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Biomedical subjects

M Kunimoto

Publications and source records attributed to M Kunimoto.

At least 55 records · Page 3Linked to original sources
PubMed1996

Animal model of focal tonsillar infection: human tonsillar lymphocytes induce skin lesion in SCID mice.

Based mainly on clinical evidence, a concept of focal tonsillar infections affecting certain skin diseases has been established. In such disorders as pustulosis palmaris et plantaris (PPP), there have been significant improvement of clinical manifestations following tonsillectomy. However, the pathophysiological mechanism of PPP due to focal tonsillar infections has not been made clear. In order to clarify the relationship between tonsil and PPP, an in vivo experimental model of this disease was developed by reconstituting severe combined immunodeficiency (SCID) mice with tonsillar lymphocytes (TL) from patients with PPP. The results can be summarized as follows: i) The SCID mice reconstituted with PPP-TL developed skin lesions with fur-loss and eruption around their cheek and forehead; ii) The reconstituted SCID mice showed long-term presence of human IgG in their sera, reaching maximum level at 6-8 weeks after the transfer; iii) Human anti-keratin antibody was found in the sera of reconstituted SCID mice reflecting that of the donors; iv) A section of the skin lesions showed thickened epidermis and blister formation. A few CD4(+) human lymphocytes were seen around the lesions, whereas CD8(+) lymphocytes and B cells were hardly seen; v) Human IgG deposits were observed in skin lesions of SCID mouse.

Animals↗
PubMed1995

Selective down-regulation of 440 kDa ankyrinB associated with neurite retraction.

Brain-specific isoforms of ankyrin, 440 kDa and 220 kDa ankyrinB, which are generated from a single gene by alternative splicing of pre-mRNA, are both expressed in human neuroblastoma NB-1 cells and the expression of the larger isoform is increased upon induction of neurite outgrowth. Exposure to methylmercury, a potent neurotoxic substance, at a sublethal dose induced dramatic retraction of neurites in NB-1 cells. Concomitantly, synthesis of 440 kDa ankyrinB polypeptide and mRNA were selectively attenuated in methylmercury-treated cells, while the 220 kDa isoform was not affected. These results indicate that the expression of 440 kDa ankyrinB is intimately associated not only with the neurite outgrowth but also with neurite retraction in neuronal cells, and is regulated at mRNA level.

Ankyrins↗
PubMed1995

Possible involvement of the 440 kDa isoform of ankyrinB in neuritogenesis in human neuroblastoma NB-1 cells.

Two isoforms of brain ankyrin, 440 kDa and 220 kDa ankyrinB, which are products of alternatively spliced pre-mRNA encoded by a single gene, are both expressed in human neuroblastoma NB-1 cells. Expression of the polypeptide and mRNA of the larger isoform increased upon induction of neurite outgrowth in NB-1 cells by dibutyryl cAMP, while those of the smaller isoform were unaffected. The expressed 440 kDa ankyrinB was concentrated at the tip of growing neurites and was partly co-localized with GAP-43. These results suggest that 440 kDa ankyrinB is one of the neuronal growth-associated proteins and provides an interesting example of gene regulation by alternative splicing in neuronal cells.

Alternative Splicing↗
PubMed1995

A neuron-specific isoform of brain ankyrin, 440-kD ankyrinB, is targeted to the axons of rat cerebellar neurons.

Two isoforms of brain ankyrin, 440- and 220- kD ankyrinB, are generated from the same gene by alternative splicing of pre-mRNA. The larger isoform shares the same NH2-terminal and COOH-terminal domains to the smaller isoform and contains, in addition, a unique inserted domain of about 220-kD in size (Kunimoto, M., E. Otto, and V. Bennett. 1991. J. Cell Biol. 115:1319-1331). Both Isoforms were expressed in primary cerebellar cells in a manner similar to that in vivo; the larger isoform appeared first when axogenesis is actively conducted and the smaller isoform came up later. 440-kD ankyrinB was localized in the axons of cerebellar neurons both in vivo and in vitro using an antibody raised against the insert region, while 220-kD isoform was rather localized in the cell bodies and dendrites of neurons by a specific antibody prepared using a synthetic peptide corresponding to the splice site as antigen. Astroglia cells also expressed 220-kD ankyrinB but not the 440-kD isoform. These results indicate that 440-kD ankyrinB is a neuron-specific isoform targeted to the axons and its unique inserted domain is essential for the targeting.

