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【目的】高年出産後の母親の母乳育児の状況と関連因子を明らかにし、今後の高年出産後の母親の母乳育児を推進するための資料を得る。【研究方法】質問紙調査。Spearman 順位相関係数で分析した。本研究は所属機関の倫理委員会の承認を得た（承認番号19 研- 002）。【結果】35 歳以上群の授乳の特徴としては、母乳栄養で不足する量を人工栄養で補い、夜間授乳回数が多く搾乳回数も多かった（p ≦ 0.01）。また、人工栄養回数の増加と 「焦りを感じる」傾向、「授乳満足感」の低下に相関があることが明らかになった。（p ≦ 0.01）【考察】35 歳以上の母親はイメージしていた直接母乳が実施できないと「授乳満足感」が低くなり、「焦りを感じる」ことにつながることが示唆された。今後は、人工栄養を追加することが「焦り」とならないような母乳育児を提案していく必要がある。さらに対象者数を増やした、より詳細な検討も必須である 。

α4-laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by blood and lymphatic vessels and some tumor cells. Laminin-411 promotes migration of leukocytes and endothelial cells, but the effect of this laminin and laminin-421 on tumor cells is poorly understood. In the present study, we demonstrate that laminin-411 and, to a greater extent, laminin-421 significantly promote migration of tumor cells originated from melanomas, gliomas and different carcinomas via α6β1 integrin. In solid-phase binding assays, both laminins similarly bound α6β1 integrin but only laminin-421, among several laminin isoforms, readily bound MCAM (CD146), a cell-surface adhesion molecule strongly associated with tumor progression. Accordingly, a function-blocking mAb to MCAM inhibited tumor cell migration on laminin-421 but not on laminins 411 or 521. In tumor tissues, melanoma cells co-expressed MCAM, laminin α4, β1, β2 and γ1 chains, and integrin α6 and β1 chains. The present data highlight the novel role of α4-laminins in tumor cell migration and identify laminin-421 as a primary ligand for MCAM and a putative mediator of tumor invasion and metastasis.

Melanoma cells express and interact with laminins (LMs) and other basement membrane components during invasion and metastasis. In the present study we have investigated the production and migration-promoting activity of laminin isoforms in melanoma. Immunohistochemistry of melanoma specimens and immunoprecipitation/western blotting of melanoma cell lines indicated expression of laminin-111/121, laminin-211, laminin-411/421, and laminin-511/521. Laminin-332 was not detected. In functional assays, laminin-111, laminin-332, and laminin-511, but not laminin-211 and laminin-411, strongly promoted haptotactic cell migration either constitutively or following stimulation with insulin-like growth factors. Both placenta and recombinant laminin-511 preparations were highly active, and the isolated recombinant IVa domain of LMα5 also promoted cell migration. Function-blocking antibodies in cell migration assays revealed α6β1 integrin as the major receptor for laminin-111, and both α3β1 and α6β1 integrins for laminin-332 and laminin-511. In contrast, isolated LMα5 IVa domain-promoted melanoma cell migration was largely mediated via αVβ3 integrin and inhibited by RGD peptides. Given the ubiquitous expression of α5 laminins in melanoma cells and in melanoma-target tissues/anatomical structures, as well as the strong migration-promoting activity of these laminin isoforms, the α5 laminins emerge as putative primary extracellular matrix mediators of melanoma invasion and metastasis via α3β1 and other integrin receptors.

The process of liver regeneration is regulated by complex mechanisms. Although signal transducer and activator of transcription-3 (STAT3), a transcription factor which targets mainly mitotic genes, definitely plays an important role in liver regeneration, the exact roles of STAT3 are not completely understood. Aim: In this report, we tried to search for a new target of STAT3 involved in liver regeneration in mice. Methods: We generated liver-specific STAT3 knockout (L-S3KO) mice and a STAT3 knockout cell line of mouse origin. Using chromatin immunoprecipitation, we screened 12 genes to which STAT3 binds after partial hepatectomy (PH). Of these genes, we analyzed the S3-IE3 clone that is located on chromosome-3 and possesses STAT3 binding sites in it. Results: We showed that STAT3 binds to a specific site on S3-IE3, and that interleukin-6 (IL-6) stimulates its transcriptional activity. The mRNA and protein levels of the net gene, which is located downstream of S3-IE3, were negatively regulated in the control cells, but not in the STAT3 knockout cells after IL-6 stimulation. Similarly in in vivo mouse PH, the mRNA and protein levels of net were also negatively regulated after PH, but not in L-S3KO mice. Conclusion: The net gene is located downstream of a newly-recognized STAT3 binding site (S3-IE3) and negatively regulated after IL-6 stimulation and PH, although its role is still unclear.

