Biomedical subjects

Y Takahama

Publications and source records attributed to Y Takahama.

At least 19 recordsLinked to original sources

PubMed1992

Post-transcriptional regulation of early T cell development by T cell receptor signals.

During differentiation in the thymus, immature T cells progress through an ordered sequence of developmental stages that are best characterized by variable expression of the co-receptor molecules CD4 and CD8. Crosslinking of T cell receptor (TCR) molecules on precursor thymocytes was found to block their differentiation into CD4+CD8+ cells by eliminating messenger RNA's encoding two families of developmentally important molecules: the co-receptor molecules CD4 and CD8 and the recombination activating genes 1 and 2. TCR-induced post-transcriptional regulation in early thymocytes was specific for selective messenger RNA's, required protein synthesis, and was itself developmentally regulated. These data identify a post-transcriptional mechanism that is influenced by TCR signals and that regulates early thymocyte development.

Animals↗

PubMed1992

Negative selection of precursor thymocytes before their differentiation into CD4+CD8+ cells.

Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation.

Animals↗

PubMed1992

Characterization of a murine monoclonal antibody, 5D-4, reacting with pancreatic cancers and islets of Langerhans.

A murine monoclonal antibody (5D-4) was prepared by immunizing mice ip with human pancreatic cancer cell line (AsPC-1). The 5D-4 MAb reacted immunohistochemically with pancreatic and gastrointestinal tract tumors as well as pancreatic islets, and to a less extent with normal tissues. The 5D-4 MAb reacted not only with ca 50 KDa and 30 KDa solubilized protein from AsPC-1 cells by Western blot analysis but also with human insulin in a competition RIA. Double immunoperoxidase staining showed that the 5D-4 MAb cross-reacted with insulin but did not react with glucagon, somatostatin or pancreatic polypeptide. Immunoelectron micrograph of Langerhans island double-stained with the 5D-4 MAb and anti-insulin Ab revealed that the 5D-4 Mab recognized human insulin and ca 50 KDa and 30 KDa antigens in B-cells of islets of Langerhans. Thus, the 5D-4 Mab may be useful for the diagnosis of islet cell tumors as well as pancreatic cancers.

Animals↗

PubMed1992

Long-term occlusal guidance of a severely intoxicated patient with yusho (PCB poisoning): a case report.

The peculiar dentoorofacial characteristics and 12 years of interdisciplinary management of a patient who was severely intoxicated with the man-made chemical polychlorinated biphenyls (PCBs) are described in this case report. Cephalometric measurements showed that the SNA and SNB angles were reduced but that the developments in height and skeletal maturity were in normal ranges. Gingival hyperpigmentation that was caused by high blood PCB concentration was extremely slow to fade. A cystic mass, diffused trabeculae, and irregular calcification, which were shown on the radiograph and which were caused by high blood levels of PCB, changed gradually. However, the patient had periodontal disease because of horizontal alveolar bone resorption and a deep periodontal pocket, despite good plaque control. After the PCB poisoning the tooth roots were hypoplastic and dilacerated. One root was extracted because of chronic periodontitis. Some teeth were impacted, malposed, or ankylosed.

Adolescent↗

PubMed1992

Maxillary lateral incisor of subjects with cleft lip and/or palate: Part 1.

As a pilot study, dental casts of 30 patients with unilateral cleft lip and palate were selected and examined from the longitudinal data in the Department of Orthodontics, Kyushu University Dental Hospital. Dental casts of the anterior teeth were sectioned at right angles to the long axis of the tooth 2 to 3 mm below the incisal edge. The teeth were differentiated according to their cross sections. They were classed as lateral incisors or other types by the ratio of labiolingual diameter to mesiodistal diameter and the flatness labiolingually. Dental casts of 309 additional patients with cleft alveolus were examined subjectively based on above findings. In primary dentition, 183 of 184 teeth on the cleft side were incisal type. One tooth was canine type. In permanent dentition, 42 of 78 teeth on the cleft side were conical type, 20 teeth were intermediate type, and 16 teeth were incisal type. As a conclusion, the tooth on the cleft side is almost certain to be a lateral incisor, not a supernumerary canine tooth. As well, their form was normal in the majority of the primary dentition, but malformed in the permanent one.

