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Biomedical subjects

S Iwasaki

Publications and source records attributed to S Iwasaki.

At least 19 recordsLinked to original sources

Ultrastructural study of the keratinization of the dorsal epithelium of the tongue of Middendorff's bean goose, Anser fabalis middendorffii (Anseres, Antidae).

BACKGROUND: Comparative studies of ultrastructural features of tongues allow deductions to be made about relationships between structure and function, as reflected by an animal's feeding habits. The present study was performed to serve as a basis for further studies of avian feeding mechanisms and of relationships between the fine structure of the lingual epithelium and the development of the expression of keratins. METHODS: The light microscope, scanning electron microscope, and transmission electron microscope were used. RESULTS: The dorsal surface of the tongue of Middendorff's bean goose, Anser fabalis middendorffii, has a distinctive anterior region that extends for five-sixths of its length and has a clear posterior region. The anterior region, when observed macroscopically and by scanning electron microscopy, is distinguished along its forward half by a clear median line. The back half of the anterior region has an indistinct median sulcus in some parts. There are no lingual papillae on the entire dorsal surface of the anterior and posterior regions. Giant conical papillae are located in a transverse row between the anterior and posterior regions. On both lateral sides of the anterior region for five-sixths of the length of the tongue, lingual hairs are compactly distributed, and small numbers of large cylindrical papillae are arranged at almost regular intervals between these lingual hairs. Examination of the dorsal lingual epithelium by light and transmission electron microscopy provided histological and cytological criteria for distinguishing the anterior and posterior regions, both of which were composed of stratified squamous epithelium. Basal cells were similar throughout the dorsal epithelium. The intermediate layer of cells in the anterior region contained numerous tonofibrils in electron-dense bundles composed of tonofilaments of 10 nm in diameter. The outer layer was composed of electron-dense, well-keratinized cells, with layers of electron-lucent cells on the outermost surface. The cells in the intermediate layer in the posterior region of the tongue were almost completely filled with unbundled tonofilaments. The surface layer exhibited features of parakeratinization. In all of the giant conical papillae, the large cylindrical papillae, and the lingual hairs, the epithelium was strongly keratinized. CONCLUSIONS: The three-dimensional microanatomy and cytological features of the dorsal lingual epithelium of avians seem to be related to the functional role and shape of the tongue of each species in feeding.

Age Factors

Interaction of arenastatin A with porcine brain tubulin.

Arenastatin A, isolated from the Okinawan marine sponge Dysidea arenaria, is an antimitotic depsipeptide containing a 16-membered ring. Interaction of the compound with tubulin was investigated by the use of [3H]arenastatin A and other microtubule disruptors. Scatchard analysis indicated the presence of one binding site for arenastatin A per tubulin heterodimer with a dissociation constant (Kd) of 1.8 x 10(-6) M. Rhizoxin was a competitive inhibitor of arenastatin A binding, and vinblastine also inhibited arenastatin A binding in a partially competitive manner. Arenastatin A had no inhibitory effect on colchicine binding to tubulin.

Animals

Photoaffinity labeling of tumor promoter-binding protein (CN-TPBP) and preparation of affinity sorbent gels.

Cytosolic-nuclear tumor promoter-specific binding protein (CN-TPBP) was photoaffinity-labeled with a specific ligand, 3beta,5alpha-dihydroxycholestan-6-one (YS-64). Analysis by ODS-HPLC of peptide fragments obtained from the labeled CN-TPBP by trypsinization indicated the existence of a single specifically labeled site. Affinity gels for the purification of CN-TPBP were then prepared. As ligands for the affinity gels, 12-O-tetradecanoylphorbol 13-acetate (TPA), a typical phorbol-type tumor promoter, and benzolactam-V8-310 (BL-V8-310), a structural/biological mimic of teleocidin-class tumor promoters, were adopted. The use of these gels afforded a protein that showed a single band of 58 kDa on SDS-PAGE.

Affinity Labels

Effects of arenastatin A and its synthetic analogs on microtubule assembly.

