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Biomedical subjects

Kazuo Motoyoshi

Publications and source records attributed to Kazuo Motoyoshi.

At least 55 records · Page 3Linked to original sources

Functional CD5+ B cells develop predominantly in the spleen of NOD/SCID/gammac(null) (NOG) mice transplanted either with human umbilical cord blood, bone marrow, or mobilized peripheral blood CD34+ cells.

OBJECTIVE: Human CD5+ B cells are the major B cell subset in fetal spleen and umbilical cord blood (CB), and their number gradually diminishes in both spleen and peripheral blood from infancy through childhood while conventional B cells increase. In this study, we investigated whether CD5+ cells differentiate from adult hematopoietic stem cells (HSCs) as well as fetal ones in immunodeficient mice. METHODS: In our system, NOD/SCID/gammac(null) (NOG) mice were transplanted with CD34+ cells from CB (hCB model), adult bone marrow (hBM model), and mobilized peripheral blood (hMPB model). RESULTS: In these model mice, a high proportion of CD19+IgM+CD5+ mature B cells appeared in the spleen, regardless of the CD34+ cell origin, 4 to 8 weeks after transplantation, while the majority were CD19+IgM-CD5- immature B cells in BM. The CD19+CD5- BM cells showed to express CD5 after the coculture with NOG spleen cells. In the sera of immunized hCB model mice with DNP-KLH, antigen-specific IgM but not IgG was enhanced. CONCLUSION: Our results show that adult CD34+ cells develop into functional CD5+ B cells in NOG spleen as much as fetal CD34+ cells do.

Animals↗

Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas.

We have examined 72 patients with B-cell non-Hodgkin lymphoma (B-NHL) in order to search for consensus sequences of the immunoglobulin heavy chain (IgH) gene, and developed consensus fluorogenically labeled probes for use in an allele-specific oligonucleotide (ASO) real-time quantitative polymerase chain reaction (RQ-PCR) assay of minimal residual disease (MRD). We detected a clonal IgH variable region (VH) sequence in 51 (70.8%) of the 72 B-NHLs, the most frequent VH gene usages being VH3 and VH4 (45/51, 88.2%). It was possible to design three consensus fluorogenic probes for the VH3 gene and one for the VH4 gene avoiding these hypermutations. Our sequencing results suggested that consensus fluorogenic probes would be best based on the 5'-side of the framework region 3 (FR3) because the frequency of somatic hypermutations was significantly lower in the regions on which the probes were based than in the remaining parts of FR3 (P < 0.05). Nineteen (54.3%) of 35 B-NHLs with the VH3 gene and 5 (50%) of 10 with the VH4 gene had sequences identical to at least one of these probes. We found that probes containing one base substitution were still applicable for a MRD study, whereas those containing two or more were not. Therefore, our four probes were applicable for 37 (82.2%) of the 45 patients with VH3 or VH4. This limited number of probes makes a large-scale study of MRD in B-NHL more feasible.

Adult↗

Probable sporadic Creutzfeldt-Jakob disease with valine homozygosity at codon 129 and bilateral middle cerebellar peduncle lesions.

We describe a 67-year-old Japanese man with probable sporadic Creutzfeldt-Jakob disease (CJD) who had valine homozygosity at codon 129, a rarity in the Japanese. T2-weighted magnetic resonance imaging (MRI) detected high-intensity lesions in the bilateral middle cerebellar peduncles and basal ganglia as well as cerebellar and cortical atrophy. He developed cerebellar ataxia and subsequent mental deterioration, myoclonus, and periodic synchronous discharge as shown in an electroencephalogram. Cerebrospinal fluid examination showed a high level of neuron-specific enolase and a positive immunoassay for the 14-3-3 protein. He died of pneumonia 10 months after the initial symptoms appeared. Whether or not the genetic polymorphism increased his susceptibility to sporadic CJD is not clear because valine homozygosity at codon 129 is less than 1% in the normal Japanese population. Although there is no convincing evidence in the present case, the MRI findings of cerebellar peduncle changes, which are rare in CJD, suggest a kind of degeneration, demyelination, or both.