Alveolar Process↗

PubMed1992

Maxillary lateral incisors of subjects with cleft lip and/or palate: Part 2.

Maxillary lateral incisors on the alveolar cleft were investigated in 431 cleft children registered in the Department of Orthodontics, Kyushu University Dental Hospital. The majority of primary maxillary lateral incisors were located on the distal side of the alveolar cleft in both unilateral cleft lip and alveolus (UCLA) and unilateral cleft lip and palate (UCLP) subjects. Permanent teeth in UCLA tend to be located distally, but in UCLP they tend to be congenitally absent (p less than .01). The majority of primary teeth had normal shapes; the majority of permanent teeth were of intermediate type or were missing congenitally. One third of the UCLA and one half of the UCLP subjects who had primary maxillary lateral incisors were not followed by permanent replacements. The location of the majority of permanent maxillary lateral incisors tallied with that of the primary ones except in four UCLA, ten UCLP, and two bilateral cleft lip and palate (BCLP) subjects. Four UCLA and ten UCLP subjects who had primary lateral incisors on the distal side were followed by their permanent successors on the mesial side. Three UCLP and one BCLP subjects had permanent maxillary lateral incisors even though they had no temporary predecessors.

Adolescent↗

PubMed1991

Expression of an unusual T cell receptor (TCR)-V beta repertoire by Ly-6C+ subpopulations of CD4+ and/or CD8+ thymocytes. Evidence for a developmental relationship between Ly-6C+ thymocytes and CD4-CD8-TCR-alpha beta+ thymocytes.

A novel thymocyte subpopulation expressing an unusual TCR repertoire was identified by high surface expression of the Ly-6C Ag. Ly-6C+ thymocytes were distributed among all four CD4/CD8 thymocyte subsets, and represented a readily identifiable subpopulation within each one. Ly-6C+ thymocytes express TCR-alpha beta, arise late in ontogeny, and appear in the CD4/CD8 developmental pathway after birth in a sequence that resembles that followed by conventional Ly-6C- cells during fetal ontogeny. Most interestingly, adult Ly-6C+ thymocytes express an unusual TCR-V beta repertoire that is identical to that expressed by CD4-CD8-TCR-alpha beta+ thymocytes in its overexpression of TCR-V beta 8 and in its expression of some potentially autoreactive TCR-V beta specificities. This unusual TCR-V beta repertoire was even expressed by Ly-6C+ thymocytes contained within the CD4+ CD8- 'single positive' thymocyte subset. Thus, expression of this unusual TCR-V beta repertoire is not limited to CD4-CD8-thymocytes, and is unlikely to be a consequence of their double negative phenotype. Rather, we think that Ly-6C+TCR-alpha beta+ thymocytes and CD4-CD8-TCR-alpha beta+ are developmentally interrelated, a conclusion supported by several lines of evidence including the selective failure of both Ly-6C+ and CD4-CD8-TCR-alpha beta+ thymocyte subsets to appear in TCR-beta transgenic mice. In contrast, peripheral Ly-6C+ T cells are developmentally distinct from Ly-6C+ thymocytes in that peripheral Ly-6C+ T cells expressed a conventional TCR-V beta repertoire and developed normally in TCR-beta transgenic mice in which Ly-6C+ thymocytes failed to arise. We conclude that: 1) expression of a skewed TCR-V beta repertoire is a characteristic of Ly-6C+TCR-alpha beta+ thymocytes as well as CD4-CD8-TCR-alpha beta+ thymocytes, and is not unique to thymocytes expressing neither CD4 nor CD8 accessory molecules; and 2) Ly-6C+ thymocytes are developmentally linked to CD4-CD8-TCR-alpha beta+ thymocytes, but not to Ly-6C+ peripheral T cells. We suggest that Ly-6C+TCR-alpha beta+ thymocytes are not the developmental precursors of Ly-6C+ peripheral T cells, but rather may be the developmental precursors of CD4-CD8-TCR-alpha beta+ thymocytes.

