[Present Execution of and Problems with Clinical Lipid Examination and Application of "the Japan Atherosclerotic Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012"].

It is well known that dyslipidemia is one of the most crucial risk factors for atherosclerosis, including cardiovascular diseases (ASCVD). In order to prevent the onset of ASCVD, the Japan Atherosclerotic Society (JAS) published the JAS Guidelines in 2012 for appropriate lipid examination and treatment. However, it is unknown how the guidelines are practically used by Japanese clinicians. Therefore, we conducted a questionnaire survey to assess the present execution of and problems with clinical lipid examination and the application of the JAS Guidelines by doctors working in hospitals and clinics of Yamagata district in Japan. We found that 16% of doctors carried out clinical lipid examination every time, but some did not examine lipids at all. Fasting blood sampling for lipid examination was performed by 44% of doctors, and the items of triglycerides, HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were measured by more than 95%. Regarding problems with clinical lipid examination, more than 40% of doctors requested the early achievement of the standardization of LDL-C. The JAS Guidelines in 2012 were unfortunately recognized by only 55% of doctors. In addition, the rate of the clinical application of the guidelines, including the absolute risk, the flowchart of LDL-C, and non-HDL-C, was less than 30%, and more than half of the doctors measured LDL-C with the direct method, but did not use the "recommended" Friedewald method. In contrast, the cardiologists and endocrinologists generally accepted the guidelines, and their clinical application rate was higher than in other doctors. Through the questionnaire survey, it was revealed that doctors in various fields have not properly accepted the use and significance of lipid examination and the JAS Guidelines, and so further educational activities are necessary.

[Clinical screening examination for impaired glucose tolerance: is it possible to diagnose impaired glucose tolerance without a 75g oral glucose tolerance test?].

It is well known that diabetes mellitus is one of the most crucial risk factors in the pathogenesis of atherosclerosis, including cardiovascular diseases (CVD). Considerable epidemiological and clinical studies, such as the Funagata study and the Diabetes Epidemiology Collaborative analysis of Diagnostic criteria in Europe (DECODE) study, have established that even a prediabetic state, including impaired glucose tolerance (IGT), is strongly associated with the occurrence of CVD. For the diagnosis of IGT, the 75g oral glucose tolerance test (75g OGTT) is required clinically, but the test takes at least 2 hours, at considerable cost. Therefore, for the prevention of atherosclerosis and subsequent CVD, another methods and/or beneficial parameters are anticipated to diagnose IGT without 75g OGTT. Recent studies have suggested that subjects beyond approximately 100 mg/dl fasting plasma glucose (FPG) might be classified into IGT by using receiver operating characteristic (ROC) analyses, and that the FPG 100 mg/dl is a suitable cut-off level between IGT and normal glucose tolerance (NGT). In contrast, although it is difficult to distinguish IGT from NGT by the HbAlc level alone, the combination of FPG with HbAlc is more beneficial for the diagnosis of IGT.

Non-obese early onset diabetes mellitus in mutant cryptochrome1 transgenic mice.

BACKGROUND: An earlier report described that transgenic mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cystein414 (CRY1-AP Tg mice) display diabetes mellitus in addition to anomalous circadian behaviours. This study examined characteristic aspects of symptoms to clarify the diabetes type and pathogenesis. MATERIALS AND METHODS: The body weights and blood glucose levels of CRY1-AP Tg mice were measured for 7weeks starting at 3weeks after birth. Glucose tolerance test for the mice of various ages and insulin tolerance test at 6weeks of age were conducted. Immunohistochemical analysis of islets was carried out for the mice of 19 and 40weeks of age. Basal and glucose-stimulated serum insulin levels of mice at 27weeks were also measured. RESULTS: Three-week-old CRY1-AP Tg mice, which showed mild retardation in growth, already displayed glucose intolerance. Hyperglycaemia progressed with age, without accompanying insulin resistance. Insulin-stained areas in islets in CRY1-AP Tg mice were smaller than that in wild-type controls. Both basal and glucose-stimulated secretion of insulin decreased in CRY1-AP Tg mice. CONCLUSION: The symptoms of diabetes in CRY1-AP Tg mice turned out to be similar to those of maturity onset diabetes of the young (MODY) in humans in terms of early onset, non-obesity and primary dysfunction of beta cells. The CRY1-AP Tg mice might serve as an animal model of early onset insulin-secretory defect of diabetes.

