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Biomedical subjects

A Saitoh

Publications and source records attributed to A Saitoh.

At least 37 records · Page 2Linked to original sources

Unilateral coronal synostosis treated by internal forehead distraction.

A 1-year-old infant with left hemicoronal synostosis was treated by distraction osteogenesis of the craniofacial skeleton using an internal distraction device. Surgery was performed through a coronal incision. The frontal bone and upper half of both orbits were first osteotomized en bloc after minimal epidural dissection of the supraorbital area and no epidural dissection around the coronal osteotomy site. The lateral one fourth of the frontal bone, including the right lateral half of the orbit, was left intact. The internal distraction device was fixed in the left temporal area. A 0.5-mm per day rate of distraction was performed up to an elongation of 17 mm after a 5-day latency period. The distraction device was removed after a consolidation period of 2 months. The results obtained were satisfactory, with symmetry of the forehead, orbit, and nose achieved without complications. The merits of this procedure are no extradural dead space after the operation (which prevents infection), shortened operative time, reduced blood loss, filling in the bone gap created by advancement with new bone, acceptable cosmesis by the parents during distraction, and no fixation device left after the second operation.

Craniosynostoses↗

Age effect on expression of myosin heavy and light chain isoforms in suspended rat soleus muscle.

This study was designed to test the hypothesis that myosin heavy (MHC) and light chain (MLC) plasticity resulting from hindlimb suspension (HS) is an age-dependent process. By using an electrophoretic technique, the distribution of MHC and MLC isoforms was quantitatively evaluated in the soleus muscles from 3- or 12-wk-old rats after 1-3 wk of HS treatment was maintained. In normal 12- and 15-wk-old rats, the soleus muscles contained a predominance of MHCI ( approximately 94%) with small amounts of MHCIIa, but not MHCIId or MHCIIb. The suspended muscles of adult rats were characterized by the appearance of MHCIIb and MHCIId, the latter reaching approximately 6% after 3 wk of HS treatment. In contrast to changes in MHC, HS did not induce a transition in the MLC pattern in the soleus muscles from adult rats. Compared with adult rats, in juveniles HS had a much more pronounced effect on the shift toward faster MHC and MLC isoform expression. The soleus muscles of 6-wk-old rats after 3 wk of HS were composed of 37.0% MHCI, 19.1% MHCIIa, 23.7% MHCIId, and 20.2% MHCIIb. Changes in MLC isoforms consisted of an increase in MLC1f and MLC2f concomitant with a decrease in MLC2s. These results indicate the existence of a differential effect of HS on MHC and MLC transitions that appears to be age dependent. They also suggest that the suspended soleus muscles from young rats may acquire the intrinsic contractile properties that are intermediate between those in the normal soleus and typical fast-twitch skeletal muscles.

Aging↗

Characterization of Wnt gene expression in murine skin: possible involvement of epidermis-derived Wnt-4 in cutaneous epithelial-mesenchymal interactions.

Wnt glycoproteins mediate short range intracellular communication that facilitates morphogenesis and, in some settings, promotes tumor formation. Although the involvement of the Drosophila homolog wingless in ectodermal patterning is well established, the role that Wnt genes play in mammalian skin biology is not defined. We detected Wnt-4 and Wnt-10b mRNA in adult murine epidermis using degenerate primers and reverse transcriptase PCR, and confirmed expression by RNase protection. Normal murine keratinocytes and a melanocyte cell line (melan-A) propagated in vitro also contained Wnt-4 mRNA, whereas dermal fibroblasts and Langerhans cell-like dendritic cells did not. Because Wnt-4 mRNA was more abundant than Wnt-10b mRNA in epidermis and Wnt-10b trancripts were not detected in cells propagated in vitro, additional studies emphasized Wnt-4 exclusively. Wnt-4 mRNA levels were increased in cultured keratinocytes as they approached confluence and were strikingly downregulated by mitogenic growth factors. Although Wnt-4 mRNA levels were not modulated during calcium-induced keratinocyte differentiation in vitro, assessment of Wnt-4 transcripts in keratinocyte cell lines suggested that loss of Wnt-4 gene expression was associated with a less differentiated, more malignant, phenotype. Despite this, epidermal abnormalities were not identified in newborn Wnt-4 null (-/-) skin, or in full-thickness -/- skin that was engrafted to nude or athymic mice and allowed to mature for as long as 3 months. However, histologic examination of newborn Wnt-4 null skin did reveal fibroplasia involving the dermis with increased accumulation of type I collagen fibrils. These results indicate that several Wnt genes are expressed in adult murine epidermis and suggest that Wnt-4 proteins may be involved in epidermal-dermal interactions in mammalian skin.