Aged↗

[Summer-type hypersensitivity pneumonitis in monozygotic twins].

We encountered a pair of monozygotic twins with summer-type hypersensitivity pneumonitis. Patients 1 and 2 were 24-year-old men who worked in the same place and shared the same room, which was built of wood. In August, patient 1, a non-smoker, was referred to our hospital because of coughing, fever and dyspnea. In November, the same symptoms appeared in patient 2, who was a smoker. The difference between the onset times in patients 1 and 2 was suspected to be due to cigarette smoking, because their occupations and other circumstances were the same and they were monozygotic twins.

Adult↗

[A case of HTLV-1-associated bronchiolitis with Sjögren's syndrome].

A 58-year-old woman was admitted because of bilateral diffuse nodular shadows on chest radiograph. Video-assisted thoracoscopic lung biopsy specimens showed marked lymphocytic infiltration into the bronchiolar wall. HTLV-1 antibody was examined because the patient's parents were born in Okinawa Prefecture. The patient turned out to be an adult T-cell leukemia-lymphoma (ATLL) carrier with positive HTLV-1 antibody. Therefore, HTLV-1 associated bronchiolitis was diagnosed. Although no dry symptoms appeared, it became clear by the saxon test that she was also complicated with Sjögren syndrome. Generally, it is reported that there is coherence with HTLV-1 infection and Sjögren syndrome. So the HTLV-1 infection might have accounted for the pathogenesis of these three disorders (HTLV-1 infection, bronchiolitis, Sjögren syndrome).

Antibodies, Viral↗

[Sjören's syndrome with infiltrative lung disease showing upper lung field predominance].

We report two cases of Sjören's syndrome (SjS) with infiltrative lung disease showing upper lung field predominance. Case 1 was seen in a 68-year-old woman, who was admitted with dyspnea on exercise. Chest CT scanning demonstrated a central predominance of irregularly shaped consolidation with tractionectasis, distributed along the broncho-vascular bundles in both upper lobes. Case 2 occurred in a 70-year-old woman, who was admitted with cough. Chest CT scan showed a central predominance of irregularly shaped opacities with multiple small cystic structures in both upper lobes. Both cases were shown to be nonspecific interstitial pneumonia (NSIP) by video-assisted thoracoscopic lung biopsy, in which lung involvements were distributed around the bronchovascular sheath with relative sparing of the subpleural region. Although neither case complained of sicca symptoms, decreased saliva production was detected using the Saxon test, and further examinations revealed the presence of primary SjS. Pulmonary involvement in SjS is variable, and distribution along the broncho-bronchioles in the majority of the upper central lung field is a characteristic appearance of SjS lung disease. In patients with such patterns in chest radiography, further diagnostic differentiation should be conducted to confirm or rule out SjS.

Aged↗

[A case of bird fanciers' lung with endobronchial polyps].

A 34-year-old woman who had been keeping five budgerigars in her home was admitted with cough and progressive exertional dyspnea that had continued for three months. Chest CT scan demonstrated diffuse centrilobular nodular opacities throughout both lung fields. Flexible bronchoscopy revealed polypoid lesions with diameters of 2-3 mm located at the right B1/B2 spur. B3a/B3b spur and middle/lower bronchus spur. Their surfaces were glossy and smooth but slightly lobulated. The histological findings were consistent with inflammatory polyps containing lymphoid follicles in a dense infiltrate of lymphocytes. A positive environmental provocation test and precipitating antibodies confirmed the diagnosis of hypersensitivity pneumonitis (HP) caused by budgerigars (bird fanciers' lung). To our knowledge, there is no previous report of HP accompanied with endobronchial polyps, but this rare case shows the involvement of large airways in HP.