[Improvement of the system for collecting blood samples, at the Division of Clinical Laboratory in Yamagata University Hospital, based on the complaints of patients: The way to perform the newly-developed 30-min changeover method for collecting blood samples by medical technologists].

The collection of blood samples is one of the most essential procedures in laboratory examinations for the clinical diagnosis of patients. However, it is not always easy to carry out the procedure smoothly. At the Division of Clinical Laboratory in Yamagata University Hospital, we have tried to employ the best way to collect blood samples without any troubles or complaints. However, there were some complaints made by patients over several years, and one of these was that the waiting time for patients was too long. Therefore, we established a new system: all medical technologists joined the program and one took charge of collecting blood samples for 30 min, and then another technologist took over. The system was important for medical technologists since the duty allocation was impartial, and their routine work was not disturbed. We are proud of this newly-developed 30-min turn in collecting blood samples in our hospital.

Karyopherin Alpha 2-Expressing Pancreatic Duct Glands and Intra-Islet Ducts in Aged Diabetic C414A-Mutant-CRY1 Transgenic Mice.

Our earlier studies demonstrated that cysteine414- (zinc-binding site of mCRY1-) alanine mutant mCRY1 transgenic mice (Tg mice) exhibit diabetes characterized by the reduction of ß-cell proliferation and by ß-cell dysfunction, presumably caused by senescence-associated secretory phenotype- (SASP-) like characters of islets. Earlier studies also showed that atypical duct-like structures in the pancreas developed age-dependently in Tg mice. Numerous reports have described that karyopherin alpha 2 (KPNA2) is highly expressed in cancers of different kinds. However, details of the expression of KPNA2 in pancreatic ductal atypia and in normal pancreatic tissues remain unclear. To assess the feature of the expression of KPNA2 in the development of the ductal atypia and islet architectures, we scrutinized the pancreas of Tg mice histopathologically. Results showed that considerable expression of KPNA2 was observed in pancreatic ß-cells, suggesting its importance in maintaining the functions of ß-cells. In mature stages, the level of KPNA2 expression was lower in islets of Tg mice than in wild-type controls. At 4 weeks, the expression levels of KPNA2 in islets of Tg mice were the same as those in wild-type controls. These results suggest that the reduction of KPNA2 might contribute to ß-cell dysfunction in mature Tg mice. Additionally, the formation of mucin-producing intra-islet ducts, islet fibrosis, and massive T cell recruitment to the islet occurred in aged Tg mice. In exocrine areas, primary pancreatic intraepithelial neoplasias (PanINs) with mucinous pancreatic duct glands (PDGs) emerged in aged Tg mice. High expression of KPNA2 was observed in the ductal atypia. By contrast, KPNA2 expression in normal ducts was quite low. Thus, upregulation of KPNA2 seemed to be correlated with progression of the degree of atypia in pancreatic ductal cells. The SASP-like microenvironment inside islets might play stimulatory roles in the formation of ductal metaplasia inside islets and in islet fibrosis in Tg mice.

Pioglitazone reduces atherogenic outcomes in type 2 diabetic patients.

AIM: The aim of this study was to evaluate the anti-atherogenic outcomes of pioglitazone, a thiazolidinedione derivative, in type 2 diabetic patients. METHODS: Eight patients with poor diabetic control were treated with 15 mg of pioglitazone for 4 months. Blood samples were collected monthly, and the levels of fasting plasma glucose (FPG), HbA1c, and lipids, such as triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were measured. Other parameters, including immunorecative insulin (IRI), remnant-like particle-cholesterol (RLP-C), adiponectin, plasminogen activator inhibitor type 1 (PAI-1), tumor necrosis factor (TNF)- alpha , leptin, brain natriuretic peptide (BNP), and high-sensitivity (hs)-C-reactive protein (CRP), were examined at the beginning and end of the study. In addition, clinically adverse side-effects were evaluated. RESULTS: Treatment with pioglitazone significantly decreased the levels of HbA1c, FPG, the homeostasis model assessment of insulin resistance (HOMA-IR) index, RLP-C, PAI-1, TNF- alpha , and hs-CRP, but not the level, IRI, lipids, or leptin. In contrast, adverse side-effects, including body weight gain, liver dysfunction and edema, were not observed during this study. CONCLUSION: These results strongly suggested that treatment with pioglitazone has a greater clinical benefit for the prevention of atherosclerosis, including coronary heart diseases, without any adverse side-effects.

