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Biomedical subjects

M Nakata

Publications and source records attributed to M Nakata.

At least 181 records · Page 10Linked to original sources
PubMed1995

Neurotrophin-3 is expressed in the posterior lobe of mouse cerebellum, but does not affect the cerebellar development.

We replaced the neurotrophin-3 (NT-3) gene with Escherichia coli-derived lacZ via homologous recombination in embryonic stem (ES) cells and generated the mutant mice. Here we show the in vivo expression of NT-3 in the cerebellum during the postnatal period. A high level of lacZ expression was found in the granular layer of posterior lobe (lobules VII to X) in the postnatal NT-3(+/-) cerebellum. The expression in these regions was reduced with age. Although the Purkinje cells are considered to be a target of NT-3 and the NT-3(-/-) mice displayed severe moving disorders like ataxia, no histological abnormality was observed in their cerebellum. These findings suggest that the NT-3 expressed in the cerebellum gives some trophic effects primarily to the posterior lobe, however, the deficiency does not affect its development.

Animals↗
PubMed1995

Oligomannose-coated liposomes as an adjuvant for the induction of cell-mediated immunity.

The effect of the coating of ovalbumin-reconstituted liposomes with various oligosaccharides on their immunogenicity was investigated in mice. The coating of liposomes with oligomannose or yeast mannan drastically enhanced their ability to induce an ovalbumin-specific delayed-type footpad swelling response with a peak at 24 to 48 h post-challenge. Among various oligosaccharides tested, only those with mannose residue at the nonreducing termini manifested the activity when applied to liposomes. Since such oligosaccharides are ubiquitously found in the body, these results suggested the usefulness of oligomannose-coated liposomes as a safe adjuvant for the induction of cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed1995

Expression of human platelet-activating factor receptor gene in EoL-1 cells following butyrate-induced differentiation.

Platelet-activating factor (PAF) is a potent lipid mediator of allergic inflammation through its interaction with eosinophils. Expression of the PAF receptor is modulated by many agents, including those responsible for cell differentiation. We report here that differentiation of a human eosinophilic leukaemia cell line, EoL-1, by sodium n-butyrate is associated with induction of PAF receptor gene expression, as indicated by: PAF receptor mRNA accumulation; increases in the binding of [3H]WEB 2086, a PAF antagonist; analysis of cell-surface expression of PAF receptor protein using a monoclonal anti-(PAF receptor) antibody; and augmentation of PAF-induced increase in the intracellular concentration of calcium. Using cDNA cloning, the receptor expressed in EoL-1 cells was identified as 'Transcript 1', one of two transcripts which was previously reported from human genomic analysis (Mutoh, Bito, Minami, Nakamura, Honda, Izumi, Nakata, Kurachi, Terano and Shimizu (1993) FEBS Lett. 322, 129-134). The PAF-induced calcium response and phosphoinositide turnover were decreased by pertussis toxin (PTX) treatment, suggesting that these signals are coupled largely with PTX-sensitive G-protein(s) in EoL-1 cells. These systems may provide a useful experimental model with which to investigate the relationship between eosinophilic differentiation and PAF receptor induction, and the role of eosinophils in allergic responses.

Amino Acid Sequence↗
PubMed1995

Targeted disruption of the neurotrophin-3 gene with lacZ induces loss of trkC-positive neurons in sensory ganglia but not in spinal cords.

We have replaced the NT-3 gene with Escherichia coli-derived lacZ gene by means of homologous recombination in embryonic stem cells and thus produced null mutant mice. Mice homozygous for this mutation developed to birth, but most of them could not suck well and died within 2 days after birth. The surviving homozygous mutant mice displayed movement disorder similar to ataxia. The expression of lacZ was widely distributed in the target tissues of peripheral nerves, spinal motor neurons, lumbar dorsal root ganglia and trigeminal ganglia during the prenatal periods. A neuroanatomical examination revealed that there was marked cell reduction present in trigeminal and lumbar dorsal root ganglia in the developing homozygous mutant mice. In these tissues, the expression of trkC, a high-affinity receptor for NT-3, was markedly reduced. In contrast, we did not find any morphological abnormalities, significant cell loss or decreased levels of trkC expression in the motor neurons present in the ventral horn of the spinal cord. These results indicate that the absence of the NT-3 gene leads to a defect in the sensory nervous system, but it may be complemented by other neurotrophins in the motor nervous system during the development.