Adult↗

Molecular cloning of a novel immunoglobulin superfamily gene preferentially expressed by brain and testis.

We have cloned and characterized a novel gene from both human and mouse that encodes a new member of the immunoglobulin superfamily. The gene is preferentially expressed in both brain and testis, and hence, termed BT-IgSF (brain- and testis-specific immunoglobulin superfamily). The predicted protein consists of V-type and C2-type immunoglobulin domains as well as a hydrophobic signal sequence, a single transmembrane region, and a cytoplasmic domain. Human BT-IgSF protein (431 amino acids) is 88% identical to the mouse protein (428 amino acids) and both show significant homology to coxsackie and adenovirus receptor (CAR) and endothelial cell-selective adhesion molecule (ESAM). We examined the expression of BT-IgSF with various cultured cells and found that the gene was expressed in both neurons and glial cells in vitro. Furthermore, the expression was preferentially detected in pyramidal cell layers of the dentate gyrus and hippocampus and in commissure fibers of the corpus callosum, in brain tissue sections examined. These findings suggest that BT-IgSF plays a role in the development or function of the central nervous system.

Amino Acid Sequence↗

Intrathecal administration of nerve growth factor delays GAP 43 expression and early phase regeneration of adult rat peripheral nerve.

Whether nerve growth factor (NGF) promotes peripheral nerve regeneration in vivo, in particular in adults, is controversial. We therefore examined the effect of exogenous NGF on nerve regeneration and the expression of GAP 43 (growth-associated protein 43) in adult rats. NGF was infused intrathecally via an osmotic mini-pump, while control rats received artificial cerebrospinal fluid. Two days after the infusion was initiated, the right sciatic nerves were transected or crushed, and the animals allowed to survive for 3 to 11 days. The right DRG, the right proximal stump of the transected sciatic nerve, and the posterior horn of the spinal cord were examined by Western blotting, immunohistochemistry, and electron microscopy. GAP 43 immunoreactivity in the NGF-treated animals was significantly lower than in the aCSF-treated controls. Electron microscopy showed that the number of myelinated and unmyelinated axons decreased significantly in the NGF-treated rats as compared with the controls. These findings are indicative that exogenous NGF delayed GAP 43 induction and the early phase of peripheral nerve regeneration and supports the hypothesis that the loss of NGF supply from peripheral targets via retrograde transport caused by axotomy serves as a signal for DRG neurons to invoke regenerative responses. NGF administered intrathecally may delay the neurons' perception of the reduction of the endogenous NGF, causing a delay in conversion of DRG neurons from the normal physiological condition to regrowth state.

Animals↗

Expression of dystroglycan and the laminin-alpha 2 chain in the rat peripheral nerve during development.

In Schwann cells, the transmembrane glycoprotein beta-dystroglycan comprises the dystroglycan complex, together with the extracellular glycoprotein alpha-dystroglycan, which binds laminin-2 (alpha 2/beta 1/gamma 1), a major component of the Schwann cell basal lamina. To provide clues to the biological functions of the interaction of the dystroglycan complex with laminin-2 in peripheral nerves, we investigated the expression of beta-dystroglycan and the laminin-alpha 2 chain in rat sciatic nerve during development by immunoblot, immunofluorescence, and immunoelectron microscopic studies. The expression of beta-dystroglycan and the laminin-alpha 2 chain in the rat sciatic nerve was low and not confined to the Schwann cell outer membrane from embryonic day 18 to birth, when there was only an immature basal lamina assembly and no compact myelin formation by Schwann cells. However, the expression of these proteins increased markedly and became clearly localized to the Schwann cell outer membrane between birth and postnatal day 7, when both basal lamina assembly and compact myelin formation by Schwann cells progressed rapidly. From postnatal day 7 to adult, there was no remarkable change in the expression of these proteins. Our results support the hypothesis that the dystroglycan complex functions as an adhesion apparatus, binding the Schwann cell outer membrane with the basal lamina, and suggest that the dystroglycan complex plays a role in Schwann cell myelination through its interaction with laminin-2.

