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Biomedical subjects

K Yamamura

Publications and source records attributed to K Yamamura.

At least 127 records · Page 7Linked to original sources
PubMed1996

Neoplastic transformation of normal hematopoietic cells by constitutively activating mutations of c-kit receptor tyrosine kinase.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is crucial to hematopoiesis, melanogenesis, and gametogeneis. Although the enzymatic activity of the c-kit product (KIT) is regulated by its ligand, both the Val559-->Gly (G559) mutation in the juxtamembrane domain and the Asp814-->Val (V814) mutation in the phosphotransferase domain lead to constitutive activation of KIT. By retroviral infection of hematopoietic progenitor cells with KIT(G559) or KIT(V814), KIT(G559) induced development of granulocyte/macrophage and mast-cell colonies in vitro without the addition of exogenous growth factors. KIT(V814) induced factor-independent growth of various types of hematopoietic progenitor cells, resulting in the development of mixed erythroid/myeloid colonies in addition to granulocyte/macrophage and mast-cell colonies. Furthermore, transplantation of KIT(G559) and KIT(V814)-infected bone marrow cells led to development of acute leukemia in one of 10 and six of 10 transplanted mice, respectively. No mice developed hematologic malignancies after transplantation of wild-type KIT-infected cells. Furthermore, transgenic mice expressing KIT(V814) developed acute leukemia or malignant lymphoma. These results demonstrate a direct role of the mutant KITs, particularly KIT(V814), in tumorigenesis of hematopoietic cells and suggest that similar mutations may contribute to the development of human hematologic malignancies.

Animals↗
PubMed1996

Accelerated disappearance of melanocytes in bcl-2-deficient mice.

Follicular melanocytes in bcl-2(-/-) mice have been reported to turn gray during the second hair cycle. Light microscopic analysis revealed that about half of bcl-2(-/-) mouse hair shafts had no detectable melanin granules after the second hair follicle cycle, but the remaining hair appeared to be pigmented normally. After depilation to induce new anagen hair, more than 97% of the hair shafts did not have visible melanin granules in bcl-2(-/-) mice, whereas 100% of the hair shafts in bcl-2(+/+) mice were pigmented. In bcl-2(+/+) mice, dopa-positive melanocytes appeared on day 4 after depilation, whereas bcl-2(-/-) mice developed few dopa-positive melanocytes after depilation, as assessed by light and electron microscopic observation. bcl-2(-/-) mouse hair in the second hair cycle contained about 60-70% less melanin than normal mouse hair, and newly generated bcl-2(-/-) mouse hair after depilation contained a level of melanin as low as that of albino mouse hair. These observations suggest that the expression of bcl-2 might be essential for melanocyte maintenance after the second hair cycle.

Animals↗
PubMed1996

E-selectin binding promotes neutrophil activation in vivo in E-selectin transgenic mice.

E-selectin is a membrane protein expressed by endothelial cells activated by cytokines released during the inflammatory process; it plays an important role in neutrophil emigration into inflamed tissues. To further explore in vivo the function of E-selectin, we have generated transgenic mouse line expressing E-selectin under the control of a chicken beta-actin promoter. In these mice, the number of blood neutrophils was reduced, without any other obvious phenotype or tissue damage. These neutrophils, however, displayed two significant changes: first, an alteration in the levels of expression of two membrane receptors involved in neutrophil adhesion to endothelial cells, namely a marked increased in the Mac-1 antigen (CD11b/CD18) and a decrease in the Mel-14 antigen (L-selectin); second, an increased oxidative activity when compared to blood neutrophils of non-transgenic mice, as shown by their capacity to oxidize 2',7'-dichlorofluorescein (DCFH) into a fluorescent compound. These observations indicate that the binding of E-selection with neutrophils bearing its ligands promotes neutrophil activation in vivo.

Actins↗
PubMed1996

Roles of basigin, a member of the immunoglobulin superfamily, in behavior as to an irritating odor, lymphocyte response, and blood-brain barrier.

Basigin is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Using the knockout mouse lacking the basigin gene (Bsg), we analyzed the function of basigin in adult mice lacking the gene [Bsg (-1-)]. Although histochemical studies on the localization of basigin (also called HT7 and neurothelin) strongly indicated that it is involved in the function of the blood-brain barrier, basigin knockout mice showed only a little difference, if any, to wild-type mice in the function of the blood brain-barrier. The mitogenic response of lymphocytes upon mixed lymphocyte reaction was greater in Bsg (-1-) mice. Finally, Bsg (-1-) mice repeatedly visited filter paper impregnated with acetic acid or isozine, indicating an abnormality in either reception of the odor or behavior as to it.

Animals↗
PubMed1996

Cell-cycle-dependent expression of the STK-1 gene encoding a novel murine putative protein kinase.