Age Factors↗

PubMed1991

Phenotype, ontogeny, and repertoire of CD4-CD8- T cell receptor alpha beta + thymocytes. Variable influence of self-antigens on T cell receptor V beta usage.

We have characterized CD4-CD8- double negative (DN) thymocytes that express TCR-alpha beta and represent a minor thymocyte subpopulation expressing a markedly skewed TCR repertoire. We found that DN TCR-alpha beta + thymocytes resemble mature T cells in that they (a) are phenotypically CD2hiCD5hiQa2+HSA-, (b) appear late in ontogeny, and (c) are susceptible to cyclosporin A-induced maturation arrest. In addition, we found that DNA sequences 5' to the CD8 alpha gene were demethylated relative to their germline state, suggesting that DN TCR-alpha beta + thymocytes are derived from cells that had at one time expressed their CD8 alpha gene locus. Because DN TCR-alpha beta + thymocytes are known to express an unusual TCR repertoire with significant overexpression of V beta 8, we were interested in examining the possible role played by self-Ag in shaping their TCR repertoire. It has been suggested that DN TCR-alpha beta + thymocytes are derived from potentially self-reactive thymocytes that have escaped clonal deletion by down-regulating their surface expression of CD4 and/or CD8 determinants. However, apparently inconsistent with such an hypothesis, we found that the frequency of DN thymocytes expressing various anti-self TCR (V beta 6, V beta 8.1, V beta 11, V beta 17a) were not increased in strains expressing their putative self-Ag, but instead were either unaffected or significantly reduced in those strains. With regard to V beta 8 expression among DN TCR-alpha beta + thymocytes, V beta 8 overexpression in DN TCR-alpha beta + thymocytes appeared to be independent of, and superimposed on, the developmental appearance of the basic DN thymocyte repertoire. Even though V beta 8 overexpression appeared to be generated by a mechanism distinct from that generating the rest of the DN TCR-alpha beta + thymocyte repertoire, we found that super-Ag against which V beta 8 TCR react introduced into the neonatal differentiation environment also significantly reduced, rather than increased, the frequency of DN TCR-alpha beta + V beta 8+ thymocytes. Thus, the present study is consistent with DN TCR-alpha beta + thymocytes being mature cells derived from CD8+ precursors, and documents that their TCR repertoire can be influenced, at least negatively, by either self-Ag or Ag introduced into the neonatal differentiation environment. However, we found no evidence to support the hypothesis that DN TCR-alpha beta + thymocytes are enriched in cells expressing TCR reactive against self-Ag.

Aging↗

PubMed1991

Relationship between tongue volume and lower dental arch sizes.

The interrelation between the tongue volume and the lower dental arch sizes (arch width and area) was studied by the original methods that we developed. A plane perpendicular to the occlusal plane and 40 mm posterior to the lower incisal point was taken as the posterior border of the tongue and the arch. The tongue volume and the lower dental arch sizes were measured anterior to this border with plaster models. The correlations between the parameters obtained from 74 Japanese adults (37 men and 37 women) with normal occlusion were statistically analyzed. The results showed that (1) both the mean tongue volume and the mean lower dental arch sizes were significantly larger in men than in women; (2) the tongue volume and the lower dental arch sizes were significantly correlated; and (3) these correlations tended to be higher at the more posterior part of the dental arch.

Adult↗

PubMed1991

Parental data used to predict growth of craniofacial form.

The sample for this study consisted of 250 families. From 850 lateral and posteroanterior cephalograms, 81 variables from the X, Y coordinates of 67 landmarks were calculated and matched with the normal distribution. Principal component analysis was used to summarize these 81 variables in proper factor scores. The craniofacial patterns of 500 adults were classified by cluster analysis on the basis of those factor scores. This study introduced the concept of "similar parent" and "dissimilar parent" instead of the father and mother equally. Finally, the following model for predicting the individual growth of craniofacial characters was obtained. The predicted value Y(t) [formula: see text] is the logistic curve used in growth studies, C1X(s) is for the similar parent of a child, and C2X(d) is for the dissimilar parent. Multiple regression functions were calculated for both sexes in each of four craniofacial patterns. The errors of prediction at the average age of 18 years from the data at the average age of 11.6 years were 1.12, 2.88, 2.87, 3.14, and 1.93 mm for the respective distances S-N, N-Me, S-Me, Gn-Cd, and G-G'. These errors in our growth prediction are much smaller than in ordinary normal facial diagrams and may be considered negligible for orthodontic clinical application.