Aging↗

Signal transduction in macrophages: negative regulation for macrophage colony-stimulating factor receptor signaling.

The receptor for macrophage colony-stimulating factor (M-CSF) is expressed in monocytes/macrophages and their progenitor cells and stimulates both the growth and development of the blood-cell lineage. Although the specific components positively regulating M-CSF receptor signaling have been relatively well defined, it is now clear that important mechanisms to control the signaling cascades also exist. This review discusses the most recent results concerning the negative regulatory molecules for M-CSF receptor signaling. In particular, we focus on negative molecules for both proliferation of monocytes/macrophages and differentiation into mature cells.

Macrophages↗

Somatosensory evoked potential in neurosyphilis.

Since the development of effective antibiotic therapy, the occurrence of neurosyphilis has become less frequent. The number of syphilitic patients is gradually increasing as a complication in acquired immunodeficiency syndrome, but the diagnosis of neurosyphilis sometimes is difficult. We describe six patients with neurosyphilis and an analysis of their tibial nerve somatosensory evoked potentials. Four of them, including two with no tabes dorsalis symptoms, had delayed P15-N21 or the absence of N21. These abnormalities were ameliorated by treatment for syphilis. Analysis of tibial nerve SEPs provides a useful tool for the diagnosis of neurosyphilis and the evaluation of the extent to which neurosyphilis has progressed.

Adult↗

Comparative study and effects of macrophage colony-stimulating factor (M-CSF) administration on NK1.1+ cells in mouse spleen and bone marrow.

We conducted a comparative study of NK1.1+ cells in spleen and bone marrow and the effects of administration of M-CSF on them. Administration of M-CSF to mice increased the number of NK1.1+ cells in spleen but not in bone marrow. The NK1.1+ cells in spleen (Spl-NK1.1) and bone marrow (BM-NK1.1) were purified by magnetic cell sorter. Their cell surface markers and functions were then examined. The percentage of Mac-1 antigen-positive cells (and F4/80 antigen-positive cells) was higher among BM-NK1.1 than Spl-NK1.1. Moreover, the administration of M-CSF increased the number of Mac-1 and F4/80 antigen-positive cells in both Spl-Nk1.1 and BM-NK1.1. The functions (cytolytic activity and IFN-gamma production) of Spl-NK1.1 and BM-NK1.1 were the same and were enhanced by the administration of M-CSF. But Spl-NK1.1 produced more IFN-gamma than BM-NK1.1 when M-CSF was administered. BM-NK1.1 showed a greater proliferative response to IL-2 than Spl-NK1.1. Administration of M-CSF augmented this response. BM-NK1.1 proliferated in response to IL-4 and IL-15, but Spl-NK1.1 responded only slightly. However, administration of M-CSF stimulated Spl-NK1.1 to respond to these cytokines. Both Spl-NK1.1 and BM-NK1.1 showed only a weak response to M-CSF in vitro. But the expression of c-fms antigen (M-CSFR) increased after the M-CSF injections in vivo. These results suggested that there are phenotypical and functional differences between Spl-NK1.1 and BM-NK1.1. The administration of M-CSF led to an accumulation of NK1.1+ cells which were mobilized from bone marrow in spleen.

Animals↗

Effect of coadministration of M-CSF and IFN-alpha on NK1.1+ cells in mice.

