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Biomedical subjects

N Nagata

Publications and source records attributed to N Nagata.

At least 271 records · Page 15Linked to original sources

[A case of vertical gaze palsy associated with a unilateral infarct in the thalamo-mesencephalic junction on MR imaging].

We report a case of a 54-year-old man with sudden-onset double-vision. On admission, neurological examination showed upward and downward gaze palsy on voluntary and smooth pursuit movements, and vertical oculocephalic maneuver elicited a full upward and downward response. Bell's phenomenon, horizontal eye movements and convergence were not impaired. Based on these findings, supranuclear dissociated vertical gaze palsy was diagnosed. T1-weighted MR images revealed low intensity on the medial side of the right thalamo-mesencephalic junction, which impaired the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). T2-weighted MR images revealed a high-intensity area. The posterior commissure was spared. The clinical signs gradually improved, and the vertical gaze palsy almost disappeared one month after onset. Based on these findings, unilateral infarct in the thalamo-mesencephalic junction in the distribution of the right paramedian thalamic artery was diagnosed. Only two cases of upward and downward gaze palsy in association with unilateral upper midbrain lesion without posterior commissure have been previously reported. Since we did not perform a pathological examination, we cannot deny that there may have been some denervation of fibers at the posterior commissure. Cases of upward and downward gaze palsy in association with unilateral upper midbrain lesion without posterior commissure are rare, and it is very interesting that the lesion in our patients, like that seen in the two pathological reports, was right-sided.

Cerebral Infarction↗

[Application of the warm heart surgery to the open heart surgery in children].

Application of the warm heart surgery to the children's open heart surgery has been reluctant, because keeping the operative field dry thought to be difficult. In this report, the clinical result of 22 cases of children's open heart surgery using warm heart surgery (Warm Group) was compared with that of other 25 cases using conventional cold cardioplegia (Cold Group). In warm group, rectal temperature was kept at 34 degrees C, continuous coronary perfusion rate was 3 ml/kg/min, and potassium ion concentration for inducing the initial cardiac arrest was 20 mEq/l, and the maintaining dose was 12-17 mEq/l. There were two deaths in Cold group. In warm group, keeping the operative field dry was not difficult by using the specially devised small sucker (2 mm diameter) and, if necessary, temporarily stopping the coronary perfusion (maximum for 7 min). Aorta cross cramping time/total extracorporeal circulation time, CK-MB at 1-POD and maximum dose of dopamine and dobutamine proved the better myocardial protection in warm group (p < 0.01). From this study, it was concluded that warm heart surgery can be applied for children with no difficulty, and showed superior myocardial protection.

Body Temperature↗

[A case of psittacosis with prolonged lymphocytosis in bronchoalveolar lavage fluid after resolution of pneumonia].

A 52-year-old man was admitted to another hospital with complaints of fever and dyspnea. Chest roentgenogram revealed bilateral widespread infiltrative opacities, and laboratory examinations showed severe hypoxia, hepatic injury and acute renal failure. In addition, hemosputum and eruption appeared, and he was transferred to our department because of the development of multi-organ failure. Moreover, about 2 weeks prior to admission, a budgerigar he had been breeding died. Although the treatment was supportive therapy alone, the abnormal shadow on chest roentgenogram and laboratory findings improved markedly. Thereafter, we made the diagnosis of psittacosis, because the serum titer of a complement fixation test against Chlamydia rose from 1:8 on admission to 1:512 after 2 weeks. On admission, PMN and lymphocyte populations increased in bronchoalveolar lavage fluid (BALF), and 2 weeks later lymphocytes alone increased markedly. Thereafter, we observed lymphocytosis in serial BALF findings for 12 weeks. These findings indicate that lymphocyte alveolitis persisted long after the pneumonia had resolved. Moreover, Ga scintigraphy also revealed accumulation in the filed of shadows which had been absorbed and disappeared on the chest roentgenogram. These results suggest that lymphocytes play a leading role in immune host defenses and that immunological reactivity is prolonged in psittacosis.