Animals↗
PubMed1995

Effect of the dam strain on the spontaneous incidence of cleft lip and palate and intrauterine growth of CL/Fr mouse fetuses.

PURPOSE: The effects of dam strain on the spontaneous incidence of the cleft lip and palate (CLP) and the intrauterine growth of transferred CLP-susceptible CL/Fr embryos were examined with an embryo transfer technique. The CL/Fr strain of embryos at the early blastocyst stage was transferred to the same dam strain and also to the CLP-resistant C57BL dam strain. A laparotomy was done on the 18th gestational day at which time the number of fetuses, the resorption sites and the fetus weight were recorded. Each fetus was checked for the presence of CLP. Five criteria to assess the reproduction and fertility as well as the fetus weight were then compared between both dam strains. RESULTS: The dam pregnancy rate and the fetus survival rate in the CL/Fr dam strain were both significantly lower than those in the C57BL dam strain. The resorption rate in the CL/Fr dam strain was significantly higher than that in the C57BL dam strain. The spontaneous incidence rate of CLP in the CL/Fr dam strain was also significantly higher than that in the C57BL dam strain. The fetus weight of the CL/Fr fetuses developed in the CL/Fr dam strain was significantly lighter than that of the CL/Fr fetuses developed in the C57BL dam strain. CONCLUSION: The results indicated that the CLP-susceptible CL/Fr dam strain provided a less favorable uterine environment for the implantation, survival and intrauterine growth of the transferred CL/Fr embryos and also caused a higher spontaneous incidence rate of CLP. Thus, it can be concluded that the effect of the dam strain appears to play an important role on the spontaneous incidence of CLP and the intrauterine growth of the CL/Fr strain embryos transferred to both CL/Fr and C57BL dam strains.

Animals↗
PubMed1995

[New anti-HIV drug which binds the oligosaccharides of HIV envelope glycoprotein].

The virion surface of the human immunodeficiency virus (HIV-1) is covered with an envelope glycoprotein gp120. Study of the oligosaccharide structures of gp120 suggests that the high mannose type of oligosaccharides are essential for HIV-1 infection. Pradimicin A, an antifungal antibiotic isolated from Actinomadura hibisca, and the derivative BMY-28864 have the ability to inhibit HIV-1 infection in vitro. The inhibitory effect was suppressed by addition of high mannose type oligosaccharides of gp120. BMY-28864 bound directly to gp120, mannose-BSA, and neoglycolipids containing high mannose type oligosaccharides but not to natural mammalian glycoproteins. The binding was Ca2+ dependent and was inhibited by mannose. BMY-28864 is a unique carbohydrate-binding antibiotic which has never been reported. It is possible to block HIV-1 infection by targeting oligosaccharide chains of the envelope glycoprotein.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Histopathological analysis of herniated cerebellar tonsils resected from the patients with Chiari type I malformation with syringomyelia].

Cerebellar tonsillectomy is a controversial treatment for Chiari type I malformation combined with syringomyelia. To demonstrate the validity of this procedure, we evaluated the postoperative clinical course, the histopathological finding in the resected cerebellar tonsils and the MR images of four patients. The patients were all women, ranging in age from 27 to 58 years old (mean: 43 years). The postoperative follows-up period lasted from 28 to 51 months (average: 38 mos), and the neurological symptoms and signs improved in all patients. Histopathological examination of the resected tonsils revealed a loss of Purkinje cells and granule cells. Vacuolated degeneration and chromatolysis were also seen, and modified Bielschowsky stain revealed axonal degeneration. These findings appeared to be irreversible. Postoperative T1-weighted MR images of the cervical and thoracic spine demonstrated a decrease in the size of the syrinx and the disappearance of evidence of tonsillar herniation in all patients. Postoperative phase-contrast MR images showed good CSF pulsation in the subarachnoid space at the craniocervical junction in all three patients examined. It was possible to avoid surgical complications by using careful microsurgical techniques. Based on these results, we concluded that cerebellar tonsillectomy is an adequate surgical strategies for treating Chiari type I malformation associated with syringomyelia.