A resected case of liver metastasis from colon cancer that occurred 13 years after a colectomy.

A 73-year-old man, who underwent a potentially curative resection of cancer of the descending colon 13 years before, was found to have a well-defined hepatic tumor on ultrasonography. A lateral segmentectomy was performed for a solitary hepatic tumor. Histopathological examination of the tumor indicated well differentiated adenocarcinoma compatible with the metastasis from the previous descending colon cancer. There have been no signs of recurrence for 5 years after the hepatic resection. This case suggests that distant metastasis from colorectal could be found several years after operation like in this case, and consequently long-term and strict follow-up is required after curative resection of the primary lesion.

[How can we contribute to Yamagata University Hospital as clinical laboratory physicians?].

In September, 2007, the Japanese Ministry of Health, Labor and Welfare legislated that clinical laboratory doctors can advocate the clinical laboratory in hospitals and clinical offices. The decision was monumentous, and we, clinical laboratory physicians, can see patients from April, 2008. Although our roles and/or details have not officially been determined, we must definite the contribution of clinical laboratory doctors. One of our plans is to set up a conference room in the Division of Clinical Laboratory to explain their medical tests to patients. Laboratory data are not always explained in detail by doctors, since they are busy and do not have enough time to see patients. Subsequently, clinical laboratory physicians will be able to comply with patients' wishes for medical testing. In addition, to prevent the development of lifestyle-related diseases and their related metabolic syndrome in Japanese people, a new specified health checkup system has recently been established by the Japanese Ministry of Health, Labor and Welfare, and the system will start from April, 2008. Since more than 20 million people from 40 to 74 years old are estimated to undergo this health checkup, total quality assurance in the clinical laboratory is required to provide accurate and precise test values by the government. Therefore, our clinical laboratory physicians should play a central role to guarantee the specified health checkup system.

Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats.

AIM: This study was investigated to characterize the activation mechanism of a mitogen-activated protein (MAP) kinase superfamily in diabetes in aortae and cultured vascular smooth muscle cells (VSMCs) from rats. METHODS: Male Sprague-Dawley rats were used for this procedure, and diabetes was induced by streptozotocin injection at 50 mg/kg. After 6 weeks, the thoracic aortae from normal and diabetic rats were removed for detection of the MAP kinase superfamily by immunoblot analysis. RESULTS: In aortae, the protein levels of extracellular signal-regulated protein kinase (ERK)-1, c-jun NH2-terminal protein kinase (JNK)-1 and -2, and p38 increased significantly more in diabetic rats than in normal rats. In contrast, phosphorylated protein levels of ERK-1 and -2, JNK-1, and p38 were significantly more elevated in diabetic rats than in normal rats. In VSMCs from normal rats, a high concentration of glucose cultured for three days significantly increased the phosphorylated protein levels of ERKs and p38, but not JNKs, without any change of these protein levels. Serum interleukin (IL)-1beta was significantly higher in diabetic rats than in normal rats. Several types of proinflammatory cytokine dose-dependently phosphorylated the levels of ERKs, JNK-1, and p38, but not JNK-2, in VSMCs from normal rats. In cells from diabetic rats, phosphorylated protein levels of ERKs and p38 were significantly elevated by IL-1beta. In addition, interferon-gamma phosphorylated the levels of ERKs in diabetic cells more than in normal cells. CONCLUSION: Our results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature; i.e., ERKs and p38 might be mainly phosphorylated by a complex of high concentrations of glucose and of several types of proinflammatory cytokines, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1beta, and/or additional unknown factors, except glucose.

Role of angiotensin II type-1 and type-2 receptors on vascular smooth muscle cell growth and glucose metabolism in diabetic rats.

