolateral to the hypoglossal nucleus, there are neurons which relay trigeminal, hypoglossal, and vagal afferents. Furthermore, some of these perihypoglossal neurons are inhibitory hypoglossal premotor neurons that are involved in the central programming of swallowing.

Afferent Pathways↗

Effects of YT-146 [2-(1-octynyl) adenosine], an adenosine A2A receptor agonist, on cAMP production and noradrenaline release in PC12 cells.

Effects of YT-146 [2-(1-octynyl) adenosine], an adenosine A2 receptor agonist, on cAMP production and noradrenaline (NA) release were investigated in PC12 cells. YT-146 caused a concentration-dependent cAMP accumulation (EC50: 1.2+/-0.9 nM). In [3H]NA-prelabeled cells, YT-146 increased the basal NA release and enhanced ATP-evoked NA release in a concentration-dependent manner (EC50: 0.23+/-0.15 nM). YT-146 augmented the maximal response to ATP without affecting the EC50 value of ATP. These effects of YT-146 were inhibited by several adenosine receptor antagonists with a characteristic of adenosine A2A receptor subtype. The effects of YT-146 were mimicked by forskolin, dibutylyl cAMP and Sp-cAMPS, and inhibited by H-89, a cAMP-dependent protein kinase inhibitor. YT-146 had little effect on ATP-induced increase in intracellular Ca2+ concentration. YT-146 enhanced the NA release induced by several different stimuli including Ca2+ ionophore A23187. The present results suggest that YT-146 is a potent agonist on adenosine A2A receptors in PC12 cells and causes a cAMP-dependent enhancement of NA release by affecting the exocytosis process at a point downstream of the intracellular Ca2+ increase.

Adenosine↗

Effects of X-ray irradiation on genomic DNA methylation levels in mouse tissues.

Effects of ionizing radiation on the level of genomic DNA methylation in liver, brain and spleen of mouse as well as in two kinds of cultured cells were examined by high-performance liquid chromatography. Ten Gy of whole body X-radiation reduced the 5-methyldeoxycytidine contents by about 40% within 8 hours after irradiation in liver. Similar effects were observed at 4 or 7 Gy of X-ray irradiation. However, no such change was detected in brain, spleen and cultured cells. The data indicate that radiation-induced alteration in genomic DNA methylation is not ubiquitous among different tissues and cells.

Animals↗

Casein phosphopeptides from casein micelles by successive digestion with pepsin and trypsin.

When milk is ingested, casein micelles will be successively digested by pepsin in the stomach and trypsin in the intestine. Therefore, we digested casein micelles successively with pepsin at pH 4.0 and trypsin at pH 7.0, and recovered casein phosphopeptides (CPP) as CPP-calcium phosphate (CP) complexes. The CPP-CP complexes contained 248 mg of calcium/g peptides and 175 mg of inorganic phosphorus/g peptides, which were higher than those of CPP-CP complexes driven from acid-precipitated casein and casein micelles by tryptic digestion only. It contained more alpha S1-CN-5P(f59-79) than the other CPP preparations did.

Calcium Phosphates↗

Effect of growth hormone therapy in children with achondroplasia: growth pattern, hypothalamic-pituitary function, and genotype.

OBJECTIVE: Although there are a few reports on GH therapy in achondroplasia, these were based on a small sample and/or short-term observation. To clarify the effectiveness of GH treatment on short stature in achondroplasia and hypochondroplasia, a long-term treatment study in a larger number of patients was performed. METHOD: Forty-two children (16 males and 26 females, age 3-14 years) with achondroplasia were examined in this study. Initially, we evaluated hypothalamic-pituitary function and point mutation analysis as previously reported. After the evaluation, the children were treated with GH for more than 2 years; then post-treatment growth velocity and body proportion parameters were determined. RESULTS: The 35 typical variants of our achondroplasia patients showed previously reported point mutation in the fibroblast growth factor receptor 3 gene. The annual height gain during GH therapy was significantly greater than that before therapy (3.9 +/- 1.0 cm/year before treatment vs 6.5 +/- 1.8 cm/year for the first year and 4.6 +/- 1.6 cm/year for the second year of treatment). The body disproportion had not been aggravated during the treatment period. CONCLUSION: We conclude that GH might be beneficial in the treatment of short stature in children with achondroplasia in the first 2 years of treatment.

Achondroplasia↗

Production of donor-derived offspring by transfer of primordial germ cells in Japanese quail.

We transfused concentrated primordial germ cells (PGCs) of the black strain (D: homozygous for the autosomal incomplete dominant gene, D) of quail into the embryos of the wild-type plumage strain (WP: d+/d+) of quail. The recipient quail were raised until sexual maturity and a progeny test of the putative germline chimeras was performed to examine the donor gamete-derived offspring (D/d+). Thirty-one percent (36/115) of the transfused quail hatched and 21 (13 females and 8 males) of them reached maturity. Five females and 2 males were germline chimeras producing donor gamete-derived offspring. Transmission rates of the donor derived gametes in the chimeric females and males were 1.8-8.3% and 2.6-63.0%, respectively. Germline chimeric and the other putative chimeric males were also test-mated with females from the sex-linked imperfect albino strain (AL: d+/d+, al/W, where al indicates the sex-linked imperfect albino gene on the Z chromosome, and W indicates the W chromosome) for autosexing of W-bearing spermatozoa: No albino offspring were born.

Animals↗

The usefulness of CYFRA 21-1 in diagnosing and monitoring malignant pleural mesothelioma.

Five patients with malignant pleural mesothelioma (MPM) were studied to determine whether CYFRA 21-1 is useful for diagnosis of this disease. In pleural effusions, the median concentration of CYFRA 21-1 from 4 patients with MPM was significantly higher than for 34 patients with benign diseases. The sensitivity of serum CYFRA 21-1 for diagnosis of MPM was 40% and its concentration changed in proportion to disease activity in all cases. Immunohistochemically, anticytokeratin 19 antibody revealed strong staining in both epithelial and sarcomatous MPM tissues. Based on these results, we conclude that measurement of CYFRA 21-1 in pleural effusions and serum may be useful for diagnosing and monitoring MPM.

Aged↗

Two familial mesothelioma cases with high concentrations of soluble cytokeratin 19 fragment in pleural fluid.

We report two cases of diffuse malignant pleural mesothelioma occurring almost simultaneously in one family. Patient 1 was a 42-year-old Japanese man who had worked as an electrical engineer for 25 years. Patient 2, his mother, was 69 years old. She lived for 10 years with patient 1 after he started his work, and also worked at a shipyard herself for 6 years. The concentrations of cytokeratin subunit 19 fragment (CYFRA 21-1) in pleural fluid of the two patients were 1,500 ng/ml, and 1,200 ng/ml, respectively. Measurement of CYFRA 21-1 concentration in the pleural fluid may be a useful tool for a diagnosis of malignant mesothelioma.

Adult↗