Significance of platelet-derived microparticles and activated platelets in diabetic nephropathy

We measured levels of platelet-derived microparticles (PMP), which have coagulative activity and are produced by platelet activation or physical stimulation, and CD62P/CD63-positive platelets in patients with diabetes mellitus to determine their clinical significance and effects on complications of diabetes including diabetic nephropathy. We also compared these levels before and after administration of the antiplatelet drug cilostazol. Plasma PMP and CD62P/CD63-positive platelet levels were significantly higher in patients with diabetes mellitus than normal controls. CD62P-positive platelet levels were significantly higher in patients with nephropathy than in patients without complications. After administration of cilostazol, PMP and CD62P/CD63-positive platelet levels were significantly decreased. The increases in platelet activity and its related procoagulant activity appear to account in part for the hypercoagulability observed in diabetes mellitus. Our findings suggest that activated platelets might play a role in the development of diabetic nephropathy. Furthermore, antiplatelet therapy with cilostazol for diabetic patients may be useful as antithrombin therapy including antiplatelet therapy, since it suppresses the production of intrinsic coagulants produced by platelet activation.     

Effects of the new angiotensin II type 1 receptor antagonist KRH-594 on several types of experimental hypertension

The antihypertensive effect of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H- tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4-thiadiazoline-2- ylidene]aminocarbonyl]-1-cyclopentenecarboxylate (CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, was studied in several experimental hypertensive models. The effects of KRH-594 on the circulating reninangiotensin system and on renal function were also investigated. Oral administration of KRH-594 (0.3 or 1 mg/kg) dose-dependently inhibited the angiotensin II-induced pressor response in common marmosets. KRH-594 (1, 3, or 10 mg/kg p.o.) dose-dependently exerted a long-lasting antihypertensive effect in spontaneously hypertensive rats (SHRs) and in 2-kidney 1-clip renal hypertensive rats (RHRs). Furthermore, repeated oral administration of KRH-594 (3 or 10 mg/kg/d) reduced blood pressure dose-dependently in SHRs, RHRs, and renal hypertensive dogs without tachycardia and with no evidence of a rebound phenomenon following drug withdrawal. On the other hand, in deoxycorticosterone acetate salt rats and normotensive rats, KRH-594 (10 or 30 mg/kg p.o.) did not have significant effects on systolic blood pressure. In SHRs, KRH-594 (3 or 10 mg/kg/d p.o. for 2 weeks) dose-dependently increased both plasma renin activity and the plasma angiotensin I concentration, but had no effect on the urinary excretion of sodium, potassium, and chloride or on creatinine clearance. These results suggest that KRH-594 should be effective in patients with essential or renal hypertension.     

A case of eosinophilic lymphfolliculosis of the skin (Kimura's disease)

Eosinophilic lymphfolliculosis of the skin (Kimura's disease) in a 31-year-old male is reported. He had two subcutaneous tumors, 10 x 9 x 3 cm and 9 x 7 x 2 cm in size, in the right retroauricular and submaxillary areas respectively. Histopathologic examination of the tumors showed marked infiltration of eosinophils, mast cells and lymphocytes, and angiomatous proliferation of blood vessels from the dermis to the skeletal muscular tissue. In subcutaneous adipose tissue, there were numerous lymphfollicles with germinal centers in which IgE deposition with reticular appearance was observed by immunofluorescent technique. Study of the peripheral blood showed marked eosinophilia and an increase of serum IgE level. These findings suggest the possibility that Type 1 allergic reaction may be involved in the histogenesis of eosinophilic lymphfolliculosis of the skin, although there is no direct evidence for the existence of antigens which react to IgE antibody in the skin lesion.     