Bronchoalveolar Lavage Fluid↗

[Autopsy case of amyloidosis with marked cardiac and pulmonary lesions associated with myeloma, initially presenting with muscle weakness].

A 69-year-old man presented initially with muscle weakness of the bilateral lower limbs. Chest roentgenogram showed diffuse reticulonodular shadows, bilateral hilar lymphadenopathy, and dullness of bilateral costophrenic angles. Chest CT showed thickening and irregularity of vascular shadows, and thickening of bronchial walls. On the first admission we could not diagnose pulmonary or muscle lesions. He was subsequently admitted for the deterioration of congestive heart failure, but there was no improvement. Myocardial biopsy demonstrated deposition of amyloid in the cardiac muscular tissue. Autopsy revealed amyloid deposition in pulmonary vasculature, alveolar septal walls and pleura. Amyloid deposition was also recognized systemically in skeletal muscles, lymph nodes, liver, kidney, spleen, stomach, and intestines. We recognized about 20% IgA lambda-positive plasma cells with atypia, and myeloma-associated amyloidosis diagnosed. This case was classified as diffuse alveolar septal form and pleural form of pulmonary amyloidosis. We could find only a few reports of pleural form, which exhibits an interesting distribution.

Aged↗

Estradiol up-regulates the stimulatory GTP-binding protein expression in the MCF-7 human mammary carcinoma cell line.

The effect of estradiol treatment of the human mammary carcinoma cell MCF-7 on the adenylyl cyclase system was examined. Treatment with 10 nM estradiol for 72 h increased the basal level of cAMP, and isoproterenol-, PGE2- or calcitonin-stimulated cAMP production. Estradiol also increased the response to cholera toxin but did not alter the response to forskolin. No significant change in growth rate was observed during the 72 h of estradiol treatment. In MCF-7 cell membranes the responsiveness to isoproterenol, PGE2, or cholera toxin was also enhanced by estradiol treatment. The cholera toxin-catalyzed ADP-ribosylation of Gs alpha in MCF-7 cell membranes was significantly increased by 72 h of treatment with estradiol. Consistent with this observation, the level of Gs alpha immunoreactivity was increased in the estradiol-treated cell membranes. On the other hand, pertussis toxin did not change the responsiveness to isoproterenol, PGE2 or calcitonin in either control or estradiol-treated cells. In addition, ADP-ribosylation with pertussis toxin also did not reveal any change in Gi. These results clearly indicate that Gs expression is under the control of estradiol, and that this effect may contribute to the increased sensitivity of hormone-stimulated adenylyl cyclase activities in MCF-7 cells.

Adenylate Cyclase Toxin↗

Differentiation of human monoblastic leukemia U937 cells induced by inhibitors of myosin light chain kinase and prevention of differentiation by granulocyte-macrophage colony-stimulating factor.

Inhibitors of protein kinase activities are useful for the study of intracellular signal transduction and some of these inhibitors are reported to induce differentiation of human leukemia cells. We examined effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with several kinase inhibitors on differentiation of human leukemia U937 cells. Nitroblue tetrazolium (NBT)-reducing activity, a typical marker of myelomonocytic differentiation, of U937 cells was induced by genistein and GM-CSF enhanced this activity. GM-CSF also induced the NBT-reducing activity of the cells in combination with 2,5-dihydroxycinnamic acid methyl ester, psi-tectorigenin and staurosporine, although each of them did not induce the activity. Inhibitors of myosin light chain kinase, 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7), induced in U937 cells NBT-reduction, and lysozyme and alpha-naphthyl acetate esterase activities. GM-CSF inhibited this differentiation and counteracted the anti-proliferation effect of the kinase inhibitors. These results suggest that some protein kinases are involved in differentiation of U937 cells and the kinases inhibited by ML-9 and ML-7 are associated with signal transduction of GM-CSF.

