Susceptibility gene for non-obstructive azoospermia in the HLA class II region: correlations with Y chromosome microdeletion and spermatogenesis

We previously reported an association between the human leukocyte antigen (HLA) haplotype DRB1*1302-DQB1*0604 in the HLA class II region and non-obstructive azoospermia in Japanese men. To identify possible associations between the HLA-DRB1*1302-DQB1*0604 allele in the HLA class II region and azoospermia factor (AZF) deletion in the Y chromosome, we performed genomic polymerase chain reaction (PCR) analysis of the AZF region. We then determined spermatogenic impairment (Johnsen score) in testicular biopsy specimens from patients with or without the DRB1*1302-DQB1*0604 haplotype. The AZF microdeletion rate in patients with this haplotype was 3.85%, compared with 11.8% in others (no correlation). However, Johnsen scores in patients with the DRB1*1302-DQB1*0604 haplotype were 3.13 +/- 1.34 (mean +/- SD), compared with 3.70 +/- 1.51 in others (p < 0.05). While the DRB1*1302-DQB1*0604 haplotype acts independently from Y chromosome deletion, the haplotype might either act directly, or be functionally related to an unknown autosomal gene. In either case, this haplotype showed association with severe spermatogenic impairment.     

IV-DSA is a new diagnostic tool for axillary lymph node metastasis in breast cancer patients

BACKGROUND AND OBJECTIVE: The aim of this study is to know whether intravenous digital subtraction angiography (IV-DSA) is useful to detect axillary lymph node metastasis of breast cancer and to evaluate the anigiogenesis of lymph nodes in the axilla. PATIENTS AND METHODS: Forty three primary breast cancer patients (N0: 26 cases, N1: 5 cases, N2: 2 cases) who underwent IV-DSA between January and November 2000 were included in the study. Infinix CB apparatus (Toshiba, Japan) was used to collect IV-DSA images and when a mass became stained in the axilla, it was considered to be metastatic. The angiogenesis was studied by examining microvessel density (MVD) after lymph node immunostaining for factor VIII. Primary tumor was detected by IV-DSA in all 43 cases. RESULTS: Axillary lymph node metastases were detected by IV-DSA in 34.9% of cases (15/43), and by pathology in 37.2% (16/43). The sensitivity, specificity, and accuracy of the diagnostic method were 75.0% (12/16), 88.9% (24/27), and 83.7% (36/43), respectively. MVD, calculated after immunostaining for factor VIII, was significantly lower in the in metastatic region of lymph nodes identified by DSA (88.5 +/- 35.0) than in metastasis-free lymph nodes (141.1 +/- 34.0, P < 0.0001). CONCLUSIONS: IV-DSA is useful in the diagnosis of axillary lymph node metastasis of breast cancer. Our results suggest that the primary factors involved in the mechanism of DSA display may be different from high/low MVC values.     

Processes and strategies for developing public health nurse directed community health projects in municipalities of Japan--focusing on setting agendas and making project alternatives

PURPOSE: The purpose of this study was to explore processes and strategies for developing community health projects directed by public health nurses (PHNs) in municipalities of Japan. METHOD: Yin's case study design was adopted into the 5-step Policy Making Process Model as the theoretical framework. The first two steps involving agenda setting and project planning were the focus of this study. PHNs who had developed new community health projects in municipalities were interviewed as study participants. In order to maintain the quality of projects at a certain level, only these approved officially by municipalities with a program and budget were selected. RESULTS: Common strategies emerged for developing community health projects in the cases presented by the 5 PHNs. Out of 891 codes, twenty-six sub-categories were identified and integrated into 9 categories. When categories were analyzed in a time series, the following common processes were found: integration of related data, identification of the health problems in the community and recognition of project needs (Phase 1); refining the concept and characteristics of the project plan (Phase 2); and assuring that resources were available for the optimal implementation of the project by consolidating ideas (Phase 3). In Phase 1, PHNs integrated the information about previous experimental cases or social circumstances to identify community health problems needing solution. PHNs' thoughts were given to problems of existing projects and daily practices were grouped to make comprehensive plans for improvement. In Phase 2, PHNs discussed ideas for the project plans and considered resources and strategies that were necessary for putting new projects into place. In Phase 3, PHNs were attentive to the factors reviewed in Phase 2, kept account of necessary resources, and made certain of timing for immediate implementation of plans. The dual roles of PHNs, both as nurses and public servants, helped to clarify and solve the community health problems. CONCLUSION: Common strategies of developing programs were explored; "Identifying the community health problems through analyzing the causes of difficult cases," "Recognizing the necessity of coverall-projects which will improve the existing projects," "Understanding the awareness of those involved and discuss ideas for the project plan." The findings have based solely on the experiences of PHNs, they can provide suggestions that are keys to efficient development of new projects.     

IGF-related proteins at birth in a case of antenatally diagnosed Silver-Russell syndrome

We report here a case with severe intrauterine growth restriction from the first trimester and clinical features of Silver-Russell syndrome including microcephaly, low-set ear, atrial septum defect, ventricular septum defect, diaphragmatic relaxation, and rocker bottom feet. Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. We measured both the maternal and cord blood levels of GH, IGF-I, and IGF-binding protein and performed an immunohistochemical study of IGF-IR in the placenta to investigate whether these IGF-related proteins were affected in this patient. The hormonal level of these proteins did not significantly differ from normal neonates, and immunohistochemical analysis suggested IGF-IR protein levels in the placenta were comparable to normal term neonates. These results support the hypothesis that growth insufficiency could occur in patients with monosomy of the distal long arm of chromosome 15 and suggest a critical threshold for IGF-related fetal growth in early pregnancy.     