Inhibition of microtubule assembly by arenastatin A (1) and five synthetic analogs (3-7) was examined. Arenastatin A and the triamide 6 showed potent and moderately strong inhibitory activities, respectively (IC50; 2.3 microM for 1, 7.8 microM for 6) and also depolymerized preformed microtubules. The other analogs tested showed no activity.

Animals

The role of a hydroxyl radical scavenger (nicaraven) in recovery of cardiac function following preservation and reperfusion.

We investigated the efficacy in reducing myocardial preservation and reperfusion (P/R) injury of direct hydroxyl radical scavenging by nicaraven as compared with scavenging of both superoxide radicals and hydrogen peroxides by superoxide dismutase (SOD) and catalase (CAT), respectively. Isolated rat hearts were mounted on a Langendorff (L) apparatus to estimate the baseline aortic flow (AF), coronary flow (CF), cardiac output (CO), systolic pressure (SP), aortic mean pressure (MP), rate pressure product, and LV dp/dt. They were divided into 3 groups: group 1, 12 hr storage in HTK solution; group 2, 12 hr storage in HTK solution containing 2.5x10(5) U/L SOD and 2x10(5) U/L mg/L CAT; and Group 3, 12 hr storage in HTK solution containing 10(-3) M nicaraven. SOD, CAT, and nicaraven were administered intraperitoneally before harvesting. Hearts were stored in each preservation solution at 4, and then reperfused. Postpreservative function and concentrations of leaked enzymes were measured. The hearts were switched back to the L-mode and paced at 330 beats/min. CF following perfusion with Krebs-Henseleit bicarbonate buffer (KHB) solution containing 10(-6) M 5-hydroxytryptamine (5-HT) or 10(-5) M nitroglycerin (NTG) then evaluated. The myocardial water content also was measured. The recovery of CF, CO, SP, MP, and LV dp/dt was significantly greater in group 3 than in group 1. The recovery of CF was superior to that in group 2 (P<0.05). There were no significant differences in the recovery of cardiac function between groups 1 and 2. 5-HT caused a decrease in CF in each group, however, CF in group 3 was higher than that in group 1 (P<0.05). NTG caused no significant differences among the groups. There were no significant differences in leaked enzymes and myocardial water content among the three groups. These results suggest that nicaraven protects against myocardial P/R injury through its hydroxyl radical scavenging activity, and that therapy with oxygen-free radical scavengers should be directed toward inactivation of hydroxyl radicals rather than superoxide radicals and/or hydrogen peroxides.

Animals

Cell type-/inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production and its enantio-dependence.

Regulation by thalidomide and phenylphthalimide analogs (FPP-33 and PPS-33) of TNF-alpha production is specific to cell type and to inducer, i.e., (i) the compounds enhance TPA-induced TNF-alpha production by human leukemia HL-60 cells, while they inhibit TPA-induced TNF-alpha production by another human leukemia cell line, THP-1, and (ii) the compounds inhibit TNF-alpha production by both HL-60 and THP-1 cells when the cells are stimulated with okadaic acid (OA). The structure-activity relationships of these compounds are similar in the four assay systems (TPA/HL-60, TPA/THP-1, OA/HL-60, and OA/THP-1). However, optically active analogs, (S)- and (R)-alpha-methylthalidomides, show distinct bidirectional regulatory effects on TNF-alpha production, i.e., only the (S)-form shows TNF-alpha production-enhancing activity in the TPA/HL-60 assay system, while the (R)-form shows much more potent TNF-alpha production-inhibiting activity than the (S)-form in the other assay systems.

HL-60 Cells

Characterization of the bone morphogenetic protein-2 as a neurotrophic factor. Induction of neuronal differentiation of PC12 cells in the absence of mitogen-activated protein kinase activation.