Animals↗

Opening-up of liposomal membranes by talin.

Morphological changes of liposomes caused by interactions between liposomal membranes and talin, a cytoskeletal submembranous protein, were studied by direct, real-time observation by using high-intensity dark-field microscopy. Surprisingly, when talin was added to a liposome solution, liposomes opened stable holes and were transformed into cup-shaped liposomes. The holes became larger with increasing talin concentration, and finally the cup-shaped liposomes were transformed into lipid bilayer sheets. These morphological changes were reversed by protein dilution, i.e., the sheets could be transformed back into closed spherical liposomes. We demonstrated that talin was localized mainly along the membrane verges, presumably avoiding exposure of its hydrophobic portion at the edge of the lipid bilayer. This is the first demonstration that a lipid bilayer can stably maintain a free verge in aqueous solution. This finding refutes the established dogma that all lipid bilayer membranes inevitably form closed vesicles and suggests that talin is a useful tool for manipulating liposomes.

Animals↗

Urinary levels of monocyte chemoattractant protein (MCP)-1 and disease activity in patients with IgA nephropathy.

Using a quantitative sandwich ELISA, we studied 17 patients with IgA nephropathy to determine if levels of urinary monocyte chemoattractant protein-1 (MCP-1) might reflect the disease activity. The levels of urinary MCP-1 in patients with the advanced stage were significantly higher than those in patients with the mild stage of the disease, or in healthy controls. The results showed a significant correlation between the levels of urinary MCP-1 and the disease activity, i.e., levels of urinary casts and urinary protein. It was thus suggested that the measurement of urinary MCP-1 is useful in evaluating the degree of renal injuries and/or prognosis in patients with IgA nephropathy.

Adult↗

Effects of the experimental diabetes on dopamine D1 receptor-mediated locomotor-enhancing activity in mice.

The effects of diabetes on the dopamine-related locomotor-enhancing activities were studied in mice. Although spontaneous locomotor activity in diabetic mice was significantly greater than that in nondiabetic mice, the locomotor-enhancing effects of methamphetamine (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.) and SKF82958 (1 mg/kg, s.c.), a selective dopamine D1-receptor agonist, in diabetic mice were significantly lower than those in nondiabetic mice. When dopamine level in the whole brain was reduced by pretreatment with 6-hydroxydopamine (6-OHDA), spontaneous locomotor activity was significantly reduced in both nondiabetic and diabetic mice. There was no significant difference in the total spontaneous locomotor activity counts within 3 h between 6-OHDA-treated nondiabetic and 6-OHDA-treated diabetic mice. Furthermore, the locomotor-enhancing effect of SKF82958 in 6-OHDA-treated diabetic mice was also significantly lower than that in 6-OHDA-treated nondiabetic mice. In a binding assay, the Bmax values of [3H]SCH23390 binding to whole-brain membranes of diabetic mice were significantly lower than those in nondiabetic mice. However, there was no significant difference in the Kd values between nondiabetic and diabetic mice. These results suggest that the decreased density of dopamine D1 receptors in diabetic mice may result in hyporesponsiveness to dopamine-related locomotor enhancement.

Animals↗

Fibrosing cholestatic hepatitis after living related-donor renal transplantation.

