Biomedical subjects
H Maeda
Publications and source records attributed to H Maeda.
XAFS spectra in the high-energy region measured at SPring-8.
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Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats.
The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was investigated by using an experimental model of herpes simplex virus type 1 (HSV-1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS) mRNA determined by Northern blotting was observed first in the olfactory bulb and the brain stem on day 5 after intranasal inoculation of HSV-1, and thereafter iNOS mRNA was detected in other brain regions, i.e., cerebrum and cerebellum. In various parts of the brain, excessive NO production was identified by electron spin resonance spectroscopy. The temporal and spatial patterns of iNOS expression coincided with those of viral propagation, as demonstrated by polymerase chain reaction for HSV-1 gene expression as well as by the plaque-forming assay. Immunohistochemical study determined that iNOS was localized mainly in monocyte-derived macrophages. Treatment of virus-infected animals with the NOS inhibitor Nomega-monomethyl-l-arginine (l-NMMA), but not Nomega-monomethyl-d-arginine, significantly ameliorated not only clinical symptoms such as paralysis and seizures but also mortality. Virus yield from brain tissue was not affected by l-NMMA treatment. It is of interest that increased expression of the antioxidant enzyme heme oxygenase-1 was observed in the HSV-1-infected brain; this increased expression was strongly inhibited by l-NMMA treatment. These data suggest that the high level of NO produced by iNOS is a pathogenic factor in HSV-1-induced encephalitis in rats.
Mechano-chemical Patterns in Collapsing Gels.
Characteristic patterns are observed in collapsing polyion gels. The symmetry axes of these patterns were found to be in the directions of external force exerted on the gel. In the present study, we examined the roles played by the mechno-chemical properties in the formation of these patterns in the polymer matrix. Copyright 1999 Academic Press.
Differential requirement of IFN consensus sequence binding protein for the production of IL-12 and induction of Th1-type cells in response to IFN-gamma.
IFN-gamma exerts multiple biological activities in the modulation of immune responses by the induction of transcription factors. One transcriptional factor of the IFN regulatory factor family found to be critical in regulating IL-12-dependent IFN-gamma production in vivo following infectious challenge has been designated IFN consensus sequence-binding protein (ICSBP). In this study, the role of ICSBP in regulating type 1 responses to T cell-specific stimulation in vitro was assessed. Total splenocytes from ICSBP-/- mice stimulated with soluble anti-CD3 were markedly impaired in the production of IFN-gamma compared with similarly stimulated cells from ICSBP+/+ mice. Consistent with the decrease in IFN-gamma production, splenocytes from ICSBP-/- mice stimulated with anti-CD3 in the presence or absence of IFN-gamma or a soluble CD40 ligand agonist failed to produce IL-12 p40 and IL-12 p70 protein; however, the deficient production of IFN-gamma from ICSBP-/- mice could be restored by the addition of anti-CD28 Ab in an IL-12-independent manner. In contrast to the previous data, production of IFN-gamma from naive CD4+/LECAM-1high cells of ICSBP-/- mice that had been primed in vitro with anti-CD3 was similar to or greater than that of ICSBP+/+ controls. In addition, the presence of IFN-gamma in priming cultures enhanced both priming for IFN-gamma and IL-12 responsiveness from ICSBP-/- CD4+ T cells. Overall, these results provide evidence that ICSBP is differentially required for the ability of IFN-gamma to regulate type 1 cytokine responses from APCs and CD4+ T cells.
Dietary restriction reduces the prevalence of osteonecrosis of the caput femoris in spontaneously hypertensive rats.