Rat pheochromocytoma PC12 cells are shown to express a single class of high affinity binding sites for bone morphogenetic protein (BMP)-2 (1,300 receptors/cell, Kd = 31.3 pM). Affinity cross-linking using radiolabeled BMP-2 demonstrated the presence of six components with apparent molecular masses of 170, 155, 105, 90, 80, and 70 kDa. BMP-2 induced morphological changes in PC12 cells with the concomitant expression of three neurofilament proteins. Thus, BMP-2 would appear to be another neurotrophic factor that, like nerve growth factor or basic fibroblast growth factor, stimulates the neuronal differentiation of PC12 cells. Unlike nerve growth factor and basic fibroblast growth factor, however, BMP-2 failed to induce the activation of either 41- and 43-kDa mitogen-activated protein (MAP) kinases or the MAP kinase/extracellular signal-regulated kinase kinase (MEK). Also, BMP-2 did not induce the expression of the c-fos gene in PC12 cells. Activin A was also capable of inducing the neuronal differentiation of PC12 cells without activating MAP kinases and MEK. These findings show a clear dissociation between the requirement for the activation of the MAP kinase cascade and the ability of BMP-2 and activin A to induce PC12 cell neuronal differentiation. In addition, these results suggest that the activation of MAP kinases and MEK is not an absolute requirement for PC12 cell differentiation.

Adrenal Gland Neoplasms

Inducer-specific bidirectional regulation by thalidomide and phenylphthalimides of tumor necrosis factor-alpha production.

Regulation by thalidomide [N(alpha)-phthalimidoglutarimide] of tumor necrosis factor (TNF)-alpha production was found to be inducer-specific. Thalidomide enhances TNF-alpha production by human leukemia HL-60 cells induced with 12-O-tetradecanoylphorbol 13-acetate (TPA), while it inhibits TNF-alpha production induced with okadaic acid (OA) in the same cell line. Some phthalimide analogs, included PP-33 [2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione] and its 4,5,6,7-tetrafluora derivative FPP-33), also showed such an inducer-specific bidirectional TNF-alpha production-regulating activity. The structure-activity relationships of the compounds tested are similar, but not identical, in the TPA-stimulated HL-60 and OA-stimulated HL-60 assay systems.

Carcinogens

Fine structure of the dorsal lingual epithelium of the juvenile hawksbill turtle, Eretmochelys imbricata bissa.

BACKGROUND: Various species of turtles are adapted to different environments, such as freshwater, seawater, and terrestrial habitats. Comparisons of histological and ultrastructural features of the tongue of the juvenile Hawksbill turtle, Eretmochelys imbricata bissa, with those of freshwater turtles should reveal some aspects of the relationship between the structure of the lingual epithelium and the environment. METHODS: The light microscope, scanning electron microscope and transmission electron microscope were used. RESULTS: Light microscopy revealed that the mucosal epithelium of the tongue was of the keratinized, stratified squamous type. Under the scanning electron microscope, no lingual papillae were visible on the dorsal surface of the tongue. Micropits and the thickening of cell margins were clearly seen on the surface of cells located on the outermost side. The transmission electron microscope revealed that the cells in the intermediate layer were gradually flattened from the basal side to the surface side, as were their nuclei. In the shallow intermediate layer, the cells were significantly flattened, and their nuclei were condensed or had disappeared. The cytoplasm contained keratohyalin granules, tonofibrils, free ribosomes, mitochondria, and rough endoplasmic reticulum. Numerous free ribosomes were attached to the surface of small keratohyalin granules. The cells of the keratinized layer were significantly flattened, and their nuclei had completely disappeared. Most of cytoplasm was filled with keratin fibers of high electron density. Keratin fibers of the shedding cells, which were located on the outermost side of the keratinized layer, appeared looser, and each fiber, which was somewhat thicker than the tonofibrils and tonofilaments, was clearly distinguishable. CONCLUSIONS: The lingual epithelium of the juvenile Hawksbill turtle differs significantly from that of the adult freshwater turtle, in spite of the similarity in gross morphology of the tongues of these species.

Adaptation, Physiological

Three-dimensional ultrastructure of the surface of the tongue of the rat snake, Elaphe climacophora.