In cases of multiple primary cancers, the combination of head/neck cancer and upper digestive tract cancer is often found. However, it is extremely rare for maxillary sinus cancer and esophageal cancer to occur simultaneously. This paper reports on an autopsy case of double primary cancers of the maxillary sinus and esophagus. The patient had been suffering from carcinoma of the maxillary sinus for about 12 months but the lesion was uncontrollable. At autopsy, the following two primary carcinomas were found : one was a moderately differentiated squamous cell carcinoma originated from the maxillary sinus infiltrating into the hard palate and tongue, with metastases in several regional lymph nodes, a para-aortic lymph node and bilateral lungs. The other was a progressive, well-differentiated squamous cell carcinoma originated from the esophagus transformed mucosa with epithelial dysplasia. Furthermore, two masses of gastrointestinal mesenchymal tumors (GIMT) of the stomach were noted.

Autopsy cases of tongue cancer in Japan were statistically analyzed. Autopsy cases were collected from the Annual of Pathological Autopsy Cases in Japan over the past five years (1997-2001). Tongue cancer was reported in 321 autopsy cases(M:241, F:79, Unknown: 1). The autopsy rate was 6.0% of 5,320 patients who died of tongue cancer in Japan. 103 of the autopsied patients (32.2%) were in their seventh decade, 74 (23.1%) were in their eighth decade, and 54 (16.9%) were in their sixth. Histologically, almost all the cases showed squamous cell carcinoma (96.8%). The cancer arose most frequently in the lateral borders (66.1%) of the tongue. Multiple primary cancers, affecting both the tongue and other organs, were found in 113 cases. The mean ages of only the autopsied cases of squamous cell carcinoma excluding the cases of multiple primary cancers were 63.8±10.1 (1997), 57.7±12.3 (1998), 65.4±13.6 (1999), 61.7±15.4 (2000) and 62.1±14.9 (2001) years old. However, the mean ages of multiple primary cancers, affecting both the tongue and the other organs, were 69.2±9.9 (1997), 70.5±11.2 (1998), 66.6±10.2 (1999), 68.2±11.6 (2000) and 69.9±15.5 (2001) years old. In cases of double cancers including tongue cancer, commonly occurring cancers were lung, liver, esophagus, thyroid and adrenal. Metastasis to other organs was frequently found in the tracheobronchus and lungs, liver, heart and aorta, bones, adrenals and thyroid. Metastasis to the lymph node was found in the cervix, lung hilum, periesophagus and peritrachea, left supraclavicula, and axilla. The most common cause of death was pulmonary infection.

The aims of this study were to investigate the proliferative activity and the localization of adhesion molecules in human healthy and inflamed portions of gingiva. Gingival biopsies were taken under informed consent from 33 patients undergoing gingivectomy at the Dental Hospital of Iwate Medical University. Adhesion molecules such as E-cadherin (of adherens junction-related molecules), desmoglein (of desmosomal cadherins), integrin α6 and integrin, β4 (of hemidesmosome-related molecules) were studied immunohistochemically to analyze the patterns of expression in the gingival epithelia. Desmoglein was detected intercellularly in the spinous layer of the lining epithelia, but not in the junctional epithelium (JE). Integrin α6 was confined to the basement membranes facing the connective tissue of all parts of the gingival epithelia. Integrin β4 was found in the basal layer of the epithelia, and it was markedly found in all layers of the JE. The expression patterns of adhesion molecules in the pocket epithelium (PE) were similar to those in the JE. The proliferative activity was analyzed by the bromodeoxyuridine (BrdU) labeling method and immunohistochemical staining for Ki-67. BrdU-positive cells were found in the basal layer of the sulcular (SE) and oral epithelia (OE), but not in the JE, and were particularly localized in the suprabasal layer at the bottom of the SE. Meanwhile, proliferative activity was found in the PE with the progression of ueriodontitis.

Dermoid cysts of the jaw are exceedingly rare, and only six such cases have been documented. The present paper reports a case with multiple microcysts showing histological characteristics of dermoid cyst in the surgically resected mandibular bone. These cysts were located near the inferior border of the mandibular bone, and histologically composed of an inner thin layer of squamous epithelium with marked hyperorthokeratinization and an outer layer of fibrous tissue containing numerous mature sebaceous glands. In addition, a hair follicle-like epithelial sphere was seen in part. The present microcysts suggest that it arises de novo, and one possible cause of jaw cysts could be sequestration of the stomadeal ectoderm that may have been trapped deep in the surface and embedded in the developing mandibular bone during embryogenesis. It may not be possible that such cysts developed from the odontogenic epithelial remnant undergoing dermoid metaplasia.