Azepines↗

Generation of hydroxyl radical from lipid hydroperoxides contained in oxidatively modified low-density lipoprotein.

When low-density lipoprotein (LDL) was oxidatively modified and incubated with an epinephrine-FeCl3 mixture, an electron spin resonance spectrum characteristic of the spin adduct of 5,5-dimethyl-1-pyrroline-N-oxide and hydroxyl radical (DMPO-OH) was obtained. The amount of DMPO-OH formed increased with an increase in the concentration of lipid hydroperoxides contained in the oxidatively modified LDL. These results indicate that oxidatively modified LDL would generate hydroxyl radicals in vivo if an appropriate iron chelate were present and that the cytotoxicity of oxidatively modified LDL is ascribable, at least in part, to its capability to generate such radicals.

Animals↗

A proteoglycan form of macrophage colony-stimulating factor that binds to bone-derived collagens and can be extracted from bone matrix.

We previously found that the human osteoblastic cell line MG-63 produces two molecular types of macrophage colony-stimulating factor (M-CSF). One is an 85-kD M-CSF, and the other is a proteoglycan form of M-CSF (PG-M-CSF) that has a binding affinity to type V collagen. The latter type of M-CSF showed dose-dependent binding to wells coated by pepsin-extracted bone collagens, whereas the 85-kD M-CSF did not. Immunoblot analysis of urea-extracted bone M-CSF revealed the presence of PG-M-CSF. PG-M-CSF contained in bone matrix may have physiological importance in the bone metabolism.

Bone Matrix↗

Prevention of autoimmune inflammatory polyarthritis in male New Zealand black/KN mice by transplantation of bone marrow cells plus bone (stromal cells).

OBJECTIVE: To prevent polyarthritis in male New Zealand black/KN (NZB/KN) mice by transplantation of both bone marrow cells (BMC) and bone (to recruit stromal cells) from normal mice. METHODS: Arthritic lesions in male NZB/KN mice injected intravenously with BMC plus bone from C57Bl/10 mice were compared with those in untreated male NZB/KN mice. RESULTS: Male NZB/KN mice engrafted with BMC plus bone were both radiologically and histopathologically normal, and had decreased production of anti-single-stranded DNA antibodies and rheumatoid factors at 8-12 months of age. CONCLUSION: Bone marrow transplantation prevented polyarthritis in male NZB/KN mice.

Animals↗

A monoclonal antibody reactive with a glycophosphatidylinositol-anchored molecule on T cells defines CD4+ T cell subsets.

A hybridoma, 25T3 (IgM, kappa), was established from MRL/+ mice immunized with an autoreactive T cell line (l/+T1). The antigenicity of the antigen recognized by hybridoma 25T3 (25T3-Ag) expressed on thymic and splenic cells was abolished by treatment with phosphatidylinositol-specific phospholipase C, showing that 25T3-Ag is a glycophosphatidylinositol-anchored Ag. 25T3-Ag was expressed on approximately 90% of thymocytes. Double-negative, double-positive and CD8 single-positive cells were highly positive for the expression of 25T3-Ag, whereas CD4 single-positive cells were weakly positive (approximately 40%) or negative (approximately 60%). In the spleen, only CD3+ cells (and not B220+ nor Mac-1+ cells) reacted with 25T3 monoclonal antibody (mAb), indicating that 25T3 mAb is specific for T cells. The majority of splenic CD8+ T cells were positive for the expression of 25T3-Ag, although the intensity was weaker than that of thymocytes. In contrast, splenic CD4+ T cells were divided into negative (60-70%) and positive (30-40%) populations. Similar staining profiles were observed in BALB/c, C57BL/6, C3H/HeN and AKR/J mice. When BALB/c CD4+ T cell subsets were sorted and cultured with irradiated (25 Gy) antigen-presenting cells, stimulation with immobilized anti-CD3 mAb for 2 days resulted in CD4+25T3+ cells secreting more interleukin-2 and less interleukin-4 than did CD4+25T3- subsets, although the proliferative responses of the cells on day 2 of culture were similar. This suggests that CD4+ T cells can be divided into two populations and relatively defined as T helper 1 and T helper 2 cells using this 25T3 mAb. Immunoprecipitation and SDS-PAGE revealed that 25T3-Ag was approximately 70 kDa. These findings are discussed in relation to CD4+ T cell subsets.