Animals↗
PubMed1995

Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus.

The mechanisms of virus-induced enhancement of intercellular adhesion molecule-1 (ICAM-1) expression in epithelial cells are unknown. In the present study, the effect of respiratory syncytial virus (RSV) infection on the expression of ICAM-1 in human pulmonary type II-like epithelial (A549) cells was evaluated. Conditioned RSV media (cRSV) produced from growth of RSV in A549 cells induced a significant increase in the expression of ICAM-1. Treatment of the cells with noninfectious cRSV prepared by ultraviolet (UV) irradiation (UV-cRSV) or ribavirin treatment resulted in the expression of ICAM-1 to a similar extent as infectious cRSV. These results suggested that RSV induces the synthesis of a soluble mediator(s) that regulates the expression of ICAM-1. Cytokine analysis by immunoassay and polymerase chain reaction showed that RSV induces the synthesis of interleukin (IL)-1 alpha and -beta, and tumor necrosis factor alpha (TNF-alpha). Preincubation of UV-cRSV with soluble IL-1 receptor (sIL-1r) almost completely blocked the enhancement of ICAM-1 expression. Furthermore, simultaneous incubation of infectious purified RSV with sIL-1r resulted in a significant reduction in enhancement of ICAM-1 expression. Preincubation with neutralizing antibodies to IL-1 alpha and -beta, and TNF-alpha showed that the predominant ICAM-1 enhancing soluble mediator in UV-cRSV was IL-1 alpha. These experiments provide direct evidence for an autocrine mechanism of enhanced ICAM-1 expression in RSV-infected epithelial cells that is mediated primarily by IL-1 alpha. Pulmonary epithelial cells may play an important immunoregulatory role in the microenvironment of the lower respiratory tract infected with RSV.

Cell Adhesion↗
PubMed1995

[A case of carpal tunnel syndrome caused by a ganglion cyst--diagnosis and follow-up study with magnetic resonance imaging].

We report a case of carpal tunnel syndrome (CTS) caused by a ganglion cyst which was diagnosed by magnetic resonance (MR) imaging of the left wrist. MR images depicted a 10-mm ganglion cyst which pressed the median nerve toward the ulnar side. The ganglion cyst was punctured under direct endoscopic visualization in the carpal canal, subsequently the clinical and the electrophysiologic findings of CTS improved. The median nerve was delineated in its proper position. MR imaging of the wrist, a noninvasive means to observe median nerve, is useful for the diagnosis and the follow-up study of CTS.

Adult↗
PubMed1994

Methylmercury induces apoptosis of rat cerebellar neurons in primary culture.

Cerebellar neurons in primary culture were exposed to methylmercury, a well-established neurotoxicant known as a cause of Minamata disease, at 0.1-1.0 microM for up to 72 hours and compared with the neurons undergoing apoptosis induced by withdrawing K+ from the medium. Cerebellar neurons treated with methylmercury at up to 0.3 microM showed morphological changes characteristic to apoptosis, depending on methylmercury dose; formation of apoptotic vesicles, disappearance of neurites and condensation of nuclear chromatin. In addition, soluble DNA prepared from the methylmercury-treated cells exhibited the typical DNA fragmentation pattern similar to that in cells undergoing apoptosis induced by K+ withdrawal. At higher concentration of methylmercury, however, a non-apoptotic pathway of cell death started to predominate over the apoptotic pathway. These results indicate that the death of cerebellar granule neurons induced by methylmercury is, at least at lower doses, apoptotic.

Animals↗
PubMed1994

Skin sympathetic nerve activity and effector function during sleep in humans.