We investigated the effects of dietary restriction (DR), an experimental intervention known to suppress several strain-specific diseases, on the prevalence of osteonecrosis of the caput femoris in spontaneously hypertensive rats (SHR). At 6 weeks of age, the food intake of DR rats was restricted to 65% of the mean intake of control rats fed ad libitum (AL). Acute osteonecrosis of the caput femoris without reparative tissue response (RTR) was observed at 10 and 15 weeks in both DR and AL groups; no such acute lesion was seen at 20 and 30 weeks. The prevalence of osteonecrosis, osteonecrosis with/without reparative tissue response was significantly reduced in DR rats at 15 and 20 weeks, but not at 10 weeks. DR reduced the body weight by 30% and the length of the femur by 10%. Ossification of the caput femoris, known to be delayed in AL rats compared with Wistar Kyoto rats, was also restored by DR. Our results showed that dietary restriction reduced the prevalence of osteonecrosis and modulated the mechanical factors involved in the lesion. They also indicate that utilization of dietary restriction is a useful research tool for investigating the underlying mechanisms of osteonecrosis of the caput femoris in SHR.
The radiological findings in chronic expanding hematoma.
OBJECTIVE: To identify the characteristic MRI findings of chronic expanding hematoma correlated with the pathology. DESIGN AND PATIENTS: Three patients who had a chronic expanding hematoma involving the musculoskeletal system were reviewed retrospectively. RESULTS AND CONCLUSION: Huge soft tissue masses suggestive of malignancy with destruction of the bony structure were revealed on radiography and computed tomography. MRI showed the masses to exhibit heterogeneous signal intensity on both T1 and T2-weighted images with a peripheral rim of low signal intensity, reflecting the central zones of fluid collection due to fresh and altered blood with a wall of collagenous fibrous tissue. These MRI findings were seen in all three patients and are considered to be characteristic; they assist in differentiation from neoplasm in consideration of the history of trauma or surgery.
Limited and selective localization of the lysosomal membrane glycoproteins LGP85 and LGP96 in rat osteoclasts.
Monospecific antibodies against two major glycoproteins of rat lysosomal membranes with apparent molecular masses of 96 and 85 kDa, termed LGP96 and LGP85, respectively, were used as probes to determine the expression and distribution of lysosomal membranes in rat osteoclasts. At the light microscopic level, the preferential immunoreactivity for both proteins was found at high levels at the side facing bone of actively bone-resorbing osteoclasts. Osteoclasts detached from bone surface were devoid of immunoreactivity for each protein. At the electron microscopic level, both proteins were exclusively confined to the apical plasma membrane at the ruffled border of active osteoclasts with well-developed ruffled border membrane. No immunolabeling for both proteins was observed in the basolateral membrane and the clear zone of bone-resorbing osteoclasts. The plasma membrane of preosteoclasts and post- and/or resting osteoclasts showed little or no reactivity against these two antibodies. The results indicate that lysosomal membrane glycoproteins are actively synthesized in active osteoclasts, rapidly transported to the ruffled border area, and contribute to the formation and maintenance of the acidic resorption lacuna of osteoclasts.
Cytologic examination of surgical margin of excised malignant pulmonary tumor: methods and early results.
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Complexed prostate-specific antigen and its volume indexes in the detection of prostate cancer.
OBJECTIVES: To evaluate complexed prostate-specific antigen (cPSA), cPSA density (cPSAD), and cPSA adjusted for the transition zone volume (cPSA-TZ) in comparison with the free-to-total PSA ratio (F/T PSA) and free-to-complexed PSA ratio (F/C PSA) as a means of diagnosing prostate cancer. METHODS: Transition zone volume was determined in 137 of 142 men who underwent systematic sextant biopsies and had total PSA (tPSA) values between 4.1 and 10.0 ng/mL. cPSAD and cPSA-TZ were calculated by dividing the cPSA value by the whole prostate volume and the transition zone volume, respectively. RESULTS: Of the 137 men, 23 (16.8%) had prostate cancer. cPSA predicted the biopsy outcome better than tPSA, F/T PSA, or F/C PSA, although the difference was not significant. A cutoff value of 4.1 ng/mL for cPSA provided a specificity of 42% and a sensitivity of 87%. A combination of cPSA and F/C PSA maintained a sensitivity of 83% and gave an increased specificity of 54%. In a subgroup of 65 patients with smaller prostate volumes (less than 45 mL), the diagnostic value of cPSA-TZ was remarkably increased. A cutoff value of 0.31 for cPSA-TZ provided a sensitivity of 93% and a high specificity of 72%. CONCLUSIONS: cPSA was more specific than tPSA and F/T PSA. As a component of F/C PSA, free PSA could provide additional value to cPSA. cPSA-TZ and cPSAD could be better indicators for prostate cancer than cPSA.