Animals↗

Passive immunization with anti-parathyroid hormone-related protein monoclonal antibody markedly prolongs survival time of hypercalcemic nude mice bearing transplanted human PTHrP-producing tumors.

Malignancy-associated hypercalcemia is mainly caused by excessive production of parathyroid hormone-related protein (PTHrP) by the tumor. Using anti-PTHrP-(1-34) monoclonal murine antibody (anti-PTHrP MoAb), we studied whether repeated injection of the homologous antibody would continuously decrease the serum calcium concentration in hypercalcemic nude mice bearing transplanted human PTHrP-producing tumors, leading to prolongation of their survival time. Daily SC injections of anti-PTHrP MoAb decreased the serum calcium concentration almost to within the normal range in nude mice bearing transplanted human PTHrP-producing tumors (T3M-1, EC-GI, PC-3, and FA-6) but not in a nude mouse bearing a transplanted parathyroid carcinoma. The antibody did not affect FA-6 tumor growth either in vitro or in vivo. Pancreatic carcinoma cells (FA-6), which caused the most severe hypercalcemia, were inoculated into 6-week-old nude mice. When severe hypercalcemia (approximately 19 mg/dl) had developed, daily SC injection of anti-PTHrP MoAb was started. Within 18 days of this time point, all untreated tumor-bearing mice (n = 10) died of hypercalcemia and cachexia, whereas all the treated mice (n = 10) showed an increase in body weight and survived for at least 25 days. Histologic examination of the treated mice revealed a marked decrease in osteoclastic bone resorption, without toxicologic findings in the kidney and liver. These results suggest that passive immunization against PTHrP can continuously ameliorate the hypercalcemia and markedly prolong the survival time of severely hypercalcemic, tumor-bearing mice. If a human monoclonal antibody against PTHrP-(1-34) could be developed, then passive immunization would be potentially one of the most effective therapies for patients with malignancy-associated hypercalcemia due to excessive production of PTHrP.

Animals↗

MR imaging findings of tremors associated with lesions in cerebellar outflow tracts: report of two cases.

Two cases with severe tremors were studied by means of electromyograms using surface electrodes and also by magnetic resonance (MR) imaging. The first case was associated with multiple sclerosis and demonstrated a severe postural cerebellar tremor and an alternate activation of antagonist muscles in the right arm. The second case, with hemorrhage in the brainstem, demonstrated a severe tremor at rest and mixed synchronous and alternating activation of antagonist muscles in the left forearm. MR imaging studies localized lesions possibly responsible for these tremors. In the first case a lesion was located in the superior cerebellar peduncle just under the decussation, and in the second case a lesion was found between the red nucleus and the thalamus, with possible involvement of both the cerebellothalamic and nigrostriatal pathways. The first case accords with the theory that a lesion located in the dentate nucleus and its projection can cause severe postural cerebellar tremor. The lesion demonstrated in the second case may be responsible for "cerebellar tremor at rest" or "static (resting) cerebellar tremor."

Adult↗

The efficacy of extracorporeal shock wave lithotripsy on single dense calcified gallstones according to computed tomography.