Adolescent↗

PubMed1991

The dimensions of the tongue in relation to its motility.

To obtain basic information about the motility and dimensions of the tongue, the tongue volume was measured and the change in its length and location was noted while the tongue was undergoing protrusion, and then the relationships among those parameters were examined statistically. The tongue was measured at rest from the tip to a point 40 mm posterior corresponding to a plane connecting the lower permanent second molars. The subjects were 100 Japanese men and women. It was found that (1) maximum protrusion of the tongue is accomplished by two functions combined--a forward movement and a longitudinal stretching; the volume of the tongue was significantly correlated with its stretching. (2) The mean length of the tongue in the most protruded position was about 20% longer than its length in the resting position; it was stretched most in the segment from 1 to 2 cm posterior to its tip. (3) The mean tongue volume was 25.3 cm3 in men and 22.6 cm3 in women, a statistically significant sex difference; the volume was about 12% larger in men than in women. (4) There was no correlation between the tongue volume and the length of the most extraorally protruded tongue. The results suggested that the volume of the tongue can be estimated from the stretched length of the tongue in the most protruded position, if it is measured properly.

Adult↗

PubMed1991

Rapid growth and spontaneous metastasis of human germinal tumors ectopically transplanted into scid (severe combined immunodeficiency) and scid-nudestreaker mice.

Xenograft acceptance, growth and spontaneous metastasis of ectopically transplanted human germinal tumors were compared among scid mice, athymic nude mice and F2 hybrids constructed from scid and nude mice, in relation to the impairments of T and B cell functions in these mice. In scid mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) that originated from the ovary grew to enormous sizes in 100% of the animals after both subcutaneous and intraperitoneal transplantation, while only half (59.1% and 51.9%) of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice (BALB/c-nu/nu and CD1-nu/nu). The YST-2 grew rapidly in scid mice, developing 3 to 10 times larger tumors compared to nude-streaker (AKR/J-nustr/nustr) and usual nude mice, respectively. Furthermore, ectopically transplanted tumors spontaneously metastasized to distant organs (mostly to the lung) in scid mice (but less frequently in leaky scid mice), while metastases have never been found in nude mice. Although a xenograft of human classic (typical or pure) seminoma of the testis has never been established in nude mice, it grows slowly in one-third (36.4%) of scid mice and very rapidly in all of scid-nustr (scid/scid; nustr/nustr) double mutant mice. Spontaneous metastases of xenografted seminomas were also observed in distant organs (lymph node, lung, liver, spleen, and kidney). The metastastic distribution of the two human germinal tumors in scid and scid-nustr mice mimics that found in human. These results (xenograft acceptance, growth of transplanted tumors and degree of metastatic spread) were compatible with the level of T and B cell impairments indicated by FACS analysis, as well as mitogen responses, serum IgG and morphological features of the thymus.

Animals↗

PubMed1991

Management and subsequent 13-year progress of a mandibular fracture with malocclusion in a child--case report.

Under acute conditions, maxillofacial injuries may be treated without the opportunity for an assessment of occlusal irregularities, even when there are mandibular fractures, because life-threatening injuries have priority over occlusion. Consequently, mandibular fractures may result in post-trauma malocclusion and facial deformity. The case history reported is of a male patient who had been involved in a traffic accident in childhood and suffered mandibular fractures. The initial incomplete management resulted in persistent deformation of the mandible, disturbance of dental occlusion and difficulty in mastication. These irregularities were corrected during childhood by non-operative orthodontic treatment. When the patient reached adulthood, some permanent teeth were malformed because the fractures had damaged some tooth germs. However, the permanent dentition in general was almost normal as a result of the corrected primary dentition. Although the alveolar deformity due to the injury remained, the mandibular base was satisfactorily remodelled. The case reported supports the view that early restoration of normal dental occlusion before the eruption of permanent teeth contributes to the establishment of good functional dental occlusion of the permanent teeth.