Multi-unit sympathetic skin nerve activity (SSA) in the peroneal nerve was recorded together with electrical skin resistance, skin blood flow and (in some subjects) finger blood pressure during sleep in 22 sleep-deprived healthy subjects. The average strength of sympathetic activity in different sleep stages was measured during 5-min periods as the area-under-curve of the integrated neurogram. Stage 2 sleep was reached by 15 subjects, stages 3-4 by nine and rapid eye movement (REM) sleep by six subjects. Non-REM sleep was always associated with an increased skin resistance, which was larger in glabrous than in hairy skin (293 +/- 48 vs. 175 +/- 4% of awake control level, n = 10, P < 0.05). Skin blood flow also increased during sleep, with a mean maximal increase of 397 +/- 79% of the awake control level (n = 11, P < 0.05). In spite of these changes of effector function no significant difference in mean SSA was found between the awake control period and periods of non-REM sleep, but during REM sleep SSA increased with 34% (P < 0.05) compared with the immediately preceding stage 2 period. In stage 2 sleep, K-complexes were associated with bursts of SSA followed by transient changes of skin resistance, blood flow and arterial blood pressure. When both skin resistance and blood flow were recorded within the innervation area of the impaled fascicle, single bursts or short periods of increased SSA could be succeeded by increased skin blood flow without concomitant skin resistance change. This indicates the existence of specific sympathetic vasodilator fibres in the skin. Therefore the unchanged strength of multiunit SSA during non-REM sleep in the face of increases of skin resistance and blood flow may be a consequence of an increased sympathetic vasodilator nerve activity combined with decreases of vasoconstrictor and sudomotor traffic.

Adult↗
PubMed1994

[Development of a polymerase chain reaction (PCR) system for detection of Epstein-Barr virus 1,2--application to various tonsillar disorders].

A one-step PCR system was developed for detection of two types of EBV, using a single pair of primers that were complementary to both sequences coding the EBV nuclear antigen (EBNA)-2, and encompassing a large deletion in the sequence of type 1 EBV. Type 1 and type 2 EBV were detected simultaneously by polyacrylamide gel electrophoresis and ethidium bromide stains after amplification. The specificity of amplification was confirmed by Southern blot hybridization with the oligonucleotide probe that was complementary to both EBNA-2 regions. Additionally, two pairs of type specific primers were synthesized from divergent sequences in the EBNA-2 regions of type 1 and type 2 EBV. The PCRs were employed for analysis of the EBV genotype in the oral cavities of healthy donors and patients with various tonsillar disorders. EBV was detected in 60 samples from healthy donors and patients with various tonsillar disorders. Fifty-six contained type 1 and four type 2. Double infection was not seen in either healthy donors or patients. These results indicate that type 1 EBV is highly dominant in Japan. It is interesting to note that patients with acute tonsillitis and palmoplantar pustulosis showed a statistically higher frequency (P < 0.01) of EBV excretion than healthy donors. In examining anti-EBV viral capsid (VCA)-IgG antibody titers and EBV excretion in the oral cavity, EBV excretion was not found to correlate with the VCA-IgG antibody titers.

Acute Disease↗
PubMed1994

[Detection of Epstein-Barr virus-1,2 in malignant head and neck tumors by newly developed polymerase chain reaction method].

The polymerase chain reaction method (PCR) was employed for the analysis of EBV genotypes in nasopharyngeal carcinoma, malignant lymphoma of head and neck origin and infectious mononucleosis. In nasopharyngeal carcinoma, type 1 EBV was detected in 12 cases and type 2 in one. Type 1 EBV was also detected in 3 out of 8 malignant lymphoma and 2 infectious mononucleosis. These results indicate that type 1 EBV is strongly predominant in nasopharyngeal carcinoma and predominant in malignant lymphoma and infectious mononucleosis. Our results may reflect the general prevalence of these two types of EBV in Japan, as we previously reported.

Adult↗
PubMed1994

[Ossified epidural hematomas: report of two cases].

Two cases of ossified epidural hematomas were reported. Patients were nine and twelve year-old boys. Initially they were both followed up conservatively after injuries. Subsequently they were found on CT scan to have calcifications in the capsules of epidural hematomas which were found four months after injury in one case and twelve days after injury in the other. Both underwent craniotomy and histological ossification was found in the capsules of the hematomas. Epidural hematomas in children are known to ossify, and this condition may prevent natural absorption of epidural hematomas. Therefore, careful follow up of hematomas seems to be mandatory on conservative therapy of epidural hematomas in children.

Child↗
PubMed1993

Detection of Haemophilus influenzae in middle ear of otitis media with effusion by polymerase chain reaction.

Otitis media with effusion (OME) is one of the major causes of hearing loss in childhood. The pathogenesis still remains unclear, though it is closely related to acute otitis media with bacterial infections. It is known that Haemophilus influenzae is one of the most common bacteria isolated from middle ear effusions (MEEs). Recently, in vitro DNA amplification by polymerase chain reaction (PCR) is a new technology that has considerable implication for diagnosis of viral and bacterial infections because of its potentially precise specificity and sensitivity. In the present experiment polymerase chain reaction (PCR) was applied to the detection of DNA genome of H. influenzae contained in middle ear effusions. By Southern blot hybridization, two characteristic bands for H. influenzae DNA were detected at 273 b.p. and 550 b.p. position in 15 of 27 MEEs. However, no organism was cultured by conventional methods. Our results indicate the PCR technique is more specific and sensitive in detection of bacteria in middle ear effusion of OME, compared with conventional methods. It strongly suggests more involvement of the bacteria, especially H. influenzae, in OME onset.