Adult↗
PubMed1995

Genetics in oral-facial growth and diseases.

Much debate has taken place over the relative importance of heredity and environment in the development of various diseases and conditions. Dental problems are not often easily categorised into either genetic or environmental, because most anomalies involve the interaction of both factors. Since many genetic disorders involve the orofacial region, the importance of the subject is paramount in dentistry to enable a proper understanding of the development of the various conditions and the treatment of patients presenting with those conditions. The incidence of newborn children with any congenital anomaly is estimated to be as high as 2 to 3 per cent, with more than half of these abnormalities, including minor manifestations, found in the head and neck region. It is therefore not unusual for dentists to be the first to recognise such conditions in their patients and be responsible for providing the necessary treatment. This paper describes many conditions, genetically or partly genetically mediated, which affect the oro-facial tissues, and offers descriptions by which the clinician can start to identify those conditions.

Environment↗
PubMed1995

Clinical results of breast-conservation therapy using a CT simulator.

The CT simulator is a real-time, CT-linked, 3-D treatment planning system which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. The clinical benefit of this system was evaluated in breast cancer patients undergoing breast-conserving therapy. Between December 1987 and March 1993, 244 breasts in 243 patients underwent breast-conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin-positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including the beam angle and head rotation angle. During follow-up for 2-66 months (median: 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has since occurred. The cumulative survival rate and the disease-free survival rate at five years were 95.2% and 91.8%, respectively. The CT simulator appears to be a useful tool for individualized optimization of tangential irradiation fields in breast-conserving therapy.

Adult↗
PubMed1994

Superantigen-like properties of an antibody bispecific for MHC class II molecules and the V beta domain of the T cell antigen receptor.

A working model for the action of superantigens (SAg) is that they are simple proteins having binding sites for both MHC class II molecules and the V beta domain of the TCR. Binding of a SAg to both molecules cross-links the TCR, inducing a biologic response. In this study, we have tested this working model using a SAg mimic consisting of a hybrid Ab bispecific for the murine MHC class II molecule I-E and the V beta 8 domain of the murine TCR. The bispecific Ab activates V beta 8-bearing T cells only in the presence of I-E molecules on APC when tested in vitro. The effect of the bispecific Ab in vivo revealed both clonal deletion and a reduction in the responsiveness of V beta 8-bearing T cells. Thus, the results suggest that molecules distinct from SAg that can bind to both MHC class II molecules and the V beta domain of the TCR can mimic the biologic actions of a SAg.

Animals↗
PubMed1994

Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction.

Soluble forms of human betacellulin (BTC) were purified to homogeneity from the conditioned medium of mouse A9 cells transfected with the BTC precursor cDNA. Three types of soluble BTC, designated BTC-1a, BTC-1b and BTC-2, were resolved by cation-exchange and size-exclusion column chromatography. Physicochemical analysis has revealed that BTC-1a represents the glycosylated, intact molecule composed of 80 amino acid residues (Asp32 to Tyr111 of the precursor molecule). BTC-1b appears to be a truncated molecule lacking 12 amino acid residues from the amino terminus of BTC-1a. BTC-2 was found to be a 50-amino acid molecule (Arg62 to Tyr111) that corresponds to the epidermal growth factor (EGF) structural unit. The biological activities of these BTC molecules were essentially identical as judged by their mitogenicity on Balb/c 3T3 fibroblasts. BTC and EGF were equipotent in stimulating Balb/c 3T3 cell proliferation and rat mesangial cell Ca2+ mobilization as well as in inhibiting the growth of human epidermoid carcinoma A431 cells. BTC and EGF antagonized each other with similar dose dependence for binding to A431 cells, indicating that these factors bind the same receptor molecules with equivalent avidity. The Kd value of EGF receptor (EGFR) and BTC is 0.5 nM as determined on Balb/c 3T3 cells. In addition, human mammary carcinoma MDA-MB-453 cells, which express multiple members of the EGFR family, were found to possess 2.7 x 10(3) BTC binding sites/cell, and the binding was readily quenched by EGF. These results suggest that the primary receptor for BTC is EGFR.