Adolescent↗

PubMed1990

Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide.

The present study has examined a functional role of Ia molecules expressed on murine B cells in polyclonal B cell differentiation induced by lipopolysaccharide (LPS). Reverse, IgM PFC responses of unprimed B cells induced by LPS in the apparent absence of T cells and adherent accessory cells were markedly inhibited in a haplotype-specific manner by Fab monomer fragment of anti-class II (Ia) but not anti-class I MHC monoclonal antibody (mAb). However, the degree of inhibition of LPS responses of H-2-heterozygous F1 B cells expressing both parental I-A products by either one of anti-I-A mAb was at best half that of the parental B cells. Interestingly, when (B10 x B10.-BR)F1 (H-2b/k) B cells were fractionated into adherent and nonadherent populations by their ability to bind to parental B10 B cell monolayers, LPS responses of F1 B cells adherent to and nonadherent to the B10 B cell monolayers were selectively inhibited by anti-I-Ab and anti-I-Ak mAb, respectively. These results suggest that LPS-responsive F1 B cells comprise at least two separate populations with restriction specificity for only one of the parental I-A products expressed on B cells. In addition, it was demonstrated that the I-A-restriction specificity of LPS-responsive B cells is "plastic" and determined by H-2-genotype of bone marrow cells present during B cell ontogeny but not by that of radiation-resistant host elements. Namely, the LPS responses of B10-derived B cells from (B10 + B10.BR) (H-2b x H - 2k)F1 radiation bone marrow chimeras but not from B10 (H-2b x H-2k)F1 chimeras became sensitive to the inhibition of anti-I-Ak mAb in the presence of mitomycin C-treated I-Ak-positive B cells, supporting a notion of receptor-Ia molecules interactions rather than like-like interactions. Thus, the present results provide evidence indicating that B-B cell interaction via recognition of self-I-A products is a crucial event in the polyclonal B cell differentiation induced by LPS.

Animals↗

PubMed1990

B-B cell interaction involved in polyclonal B cell activation is restricted by I-A but not by I-E molecules.

We have previously demonstrated that the class II MHC restricted B-B cell interaction is involved in the polyclonal differentiation of unprimed murine B cells into IgM-producing cells induced by a T cell-derived lymphokine B151-TRF2 or bacterial LPS. The present study has addressed the question of whether I-A and/or I-E molecules function as restriction elements for the B-B cell interaction. The results revealed that (B10 x B10.BR)F1(H-2b/k) B cells could be separated into I-Ab- and 1-Ak-restricted subpopulations by their ability to bind to B10(H-2b) or B10.BR(H-2k) B cell monolayers, whereas an I-E-restricted F1 B cell population was not obtained. Moreover, B10-derived B cells isolated from (B10 + B10.BR) - (B10 x B10.BR)F1 but not from B10 - (B10 x B10.BR)F1 radiation-induced bone marrow chimeras acquired newly the ability to co-operate with mitomycin C-treated auxilary B cells expressing I-Ak but not I-Ek molecules. Thus, these results indicate that I-E molecules, unlike I-A molecules, do not serve as restriction elements for the B-B cell interaction, and that I-A and I-E molecules on B cells play functionally disparate roles in the activation of polyclonal B cells.

Animals↗

PubMed1990

SCID (severe combined immunodeficiency) mice as a new system to investigate metastasis of human tumors.