BACKGROUND: Many studies have been performed to clarify the relationship between behavioral performance of the tongue and Jacobson's organ. The purpose of the present study was to examine the ultrastructural features of the surface of the tongue of the rat snake, Elaphe climacophora, and to delineate the functional relationship between the tongue and Jacobson's organ from a morphological perspective. METHODS: The three-dimensional ultrastructure of the surface of the tongue of the rat snake Elaphe climacophora was investigated by scanning electron microscopy. RESULTS: Most of the surface of the bifurcated apex of the tongue was relatively smooth. Dome-shaped, hemispherical bulges or microfacets were compactly arranged on the epithelial cell surface over this entire region. Intercellular borders were clearly recognizable as striations. These features were almost the same as those of the dorsal surface of the transitional area between the bifurcated lingual apex and the anterior part of the lingual body. In the posterior half of the lingual body, no microfacets were seen at all. Both microridges and microvilli were compactly distributed on cell surfaces. CONCLUSIONS: No evidence was obtained from our ultrastructural analysis for an important role of the lingual apex in the vomeronasal system. By contrast, the epithelial surface of the body of the tongue appeared suitable for retaining stimulating compounds.

Animals

Ultrastructural study of the dorsal lingual epithelium of the soft-shell turtle, Trionyx cartilagineus (Chelonia, Trionychidae).

BACKGROUND: The soft-shell turtle, Trionyx cartilagineus, is classified phylogenetically to the family Trionychidae, whose members live in small rivers or ponds. The purpose of the present study was to examine the ultrastructure of the dorsal epithelium of the tongue of the soft-shell turtle and to compare the results of the observations with those reported for the tongue of other freshwater turtles. METHODS: Light microscopy, transmission electron microscopy, and scanning electron microscopy were used to examine the dorsal epithelium of the tongue of the soft-shell turtle. RESULTS: The tongue is triangular with a slightly round apex when viewed dorsally but it appears flattened when viewed laterally. Lingual papillae were visible on the dorsal surface of the tongue with some localized variations. Irregular, dome-shaped or ridge-like papillae were observed on the anterior part of the dorsal lingual surface. Large, cylindrical papillae were located along the midline of the posterior part of the tongue. Low, disk-like papillae were located on both sides of the dorsal surface of the posterior part of the tongue. Taste pores were recognizable in the center of the disk-like papillae. At higher magnification, scanning electron microscopy revealed microridges on the surface of cells located on the outermost side of the anterior part of the tongue, and the thickenings of cell margins were clearly seen. Microvilli were distributed compactly over the entire posterior part of the tongue. Light microscopy revealed that the mucosal epithelium of the anterior part of the tongue was of the keratinized, stratified squamous type, while the mucosal epithelium of the posterior part of the tongue was of the nonkeratinized, stratified cuboidal type. In the latero-posterior part of the tongue, taste buds were recognized. Transmission electron microscopy revealed that the epithelium of the anterior part of the tongue was of a typical keratinized type. Small numbers of keratohyalin granules and membrane-coating granules appeared in the cytoplasm of the shallow intermediate layer. On the apical side of the lingual papillae located on the posterior side of the tongue, cells from the intermediate layer to the surface layer of the non-keratinized epithelium contained many fine, discoidal granules. A large part of the epithelium consisted of mucous cells in the concave area on the posterior side. CONCLUSIONS: The dorsal surface and epithelium of the tongue of the soft-shell turtle differed significantly from those of other freshwater turtles, in spite of the similarity in terms of gross morphology among the tongues of such turtles.

Animals

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure.

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Acute Kidney Injury

Ultrastructural study of the dorsal lingual epithelium of the Asian snail-eating turtle, Malayemys subtrijuga.