This study investigates the mechanisms whereby angiotensin II (Ang II) signaling contributes to cell growth and glucose metabolism in cultured vascular smooth muscle cells (VSMCs) from male Wistar fatty rats (WF) and their littermates (Wistar lean rats, WL). The levels of the medial outgrowth rate of VSMCs and Ang II type-1 receptors (AT1R) in aortae from WF were more enhanced than those in aortae from WL, but the level of Ang II type-2 receptors (AT2R) was not different. A mixture of insulin and Ang II additively increased the values of [(3)H]-thymidine incorporation in WF and WL, which was inhibited by olmesartan, an AT1 receptor blockade (ARB), but not by PD123,319, an AT2 receptor blockade. Similarly, insulin and Ang II phosphorylated extracellular-regulated protein kinase 1/2, retinoblastoma tumor suppressor protein, and cyclic AMP response element binding protein, and these levels were higher in WF than in WL. In contrast, the phosphorylation was suppressed by olmesartan but not PD123,319. Insulin-stimulated Akt phosphorylation and 2-deoxy-d-glucose uptake in WF were significantly reduced by Ang II, and the reduction was ameliorated by olmesartan but not PD123,319. Differently from the result of Akt, the phosphorylation of the insulin-stimulated insulin receptor beta-subunit was not affected by Ang II, olmesartan, or PD123,319. However, the phosphorylation of insulin-stimulated insulin-related substrate (IRS)-1 was suppressed by Ang II, and the suppression was ameliorated by olmesartan, but not PD123,319, in both WF and WL. In contrast, the phosphorylation of IRS-1 on Ser(307) was elevated by the Ang II, and the elevation was suppressed by olmesartan, but not by PD123,319, in both WF and WL. These findings demonstrated that Ang II signaling contributes to cell proliferation and inhibition of the insulin signaling pathways through AT1R, but not trough AT2R, in both non-diabetic and diabetic VSMCs.

Effect of pioglitazone on atherogenic outcomes in type 2 diabetic patients: a comparison of responders and non-responders.

The aim of this study was to evaluate the anti-atherogenic efficacy of pioglitazone, a thiazolidinedione derivative, on the change in atherogenic outcomes by comparing responder and non-responder groups in type 2 diabetic patients. Twenty-three patients with poor diabetic control were treated with 15 mg of pioglitazone for 12 months. The levels of fasting plasma glucose (FPG), HbA1c, triglycerides (TG), total cholesterol (T-Cho), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were measured monthly, and those of remnant-like particle-cholesterol (RLP-C) and lipoprotein (a) [Lp (a)] were measured every 3 months. In Month 6, the patients were divided into two groups according to the decrease in HbA1c level: the responder group showed a decrease of > or =1%; the non-responder group, a decrease of <1%. In the responder group, the levels of FPG and HbA1c decreased significantly after Month 3. The values of the body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) index, LDL-C, and RLP-C were significantly higher in the responder group than in the non-responder group. Although the levels of T-Cho and HDL-C were unchanged in both groups, those of TG and RLP-C were drastically reduced in the responder group. Interestingly, the relative change in Lp (a) was significantly decreased in both groups. These results strongly suggest that pioglitazone is beneficial for type 2 diabetic patients with high levels of BMI, HOMA-IR, LDL-C, and RLP-C, as it helps to prevent the progression of atherosclerosis, including coronary heart diseases.

Association of decrease in serum dehydroepiandrosterone sulfate levels with the progression to type 2 diabetes in men of a Japanese population: the Funagata Study.

Association of serum dehydroepiandrosterone sulfate (DHEAS) levels with insulin resistance and impairment of insulin secretion have been reported. We here examined the association of serum DHEAS levels with type 2 diabetes mellitus (DM) and the progression to DM. The serum DHEAS levels at baseline (from 1995 to 1997) were evaluated in 1709 individuals (998 women and 711 men) from a cohort population (n = 3706) of the Funagata Study. Glucose tolerance was evaluated at baseline as well as at 5-year follow-up examinations (n = 970, follow-up rate, 56.8%) according to the 1985 World Health Organization criteria. The statistical significance of the difference between any 2 groups was determined by the Student t test. Multiple logistic regression analysis determined the association of the traits with the progression to DM at the 5-year follow-up examinations. P < .05 was accepted as statistically significant. The serum DHEAS levels were significantly lower in DM than in normal glucose tolerance. However, this difference was not significant when adjusted for age. In men, the decrease in serum DHEAS levels by the 5-year follow-up examinations was significantly larger in the subjects who became diabetic than in the subjects who remained normal glucose tolerance, even when adjusted for age ( P = .0003). Multiple logistic regression analysis revealed a significant association of the decrease in serum DHEAS levels with the progression to DM, with an odds ratio (per 0.1 log ng/mL) of 1.410 (95% confidence interval [CI], 1.020-1.948, P = .038), independently from age, height, and 2-hour plasma glucose in men. A decrease in serum DHEAS levels seems to be associated with the progression to DM in Japanese men.

Altered PDGF-BB-induced p38 MAP kinase activation in diabetic vascular smooth muscle cells: roles of protein kinase C-delta.