Child↗
PubMed1993

Genotypic analysis of Epstein-Barr virus associated with nasopharyngeal carcinoma of Japanese patients.

Types and certain genetic markers were studied for Epstein-Barr virus present in 10 specimens of nasopharyngeal carcinoma (NPC) from Japanese patients. The type 1 virus was predominant in our NPC specimens, as in the general Japanese population, and the type 2 virus was found only in one NPC specimen. The type C variant, which lacks the BamHI site between the BamHI-W1* and -I1* regions, appeared to be common among Japanese strains as in those in Southern China. The type f variant which has an extra BamHI site in the BamHI-F region and has been shown to be strongly associated with NPC in Southern China was found in only one NPC specimen. This virus strain was also the only type 2 virus among our specimens. The present study, therefore, does not show any specific association of the type f variant with NPC in Japan.

Adult↗
PubMed1993

Analysis of viral infection in patients with IgA nephropathy.

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.

Adult↗
PubMed1992

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activity in humans.

To clarify the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine (NE), the effect of this drug on microneurographically recorded muscle sympathetic nerve activity (MSA) from the tibial nerve was analyzed in ten healthy male volunteers. A single dose of 600 mg of L-threo-DOPS was orally administered and the effect of this norepinephrine precursor on MSA at resting and at upright standing positions, as well as the MSA responsiveness to head-up tilting was examined by comparing the data obtained after administration of the drug with those obtained under control conditions. The plasma NE levels were determined in two subjects. The results were as follows: (1) resting MSA increased significantly 80 min after administration of L-threo-DOPS and was accompanied by an increase in plasma NE levels; (2) standing MSA when treated with the drug was not significantly different from values obtained under control conditions; and (3) MSA responsiveness to orthostasis was reduced after L-threo-DOPS. We conclude from the activation of MSA by L-threo-DOPS that this drug raised blood pressure not only through an increase in metabolized plasma NE levels, but also through the enhancement of MSA by activation of descending noradrenergic or adrenergic pathways proximal to the recording site of the sympathetic discharge.

Adult↗
PubMed1992

One-step typing of Epstein-Barr virus by polymerase chain reaction: predominance of type 1 virus in Japan.

The prevalence of two types of Epstein-Barr virus (EBV) in Japan was studied by using the polymerase chain reaction (PCR). The U2 region encoding EBV nuclear antigen 2 (EBNA-2) was chosen as the target of amplification. Consensus primers were synthesized from sequences common to the two types but encompassing a large stretch of deletion in the sequence of type 1 EBV. The primers were capable of amplifying both types at the same time but allowed differentiation of each type by the size of the amplification products. Thus we could carry out detection and typing of EBV in a one-step PCR. EBV was detected in mouth washings of 21 (23%) of 91 seropositive healthy adults. Twenty samples (22%) contained type 1 and only one (1%) type 2. Seventy-nine patients suffering from various types of tonsillitis were also studied. EBV was detected in mouth washings of 37 patients (47%). Thirty-four (43%) contained type 1 and three (4%) type 2. Double infection was not seen in either healthy donors or patients. These results indicate that type 1 EBV is highly dominant and the type 2 variant is quite rare in Japan.

Base Sequence↗
PubMed1992

Impaired long-term T cell immunity to Epstein-Barr virus in patients with nasopharyngeal carcinoma.

The long-term T cell immunity to Epstein-Barr virus (EBV) is considered to play an important role in suppressing proliferation of EBV-infected B cells and outgrowth of EBV-associated tumors. It can be manifested and quantified by the EBV-induced focus regression assay. In the present study, we examined the strength of T cell immunity to EBV in patients with nasopharyngeal carcinoma (NPC) and other cancers originating from the head and neck region. In contrast to patients with other types of cancers, including EBV-negative NPC, patients with EBV-positive NPC were found to have a profound impairment in the long-term T cell immunity to EBV.

Adolescent↗