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Biomedical subjects

S Nakao

Publications and source records attributed to S Nakao.

At least 19 recordsLinked to original sources
PubMed1995

Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro.

Murine bone marrow cells with lineage phenotypes (Lin)-Sca-1+c-kit+ and Lin-Sca-1-c-kit+ cells represent primitive hematopoietic stem cells (HSCs) and committed hematopoietic progenitor cells, respectively. The number of Lin-Sca-1+c-kit+ HSCs in bone marrow was significantly increased in tumor necrosis factor (TNF) receptor p55-deficient (TNF-R55-1-) mice compared with the TNF-R55+/+ wild-type mice without a marked change in bone marrow cellularity. In both the methylcellulose culture and a single-cell proliferation assay, mouse TNF alpha (mTNF alpha) inhibited in vitro the proliferation of wild-type mouse-derived Lin-Sca-1+c-kit+ cells in response to a combination of multiple growth factors. The same is true for that of Lin-Sca-1+c-kit+ cells stimulated with granulocyte colony-stimulating factor (G-CSF) plus stem cell factor (SCF). Moreover, mTNF alpha significantly arrested the entry into S-phase from G0/G1 phase of Lin-Sca-1+c-kit+ cells stimulated with multiple growth factors and Lin-Sca-1-c-kit+ cells stimulated with G-CSF plus SCF. In contrast, mTNF alpha failed to affect the growth and cell cycle progression of Lin-Sca-1+c-kit+ cells and Lin-Sca-1-c-kit+ cells that were obtained from TNF-R55-deficient mice. These data suggest that TNF may be an important physiologic regulator of hematopoiesis and that TNF-R55 may be essentially involved in TNF-mediated inhibition of the growth of both primitive stem and more committed progenitor cells.

Animals↗
PubMed1995

An atypical variant of Fabry's disease in men with left ventricular hypertrophy.

BACKGROUND: Fabry's disease is considered very rare. Left ventricular hypertrophy is one of the common manifestations in adults with classic hemizygous disease. Recently, several cases of an atypical variant of hemizygous Fabry's disease, with manifestations limited to the heart, have been reported. Therefore, we assessed the incidence of hemizygosity for Fabry's disease among male patients with left ventricular hypertrophy. METHODS: We measured plasma alpha-galactosidase activity in 230 consecutive male patients with left ventricular hypertrophy. Clinical manifestations were assessed, endomyocardial biopsies were performed, and the patients were screened for mutations in the alpha-galactosidase gene. RESULTS: Seven of the 230 patients with left ventricular hypertrophy (3 percent) had low plasma alpha-galactosidase activity (0.4 to 1.2 nmol per hour per milliliter; 4 to 14 percent of the mean value in normal controls). These seven unrelated patients, ranging in age from 55 to 72 years, did not have angiokeratoma, acroparesthesias, hypohidrosis, or corneal opacities, which are typical manifestations of Fabry's disease. Endomyocardial biopsy was performed in five patients and revealed marked sarcoplasmic vacuolization in all five. Samples from four patients were examined by electron microscopy and revealed typical lysosomal inclusions with a concentric lamellar configuration in all four. Two patients had novel missense mutations in exon 1 (Ala20Pro) and exon 6 (Met296lle). The remaining five had no mutations in the coding region of the alpha-galactosidase gene, but the amounts of the alpha-galactosidase messenger RNA were markedly lower than normal. CONCLUSIONS: Seven unrelated patients with atypical variants of hemizygous Fabry's disease were found among 230 men with left ventricular hypertrophy (3 percent). Fabry's disease should be considered as a cause of unexplained left ventricular hypertrophy.

Adolescent↗
PubMed1995

Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects.