OBJECTIVE: We investigated the regulation of p38 mitogen-activated protein kinase (MAPK) by platelet-derived growth factor (PDGF)-BB and its biological effects in cultured normal and diabetic rat vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMC growth from diabetic rats was faster than that from normal rats. The expression of the PDGF beta-receptor in diabetic VSMCs was significantly elevated compared with that in normal cells, and PDGF-BB-induced p38 phosphorylation in diabetic cells was more enhanced via MAPK kinase (MKK) 3/6. The level of PKC activity in diabetic cells increased more than that in normal cells with or without PDGF-BB. Although protein kinase C (PKC)-betaII and PKC-delta were activated by diabetes, PDGF-BB could further enhance the level of PKC-delta alone. PDGF-BB-induced cell migration was more elevated in diabetic VSMCs, and the increase was significantly inhibited by SB-203580, rottlerin, and antisense oligodeoxynucleotides for PKC-delta. PDGF-BB-induced p38 phosphorylation also regulated cell growth, cyclooxygenase-2 levels, and arachidonic acid release, but not apoptosis. These levels were more elevated in diabetic cells, which were inhibited by SB-203580. CONCLUSIONS: Our study established that PDGF-BB phosphorylated p38 via PKC-delta and the subsequent MKK 3/6, leading to cell growth regulation and the progression of a chronic inflammatory process in diabetic VSMCs.

Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study.

OBJECTIVE: To examine whether decreased serum levels of adiponectin are an independent risk factor for the progression to type 2 diabetes in a Japanese population. RESEARCH DESIGN AND METHODS: The serum levels of adiponectin and tumor necrosis factor-alpha (TNF-alpha) at baseline (from 1995 to 1997) were evaluated in 1,792 individuals (1,023 women and 769 men, aged 58.5 +/- 12.5 years) from a cohort population (n = 3,706) of the Funagata study. Glucose tolerance was evaluated at baseline and also at 5-year follow-up examinations (n = 978, follow-up rate, 54.6%) according to the 1985 World Health Organization criteria. The correlation of clinical traits with serum levels of adiponectin was examined. The association of the traits with the progression to type 2 diabetes at the 5-year follow-up was also examined. RESULTS: Among the traits examined, the correlation with aging was highest (r = 0.312, P < 0.001). Eighteen subjects with normal glucose tolerance (NGT) developed diabetes, and 709 remained NGT at the 5-year follow-up examinations. The subjects who became diabetic had decreased serum levels of adiponectin (7.29 +/- 2.35 vs. 9.13 +/- 2.35 10 x log microg/ml, P = 0.009). Multiple logistic regression analysis with age, sex, waist-to-hip ratio, and 2-h plasma glucose as the variables revealed that serum adiponectin level (odds ratio [per 0.1 log microg/ml] 0.766, P = 0.029) was an independent risk factor for the progression to type 2 diabetes. The subjects whose serum levels of adiponectin were in the lowest tertile were 9.320 times (95% CI 1.046-83.1) more likely to develop diabetes than those in the highest tertile (P = 0.046). CONCLUSIONS: Decreased serum adiponectin level is an independent risk factor for progression to type 2 diabetes.

[Development of a new method for diagnosing the origin of urinary bleeding by doghnut-shape urinary red blood cells].

Although the presence of acanthocytes (AC) is a reliable indicator of glomerular bleeding, acanthocytes could be observed in only 60% of patients with glomerulonephritis. Therefore, we attempted to develop a new method for diagnosing the origin of urinary bleeding by the morphological characteristics of doughnut-shaped of urinary red blood cells (RBC). In the present study, urine samples from 7 patients with glomerular bleeding and 4 patients with non-glomerular bleeding, and from 35 urine samples of the glomerular bleeding and non-glomerular bleeding-model were examined. The various type of RBC were observed by a phase contrast microscopic examination. The doughnut-shaped RBC were divided into three shapes (namely, smooth, uneven, target-shaped RBC) by individual characteristics. The appearance rate of each shape was calculated, and both outer and inner diameters of doughnut-shaped RBC in the photographs were also measured. Although there was no change in the value of outer diameter of doughnut-shaped RBC between glomerular bleeding and non-glomerular bleeding, the values of inner diameter of doughnut-shaped RBC in non-glomerular bleeding was significantly smaller than those in glomerular bleeding in all shapes. These results strongly suggested that the measurement of inner diameters of doughnut-shaped RBC is one of the useful diagnostic methods to distinguish the origin of urinary bleeding when AC could not be observed.