3T3 Cells↗
PubMed1994

Pituitary adenylate cyclase activating polypeptide is an extraordinarily potent intra-pancreatic regulator of insulin secretion from islet beta-cells.

Insulin secretion from pancreatic islets is controlled by peptides as well as by nutrients. We report here a novel, extraordinarily potent peptidergic regulation of insulin secretion. A 27-residue form of pituitary adenylate cyclase activating polypeptide (PACAP27) as low as 10(-14) to 10(-13) M stimulated insulin release from rat islets in a glucose-dependent manner. PACAP27 also increased cytosolic free Ca2+ concentration ([Ca2+]i) in islet beta-cells. Nitrendipine, a blocker of the L-type Ca2+ channel, abolished both [Ca2+]i and insulin responses. Vasoactive intestinal peptide, a peptide exhibiting 68% amino acid homology with PACAP, also increased [Ca2+]i in beta-cells but only at concentrations in the nanomolar range, indicating that PACAP27 is 4 logs more potent. A 38-residue form of the peptide (PACAP38) stimulated insulin release and increased beta-cell [Ca2+]i in a manner similar to that of PACAP27. PACAP-like immunoreactivity was demonstrated in pancreatic nerve fibers, islets, and capillaries. The results indicate that PACAP is a physiologically occurring peptide in pancreas and that PACAP, in a glucose-dependent manner, activates beta-cells presumably via a high affinity PACAP-selective receptor, raises [Ca2+]i by increasing the activity of L-type Ca2+ channels, and consequently stimulates insulin release. PACAP appears to be by far the most potent insulinotropic peptide known.

Animals↗
PubMed1994

The effect of dam's strain on the intrauterine craniofacial growth of mouse fetuses.

PURPOSE: The maternal effect is one of the important factors in mammalian growth in conjunction with the genetic effect. The present study investigated the prenatal maternal effect of a dam on the intrauterine craniofacial growth of a mouse fetus using embryo transfer and cephalometry. DDD/Qdj strain mouse embryos were transferred to four strains of recipient female mice (DDD/Qdj, C3H/Qdj, C57BL/Qdj, and DBA/1J Sea). Just after parturition cephalometric observation of the newborn offspring, which developed in the uteri of the four strains of dams, was performed and then the craniofacial size of the newborn offspring was calculated on the lateral cephalogram. Statistical analyses were performed to examine the correlation between the dam's weight and the craniofacial size of the newborn offspring, to test the significance of the effect of the dam's strain on the craniofacial size of the newborn offspring, and to evaluate the interstrain difference of the intrauterine craniofacial growth of the mouse fetuses. RESULTS: It was disclosed that there were a direct relation between the dam's weight and the craniofacial size of the newborn offspring, a significant effect of the dam's strain on the craniofacial size of the newborn offspring, and a significant interstrain difference in the craniofacial size of the newborn offspring after eliminating the effects of litter size and gestation period on the craniofacial size of the newborn offspring (DDD/Qdj > C3H/Qdj = C57BL/Qdj > DBA/1J Sea). CONCLUSION: Thus, it could be concluded that the four strains of dams affected differently the intrauterine craniofacial growth of the DDD/Qdj strain fetuses through each uterine condition, indicating that the dam's weight played an important role as one of the prenatal maternal effects on the intrauterine craniofacial growth of mouse fetuses.

Animals↗
PubMed1994

Immunohistochemical evidence for the presence of nerve fibres with substance P- or calcitonin gene-related peptide-like immunoreactivity in the proliferating epithelium in the developing teeth of rats.

