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SUMMARYTo continue the search for immunological roles of breast milk, cDNA microarray analysis on cytokines and growth factors was performed for human milk cells. Among the 240 cytokine-related genes, osteopontin (OPN) gene ranked top of the expression. Real-time PCR revealed that the OPN mRNA levels in colostrum cells were approximately 100 times higher than those in PHA-stimulated peripheral blood mononuclear cells (PBMNCs), and 10 000 times higher than those in PB CD14+ cells. The median levels of OPN mRNA in early milk or mature milk cells were more than three times higher than those in colostrum cells. Western blot analysis of human milk showed appreciable expression of full-length and short form proteins of OPN. The concentrations of full-length OPN in early milk or mature milk whey continued to be higher than those in colostrum whey and plasma as assessed by ELISA. The early milk (3-7 days postpartum) contained the highest concentrations of OPN protein, while the late mature milk cells (1 years postpartum) had the highest expression of OPN mRNA of all the lactating periods. The results of immunohistochemical and immunocytochemical staining indicated that OPN-producing epithelial cells and macrophages are found in actively lactating mammary glands. These results suggest that the persistently and extraordinarily high expression of OPN in human milk cells plays a potential role in the immunological development of breast-fed infants.

We have carried out an autosomal genome scan for genes contributing to the development of type 2 diabetes and affecting BMI in the Japanese population (164 families, 256 affected sib-pairs). We found 12 regions that showed nominally significant multipoint evidence of linkage with type 2 diabetes (i. T ype 2 diabetes is one of the most common diseases of middle-age, and its prevalence is increasing in many countries, including Japan (1,2). The increase in prevalence of type 2 diabetes is due, at least in part, to the presence of latent genetic risk factors that are being unmasked by changing patterns of diet, exercise, and other lifestyle/environmental factors. Clinical studies indicate that type 2 diabetes is a phenotypically heterogeneous disorder, and it is likely that it is not one disease but many, with hyperglycemia resulting from different combinations of susceptibility genes superimposed on different nongenetic factors. This heterogeneity is evident on comparing the clinical characteristics of diabetic individuals of different racial groups. For example, Japanese patients are characterized by a lower BMI (25.84 Ϯ 4.01 kg/m 2 ) and lower fasting insulin levels (8.74 Ϯ 6.91 U/ml) than individuals of European descent (30.43 Ϯ 6.72 kg/m 2 and 14.01 Ϯ 13.26 U/ml), Mexican-Americans (31.61 Ϯ 8.18 kg/m 2 and 15.71 Ϯ 11.55 U/ml), or African-Americans (33.04 Ϯ 8.69 kg/m 2 and 17.39 Ϯ 21.42 U/ml) (3). It has been suggested that ␤-cell dysfunction is the primary physiological defect that leads to type 2 diabetes in Japanese subjects, whereas it is insulin resistance in European subjects (4). Both genetic and nongenetic factors are likely to contribute to these clinical differences, and genetic studies in diverse populations may identify the molecular bases for the phenotypic differences between and within populations.eWe carried out an autosomal genome scan for type 2 diabetes genes in Japanese subjects. Since obesity is a risk factor for type 2 diabetes (1), we also tested for linkage to log-transformed BMI (lnBMI). The study population (164 families, 368 subjects, and 256 affected sib-pairs [ASPs]), including sibship structure and baseline clinical and biochemical features is summarized in Tables A1 and A2 in the online supplement at http://diabetes.diabetesjournals. org. This sample size has Ͼ80% power for detecting a locus with a s Ͼ1.6 (suggestive evidence for linkage, P Ͻ 0.00074) (5) and 50% power to detect a locus with a s Ͼ1.4. The study population was genotyped using a panel of 414 autosomal microsatellite markers with an intermarker interval of 8.6 Ϯ 5.2 cM and average heterozygosity of 0.70. A total of 19 markers showed nominal evidence for linkage

The concentration of 1-deoxyglucose(1,5-anhydroglucitol) in plasma from patients with insulin-dependent diabetes mellitus was measured by gas-liquid chromatography with an all-glass capillary column. Twenty-one plasma samples were obtained from 21 patients before insulin therapy, and 34 more from 13 patients receiving insulin therapy. 1-Deoxyglucose was generally not detectable in plasmas of diabetic patients before they received insulin; it was measurable in the patients who had received insulin, although its concentration was low compared with that of healthy subjects. We therefore suggest that the absence of 1-deoxyglucose in plasma is one of the markers of metabolic states of diabetes, perhaps reflecting a disturbed function of carbohydrate metabolism; its presence in plasma within a normal range may reflect the better control of diabetic patients.

Abstract. The efficacy and safety of the long-acting repeatable formulation of octreotide (OCT-LAR) treatment in patients suffering from acromegaly was investigated retrospectively in Shizuoka prefecture, Japan. Thirty patients (11 male, 19 female; average age, 48.9 years old), 29 of whom had undergone transsphenoidal surgery previously, were treated with OCT-LAR. OCT-LAR was injected i.m. every 4 weeks with an intended protocol of 20 mg over 24 months, however, 46.7% of patients required the dose of OCT-LAR to be increased. The final average dose of OCT-LAR was 25.0 ± 6.8 mg. Administering OCT-LAR significantly decreased serum GH and insulin-like growth factor 1 (IGF-1) levels (from 13.7 ± 11.9 to 5.8 ± 7.3 µg/L and from 585 ± 263 to 339 ± 193.7 µg/L after 3 months, respectively). Among patients treated with OCT-LAR, 56.7% expressed ≤2.5 µg/L serum GH and 53.3% displayed serum IGF-1 levels within the normal range, while 36.7% met both criteria that indicated treatment success. A sufficient outcome was achieved in 73.3% of patients when the rate of GH ≤2.5 µg/L or normalization of IGF-1 was accumulated. OCT-LAR did not have a negative effect on glucose tolerance when hemoglobin A1c was used as a marker. A gallbladder polyp was found only in 1 patient but it was uncertain whether OCT-LAR was involved in its development because the patient was not examined before OCT-LAR treatment. There were no abnormalities on liver function tests in any patients. In conclusion, our results showed that OCT-LAR was safe and effective as a therapeutic option for Japanese patients with acromegaly in a postoperative setting, by controlling the disease activity.Key words: Octreotide, Acromegaly, GH, Insulin-like growth factor 1 (Endocrine Journal 56: [1095][1096][1097][1098][1099][1100][1101] 2009) The mAjoriTy of patients with acromegaly suffer from pituitary adenoma, from which excessive secretion of GH induces a high incidence of pathological complications including maladaptive changes in the face and limbs, as well as diabetes mellitus, hypertension, hyperlipidemia, arteriosclerosis, and cardiovascular disorders [1]. According to a previous report, acromegaly increased the rate of mortality, while the cumulative survival rate of untreated patients was <40% over the last 20 years [2]. Observing the relationship between GH level and mortality, the 50% survival rate in three groups with GH levels of >5 μg/