A 43-year-old man underwent living related-donor renal transplantation because of chronic renal failure in 1991. During the transplant period, both donor and recipient were seronegative for hepatitis B surface antigen (HBsAg). The donor was seropositive for antibody to hepatitis B surface antigen (anti-HBs) due to hepatitis B virus (HBV) vaccination. After transplantation, FK506 and methylprednisolone had been administered to the patient as immunosuppressants. In 1993, HBsAg appeared in his serum. His alanine aminotransferase level elevated gradually during 1995 and then in 1996, general fatigue, ascites and jaundice developed. At this time his serum was positive for hepatitis B e antibody, contained more than 100000 Meq/mL HBV-DNA and 100% precore mutant. Despite subsequent intensive therapy, liver dysfunction progressed and this patient died of hepatic failure 2 months following admission. At autopsy, the liver exhibited cholestasis, fibrosis extending from the portal tracts, mild inflammation and hepatocytes with a ground-glass appearance. In addition, HBsAg and hepatitis B core antigens had accumulated in the hepatocytes. Consequently, the final diagnosis was fibrosing cholestatic hepatitis (FCH) due to precore mutant HBV infection contracted after renal transplantation. It is unclear when and where the recipient liver became HBV infected. Nevertheless, after renal transplantation, while receiving immunosuppressive drugs, HBV appeared to have the potential to cause hepatic failure and FCH may have been a fatal complication for the recipient.

Adult↗

[Legionella pneumonia caused by aspiration of hot spring water after sarin exposure].

A 72-year-old man was exposed to the sarin gas attack in a Tokyo subway on March 20 th, 1995. After exposure, he noticed eye discomfort, chest tightness, headache and weakness of the lower limbs and oropharyngeal muscles. Despite these symptoms, he visited a hot spring on the same day with his family. On March 25 th, his muscle weakness progressed, and a low grade fever appeared. His muscle weakness disappeared 8 days after exposure to sarin, but respiratory failure rapidly developed, necessitating artificial ventilation within four day after hospitalization on March 28th. Chemotherapy with erythromycin, imipenem/cilastatin, and steroid pulse therapy was begu. PCR and culture of sputum collected by bronchofiberscopy were positive for Legionella pneumophila, serogroup I. His respiratory state improved, but subsequent infection with Pseudomonous aeruginosa. Enterobacter cloacae, and Candida tropicalis/glabrata caused his death 71 days after admission. Oropharyngeal muscle weakness caused by sarin-mediated cholinesterase inhibition was strongly suspected as the cause of hot spring water aspiration. Transbronchial lung biopsy revealed organizing pneumonia with fibrosis. Bronchoscopic findings included redness, edema and fragility of all visible areas of the airway, which was thought to be due to bronchitis caused by Legionellosis.

Aged↗

Anticoagulation therapy and ocular surgery.

BACKGROUND AND OBJECTIVE: It is not rare for patients receiving anticoagulant therapy to undergo ocular surgery; however, there are no clear guidelines with reference to the operative management of the eye. This study examines the complications in patients receiving anticoagulant therapy who undergo ocular operations and suggests a management regimen for these patients. PATIENTS AND METHODS: The authors retrospectively analyzed 52 patients receiving anticoagulant therapy who underwent ocular surgery between 1993 and 1995. Data included sex, age, reason for anticoagulant therapy, operative procedure, complication rate, and length of time anticoagulant therapy was stopped or reduced prior to surgery. To show the base-line complication rate at their institution, data of patients not receiving anticoagulation therapy were added. RESULTS: Ticlopidine hydrochloride, an antiplatelet drug, was administered to 24 patients. Warfarin sodium was administered to 8 patients, heparin was administered to 8 patients, and other anticoagulants were administered to 20 patients. There were no significant differences in complications between the groups that stopped or reduced anticoagulant therapy and those that did not, but speech disturbance due to thrombotic complication occurred in 1 of 10 patients in whom ticlopidine hydrochloride was stopped or reduced. Hemorrhagic complications occurred in 50% of those who continued ticlopidine hydrochloride, but in none of those who discontinued it (P = .019). There was a significant difference in hemorrhagic complications after cataract surgery between the phacoemulsification, aspiration, and intraocular lens implantation (PEA + IOL) and the planned extracapsular cataract extraction and intraocular lens implantation (PECCE + IOL) groups that continued the drug (P = .0011). No patients showed visual acuity reduction due to hemorrhagic complications. CONCLUSIONS: To avoid life-threatening systemic complications, one need not always stop anticoagulant therapy before performing only cataract surgery. Cataract surgery in patients receiving ticlopidine hydrochloride should be performed with PEA + IOL via a small sclerocorneal or a corneal incision. In cataract surgery for patients receiving anticoagulant therapy, hemorrhagic complications are more frequent than in patients not receiving anticoagulant therapy.

