Aims: To investigate collagen remodelling in the interstitium of the heart in patients with diabetes. Methods: Immunohistochemical study of the biopsied myocardium using type specific anticollagen antibodies (I, III, IV, V, VI) was performed in 12 patients with non-insulin dependent diabetes mellitus and six non-diabetic patients. There was no history of hypertension or coronary artery stenosis in any of the patients. Results: Noticeable accumulations of collagen types I, III, andVI in the myocardial interstitium were recognised in both groups, but little accumulation of types IV or V was found. Types I and III mainly stained in the perimysium and perivascular region, while type VI predominantly stained in the endomysium. There was no disease specific accumulation of collagen in diabetes mellitus. The percentage of total interstitial fibrosis in the myocardium was significantly higher in the diabetic group than in the control group (p < 0.05). Although the percentages of coliagen types I and VI did not differ between the two groups, the percentage type of III was significantly higher in the diabetic group than in the controls (p < 0-01). Conclusions: Collagen remodelling mainly as a result of an increase in collagen type III in the perimysium and perivascular region, occurs in the hearts of patients with diabetes.

Antimicrobial peptides/proteins are widespread in nature and play a critical role in host defense. To investigate whether these components contribute to surface protection of newborns at birth, we have characterized antimicrobial polypeptides in vernix caseosa (vernix) and amniotic fluid (AF). Concentrated peptide/protein extracts were obtained from 11 samples of vernix and six samples of AF and analyzed for antimicrobial activity using an inhibition zone assay. Proteins/peptides in all vernix extracts exhibited strong antibacterial activity against Bacillus megaterium (strain Bm11), in addition to antifungal activity against Candida albicans, whereas AF-derived proteins/peptides showed only the former activity. Fractions obtained after separation by reverse-phase HPLC exhibited antibacterial activity, with the most pronounced activity in a fraction containing alpha-defensins (HNP1-3). The presence of HNP1-3 was proved by dot blot analysis and confirmed by mass spectrometry. Lysozyme and ubiquitin were identified by sequence analysis in two fractions with antibacterial activity. Fractions of vernix and AF were also positive for LL-37 with dot blot and Western blot analyses, and one fraction apparently contained an extended form of LL-37. Interestingly, psoriasin, a calcium-binding protein that is up-regulated in psoriatic skin and was found recently to exhibit antimicrobial activity, was characterized in the vernix extract. The presence of all of these antimicrobial polypeptides in vernix suggests that they are important for surface defense and may have an active biologic role against microbial invasion at birth.

Anomalous origin of the coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death in the absence of atherosclerosis. However, in Japan, this anomaly is usually treated medically rather than surgically. To clarify the clinical features of anomalous origin of the coronary artery in Japanese and the prognosis of such patients who are treated medically, we reviewed 56 patients with anomalous origin of the coronary arteries. The mean age of these patients was 55.9 +/- 11.5 years. Anomalous origin of the right coronary artery from the left sinus of Valsalva was seen most frequently (78.6%). In contrast, we found no cases of anomalous origin of the left coronary artery from the right sinus of Valsalva traversing between the aorta and the pulmonary trunk. A history of syncope (14.3%) and aorta regurgitation (21.4%) was frequent and serious complications during exercise stress testing occurred in 5 patients. These patients were treated medically, such as by limiting exercise or by the oral administration of medicine. During the follow up period (mean 5.6 +/- 4.2 years), death directly related to anomalous origin of the coronary artery was not found despite the lack of surgical treatment. Our results suggest that the prognosis of these middle-aged-to-elderly patients without atherosclerosis is relatively good, despite the lack of surgical treatment.

Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs) and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP) that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner. The induction was suppressed by two different p38 antagonists, indicating an effect via the p38-dependent pathway. Lactose also induced CAMP in the colonic epithelial cell line T84 and in THP-1 monocytes and macrophages. It further exhibited a synergistic effect with butyrate and phenylbutyrate on CAMP induction. Together, these results suggest an additional function of lactose in innate immunity by upregulating gastrointestinal AMPs that may lead to protection of the neonatal gut against pathogens and regulation of the microbiota of the infant.

The Lys183 del mutation in the cTnI gene in patients with HCM is associated with variable clinical features and outcomes. HCM caused by the Lys183 del mutation has a significant disease penetrance. This mutation is associated with sudden death at any age and dilated cardiomyopathy-like features in those aged >40 years. However, it remains unclear whether screening of families with HCM for this mutation will be useful in patient management and counseling.