By immunohistochemistry using the avidin-biotin peroxidase complex method, nerve fibres with substance P- or calcitonin gene-related peptide (CGRP)-like immunoreactivity (IR) were examined in the dental lamina, cells external to the reduced ameloblasts and oral epithelium in the developing upper first molars of postnatal rats. At birth, very few varicosities with substance P- or CGRP-IR were found in the dental lamina over the mesial cusp of the dental germ. In 5-day-old rats, nerve fibres with substance P- or CGRP-IR in the dental lamina over the mesial cusp gradually increased in number. In 7-day-old rats, over the mesial portion of the dental germ, the oral half of the dental lamina began to thicken on the buccopalatal side, in which many nerve fibres with substance P- or CGRP-IR were observed. A few nerve fibres began to penetrate the cells external to the reduced ameloblasts over the middle buccal cusp. In 10-day-old rats, the oral epithelium over the mesial cusp gradually thickened, and nerve fibres with substance P- or CGRP-IR were found especially in its basal layer. In 13-15-day-old rats, a great many nerve fibres with substance P- or CGRP-IR were distributed all over the fused, thickened dental lamina and cells external to the reduced ameloblasts proliferated over the middle and distal cusps. Nerve fibres with substance P- or CGRP-IR formed a plexus in the thickened oral epithelium, which spread to the mesiopalatal end of the mesial cusp.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Use of a CT simulator in radiotherapy treatment planning for breast conserving therapy.

A CT simulator (CT-S) is a real-time, CT-linked, 3-D treatment planning system, which consists of a CT scanner, a multi-image display, a treatment planning device with real-time visual optimization, and a laser beam projector. This system was clinically evaluated in 339 Stage 0, I and II breast cancers in 337 patients who received breast conserving therapy. Following quadrantectomy or wide excision with complete axillary dissection, a total of 50 Gy was delivered to the ipsilateral breast using 60Co gamma-rays. In patients with involved surgical margins, boost electron irradiation was also given. Treatment planning could be accomplished within 40-50 min using the CT-S. The parameters for the tangential portals could be optimized for each patient, and the wedge filters and the electron energy for boost irradiation could be appropriately selected. The incidence of moist desquamation and depigmentation at the areola was slightly decreased with the use of wedge filters. During the follow-up for 2-71 months (median, 22 months), local recurrence and symptomatic radiation pneumonitis occurred in one patient each. The CT-S appears to be useful for the individualized optimization of tangential irradiation fields in breast conserving therapy.

Adult↗
PubMed1994

Decreased collagenase expression in cultured systemic sclerosis fibroblasts.

One cause of the excessive deposition of collagen in systemic sclerosis is thought to be abnormal functioning of fibroblasts. The purpose of this study is to determine whether there is decreased expression of collagenase in systemic sclerosis fibroblasts. In this study, we analyzed collagen and collagenase expression in dermal fibroblasts derived from eight patients with systemic sclerosis and compared the findings with those from nine sex- and age-matched healthy subjects. Increased collagen synthesis accompanying enhanced mRNA levels was observed in two of eight strains, whereas all eight strains showed remarkable decreases in collagenase activity and production. There were no differences in the levels of collagenase mRNA between the systemic sclerosis strains and the normal strains. Results suggest that decreased collagenase expression is a characteristic of systemic sclerosis fibroblasts, and both increased collagen expression and decreased collagenase expression in systemic sclerosis fibroblasts may result in the excessive accumulation of collagen in patients with systemic sclerosis. It is also suggested that decreased collagenase expression is altered at translational and/or post-translational levels.

Adult↗
PubMed1994

Genetic variation in experimental dental caries in four inbred strains of rats.

The relative contribution of the host genetic effect on the susceptibility to dental caries was examined. Four inbred strains of male rats (BN/Sea, F344/Ms, PVG/cSea, and WKA/Sea) were inoculated with Streptococcus mutans and fed a cariogenic diet. The caries scores of the molar teeth were compared among these four strains, and the degree of genetic determination was estimated by analysis of variance. Statistically significant differences in caries scores were found among these strains (F344 > WKA > PVG/c > BN), and a high degree of genetic determination was obtained.

Analysis of Variance↗