In severe combined immunodeficiency (scid) mice which are deficient in T and B cell functions, human yolk sac tumor (YST-2) grew rapidly to enormous sizes in all of the animals after both subcutaneous and intraperitoneal transplantation, while only half of the subcutaneous and none of the intraperitoneal transplants were accepted in usual athymic nude mice. Furthermore, transplanted tumors metastasized spontaneously to distant organs such as lung, liver, kidney, pancreas, and spleen in scid mice, while metastases were not found in athymic nude mice. Similar results were observed in scid mice and scid-nude (streaker) double mutant mice with human classic (typical) seminoma which has been neither transplantable nor metastatic in athymic nude mice. Thus, scid mice provide an invaluable experimental system to investigate the mechanism of metastasis which is the most important and life-threatening problem in cancer patients.

Animals↗

PubMed1989

Disparate functions of I-A and I-E molecules on B cells as evidenced by the inhibition with anti-I-A and anti-I-E antibodies of polyclonal B cell activation.

Polyclonal differentiation of unprimed B cells into IgM-producing cells induced by lipopolysaccharide (LPS) or T cell-derived lymphokine B151-TRF2 has been shown to contain a process of I-A-restricted B-B cell interaction, so that the B cell responses are inhibited by monoclonal antibodies (mAb) specific for I-A molecules. On the other hand, the B cell responses are also inhibited by anti-I-E mAb, although I-E molecules are not involved in such B-B cell interaction. In this study, we examined the mechanism underlying the anti-I-E-mediated inhibition of the B cell responses. The B cell responses induced by LPS or B151-TRF2 were inhibited by either anti-I-A or anti-I-E mAb added on day 0 over a 5-day culture period, whereas when added on day 3 the responses were inhibited only by anti-I-E mAb and not by anti-I-A mAb. To gain insight into the mechanism underlying the anti-I-E-mediated inhibition, we prepared monovalent Fab and divalent F(ab')2 fragments of anti-I-A and anti-I-E mAb and examined their effects on the B cell responses. We found that the B cell responses were inhibited by the F(ab')2 but not Fab fragment of anti-I-E mAb, whereas the Fab fragment of anti-I-A mAb still gave effective inhibition. The F(ab')2 but not Fab fragment of anti-I-E mAb induced increases in cyclic AMP (cAMP) levels in B cells, whereas the undigested anti-I-A mAb did not induce such increases. Furthermore, adenylate cyclase inhibitors, which inhibit cellular cAMP accumulation, circumvented the B cell responses inhibited by anti-I-E but not anti-I-A mAb. Thus, these results indicate that the anti-I-E-mediated inhibition of the B cell responses requires increases in intracellular cAMP levels induced by cross-linking of I-E molecules. In contrast, anti-I-A mAb inhibits the B cell responses without cross-linking of I-A molecules and cAMP accumulation. These results reinforce a unique function of I-A molecules as restriction elements in the Ia-restricted B-B cell interaction.

Animals↗

PubMed1989

Periodontal changes after experimentally induced intrusion of the upper incisors in Macaca fuscata monkeys.

We are studying the biologic aspects of vertical movement of teeth, which are often used in orthodontic treatment involving variations in alveolar tissue. In the present study, the four upper incisors of five infant Macaca fuscata monkeys were intruded vertically from 1.1 to 5.5 mm. The following effects were examined: (1) movement of the gingiva, (2) change in the depth of the gingival sulcus, and (3) microscopic effects on the alveolar tissue. The results were as follows. (1) The gingiva moved in the same direction that the teeth were intruded, but only about 60% as far. (2) The clinical crown shortened and the gingival sulcus deepened. The shortening of the crown and the deepening of the sulcus were both approximately 40% as much as the tooth intrusion. (3) There was no inflammation or swelling microscopically in the gingiva of either the experimental animals or the controls. (4) The epithelium was always attached in the cementoenamel junction, even when the tooth was intruded. As the tooth intrusion was increased, the dentoperiosteal fiber (DPF) and the dentogingival fiber (DGF) terminating in the cementum gradually parted from it; when the tooth was intruded more than 5.0 mm, few fibers terminated in the cementum. It was concluded that the gingival sulcus deepened with horizontal tooth intrusion because of an accumulation of gingival tissue applied with good oral hygiene--not because of swelling around the gingival margin or apical movement of the gingival pocket--and the DPF and the DGF were parted from the cementum gradually as the tooth intrusion increased.

Animals↗