Adult↗

E-cadherin-mediated adhesion involving Langerhans cell-like dendritic cells expanded from murine fetal skin.

Langerhans cells (LC), the epidermal contingent of the dendritic cell (DC) lineage, migrate from skin to regional lymph nodes to initiate primary immune responses against Ag encountered in skin. Because E-cadherin mediates LC-keratinocyte adhesion, E-cadherin expression and/or function must be modulated during LC migration. To facilitate studies of LC/DC cadherin biology, we defined culture conditions that allowed expansion of LC-like cells from fetal murine skin. Fetal skin-derived dendritic cells (FSDDC) were propagated from C57BL/6 day 16 fetal skin in GM-CSF- and CSF-1-supplemented media. After 14 days, aggregates of E-cadherin+ FSDDC (FSDDC-A) that resembled freshly-obtained LC with regard to phenotype and function were isolated. Nonadherent FSDDC (FSDDC-NA) with dendritic morphology, surface phenotype identical to that of interdigitating DC and potent allostimulatory capacity were released from FSDDC-A with continued incubation. A survey of cytokine mRNAs expressed by FSDDC revealed that FSDDC-A expressed predominantly TNF-alpha, TGF-beta1, and MIF mRNA. In contrast, FSDDC-NA exhibited de novo expression of IL-1beta, IL-12 (p40), increased levels of TNF-alpha and decreased MIF mRNA. Neutralizing anti-E-cadherin mAb dissociated FSDDC-A into single cells, whereas functionally inactive anti-E-cadherin mAb and mAb reactive with other adhesion molecules did not, demonstrating that adhesion within FSDDC-A was E-cadherin-mediated. FSDDC-A also preferentially adhered to E-cadherin-transfected fibroblasts. Spontaneous dissociation of FSDDC-A was accompanied by a reduction in cell surface E-cadherin expression. The availability of large numbers of cells with characteristics of LC in situ that spontaneously mature into interdigitating DC will permit detailed studies of LC/DC cadherin biology and LC/DC differentiation.

Animals↗

A role for TGFbeta1 in langerhans cell biology. Further characterization of the epidermal Langerhans cell defect in TGFbeta1 null mice.

Previous studies of TGFbeta1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after transfer into lethally irradiated recipients. Thus, the LC defect in TGFbeta1 null mice does not result from an absolute deficiency in bone marrow precursors, and paracrine TGFbeta1 production is sufficient for LC development. Several approaches were used to assess the suitability of -/- skin for LC localization. A survey revealed that although a number of cytokine mRNAs were expressed de novo, mRNAs encoding proinflammatory cytokines known to mobilize LC from epidermis (IL-1 and TNFalpha) were not strikingly overrepresented in -/- skin. In addition, bone marrow-derived LC populated full-thickness TGFbeta1 null skin after engraftment onto BALB/c nu/nu recipients. Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant-negative TGFbeta type II receptor contained normal numbers of LC. Because TGFbeta1 signaling in these mice is disrupted only in keratinocytes and the keratinocyte hyperproliferative component of the TGFbeta1 -/- phenotype is reproduced, these results strongly suggest that the LC defect in TGFbeta1 null mice is not due to an epidermal abnormality but reflects a requirement of murine LC (or their precursors) for TGFbeta1.

Animals↗

Supraspinal delta 1-opioid receptor-mediated antinociceptive properties of (-)-TAN-67 in diabetic mice.