An unusual case of sialolith with bone formation, occurring in the submandibular gland of a 33-year-old woman, is reported. In addition to the irregularly laminated structure of sialolith, sparsely scattered foci of bone tissue were found. Some of them were mature, lamellar bone with lacunae containing osteocytes, endosteum and a bone marrow-like element. Others were immature bone associated with or without multinucleated giant cells. Foci of bone tissue were in contact with caliculi or fibrous tissue, and no epithelial component was seen around them. These observations suggest that bone formation in the present case may be in the nature of pathological ossification, and that in the earlier stage, the bone that is deposited is woven and is replaced through successive remodeling cycles by lamellar bone. This is the first case of sialolith with bone formation, although sialolithiasis is a common disease of the salivary glands.

Pathological examinations diagnosed at our department in 2001 were statistically reviewed. There were 641 examinations for 516 cases (Male: 244, Female 272). Cases were most frequent in patients in their seventh decades (106 cases). In histological classifications of the lesions (mean age ±SD), odontogenic tumors consisted of 5 ameloblastomas (40.4±25.2), 2 odontomas (20.2±8.0), and one malignant ameloblastoma (33.0). The non-oclontogenic benign lesions were 44 fibrous hyperplasias (55.2±18.9), 28 hyperkeratosis (leukoplakia) (55.7±13.4), 7 hemangiomas (65.6±5.9), 6 pleomorphic adenomas (56.7±11.5), 6 osteomas (exostosis, enostosis), 4 papillomas (80.7±7.4), 4 epithelial dysplasias (61.5±11.9) and 3 periapical cemental dysplasias (30.1±13.7). Non-odontogenic malignant tumors consisted of 53 squamous cell carcinomas (68.1±12.6) and 3 verrucous carcinomas (71.7±4.8). The odontogenic cysts consisted of 45 radicular cysts (45.2±14.3), 21 dentigerous cysts (41.4±19.9) and 8 primordial cysts (29.9±11.3). The non-odontogenic cysts consisted of 44 mucoceles (30.3±22.6), 18 postoperative maxillary cysts (56.1±11.4), 3 incisive canal cysts (54.3±9.9) and 2 dermoid cysts (16.5±2.5). In addition, 10 Sjogren syndromes (53.9±11.0), 7 lichen planus (69.1±12.9), 26 chronic localized hyperplastic gingivitis (epulis) (60.1±15.7) and 6 dental granulomas (50.5±16.9) were revealed.

Infiltration of eosinophils io the stroma is occasionally seen in malignant tumors, and there is some relation between eosinophilic infiltration and prognosis of squamous cell carcinoma (SCC) originating in the esophagus, lung and other organs. However there are few reports of oral SCC with infiltration of eosinophils. The present paper reports a case of oral SCC with a severe degree of eosinophilic infiltration. The patient was a 71-year-old female whose chief complaint was a white lesion in her tongue. Histologic examination revealed the lesion to he well differentiated SCC with infiltration of numerous eosinophils in the stroma. A few eosinophils had infiltrated in the parenchyma. Infiltration of eosinophils was clearly demonstrated by Luna stain. Chemotherapy had effect on the lesion and surgically resected material showed complete disappearance of SCC.

The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues requiring protection from exposure to bacteria and their products. However, the molecules comprising the gingival epithelial cell junction remain poorly characterized. Thus, the aim of the present study was to characterize the desmosome-associating proteins (desmoglein 1 and 3), desmosome-associating cytoskeleton (keratins), and tight junction-associating protein (claudin-1) within the oral gingival epithelium (OGE), sulcular epithelium (SE), and junctional epithelium (JE). Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were used to examine expression of adhesion molecules by immunofluorescence. In the OGE and SE, but not JE, desmoglein 1 was more abundant in the cell-cell contact sites of the upper than the suprabasal layer, while desmoglein 3 and desmoplakin were present in the cell-cell contact sites in all layers of the JE as well as the OGE and SE. Keratin 14 and 19, but not keratin 13 and 4, were present in the JE. Claudin-1 was expressed only in the intermediate layers in the uppermost flat layers in the OGE. These data indicated that the JE contained only few desmosomes composed of desmoglein 3. Thus, it is thought that the anchoring junction connecting JE cells is not firm, causing widened intercellular spaces in the JE. In contrast, the OGE, which has tight junctions, functions as a barrier.