BACKGROUND: Mutations of mitochondrial DNA have been demonstrated as causes of human mitochondrial diseases. While these disorders typically involve multiple organs, the effect of mitochondrial mutations on the heart has not been systematically studied. METHODS AND RESULTS: We studied mitochondrial mutations and cardiac changes in 17 patients with Kearns-Sayre syndrome; ocular myopathy; myoclonus epilepsy with ragged red fibers (MERRF); and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Cardiac involvement was evaluated by chest radiograph, ECG, His-bundle electrogram, and echocardiogram. All 3 patients with Kearns-Sayre syndrome had large deletions of mitochondrial DNA and disturbances in cardiac conduction. ECG abnormalities were found in 2 of 6 patients with ocular myopathy who showed large deletions of mitochondrial DNA. All 3 patients with MERRF had an A-to-G mutation at nucleotide position 8344; 2 had cardiomegaly, asymmetrical septal hypertrophy, and diffuse hypokinesis of the left ventricle. One patient with asymmetrical septal hypertrophy developed dilated cardiomyopathy 2 years later. All 5 patients with MELAS had an A-to-G mutation at nucleotide position 3243, and 2 had symmetrical left ventricular hypertrophy with or without abnormal wall motion. CONCLUSIONS: The clinical features of cardiac involvement in mitochondrial diseases vary in the different subgroups of these disorders. Particular mitochondrial mutations can cause characteristic cardiac abnormalities.

Adult↗
PubMed1995

Chronic treatment with nitric oxide synthase (NOS) inhibitor profoundly reduces cerebellar NOS activity and cyclic guanosine monophosphate but does not modify minimum alveolar anesthetic concentration.

We previously found that acute administration of a nitric oxide synthase (NOS) inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a recent study has suggested that brain NOS activity could not be inhibited by more than approximately 50% by acute administration of L-NAME. To investigate the effect of marked inhibition of NOS activity on the MAC of halothane, we measured cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels, and halothane MAC in rats chronically treated with L-NAME and compared the results to those of the saline-treated control group. Although the cerebellar NOS activity and cGMP levels were significantly decreased (14% and 2.7% of control, respectively) by L-NAME, the value of the halothane MAC was not significantly affected. These results suggest that the anesthetic action of halothane, as measured by its MAC in rats, is not related to NOS activity or cGMP levels in the brain.

Animals↗
PubMed1995

Differential locations in the midbrain of distinct groups of vertical eye movement-related neurones in cat: their projections and direct connections with oculomotor neurones.

The present study was undertaken to investigate the firing patterns, location and projections of vertical eye movement-related neurones in the Forel's field H (FFH), the interstitial nucleus of Cajal (INC), and reticular formation of the mesodiencephalic junction (MDJ) in chronically prepared alert cats. A total of 456 neurones in the medial MDJ with firing closely related to vertical eye movements was examined using antidromic microstimulation and spike-triggered averaging technique. On the basis of their firing patterns, these neurones were classified into five groups, i.e. burst neurones (BNs), burst-tonic neurones (BTNs), tonic neurones (TNs), augmenting neurones (ANs) and pause neurones (PNs). BNs were located mainly in the dorsomedial part of the FFH. Most of TNs were found more caudally than BNs. BTNs and PNs were located further caudally, within the INC and nearby reticular formation. ANs were located mainly in the dorsolateral part of the FFH. Both medium-lead BNs (MLBNs) and BTNs projected to the inferior rectus (IR) subdivision of the oculomotor nucleus on both sides. MLBNs projected to the trochlear nucleus as well through collateral branches of the axon projecting to the oculomotor nucleus. Downward and upward MLBNs made direct excitatory and inhibitory connections, respectively, with IR motorneurones. These results suggest that many kinds of neurones in the paramedian regions of MDJ play a significant role in the genesis of vertical eye movements.

Animals↗
PubMed1995

Adult-onset Still's disease with submassive hepatic necrosis.

We present a 74-year old woman who was hospitalized because of typical spiking fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation of serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal laboratory findings were dramatically improved after treatment with prednisolone. The clinical course of this patient indicates that AOSD with severe hepatic necrosis can successfully be treated with early administration of corticosteroid, although it remains unknown whether the disease can remain in remission with no or minimal treatment.