The efficacy and complications of extracorporeal shock wave lithotripsy (ESWL) for single gallstones were compared between 15 patients with a CT-lucent stone and 18 patients with a dense calcified stone. In all of five patients with a stone smaller than 10 mm in diameter, complete or sufficient clearance was observed, regardless of calcification. However, in 28 patients with a stone larger than 11 mm in diameter, the rates of complete or sufficient clearance were lower in those with a dense calcified stone (64%) than in those with a computed tomography (CT) lucent stone (93%). There was no difference in the rate of complications between patients with a CT-lucent stone and those with a dense calcified stone. These results thus suggest that extracorporeal shock wave lithotripsy may be safely employed for patients with a single calcified gallstone.

Adult↗

Genistein exhibits preferential cytotoxicity to a leukemogenic variant but induces differentiation of a non-leukemogenic variant of the mouse monocytic leukemia Mm cell line.

Mouse leukemia Mm-A and Mm-S2 cells are subclones of mouse monocytic leukemia Mm cells, Mm-A cells having much higher leukemogenicity than Mm-S2 cells. The growth-inhibitory effects of several protein kinase inhibitors on leukemogenic Mm-A and non-leukemogenic Mm-S2 cells were examined. Most inhibitors of protein serine/threonine kinases inhibited the growth of Mm-A and Mm-S2 cells similarly, but some protein tyrosine kinase inhibitors exhibited differential inhibitory effects on Mm-A and Mm-S2 cells. Genistein inhibited growth of Mm-A cells more effectively than that of Mm-S2 cells, but another inhibitor of tyrosine kinase, herbimycin A, preferentially inhibited growth of non-leukemogenic Mm-S2 cells. Genistein induced or enhanced several differentiation markers of Mm-S2 cells, such as cell spreading, immunophagocytosis, nitroblue tetrazolium (NBT) reduction and lysozyme activity in a dose-dependent manner, but herbimycin A did not. Genistein was cytotoxic to Mm-A cells rather than inducing cell differentiation. Genistein has effects on several other cellular events as well as inhibition of tyrosine kinases. However, it effectively inhibited protein tyrosine phosphorylation in Mm-A cells and its decrease of tyrosine phosphorylation was closely associated with its inhibition of cell growth. Thus, a genistein-sensitive tyrosine kinase(s) may play an important role in the growth and/or survival of leukemogenic Mm-A cells.

Animals↗

Transplantability and MHC antigen expression of tumor mast cells.

A cloned cell line was established from tumor cells spontaneously developed in a coculture of an autoreactive T cell line (1/+ T1) and 30 Gy-irradiated MRL/+ spleen cells with Con A supernatants. Morphological studies and studies of histamine content and modes of histamine release after stimulation with compound 48/80 revealed that the cell line (MRL-MC3) had mast cell characteristics. MRL-MC3 was transplantable not only to MRL/+, MRL/lpr and AKR/J (H-2k) mice but also to BALB/c and (BALB/c x DBA/2) F1 (H-2d) mice, although the allogeneic mice survived twice as long as syngeneic mice after i.v. injection. In addition, after i.v. injection, the mast cells infiltrated the livers and spleens of syngeneic (MRL/+) mice, however the lymph nodes around the mesenterium to the parapylorus in allogeneic (BALB/c) mice. A mast cell line (BALB-MC) was also established from a lymph node of MRL-MC3-injected BALB/c mice. Cell surface marker analyses revealed clear differences between the BALB-MC and the original MRL-MC3, which was positive for the expression of MHC class I antigens (K, D), I-E antigen and c-abl-encoded (anti-pEX-2 antibody-reactive) proteins, but not for I-A on the cell surface. In contrast, BALB-MC showed positive only for the MHC class I antigens (K, D) on the surface, and also positive for anti-pEX-2 antibody-reactive cytoplasmic proteins, as seen in MRL-MC3. Mast cells obtained from MRL-MC3-injected MRL/+ mice showed the same staining pattern as MRL-MC3. BALB-MC induced shorter survival times (approximately half) in both MRL/+ and BALB/c mice than MRL-MC3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