We have cloned a novel putative serine/threonine kinase-encoding gene, designed STK-1, from murine embryonic stem (ES) cell and testis cDNA libraries. The kinase most closely related to STK-1 is Xenopus laevis XLP46 protein kinase which shows 71% amino-acid identity to STK-1 between their kinase domains. Nevertheless, STK-1 is conserved throughout phylogeny with hybridizing sequences being detected in DNA from mammals, amphibians, insects and yeast. STK-1 mRNA is detected in testis, intestine and spleen, tissues that contain a large number of proliferating cells, but not in other tissues. All cell lines tested expressed STK-1 mRNA with levels being dependent upon proliferation rates. In NIH 3T3 cells, STK-1 is expressed in a cell-cycle-dependent fashion. These findings suggest a role for STK-1 in cell growth.

3T3 Cells↗
PubMed1996

The expression of truncated MK in human tumors.

Midkine (MK) is a heparin binding growth/differentiation factor different from fibroblast growth factors (FGFs), and is largely composed of two domains which are found by a folded polypeptide chain interconnected by disulfide bridges. Polymerase chain reaction revealed the presence of a short MK mRNA in 7 among 12 human tumor cells which expressed MK mRNA. All of 4 pancreatic carcinoma cell lines expressed the short species in addition to the full size mRNA. The short mRNA lacked an exon and resulted in the lack of a more N-terminally located domain. The truncated form of MK was found also in some surgically removed specimens of human tumors, but not in noncancerous tissue.

Base Sequence↗
PubMed1996

Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain.

The interleukin-2 (IL-2) receptor gamma chain is indispensable for IL-2-, IL-4-, IL-7-, IL-9-, and IL-15-mediated signaling. Mutations of the human gamma chain cause the X-linked severe combined immunodeficiency (XSCID), showing that T and natural killer cells absolutely require the gamma chain for their development in humans. To elucidate the roles of the gamma chain in hematopoiesis, we have generated mice, by gene targeting, that express a form of the gamma chain lacking the cytoplasmic region. Male mice carrying the truncated gamma-chain mutant, which mimics mutations in patients with XSCID, showed a decrease in the number of lymphocytes and an increase in monocytes; the number of T cells was profoundly reduced and no natural killer cells were detected, which is similar to the characteristic of human XSCID. Unlike human XSCID, the levels of B cells were also reduced. In spite of the severe decrease in CD45R+/sIgM+ B cells, the level of IgM in serum of the 8-week-old mutant mice was higher than that of control littermates. Interestingly, the stem cell population with surface phenotypes of CD34, c-kit, and Sca-1 was significantly increased. Furthermore, the colony-forming assay showed that the mutant mice had 15-fold higher numbers of hematopoietic progenitor cells in the spleen as compared with that of controls. These results indicate that functional loss of the gamma chain causes significant effects on the immunological system in mice.

Animals↗
PubMed1996

Possible factors which may affect phase durations in the natural chewing rhythm.

To study central and peripheral control mechanisms maintaining rhythmical jaw behaviors, chewing movements with different foods in texture were obtained in the freely behaving rabbit. Jaw movement trajectories and muscle activities (masseter, digastric, thyrohyoid) were recorded and the durations in total cycle, fast closing (FC), slow closing (SC), and opening (OP) phases were obtained as well as the burst duration in the muscles. Durations varied cycle-by-cycle and among the foods, however, the total cycle duration was found to have little differences among the foods tested. Regression analyses were applied to seek time relations to the change in total cycle duration with the duration in its constituent phases. Results suggested that changes in the total cycle duration may be due to those in the SC duration (power phase) with hard food (heavy load), but due to those in the OP duration (reverse phase) with soft food (light load). The duration of the FC was fairly constant for all the foods tested. In conclusion, the chewing rhythm may be controlled centrally to be independent of the load, and chewing cycles may begin at the middle of the opening phase.

Analysis of Variance↗
PubMed1996

Neural and skin cell-specific expression pattern conferred by steel factor regulatory sequence in transgenic mice.

We have produced transgenic mice expressing a lacZ reporter gene under the control of a fragment of a Steel factor (SLF). The function of this gene is essential for the development of hematopoietic cells, germ cells, melanocytes and pacemaker cells of the intestine. The expression of the transgene, containing 2 kb DNA 5' regulatory sequence, was restricted to neural and skin tissues in appropriate spatial and temporal pattern compared with endogenous SLF mRNA expression. This indicates that the regulatory elements necessary for the neural and skin specific expression are present in this 2 kb DNA sequence, although strong position-dependence of transgene expression was observed. As we could not detect transgene expression in hematopoietic tissues and germ cells after extending 10 kb upstream, elements important for these organs must reside in other regions. Our results indicate that neural crest derived enteric ganglion cells provide SLF to the neighboring pace maker cells expressing c-kit, the receptor for SLF. Cells expressing the transgene in the intestine are ganglion cells derived from neural crest since homozygosity for the lethal spotting (Is) mutation results in loss of such ganglion cells in transgenic mice. We have also shown that the dermal papillae of the hair follicle expresses the transgene, suggesting its roles to support the c-kit dependent growth and development of melanocytes in the hair follicle.