The antinociceptive potencies of the enantiomorphs of TAN-67 (2-methyl-4-alpha alpha-(3-hydroxyphenyl)-1,2,3,4,4 a 5, 12, 12 a alpha-octahydroquinolino[2,3,3,-g]isoquinoline), (-)-TAN-67 and (+)-TAN-67, given intracerebroventricularly (i.c.v.) on the antinociceptive response were studied in streptozotocin-induced diabetic mice using the tail-flick test. (-)-TAN-67 at doses of 3-10 micrograms given i.c.v. produced dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice. The antinociceptive effect of (-)-TAN-67 in the tail-flick test in diabetic mice was greater than that in non-diabetic mice. The antinociceptive effect of (-)-TAN-67 was not antagonized by pretreatment with either beta-funaltrexamine, a selective mu-opioid receptor antagonist, or nor-binaltorphimine, a selective kappa-opioid receptor antagonist. When 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, was administered 10 min before treatment with (-)-TAN-67, the antinociceptive effect of (-)-TAN-67 was significantly antagonized. However, naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on the antinociceptive effect of (-)-TAN-67. On the other hand, in the tail-flick test. (+)-TAN-67 at doses of 3-30 micrograms given i.c.v. did not produce dose-dependent inhibition of the tail-flick response in either non-diabetic or diabetic mice. In conclusion, (-)-TAN-67, but not its enantiomer (+)-TAN-67, produced an antinociceptive effect through the activation of delta 1-opioid receptors.

Analgesics↗

Denervation-induced region-specific changes in fibre types in the soleus and plantaris muscles of rats.

Muscle fibre composition was compared among the proximal (25%), middle (50%) and distal (75%) regions of muscle to investigate whether denervation induces region-specific changes of fibre types in the soleus and plantaris muscles of rats. Decreases in mass were observed in both muscles after denervation. In the soleus muscle, denervation increased the percentage of type I fibres with a concomitant increase in the proportion of type IIC and IIA fibres. The extent of such transformations was greater in the proximal region than the middle and distal regions. In normal plantaris muscle, the middle region showed a higher proportion of type IIA fibres with a lower percentage of type IIB fibres reciprocally than other regions. These regional differences in fibre types were not detected in the 4-week denervated plantaris muscle. These findings suggest that denervation-induced transformations from type I to type II fibres begin in the proximal region in the soleus muscle of rats. In addition, regional differences in fibre types along the muscle length could be regulated by neuromuscular activity through normal innervation in the plantaris muscle.

Animals↗

Evidence for the modulation of spontaneous locomotor activity by higher serum glucose levels and/or spleen-derived factor(s) in diabetic mice.

We investigated whether enhanced spontaneous locomotor activity in streptozotocin (STZ)-induced diabetic mice is associated with serum glucose levels. Furthermore, the role of factor(s) derived from spleen cells on the enhanced spontaneous locomotor activity in diabetic mice was also examined. Serum glucose levels were significantly increased on day 4 after STZ administration and remained increased at 7, 14, 28 and 56 days after STZ administration. A significant increase in spontaneous locomotor activity in diabetic mice as compared to that in non-diabetic mice was observed 4, 7, 14 or 28 days after STZ treatment. The increase in spontaneous locomotor activity in diabetic mice was not observed when insulin was chronically administered to mice 3 to 7 days after administration of STZ. Splenectomized diabetic mice, which were operated upon 7 days after STZ administration, still had a significantly higher spontaneous locomotor activity than non-diabetic mice. In contrast, spontaneous locomotor activity in diabetic mice that were splenectomized either before or 3 days after administration of STZ returned to the levels in non-diabetic mice. The rate of dopamine (DA) turnover in the limbic forebrain of diabetic mice on day 14 was significantly higher than that in age-matched non-diabetic. Although the rate of DA turnover in the diabetic mice that were splenectomized 7 days after STZ administration was significantly higher than that in non-diabetic mice, an increased the rate of DA turnover was not observed when mice were splenectomized either before or 3 days after administration of STZ. These results suggest that the lasting hyperglycemia may be responsible for their hyperlocomotion in diabetic mice within 14 days sfter STZ treatment, perhaps due to an increase in dopamine release in mesolimbic dopamine systems. Furthermore, factor(s) derived from spleen cells of diabetic mice during the incipient stages of diabetes may play a role in the enhancement of dopaminergic neurotransmission.