Aged↗
PubMed1995

Quality of hematologic recovery in patients with aplastic anemia following cyclosporine therapy.

To evaluate quality of hematologic recovery in aplastic anemia (AA) patients treated with cyclosporine A (CyA), we examined polymorphonuclear leukocytes (PMNCL) from 25 AA patients for clonality and glycosyl-phosphatidylinositol (GPI)-anchored membrane protein expression. Using three different X-linked gene probes, we failed to detect clonal hematopoiesis in seven CyA-responsive female patients. Clonal hematopoiesis was detected in two of six female patients refractory to CyA therapy, although one of these two patients had shown monoclonality before therapy. Flow-cytometric analysis revealed a normal expression of GPI-linked membrane proteins, including CD55, CD59, and CD16 on PMN in all patients treated with CyA, irrespective of response, except for one patient who had a small proportion of GPI-anchored membrane protein-negative cells before therapy. The proportion remained unchanged 41 months after hematologic recovery following CyA therapy. These findings suggest that successful therapy of AA with CyA may not be associated with a significant risk of developing late clonal complications, such as paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplasia.

Adolescent↗
PubMed1995

[Successful treatment of recurrent chronic myelogenous leukemia in allogeneic marrow transplant recipient with the donor leukocyte transfusion, without induction of acute graft-versus-host disease].

A 45-year-old female developed cytogenetic relapse of chronic myelogenous leukemia 4 years after allogeneic bone marrow transplantation. To induce a graft-versus-leukemia effect, peripheral blood buffy-coat cells were collected from the original marrow donor during 5 rounds of leukapheresis over 3 weeks, and 2.47 x 10(8) cells/kg were infused into the patient. Acute graft-versus-host disease (GVHD) did not develop even after an interval of 50 days from the last donor leukocyte transfusion (DLT). However, karyotypic analysis of bone marrow cells performed on the same day showed an apparent decrease in the proportion of Ph1 chromosome-positive cells (1/20) among all dividing cells, compared with the proportion (13/20) observed before DLT. At the same time, the proportion of red blood cells (RBCs) of donor origin among the peripheral RBCs of the patient, which was less than 10% before DLT, began to rise and reached 100% at 4 months after DLT. The karyotype of bone marrow cells obtained on day 90 after DLT was completely normal. Although chronic GVHD of the buccal mucosa and liver developed in association with pancytopenia on day 71 after DLT, this improved rapidly with oral administration of cyclosporine. The clinical course of this patient suggests that acute GVHD is not a prerequisite for elimination of Ph1-positive cells by DLT.

Acute Disease↗
PubMed1995

[A case of successful treatment of chronic sternal osteomyelitis and mediastinitis after ascending aorta and hemiarch reconstruction].

Mediastinitis is one of severe and fatal complications after cardiac surgery, especially in the presence of a prosthetic graft. A 70-year-old male, who was suffered from chronic sternal osteomyelitis and mediastinitis after ascending aorta and hemiarch reconstruction was reported. He developed high fever and leucocytosis on the 16th postoperative day. Wound culture was positive for Grampositive organisms. He was diagnosed as having sternal osteomyelitis and mediastinitis and treated by sternal bone debridement and irrigation with dilute povidone iodine solution with no effects. Total excision of the infected sternum, irrigation with non-diluted solution of povidone iodine and omental transfer were performed successfully. The literature regarding omental transfer for mediastinitis and infected prosthetic grafts was briefly reviewed.

Aged↗
PubMed1995

Early recovery of host-derived hematopoiesis in marrow transplant recipients conditioned with high-dose busulfan and cyclophosphamide.