Animals↗
PubMed1996

A comparative study on the effect of pure-tone exposure of the guinea pig cochlea.

Electrophysiological methods were applied to 160 healthy adult male guinea pigs in order to investigate the effects of pure-tone exposure for 24 h on the inner ear. A reduction in cochlear microphonics (CM), action potential (AP) and endocochlear potential was observed following exposure to 110 dB at 100 Hz, 100 dB at 200 and 600 Hz and 95 dB at 2 kHz. The observed K+ endolymphatic concentration during 40 min anoxia remained unchanged. In contrast K+ decreased in control animals and following exposure to pure tones varying from 110 dB at 60 Hz to 85 dB at 2 kHz. These findings indicate that high frequency tones have a greater effect on inner ear functions than those of lower frequency, decreasing the maximum output voltage of CM and AP but not changing K+ endolymphatic concentration.

Acoustic Stimulation↗
PubMed1996

Combined effects of acute lead acetate exposure and tone exposure of the guinea pig cochlea.

Lead acetate exposure to humans can induce various disorders of the cranial nerves. Although vertigo and sensorineural deafness have been reported in lead workers, the dose effects of lead acetate on the cochlea and eighth cranial nerve are not well documented. We investigated the effects of lead acetate on the male albino Hartley guinea pig cochlea by measuring cochlear microphonics (CM), whole nerve action potential (AP), endocochlear potential (EP) and K+ ion concentration of the endolymph. Animals were given lead acetate by intraperitoneal injection as 20 mg/week for 4 consecutive weeks. A total dose < 80 mg did not induce electrophysiological changes in the cochlea. However, the AP output voltage (N1) decreased if the 80 mg lead acetate treatment was followed by an 80 dB tone exposure at 6 kHz during 24 h. A change was observed in CM and EP but not K+ ion concentration in the scala media.

Action Potentials↗
PubMed1996

In situ ocular absorption of tilisolol through ocular membranes in albino rabbits.

The purpose of this study is to characterize the in situ absorption properties of ocular membranes using a cylindrical cell. Drug disappearance in the cell was determined as in situ absorption after an application of drug solution into the cell on the comea, sclera (bulbar conjunctiva and sclera layer), or palpebral conjunctiva. Tilisolol was used as a model of an ophthalmic beta-blocker. Tilisolol disappeared from the conjunctival and scleral surfaces although hardly any disappearance of tilisolol from the corneal surface was observed. Depletion of drug from the precorneal space was much faster in situ than extrapolated from permeability measurements (in vitro) of the separate tissues. This may arise from an influence of blood flow. The in situ apparent permeability coefficient of tilisolol through the conjunctiva was almost constant at various concentrations of drug (5-100 mM), suggesting a passive diffusion of tilisolol that was affected by medium pH. A high concentration of tilisolol in the aqueous humor was observed in the corneal application although the scleral and conjunctival applications showed a slight concentration of tilisolol. The corneal route was a dominant route of access to the aqueous humor. Access to the vitreous body for tilisolol was 4 times more effective through the sclera than through the cornea. On the other hand, the corneal application showed an extremely low concentration of tilisolol in plasma compared to the scleral and conjunctival applications. Thus, the in situ method using a cylindrical cell is a useful method for investigation of the ocular absorption of ophthalmic drugs.

Absorption↗
PubMed1996

Immune response to heat-shock protein correlates with induction of insulitis in I-E alpha d transgenic NOD mice.

To evaluate the correlation between heat-shock protein (HSP) and insulitis, we compared lymphocyte proliferative response to Mycobacterium leprae HSP65 of NOD mice with that of I-E alpha d transgenic NOD (I-E+NOD) mice, which show no insulitis. We found that splenocytes from 15-week-old NOD mice showed a more marked proliferative response to HSP than did those from age-matched I-E+NOD mice (P < 0.05). We then transferred splenocytes from 12-week-old NOD mice into I-E+NOD mice to induce insulitis in the recipients and examined antibody levels against HSP. By 6 weeks posttransfer, insulitis was successfully transferred to four out of five recipients of NOD splenocytes and antibody levels against HSP were significantly higher in the NOD splenocyte-transferred group than in controls, which showed no insulitis (P < 0.01). These results suggest that immune response to HSP correlates with insulitis in NOD mice. Our results support the assertion that HSP is a useful antigen for investigating the etiology of IDDM.