3,4-Dihydroxyphenylacetic Acid↗

Pharmacologic inhibition of twin-pulse facilitation of release of transmitter quanta at the mouse neuromuscular junction.

1. The frequency (F,s-1) of miniature endplate potentials and the quantal content (m) of endplate potentials were simultaneously measured intracellularly at mouse diaphragm endplates in a bath solution that contained 0.6 mM Ca2+ ions and 5 mM Mg2+ ions. 2. Twin pulses at 4-ms intervals gave the quantal contents of the first (m1) and second (m2) responses. The ratio of m2/m1 was taken as an indicator of the temporal facilitation of the release of transmitter. 3. Lead ions (Pb2+; 10 microM), bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; loaded for 60 min at 200 microM), and chlortetracycline (CTC; loaded for 30 min at 80 microM) reduced the values of F and m2/m1. Pb2+ ions and CTC reduced the value of m, whereas BAPTA did not.omega-Agatoxin (omega AGT; 10 ng/ml) reduced the value of m without affecting F or m2/m1. 4. These results suggest that synaptic facilitation is modifiable by agents that can affect systems which buffer intracellular levels of Ca2+ ions.

Animals↗

Giant cell tumor of bone: frequent actin immunoreactivity in stromal tumor cells.

Although giant cell tumor (GCT) of bone is a well-recognized neoplasm with distinctive clinical and histopathological features, the origin of tumor cells, particularly of mononuclear cells, has not yet been established. An immunohistochemical study was carried out on 11 cases of GCT of bone to examine the cellular natures of stromal mononuclear cells. In all cases, stromal cells were positive for muscle actin (HHF35) or alpha-smooth muscle actin, and in eight of 11 cases, positivity was intense and extensive. The cell margin of osteoclast-like giant cells (OGC) was stained positively by muscle actin, in addition to intense and diffuse positive staining of the cytoplasm for KP1 (CD68), whereas alpha-smooth muscle actin exhibited a negative reaction on the OGC. In conclusion, the tumor cells with muscle actin and alpha-smooth muscle actin positivities are not rare but frequently numerous in the GCT of bone; whereas further observation is necessary to elucidate whether the stromal cells exhibit myofibroblastic cell differentiation exactly.

Actins↗

Epitope analysis of human T-cell response to MSP-1 of Plasmodium falciparum in malaria-nonexposed individuals.

BACKGROUND: MSP-1 of Plasmodium falciparum induces strong proliferative T cell responses even in malaria-nonexposed individuals. Epitopes recognized by malaria-nonimmune T cells have not been identified, and immunological mechanisms inducing such T cell responses remain to be uncovered. MSP-1 is a vaccine candidate, and it should be understood whether those epitopes have any roles in MSP-1-mediated protective immunity. The T epitopes-inducing malaria-naive T cell response was analyzed in the hope of understanding the underlying mechanisms. METHODS: Human T cell lines and clones reactive to MSP-1 of P. falciparum were established from malaria-nonexposed Japanese donors in vitro, and epitope peptides were identified. Sequences of those epitope peptides were compared to unrelated peptides in the data base. One of those peptides was tested for both binding to HLA-DR molecules and inducing proliferative responses of MSP-1-reactive T cells. RESULTS: There are at least 6 epitopes recognized by malaria-naive T cells under the restriction by HLA-DRB1*1502 or 0802. Important amino acids for the T cell recognition were identified for an MSP-1 peptide. A yeast peptide which shared those residues induced proliferative responses of MSP-1-reactive T cells. CONCLUSION: We identified T epitopes in the N-terminal region of MSP-1, some of which showed molecular similarities with unrelated environmental antigens, suggesting the presence of cross-reactive T epitopes in MSP-1. Cytokine production in response to those epitopes suggests regulatory functions of those T cells during primary infection with P. falciparum.

Amino Acid Sequence↗