Three marrow transplant recipients with hematologic malignancies (two AML, one myelodysplastic syndrome) experienced prolonged pancytopenia after allogeneic BMT following conditioning with non-TBI regimens containing high-dose busulfan and cyclophosphamide (Bu/CY), despite the use of G-CSF. Early recovery of host-derived hematopoiesis ensued. Although neutrophil counts in these patients exceeded 500 x 10(6)/l by day 30 after transplant, these cells were of host origin. This early recovery of host-derived hematopoiesis has been observed rarely among patients conditioned with TBI-based regimens. When patients conditioned with Bu/CY show delayed hematologic recovery, mixed chimerism should be considered even in the presence of normal neutrophil recovery.

Adolescent↗
PubMed1995

[Analysis of chronic graft-versus-host disease after unrelated-donor bone marrow transplantation. Kanazawa University Bone Marrow Transplant Team].

Six patients with hematologic diseases who received bone marrow from an unrelated donor (URD) from 1992 through 1993 and survived for more than 100 days after bone marrow transplantation (BMT) were assessed for the incidence, time of onset, and extent of chronic graft-versus-host disease (cGVHD). Five patients (83%) developed cGVHD, compared with 41% of a control group consisting of 34 patients who received bone marrow from a related donor during the same period. In 4 (80%) of the 5 patients, cGVHD occurred within 70 days after BMT. This early occurrence of cGVHD was observed in only 7% of the control group (P = 0.006). cGVHD tended to involve more organs in the URD-BMT patients than in the control group. In two patients with cGVHD, an allele mismatch in HLA-DRB1 gene between the patients and donor was disclosed by DNA typing. These findings indicate that it is important to strengthen post-transplant immunosuppression, to initiate screening tests from the early post-transplant period, and to select a suitable donor matched with HLA-DRB1 alleles for the prevention of cGVHD in the URD-BMT patients.

Adolescent↗
PubMed1995

Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia.

In some patients with aplastic anemia (AA), hematopoietic function is dependent on continuous administration of cyclosporine A (CyA). These AA patients may have T lymphocytes whose myelosuppressive effect is mitigated by CyA. We established a total of 29 T cell clones from the bone marrow of a CyA-dependent AA patient in relapse. Some of the CD4+ T cell clones demonstrated a specific proliferative response to irradiated autologous bone marrow cells enriched for CD34+ cells (CD34(+)-rich cells) obtained from the patient in remission. One of the T cell clones showing the best proliferative response to CD34(+)-rich cells carried the T cell receptor V beta 17 and produced interferon-gamma (IFN-gamma) only when cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony formation by colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) by approximately 60% when it was cultured with autologous CD34(+)-rich cells in methylcellulose medium, although the clone did not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in vitro hematopoietic progenitor cell growth by the T cell clone was partially abrogated by the addition of CyA to the culture. These findings suggest that in some patients with CyA-dependent AA, CD4+ T cells autoreactive to hematopoietic progenitor cells exist and may play an important role in the pathogenesis of bone marrow failure.

Adult↗
PubMed1994

Ascending projections of posterior canal-activated excitatory and inhibitory secondary vestibular neurons to the mesodiencephalon in cats.

The axonal projections of 62 posterior canal (PC)-activated excitatory and inhibitory secondary vestibular neurons were studied electrophysiologically in cats. PC-related neurons were identified by monosynaptic activation elicited by electrical stimulation of the vestibular nerve and activation following nose-up rotation of the animal's head. Single excitatory and inhibitory neurons were identified by antidromic activation following electrical stimulation of the contralateral and ipsilateral medial longitudinal fasciculus, respectively. The oculomotor projections of identified neurons were confirmed with a spike-triggered averaging technique. The axonal projections of the identified neurons were then studied by systematic, antidromic stimulation of the mesodiencephalon. Excitatory neurons showed two main types of axonal projections. In one type, axonal branches were issued to the interstitial nucleus of Cajal, central gray, and thalamus including the ventral posterolateral, ventral posteromedial, ventral lateral, ventral medial, centromedian, central lateral, lateral posterior, and ventral lateral geniculate nuclei. The other type was more frequently observed, giving off axon collaterals to the above-mentioned regions and to Forel's field H as well. Inhibitory neurons issued axonal branches to limited areas which included the central gray, interstitial nucleus of Cajal, its adjacent reticular formation and caudalmost part of Forel's field H, but not the rostral part of the Forel's field H and the thalamus. These results suggest that PC-related excitatory neurons participate in the genesis of vertical eye movements and in the perception of the vestibular sensation, and that PC-related inhibitory neurons seem to take part only in the genesis of vertical eye movements.