α4-Laminins, such as laminins 411 and 421, are mesenchymal laminins expressed by vascular and lymphatic endothelial cells, leukocytes and other normal cell types. These laminins are recognized by α6β1 and α6β4 integrins and MCAM (CD146), and promote adhesion and migration of the cells. α4-Laminins are also expressed and secreted by some tumor cells and strongly promote tumor cell migration. Moreover, the abluminal side of blood and/or lymphatic vessels and the nerve perineurium, common tracks of tumor cell dissemination, express α4-laminins, and these laminin isoforms, when expressed in the stroma, may contribute to tumor invasion. In the present study, we examined ten mAbs to human laminin α4 chain for their reactivity with the isolated laminin α4 globular domain, their ability to inhibit tumor cell adhesion and migration on laminins 411 and 421, and their effect on the binding of α6β1 integrin and MCAM to both α4-laminins. Most of the mAbs reacted with the laminin α4 globular domain, but only two, mAbs FC10 and 084, significantly inhibited tumor cell adhesion and migration on laminin-411. When used in combination, these antibodies practically abolished the cell adhesion and migration on laminin-411 and significantly reduced the cellular responses on laminin-421. Accordingly, mAbs FC10 and 084 significantly inhibited the binding of purified α6β1 integrin and MCAM to laminins 411 and 421. These results indicate that mAbs to the laminin α4 globular domain are able to inhibit tumor cell adhesion and migration on laminins 411 and 421, and that α6β1 integrin and MCAM bind α4-laminins at very close sites on the globular domain. These reagents contribute to a better understanding of the biology of α4-laminins and may have a therapeutic potential in malignant and inflammatory diseases.

Background/Aims Ischemia/reperfusion damage to the liver remains a serious concern in many clinical situations. Major mechanisms for this certainly include oxidative stress. Methods The effects of ablating the p66 isoform of ShcA (p66 shc ) on hypoxia/reoxygenation (H/R)-induced oxidative stress and cell injury in hepatocytes were investigated. Results Immediately after reoxygenation, AML12 cells were clearly under oxidative stress; many cells underwent apoptosis. However, knockdown of p66 shc by specific RNAi markedly decreased cellular oxidative stress and H/R-induced apoptosis, as well as conferring resistance to H 2 O 2 insult. These data suggest that prevention of apoptosis conferred by ablation of p66 shc results from changed ROS-scavenging, but not inhibition of ROS generation. These data were also confirmed in fibroblasts from p66 shc knockout mice. Anti-oxidant molecules, such as MnSOD and Ref-1 and the anti-apoptotic molecule Bcl-xL were up-regulated, and pro-apoptotic FLICE was down-regulated, by ablation of p66 shc . Interestingly, catalase expression was not affected in p66 shc -knockdown-AML12 cells although it is a major target in other cell types. Conclusions Our findings suggest that in hepatocytes, ablation of p66 shc is cytoprotective against H/R-induced oxidative stress, with MnSOD and Ref-1 playing critical roles, and with up-regulation of Bcl-xL and down-regulation of FLICE contributing jointly to preventing cells from undergoing oxidant-induced apoptosis.

The incidence of mucous and ciliated cells in epithelial linings was examined among odontogenic inflammatory cysts (radicular cysts) and developmental cysts (dentigerous and primordial cysts). Mucous cells were found in 20.8% of all cysts examined, while ciliated cells were found in 11.4%; however, ciliated cells were always accompanied by mucous cells. The incidence of mucous cells in radicular cysts and dentigerous cysts and that of ciliated cells in radicular cysts was higher in the maxilla than in the mandible, while the incidence of mucous cells in primordial cysts and that of ciliated cells in dentigerous cysts and primordial cysts was higher in the mandible than in the maxilla. The present results regarding mucous cells and ciliated cells in the epithelial linings of intraosseous odontogenic cysts indicate a metaplasic origin, but the cause and biological significance of this phenomenon is not known. Mucous cells were present in the surface layer of epithelial linings, and intraepithelial gland-like structures lined with mucous cells were observed in the hyperplastic regions of epithelial linings of several radicular and dentigerous cysts. Such gland-like structures lined by mucous cells in the thickened epithelial lining, which have not been demonstrated previously, resembled the glandular structures of "glandular odontogenic cysts".

Laparoscopically, patchy liver and nodular liver were considered as features of regeneration of liver cells. In this study, the regenerating capacity of liver cells obtained by a liver biopsy from laparoscopically identified patchy liver and nodular liver was estimated by Bromodeoxvuridine (BrdU)-anti-BrdU method. BrdU labeling indices (L. I.), of liver cells in biopsy specimens from 6 normal livers, 12 patchy livers, and from 15 nodular livers were examined using an in-vitro labeling technique. Liver biopsy specimens obtained by a Tru-cut needle were immediately incubated for 45 min. in 0.1% BrdU solution in RPMI 1640 at 37°C under a pressure of 3 atmospheres in a mixture of 95% O2 and 5% CO2. Immunohistochemical detection of BrdU was performed by the Avidin-Biotin-Peroxidase Complex (ABC) method. The mean BrdU L. I. (±SE) of normal liver, patchy liver, and of nodular liver was 0.25±0.09%, 1.4±0.2%, and 1.7±0.4% respectively. Among the nodular liver, flat shaped ones showed a low level (0.5±0.1%), in contrast to the high level (2.4±0.7%) in the semispherical nodular liver. The BrdU L. I. of both the patchy liver and the nodular liver was significantly higher than that in the normal liver (p