Cholesterol synthesis in mice is suppressed but lipofuscin formation is not affected by long-term feeding of n-3 fatty acid-enriched oils compared with lard and n-6 fatty acid-enriched oils

Hypocholesterolemic activity of dietary polyunsaturated fatty acids is observed after relatively short-term but not long-term feedings, and their long-term feedings are suspected to accelerate aging through tissue accumulation of lipid peroxides and age pigments (lipofuscin). To define the long-term effects of fats and oils in more detail, female mice were fed a conventional basal diet supplemented with lard (Lar), high-linoleic (n-6) safflower oil (Saf), rapeseed oil (Rap), high-alpha-linolenic (n-3) perilla oil (Per), or a mixture of ethyl docosahexaenoate and soybean oil (DHA/Soy) from 17 weeks to 71 weeks of age. The DHA/Soy and Per groups had decreased serum cholesterol levels compared with the Lar and Saf groups, but the difference between the Lar and Saf groups was not significant. The 3-hydroxy-3-methyglutary-CoA (HMG-CoA) reductase activity in the liver was also significantly lower in the Per and DHA/Soy groups. However, no significant difference in lipofuscin contents in the brain and liver was observed among the 5 dietary groups, despite significant differences in peroxidizability indices of the dietary and/or tissue lipids. These results indicate that n-3 fatty acid-rich oils are hypocholesterolemic by suppressing hepatic HMG-CoA reductase activity compared with animal fats and high-linoleic (n-6) oil, but tissue lipofuscin contents are not affected by a long-term feeding of fats and oils with different degree of unsaturation in mice.     

Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers

An important method for silencing tumor suppressor genes in cancers is by aberrant methylation (referred to as methylation) of CpG islands in gene promoter regions. In lung cancer, methylation of the genes retinoic acid receptor beta-2 (RARbeta-2), CDH13 (H-cadherin), p16(INK4a) (p16), RASSF1A (RAS association domain family I) is frequent. Thus, we investigated methylation of these genes in 4 different types of specimens (oropharyngeal brushes, sputum samples, bronchial brushes and bronchioloalveolar lavage [BAL] samples) of the upper aerodigestive tract epithelium from heavy smokers without evidence of cancer but with morphometric evidence of sputum atypia and compared the frequencies of methylation in the different types of specimens. In addition, we also analyzed sputum samples from 30 never smokers for methylation of these genes. Our major findings are: (i) At least one gene was methylated in one or more specimens from 48% of the smokers. However, methylation was statistically significant less frequently in never smokers compared to smokers. (ii) In general, methylation occurred more frequently in samples from the central airways (sputum, bronchial brushes) compared to the peripheral airways (BAL) and only occasionally in the oropharynx. (iii) RARbeta-2 was the most frequently methylated gene, whereas the frequency of methylation for the other genes was lower. (iv) Data from sputum samples and bronchial brushes were comparable. Our findings suggest that detection of methylation should be investigated as an intermediate marker for lung cancer risk assessment and response to chemopreventive regimens.     

Lymphokine-activated killer cells can kill target cells not only by early killing but also by late killing,and the late killing level against autotumor cell line

Generally, lymphokine-activated killer (LAK) cells kill target cells early after the LAK cells adhere to them. In this study, we describe that LAK cells can also kill at a later time, such as 24-96 h. LAK cells were generated from a cancer patient and healthy volunteers. As target cells, the patient's autotumor cell line H41 was used. When LAK cells were added to the target cells in a culture well, the LAK cells killed the target cells by cell-cell adhesion within 1-4 h (early killing), but not all cells were killed. The LAK cells were then removed. However, the remaining cells ultimately died 24-96 h later (late killing). The late killing was different from the early killing because numerous granules and vacuoles appeared in the cytoplasm. The late killing was not induced by adding supernatant of the LAK cell culture, suggesting that LAK-target cell contact may be necessary for the killing. The cell injury was inhibited by 3-methyladenine (lysosome inhibitor). It suggests that the vacuoles may be caused by activated lysosome. The patient's LAK cells induced late killing at high levels. There was a high percentage of CD8(+)CD16(+) cells in the peripheral blood lymphocytes (PBL). This subset induced late killing more effectively than the CD8(-)CD16(+) subset. Killing was more conspicuous against H41 than against allogeneic cell line T98G. This type of killing is noteworthy for understanding of killing mechanism of LAK cells.     

Factors of positive appraisal of care among Japanese family caregivers of older adults

The purpose of this study was to examine factors of positive appraisal of care among Japanese family caregivers of older adults. The Positive Appraisal of Care (PAC) scale used in this study is a multidimensional Japanese measure and has four domains: relationship satisfaction, consequential gain, role confidence, and normative fulfillment. Three hundred and thirty-seven caregivers participated in this survey. Multiple regression analyses revealed that social support and caregiver belief in caregiving had a consistent impact on all domains of the PAC, whereas the impact of caregiver and care recipient characteristics varied among the domains. For example, caregiver age had a significant impact on role confidence and normative fulfillment but not on relationship satisfaction and consequential gain. The differential impact of caregiver and care recipient characteristics on the domains of the PAC underlines the usefulness of a multidimensional measurement.