The Asian snail-eating turtle, Malayemys subtrijuga, is classified phylogenetically as a member of the family Emydinae. Members of this family usually live in small rivers or ponds. However, this species is relatively well-adapted to terrestrial life. We describe here the light, scanning electron and transmission electron microscopic appearance of the dorsal lingual epithelium of the snail-eating turtle and we compare the results to those obtained from other freshwater turtles in an attempt to clarify the relationship between the histological and ultrastructural differences in the lingual epithelium and the living circumstances of the turtles. The tongue is triangular with a rounded apex when viewed dorsally but it appears flattened when viewed laterally. Under the scanning electron microscope, no lingual papillae were visible on the dorsal surface of the tongue. Instead, plicae were seen all over the dorsal surface. On the surface of the epithelium of the outermost side, dome-shaped bulges, each of which was coincident with an individual cell, were compactly distributed. At higher magnification, scanning electron microscopy revealed numerous microvilli and microridges on the surface of these cells, and the thickening of cell-margins was clearly seen. Light microscopy revealed that the mucosal epithelium of the tongue was of the non-keratinized, stratified squamous type. Under the transmission electron microscope, the cells of the basal and deep intermediate layers of the epithelium appeared irregularly elliptical in shape. The nucleus was large and also irregularly elliptical, lying in the central region of each epithelial cell. The cytoplasm of these cells contained mitochondria, free ribosomes, rough endoplasmic reticulum and bundles of tonofibrils. Cell membranes formed processes around individual cells. Desmosomes were intercalated between the processes of adjacent cells. In the shallow intermediate layer, the cells were also elliptical, and the elliptical nucleus was located in the central area of each cell. A large part of the cytoplasm was occupied by electron-dense, discoid granules. Filamentous structures filled the spaces between these granules. Small numbers of free ribosomes, mitochondria and rough endoplasmic reticulum were scattered in the cytoplasm. Cell membranes still formed processes around cells. Desmosomes were intercalated between the processes of adjacent cells. The cells of the surface layer were still elliptical, as were their nuclei. Most of the cytoplasm was filled with electron-dense, discoid granules. Fine filamentous structures were dispersed between these granules. Cell membranes formed processes around cells which were coincident with microvilli and microridges. Intercalated desmosomes were also seen. In some cells, many of the electron-dense, discoid granules were secreted into the oral cavity. In conclusion, the histology of the lingual epithelium of the snail-eating turtle is very similar to that of the freshwater turtle, reflecting similarities in the gross morphology of the tongues of these species, in spite of the differences in their life styles.

Animals

Histological and ultrastructural study of the lingual epithelium of the juvenile Pacific ridley turtle, Lepidochelys olivacea (Chelonia, Cheloniidae).

Histological and ultrastructural studies ot the dorsal lingual epithelium of the juvenile Pacific ridley turtle, Lepidochelys olivacea, were performed by light and electron microscopy, and the results were compared to those of freshwater turtles in order to clarify the relationship between the histological and cellular differences of the lingual epithelium and the habitat of the turtles. The tongue of the juvenile Pacific ridley turtle is triangular with a round apex when viewed from above, but it appears flattened in lateral view. Scanning electron microscopy (SEM) revealed no lingual papillae on the dorsal surface of the tongue. Instead, transverse plicae are found on the surface of the body and the radix. The surface of the apex is smooth. Microridge-like structures are present on the surfaces of the cells, and the cell margins are thickened. The mucosal epithelium is keratinized, stratified squamous with a relatively thick layer of desquamating cells. Cells of the basal and deep intermediate layers appear elliptical in shape; and their nuclei are elliptical and centrally located. Numerous desmosomes join the processes of adjacent cells; and hemidesmosomes anchor the basal cells to the basal lamina. The cytoplasm of these cells contains mitochondria, free ribosomes, rough endoplasmic reticulum, vacuoles, and bundles of tonofilaments. Cells and their nuclei in the intermediate layer display gradual flattening. In the shallow intermediate layer, the cells are significantly flattened, with nuclei condensed or absent. The cytoplasm contains many tonofibrils or bundles of tonofilaments, free ribosomes and keratohyalin granules, with numerous ribosomes attached to their surfaces. A few collapsed mitochondria are visible. Cell membranes of the shallow intermediate cells are smooth and attached to those of adjacent cells by desmosomes. The keratinized layer is located on top of the shallow intermediate layer, and consists of significantly flattened cells lacking nuclei and filled with keratin fibers. Very fine cellular processes joined by desmosomes are visible. The desquamating cells located on top of the keratinized layer contain keratin fibers that are somewhat thicker than tonofibrils and tonofilaments, and clearly distinguishable individually. The microridge-like structures visible by SEM could be attributed to the persistence of cells formed in underlying layer. In conclusion, the histology of the lingual epithelium of the juvenile Pacific ridley turtle differs significantly from that of the adult freshwater turtle in spite of the similarity of the gross morphology of their tongues.