Histological study of periapical tissue healing in the rat molar after retrofilling with various materials.
We histologically examined the effects on the periapical tissue of various dental filling materials applied as retrofillings in rats and compared them with those of amalgam. The 4-META-TBB resin Superbond and the light-cured composite resin produced the least severe inflammatory reaction, with the greatest amount of new bone. In these specimens, regeneration of a part of the periodontal ligament was also observed. These results indicate that these materials might be very biocompatible and thus foster the natural regeneration of the periapical tissue.
Kallikrein-kinin in infection and cancer.
This review article describes the mechanism of enhancement of vascular permeability in infectious disease and cancer. This phenomenon is primarily mediated by bradykinin, nitric oxide and other unique vascular mediators. They are highly intermingled with each other in these disease states. Furthermore, these mediators are elicited in various in vivo settings most frequently induced by bacterial proteases, and indirect or direct activation of kallikrein-kinin cascade at one or more steps. The key steps involve bacterial proteases or cellular components including lipopolysaccharides. Thus, the use of appropriate protease inhibitors or antagonists, or scavengers in the case of nitric oxide, superoxide or peroxynitrite, are anticipated to attenuate the clinical manifestation induced by such mediators. It also explained that fluid accumulation in ascitic or pleural compartments in the case of carcinomatosis in terminal cancer patients can be largely attributed to bradykinin or related mechanism. Systemic bacterial dissemination is also facilitated by bradykinin, or suppressed by kinin antagonists as well as by the inhibition of kinin production, respectively. Thus, control of the level of such vascular mediators appears important both in infectious disease and in cancer. alpha1-Protease inhibitor, which inhibits neutrophil elastase, is inactivated by oxidative metabolites such as superoxide and peroxynitrite, and this effect activates matrix metalloproteinases. This indicates that oxidative stress activates proteolytic potential, and thus accelerates the degenerative process upon infection.
Supralinear Ca2+ signaling by cooperative and mobile Ca2+ buffering in Purkinje neurons.
Endogenous high-affinity Ca2+ buffering and its roles were investigated in mouse cerebellar Purkinje cells with the use of a low-affinity Ca2+ indicator and a high-affinity caged Ca2+ compound. Increases in the cytosolic Ca2+ concentration ([Ca2+]i) were markedly facilitated during repetitive depolarization, resulting in the generation of steep micromolar Ca2+ gradients along dendrites. Such supralinear Ca2+ responses were attributed to the saturation of a large concentration (0.36 mM) of a mobile, high-affinity (dissociation constant, 0.37 microM) Ca2+ buffer with cooperative Ca2+ binding sites, resembling calbindin-D28K, and to an immobile, low-affinity Ca2+ buffer. These data suggest that the high-affinity Ca2+ buffer operates as the neuronal computational element that enables efficient coincidence detection of the Ca2+ signal and that facilitates spatiotemporal integration of the Ca2+ signal at submicromolar [Ca2+]i.
Effects of qing fei tang (TJ-90) on aspiration pneumonia in mice.
The effects of Qing Fei Tang (Sei-hai To in Japanese), a Chinese traditional medical mixture, on aspiration pneumonia were studied using mice inoculated with both Streptococcus pneumoniae and gastric juice as aspiration pneumoniae models. Daily (4 weeks) oral usage of Qing Fei Tang before inoculation reduced remarkably the mortality rate of mice. In this aspiration pneumonia model, xanthine oxidase (XO) activity in the lung tissues was elevated, but this elevation was remarkably decreased by use of Qing Fei Tang. These results suggest that Qing Fei Tang pretreatment can reduce oxygen radical production in inflammed lungs and may reduce the mortality for aspiration pneumonia.
Ventilatory muscle recruitment and work of breathing in patients with respiratory failure after thoracic surgery.