Changes in patterns of left ventricular hypertrophy after aortic valve replacement for aortic stenosis and regurgitation with St. Jude Medical cardiac valves

In this study, we analyzed the extent and pattern of regression of left ventricular (LV) hypertrophy after aortic valve replacement in patients with aortic stenosis (AS) and compared the results with those of another group of patients with aortic regurgitation (AR). Seventy patients who underwent isolated aortic valve replacement were divided into 2 groups. Group 1 was comprised of 29 patients who underwent aortic valve replacement for aortic stenosis, and Group 2 of 41 patients who underwent aortic valve replacement for aortic regurgitation. A third group of 10 healthy subjects served as a healthy control group. Echocardiographic studies were done before the operation and 5 years postoperatively. At follow-up, a significant reduction in the left ventricular mass was found in both groups, but it remained significantly greater than in the healthy control group. The ratio of LV wall thickness to radius (th/r) in Group 1 decreased significantly, and at follow-up it was within the normal value. In Group 2, the th/r ratio increased, and at follow-up it was within the normal value. After aortic valve replacement, the wall thickness remained significantly greater than normal for patients with AS, and the chamber radius remained significantly greater than normal for patients with AR. For these reasons, LV hypertrophy still existed in both groups at postoperative follow-up. The actuarial survival rate was 85.3% at 16 years for Group 1 and 83.4% at 18 years for Group 2. There was no significant difference in the long-term survival rates between the 2 groups. Actuarial freedom from valve-related events was 91.9% at 16 years for Group 1 and 82% at 18 years for Group 2. There was no significant difference in the valve-related event free curves between groups. After 5 years of follow-up, th/r reached normal for both groups, indicating remodeling of the LV geometry after aortic valve replacement.     

Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression

Background. The phenotypic expression of tumor cells is widely thought to resemble that of the tissue of origin. In the present study, to assess phenotypic changes that occur with disease progression, we investigated human differentiated gastric cancers at different depths of invasion for component cancer cell types. Methods. Using a combined mucin histochemical and immunohistochemical approach, we classified surgical specimens of 301 differentiated gastric cancers into three types: gastric epithelial cell (G) type, intestinal epithelial cell (I) type and mixed gastric and intestinal (GI) type, according to the phenotypic differentiation of the component cancer cells. The relation between the phenotypic type of cancer and their depth of invasion was evaluated. Results. The proportion of G type cancers was 41.4% in early (tumor invasion of mucosa or submucosa) cases, decreasing to 22.2% in advanced (tumor invasion of muscularis propia or deeper) cases, whereas the proportion of I type cancers increased with progressive disease from 23.5% to 31.1% (P < 0.01). Cancers invading the subserosa or deeper included more I type cases and fewer G type than cancers limited to the mucosa (P < 0.01). In most cases of each phenotypic type, intestinal metaplasia was recognized in the surrounding background mucosa, but no clear relation was shown between the phenotype of cancers and the degree of intestinal metaplasia in the background mucosa, suggesting that intestinal metaplasia is not always a preneoplastic lesion. Conclusions. A phenotypic shift from G to I type expression was observed with the progression of human differentiated gastric cancers. Intestinalization may occur independently in cancerous and noncancerous gastric mucosa. Received for publication on May 1, 1998; accepted on Oct. 22, 1998     

Penetrating lung and diaphragmatic injuries with no abnormal finding of chest X-ray: a case report

A case of penetrating lung and diaphragmatic injuries with no abnormal findings of chest X-ray is reported. A 76-year-old man was admitted to our hospital due to penetrating chest trauma. A simple X-ray film of the chest on admission revealed no abnormal finding. An emergency operation was performed. On exploring the back open wound, we found a laceration of 7 cm in diameter in the right diaphragm and lung laceration. Then we repaired primarily with absorbable material. The postoperative course was uneventful, and the patient was discharged 12 days later. Penetrating truncal traumas can result in diaphragmatic injury. Sometimes the clinical and roentgenographic findings are unreliable. If the diagnosis is missed, a diaphragmatic injury may occur delayed diaphragmatic hernias within hours to years. Accordingly, initial wound exploration are important for the diagnosis of diaphragmatic injury in avoiding serious complications.     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.