Animals↗
PubMed1996

[A case report of chronic encapsulated intracerebral hematoma].

Chronic encapsulated intracerebral hematoma is a rare clinicopathological entity. The authors reported a case of a 52-year-old male who presented with progressive sensory disturbance of the left extremities three weeks prior to admission. Plain CT and MRI scans revealed a subcortical mass in the right temporal lobe associated with extensive peritumoral edema and intratumoral hemorrhage (mixed intensity on T1WI, low intensity on T2WI). There was a ring-like enhancement with GdDTPA. These findings strongly suggested metastatic melanoma associated with intratumoral hemorrhage. During the operation, the mass appeared partly at the surface of the brain and was easily extirpated totally. Histologically, the specimen showed chronic encapsulated hematoma with a thick, fibrous capsule and there was no evidence of neoplasm. The postoperative course was uneventful and follow up CT scan showed disappearance of the mass and the surrounding edema. The relevant literature was reviewed, and the pathogenesis of this entity was discussed.

Cerebral Hemorrhage↗
PubMed1996

[Acute epidural hematoma of posterior fossa: comparative analysis between 20 cases in adults and 10 cases in children].

A comparative study of the clinical features was made among 30 patients, 10 children (less than 14) and 20 adults (older than 15) with traumatic acute epidural hematoma of the posterior fossa (PFEDH). The characteristic findings in both groups were as follows: 1) PFEDH accounted for 15% of 200 epidural hematoma cases. Incidence of PFEDH was 23.3% (10/43) in children and 12.7% (20/157) in adults. Thus, PFEDH is more common in children than in adults. 2) In seven out of 10 children, PFEDH was confined to the posterior fossa but in the other three children, PFEDH extended to the supratentorial area. On the other hand, in all the adult cases PFEDH extended over the supratentorial space. 3) Hematoma density was high in 5 out of 10 children and 18 in out of 20 adults. Mixed (including low) density occurred at a higher rate in children (50%) than in adults (10%). 4) Brain contusion associated with PFEDH was found by CT scan in 12 adult cases and one child case. Subarachnoid hemorrhage was found by CT scan in 4 adult cases. Subdural effusion was found by CT scan in 1 adult case. Thus, intracranial complications associated with PFEDH occurred in a significantly higher number in adults than in children. 5) 20 cases (4 children, 16 adults) of 30 underwent surgery, and 10 cases (6 adults, 4 children) were given conservative treatment. Results (GOS); GR was observed in 22 cases (in all 10 children and in 12 adults), and MD in 8 cases. There were no SD, VS or cases ending in death.

Acute Disease↗
PubMed1996

[Unilateral dissection of the cervical portion of the internal carotid artery and ipsilateral multiple cerebral infarctions caused by suicidal hanging: a case report].

This paper presents a case of traumatic dissection of the unilateral internal carotid artery of the cervical portion caused by hanging. A 63-year-old man attempted suicide by hanging and was rescued immediately after. No neurological deficits were detected for the first 4 hours. But then, right hemiplegia, aphasia and disturbed consciousness suddenly developed. On the 2nd day, MRI revealed multiple infarctions in the left cerebral hemisphere. MR angiography demonstrated severe stenosis at the cervical portion of the left internal carotid artery due to dissection. The left middle cerebral artery was not demonstrated. The patient was conservatively treated with fibrinolytic agents and regained consciousness gradually. But aphasia and right hemiplegia remained. During the next few weeks, the stenosis at the ICA slightly improved and the MCA was completely recanalized. Extracranial Doppler sonography revealed chronological hemodynamic changes of mean flow velocity and pulsatility index at the proximal and distal portion of the ICA stenosis.

Carotid Artery Diseases↗
PubMed1996

[Putaminal abscess occurring at the site of hemorrhage: a case report].

Brain abscesses following stroke have been reported only rarely. We presented a case of putaminal abscess following putaminal hemorrhage. The patient was admitted to our hospital because of acute onset of left hemiplegia. The size of the hematoma was medium and the patient was conservatively treated. In about two months after the ictus, he became intermittently febrile and laboratory examinations suggested the presence of general infections including meningitis. Meanwhile, CT and MRI revealed clearly abscess formation at the site of the hematoma with remarkable brain edema. Cerebrospinal fluid analysis showed the findings of meningitis. On diagnosis of brain abscess, stereotactic exploration was performed and pus mixed with old blood was aspirated. Bacteriological study of the specimen demonstrated Morganella morganii. Postoperative course was uneventful and the abscess cavity gradually subsided following drainage and irrigation of the abscess cavity.

Brain Abscess↗