OBJECTIVES: Increased work of breathing (WOB) and respiratory muscle weakness have been identified as major causes of respiratory failure after thoracic surgery. This study was undertaken firstly to characterize the mechanical impairment in patients with respiratory failure after cardio-thoracic surgery, and secondly, to determine how diaphragmatic paralysis affects deterioration in the ventilatory mechanics. METHODS: We evaluated the respiratory mechanics of 24 patients following cardiac and thoracic surgery. Ten patients without respiratory problems were examined as control subjects. There were nine patients with phrenic nerve injury and five patients without phrenic nerve injury who required mechanical ventilation for more than 7 days. Phrenic nerve injury was assessed with a phrenic nerve stimulation test. We measured the respiratory variables, the esophageal, gastric and transdiaphragmatic pressure swing (deltaPes, deltaPga and deltaPdi, respectively), and the work of breathing during quiet tidal breathing. RESULTS: Both the groups requiring mechanical ventilation exhibited abnormally negative deltaPga/deltaPes values, compared with the control subjects. A significant increase in WOB with the normal generation of deltaPdi was seen in the patients without phrenic nerve injury. In contrast, the poor generation of deltaPdi with a slight increase in work of breathing was noted in patients with phrenic nerve injury. CONCLUSIONS: These results demonstrated two different types of respiratory failure in thoracic surgery patients, focusing on the impact of phrenic nerve paralysis. Diaphragmatic dysfunction should not be overlooked in postoperative care, and the amelioration of this compromise in respiratory mechanics is an important aspect of good patient management.
Interleukin-2 expression by a subpopulation of primary T cells is linked to enhanced memory/effector function.
Single cell studies have identified intraclonal heterogeneity of cytokine production by activated T cells. To investigate implications of cytokine heterogeneity for cell fate, an interleukin (IL)-2 promoter-green fluorescent protein (GFP) reporter transgenic model was developed to track IL-2+ and IL-2- T cells during differentiation from naive precursors. Antigen-activated IL-2+ and IL-2- cells had comparable proliferative capacities in primary responses. However, T cells that expressed IL-2 in primary responses demonstrated enhanced antigenic sensitivity and increased expression of effector cytokines in secondary responses in vitro and in vivo. Thus, heterogeneity of activation during a primary response translates into heterogeneous secondary responses, in which enhanced memory/effector function is linked to cells that previously exceeded an activation threshold associated with IL-2 gene transcription.
Pulmonary embolism: a case of sudden unexpected death in a psychiatric hospital.
We report a case of suspected fatal physical abuse in which the cause of death was proved to be pulmonary embolism. A patient with mental retardation presenting aggressive behavior was admitted to a psychiatric hospital and was treated with major tranquilizers. She suddenly died subsequent to an angina-like attack. For several days before her death, she had been confined to her bed because of very low physical and mental activity. Bruises and abrasions were observed on the extremities, suggesting the recent restraints. There was no positive evidence of physical abuse. At autopsy, the cause of death was elucidated to be pulmonary embolism originating from thrombi in the left popliteal vein. This case indicates the risk of pulmonary embolism in immobilized patients in psychiatric hospitals.
A sudden death due to cardiac conduction system injury from a blunt chest impact.
We report a case of sudden death due to cardiac conduction system injury from a blunt chest impact. A 20 year old male, kicked in the precordial region, lost consciousness, and was confirmed dead on arrival at a hospital emergency care unit. According to his friends, they played a golf competition accompanied with a physical punishment. The victim, losing the game, allowed the winner to give him several kicks in the chest. Although well prepared against each kick, he fell down instantaneously after the final impact, and death was confirmed at a hospital. There was no apparent sign of injury on the body surface. At autopsy, there was no evident subcutaneous or intramuscular hemorrhages, rib or sternum fracture. Subendocardial hemorrhage in the region of the atrioventricular node and a contusion extending from the posterior wall of the left ventricle to the upper ventricular septum were observed. Histological examination revealed injury of atrioventricular node and His' bundle. Although the cardiac injury including contusion of the myocardium itself was not so extensive, it was considered that arrhythmia was induced by the cardiac conduction system failure, which was considered to be the cause of death.