Animals

Antineoplastic agents; I. Three spirostanol glycosides from rhizomes of Dioscorea collettii var. hypoglauca.

By activity-guided fractionation, three known steroidal saponins, prosapogenin A of dioscin, dioscin and gracillin, were isolated from the total saponin fraction of Dioscorea coiletti var. hypoglauca as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic activity against the cancer cell line K562 in vitro. The structures of the compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H-NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis.

Antineoplastic Agents

Different rifampicin inactivation mechanisms in Nocardia and related taxa.

Mycolic acid-containing bacteria inactivate rifampicin in a variety of ways such as glucosylation, ribosylation, phosphorylation and decolorization. These inactivations were found to be a species-specific phenomena in Nocardia and related taxa. Gordona, Tsukamurella and fast-growing Mycobacterium modified rifampicin by ribosylation of the 23-OH group of the antibiotic. Such ribosylation was not observed in Rhodococcus and Corynebacterium, but phosphorylation of the 21-OH group of rifampicin was observed in one strain of Rhodococcus. Nocardia modified the antibiotic by glucosylation (23-OH group) and phosphorylation, but ribosylation was not observed.

Actinomycetales

Direct effects of testosterone, dihydrotestosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in castrated F344 rats.

The present experiment was carried out to explore the effect of endogenous androgen on rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP) or 5alpha-dihydrotestosterone (DHT) with or without ethinyl estradiol (EE). In order to eliminate the influence of endogenous androgen, F344 rats were orchiectomized just after initiation with the prostate carcinogen, DMAB, and then given TP, DHT, TP plus EE or DHT plus EE for 40 weeks. The results demonstrated that while administration of TP following DMAB treatment causes invasive carcinomas in the lateral and anterior prostate and seminal vesicles, DHT does not exhibit equivalent effects. Synergistic enhancement was also evident with TP plus EE, but not with DHT plus EE. The incidences of prostatic and seminal vesicle lesions in all groups of the present experiment, except for the group given castration without hormonal supplement, were equivalent to those previously found in non-castrated animals. Therefore, the present findings indicate that endogenous testosterone may not be required for promotion by TP/EE of DMAB-initiated prostate carcinogenesis and that it may not contribute to the actions of DHT.

Aminobiphenyl Compounds

Specialty choice and understanding of primary care among Japanese medical students.

To assess specialty choice and understanding of primary care among Japanese medical students, all students from seven Japanese medical schools (three public and four private) were surveyed, using a written questionnaire. A total of 3377 students provided data for the study. Of the students surveyed, 89.8% wanted to become clinicians, and 79.3% wanted to have general clinical ability. About half of the respondents, 54.9%, replied that they had some, or great, interest in primary care, but it was found that their understanding of primary care was inadequate. Almost half (56.3%) of the students answered that they had some idea of what a general practitioner did. This proportion was nearly the same through all years of medical school. While 1245 (36.9%) students (most of them in the fifth or sixth year) replied that they had received some clinical training while working in hospitals, only 203 (6.0%) students had worked in private clinics (the sites where most primary care is still provided), and 129 (3.8%) students had experience in providing home visits and home care. An even greater number, 64.3%, replied that they had inadequate information about the career options available to them. The study found that although many Japanese medical students want to obtain broad clinical competence, their understanding of primary care is insufficient. In order to increase the number of primary care providers the system of medical education in Japan must provide primary care doctors to act as role models, and must make available information about postgraduate primary care programmes. These programmes need to be increased, as do rewarding positions for programme graduates.

Career Choice