The purpose of this study was to evaluate the effect of coadministration of macrophage colony-stimulating factor (M-CSF) and interferon-alpha (IFN-alpha) on NK1.1(+) cells in mice. Administration of M-CSF, but not IFN-alpha, increased the number of NK1.1(+) cells and CD11b(+) cells in spleen and blood. Coadministration of the two agents induced a greater increase in NK1.1(+) cells than did administration of M-CSF alone. Administration of M-CSF or IFN-alpha augmented the clearance activity of Yac-1 cells in lung, and coadministration of these agents further augmented this effect. The combination of M-CSF and IFN-alpha effectively reduced the formation of tumor nodules in lung and liver in an experimental metastasis model using B16 melanoma. The combination of M-CSF and IFN-alpha induced the increase and activation of NK1.1(+) cells more than either agent alone. These effects may contribute to the antimetastatic reaction by NK1.1(+) cells in vivo.

Animals↗

Polycystic kidney disease associated with cervical arteriovenous shunt and bilateral jugular vein occlusion.

A 59-year-old man with abnormal vascular features (intracranial aneurysm, a cervical arteriovenous shunt, bilateral internal jugular vein occlusions, and left transverse sinus hypoplasia), as well as left optic atrophy was suspected to have familial polycystic kidney disease. The possibility of autosomal dominant polycystic kidney disease complicated by Ehlers-Danlos syndrome type IV due to the coexistence of vasculopathy and polycystic kidneys was considered. However, the negative results of a skin fibroblast culture rendered the diagnosis of Ehlers-Danlos syndrome type IV unlikely. The cause of left optic atrophy in our patient remains unclear although it was suspected to be a secondary consequence of papilledema, which was caused by intracranial hypertension.

Arteriovenous Fistula↗

Motor dominant neuropathy in Sjögren's syndrome: report of two cases.

Most of the peripheral neuropathies in Sjögren's syndrome (SS) are sensory- or autonomic-dominant. In this report, we present two cases of a rare type of neuropathy, motor dominant neuropathy, in SS. One showed signs similar to those of Guillain-Barré syndrome, and the other showed signs characteristic of chronic inflammatory demyelinating polyradiculoneuropathy. These patients received i.v. immunoglobulin therapy. To our knowledge, this is the first report indicating that i.v. immunoglobulin has beneficial effects on motor dominant neuropathy in SS.

Aged↗

[Pulmonary involvement in sarcoidosis: CT findings at diagnosis and their changes at follow-up in cases without corticosteroid treatment].

To review the pulmonary CT findings in sarcoidosis at diagnosis, and to analyze the change in each finding at follow-up in cases without corticosteroid treatment. The study included 21 cases of pulmonary involvement of sarcoidosis. We analyzed the presence or absence and grade of each HRCT finding: bronchial wall thickening, enlargement of vascular shadows, pleural involvement, septal thickening, small nodules, ground-glass opacities, centrilobular opacities, consolidation, nodules, and volume loss. Afterwards, we compared the initial CT with the follow-up CT, and described the change of each finding as "improved" or "not improved". Furthermore, we decided if each case as a whole was improved or not after considering all of the pulmonary CT findings. Twelve of the 21 cases were improved. Small nodules, ground-glass opacities, centrilobular opacities, and nodules had improved in more than 50% of the cases since the initial CT. However, pleural involvement (10/11) and volume loss (6/9) were not improved. Pleural involvement and volume loss correlated the radiological irreversibility (p < 0.05). Of the several pulmonary CT findings in sarcoidosis, pleural involvement and volume loss show the highest rates of irreversible pulmonary changes.

Adrenal Cortex Hormones↗

Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

Dendritic cells (DCs) are known to be generated from leukemic clone from patients with acute and chronic leukemia when cultured in the presence of combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4. However, there have been few reports that showed DCs could be effectively differentiated from human leukemia cell lines. In this study, we have shown that a human monoblastic cell line, UG3, was inducible to differentiate into DCs in the presence of GM-CSF and TNF-alpha along monocyte-macrophage lineage. These DCs, consistently displayed dendritic morphology, phenotypes and allogeneic T-cell stimulating capacity. UG3 cells thus may represent a suitable model to further elucidate characteristics of DC differentiation.

Antigen Presentation↗