Animals↗
PubMed1994

Influence of left ventricular filling profile during preceding control beats on pulse pressure during ventricular premature contractions.

We investigated whether the left ventricular filling profile, defined as the early to late diastolic left ventricular filling volume ratio, during the preceding control beats actually affects the pulse pressure during a ventricular premature contraction (PVC). Twenty patients underwent invasive electrophysiological study for sinus bradycardia. VPCs with various coupling intervals were induced by right ventricular electrical stimulation, and the mitral filling flow velocity by pulsed Doppler echocardiography, the femoral arterial pressure curve and the electrocardiogram were simultaneously recorded. The early to late diastolic velocity-time integral ratio (Ei/Ai ratio) of the mitral filling flow velocity during the control beats which preceded the VPC was measured as an index characterizing left ventricular filling profile. The coupling interval of each VPC and the extrasystolic beat pulse pressure were measured. The ratio of the extrasystolic beat pulse pressure to the control beat pulse pressure was expressed in % (% extrasystolic beat pulse pressure). The correlation between the coupling interval and the % extrasystolic beat pulse pressure was investigated. Coupling intervals of 0.80, 0.70, 0.60, 0.50, and 0.45 s were used. At a coupling interval of 0.80 or 0.45 s, the % extrasystolic beat pulse pressure showed no significant correlation with the Ei/Ai ratio. In contrast, the % extrasystolic beat pulse pressure with coupling intervals of 0.70, 0.60, and 0.50 s showed a significant positive correlation with the Ei/Ai ratio (r = 0.67, 0.74, and 0.66, P < 0.01, respectively). In addition to the prematurity and the site of origin of the VPCs, the left ventricular filling profile during the preceding control beats may significantly affect the height of the pulse pressure during extrasystoles with medium length coupling intervals.

Adolescent↗
PubMed1994

Activation of the cortical and medullary dopaminergic systems by nitrous oxide in rats: a possible neurochemical basis for psychotropic effects and postanesthetic nausea and vomiting.

To provide a neurochemical basis for the central nervous system actions of nitrous oxide, the changes of brain dopamine (DA), serotonin (5-HT), norepinephrine (NE), and metabolites of DA and 5-HT were studied in rats. Thirty male Wistar rats were assigned to one of five groups according to the type of gas and the duration of gas exposure. The rats in one group, which served as control, were exposed to air for 30 min, and the rats in four other groups were exposed to 75% nitrous oxide in oxygen for 0.5, 1, 2, and 4 h, respectively. Animals were killed with microwave irradiation, and the brains were divided into seven sections: the cerebral cortex, cerebellum, striatum, hippocampus, midbrain-thalamus, hypothalamus, and medulla-pons. The contents of NE, DA, 3,4-dihydroxyphenyl-alanine (DOPAC), homovanillic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in each discrete area were measured with high-performance liquid chromatography. Nitrous oxide had no significant effect on the contents of NE, 5-HT, nor 5-HIAA, but decreased that of DA in the striatum and midbrain-thalamus after 4 h of exposure (P < 0.05). Levels of DOPAC, but not DA, in the cerebral cortex and medulla-pons were increased significantly at exposures up to 2 h (P < 0.05), but were not significant from control levels after a 4-h exposure. Increased levels of DOPAC indicate that nitrous oxide increases dopaminergic neuronal activities in the mesocortical projection and the medullary network.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