Mechanism of an inhibitory effect of nipradilol on rat vascular smooth muscle cell growth.

The aim of this study was to clarify the mechanism of an inhibitory effect of nipradilol on cultured rat vascular smooth muscle cell (VSMC) growth. After being starved, cultured VSMCs were stimulated by 5% fetal bovine serum with various concentrations of nipradilol. Nipradilol dose-dependently decreased the values of [(3)H]-thymidine incorporation, cell numbers and total cellular protein content, and the levels of phosphorylated extracellular signal-regulated protein kinase 1/2 and p38. It also suppressed the level of proliferative cell nuclear antigen in a dose-dependent manner. In contrast, nipradilol did not change the level of the phosphorylated value of c-jun NH(2)-terminal protein kinase or cytoplasmic histone-associated DNA fragments in VSMCs. These results indicate that nipradilol suppresses cell growth without apoptosis in rat VSMCs, suggesting that it could be effective for preventing the progression of restenosis after angioplasty.

Clinical utility and approach to estimate postprandial hypertriglycemia by a newly designed oral fat-loading test.

The objective of this study was to estimate postprandial hypertriglycemia by a newly designed oral fat-loading test. Twenty-three healthy normolipidemic volunteers were orally administered a test meal consisting of a mixture of Telmeal 2.0 and 20 g of salt-free butter after fasting for 12 h. To measure the levels of total cholesterol (T-Cho), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), remnant-like particle-cholesterol (RLP-C), lipoprotein (a) [Lp (a)], free fatty acid, apolipoproteins (Apos), plasma glucose (PG), immunoreactive insulin (IRI), and high-sensitivity C-reactive protein (hs-CRP), venous blood samples were collected before the meal and at each hour until 9 h after fat-loading. The levels of both TG and RLP-C were drastically elevated at 2 h after fat-loading and these levels remained high until 4 h (p < 0.01). A significant correlation between TG and RLP-C was also observed at 2, 3 and 4 h, and the values of the correlation coefficients (r) were 0.837, 0.838, and 0.908, respectively. In contrast, the levels of T-Cho, HDL-C, Lp (a), Apos, PG, and hs-CRP did not change. Furthermore, there were no gastrointestinal symptoms during or after the study. These results strongly suggested that this newly designed fat-loading test was very useful for evaluating postprandial hypertriglycemia, including remnant concentrations.

Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese.

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.

[Our practical training program in laboratory medicine for medical students--Yamagata University].

At the Department of Laboratory Medicine at Yamagata University, our medical students are trained to have practical knowledge and the ability to plan laboratory examinations for the clinical diagnosis of patients. For 4th-year medical students, 31 clinical lectures are scheduled on a variety of subjects concerning laboratory findings. The 2-week practical training of 5th-year students includes an educational curriculum that allows them to master the various aspects of laboratory examinations, such as collecting blood samples, determining flow-volume curves, and conducting abdominal echograms. Finally, 6th-year medical students undergo a 5-week training period during which they learn the essentials of laboratory examinations. We are proud of our present clinical curriculum for medical students. However, within a couple of years, the clinical educational program for medical students will be changed for the purpose of better preparing medical doctors in Japan. The advisory organ of the Japanese Ministry of Health, Labor, and Welfare has recommended the induction of a newly developed model core curriculum that will be nationally standardized and will focus on problem-based learning for medical students. Therefore, the present educational system, even in the field of laboratory medicine, will have to be changed.

[Evaluation of a new method for diagnosing the origin of urinary bleeding by the morphological characteristics of urinary red blood cells].

In this study, we attempted to develop a new method for diagnosing the origin of urinary bleeding by the morphological characteristics of urinary red blood cells (RBC). Seventy-five samples were divided into five types by individual features using phase-contrast microscopy. It was revealed that the ratios of type III, namely acanthocytes, and IV, namely donut-shaped RBC, were significantly higher in patients with glomerular bleeding than those with non-glomerular bleeding. Acanthocytes seemed to be specific to glomerular bleeding, but some urinary samples from patients with glomerular bleeding did not show acanthocytes. Therefore, we suggest that the detection of a combination of acanthocytes and donut-shaped RBC in a urine sample is useful for the diagnosis of glomerular bleeding.