Search

AIM: Pyridoxamine inhibits the development of diabetic complications. CD36 is a receptor/transporter which binds fatty acids of lipoproteins. The objective of the present study was to examine the pleiotropic effects of pyridoxamine, especially CD36 expression in KK-A(y)/Ta mice with type 2 diabetic nephropathy. METHODS: KK-A(y)/Ta mice were divided into 2 groups as follows: pyridoxamine treatment group and a tap water group as controls. The urinary ACR, fasting serum insulin, TG and lipoprotein subclasses were measured as biochemical parameters. The renal expressions of malondialdehyde (MDA) were evaluated by immunohistochemistry. CD36 mRNA expressions in kidney and adipose tissue were also evaluated using real-time PCR. RESULTS: Pyridoxamine decreased levels of urinary ACR, serum TG, especially VLDL and fasting serum insulin. MDA accumulation in the pyridoxamine treated group was significantly lower than those in the non-treatment group. The CD36 accumulation and mRNA expressions in kidney and adipose tissue in the treatment group were significantly higher than those in the non-treatment group. CONCLUSIONS: It appears that pyridoxamine ameliorated lipid peroxidation and insulin resistance in KK-A(y)/Ta mice. This pleiotropic effect of pyridoxamine was related to CD36 expression in the kidney and adipose tissue. [ABSTRACT FROM AUTHOR]

Differentiating nonspecific interstitial pneumonia (NSIP) from usual interstitial pneumonia (UIP) is important for the determination of both treatment and prognosis. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we examined 8 UIPs, 8 NSIPs, and 30 normal lung tissues. Comparisons with control in 2D-DIGE showed that (a) in UIP, nine protein spots were significantly upregulated and seven were significantly downregulated, (b) in NSIP, four protein spots were significantly upregulated and nine were significantly downregulated. The detected proteins were analyzed by MALDI-TOF mass spectrometry, allowing qualitative differences in vimentin subtypes to be characterized. One vimentin subtype was upregulated in UIP, while another one was downregulated in NSIP (vs. control). These different characteristics were partially supported by the results of Western blot analysis. Our immunohistochemistry revealed vimentin expression within fibroblasts (a) in fibroblastic foci in UIP and (b) in fibrotic alveolar walls in NSIP. Differences in vimentin subtypes may provide useful biomarkers for separating NSIP from UIP, alongside differences in histological characteristics.

Background: Recently, the role of aldosterone in metabolic syndrome (MS) has aroused interest and several reports have suggested that aldosterone blockade could be beneficial in reducing blood pressure (BP)., Methods: To examine the add-on effects of eplerenone (EP) on BP in patients with MS, 54 hypertensive patients with MS and 44 without MS were recruited. Systolic and diastolic BPs in mmHg before the initiation of EP was 144/84 ± 13/12 (MS group) and 147/85 ± 12/14 (non-MS group). Before the start of EP, all patients in both groups were treated with at least one antihypertensive drug. BPs were checked on every visit (at least every 2 months) and serum chemistries were measured every 4 months. The levels of microalbuminuria and aminoterminal pro-brain natriuretic peptide (NT pro-BNP) were determined before the start of and at the end of the study. Patients were followed for 1 year. If adverse effects were reported by patients or found in laboratory studies, EP was withdrawn., Results: One month after the start of EP, BPs were decreased to 140/80 ± 12/12 mmHg (MS group) versus 142/82 ± 11/12 mmHg (non-MS group) and there was no difference between the two groups. Towards the end of the study, BPs of both groups gradually decreased. At the end of the study, BPs of both groups were 129/76 ± 15/13 mmHg (MS group) versus 133/78 ± 13/11 mmHg (non-MS group). There was a significant difference in reduction of systolic BP between the two groups (p < 0.05). Add-on EP significantly decreased the levels of urinary excretion of albumin in MS patients but not in non-MS patients (p < 0.05). There was a significant correlation between reduction of systolic BP and NT pro-BNP but not microalbuminuria in the MS group (p < 0.05). There were no serious adverse effects in both groups., Conclusion: EP may have some beneficial effects in lowering BP in patients with reduction of microalbuminuria.

In the duodenum, mixed exocrine-endocrine tumors exhibiting both neuroendocrine and glandular differentiations [cf. appendiceal goblet cell carcinoids (GCCs)] are rare. We present a Japanese case with a duodenal GCC that was found during pathologic examination of a gastrectomy specimen removed for gastric mucosal cancer. The tumor was widely distributed within both the first portion of the duodenum and the gastric antrum, although mucosal involvement was observed only in the duodenum. The tumor cells formed solid nests, trabeculae, or tubules, and some displayed a goblet cell appearance. They were immunoreactive against antibodies for both serotonin and somatostatin, and showed an argentaffin reaction (similar to a "midgut" enterochromaffin cell carcinoid). Ultra-structurally, the tumor cells had an amphicrine nature. Physicians encounter GCC in the duodenum only rarely, and its discovery may be incidental. Its diagnosis will be challenging and will require careful clinical and pathologic examinations.

ANG-(1-7) is associated with vasodilation and nitric oxide synthase stimulation. However, the role of ANG-(1-7) in type 2 diabetes mellitus is unknown. In this study, we examined the hypothesis that ANG-(1-7) attenuates ANG II-induced reactive oxygen species stress (ROS)-mediated injury in type 2 diabetic nephropathy of KK-A(y)/Ta mice. KK-A(y)/Ta mice were divided into four groups: 1) a control group; 2) ANG II infusion group; 3) ANG II+ANG-(1-7) coinfusion group; and 4) ANG II+ANG-(1-7)+d-Ala(7)-ANG-(1-7) (A779) coinfusion group. In addition, primary mesangial cells were cultured and then stimulated with 25 mM glucose with or without ANG II, ANG-(1-7), and A779. The ANG II+ANG-(1-7) coinfusion group showed a lower urinary albumin/creatinine ratio increase than the ANG II group. ANG-(1-7) attenuated ANG II-mediated NAD(P)H oxidase activation and ROS production in diabetic glomeruli and mesangial cells. ANG II-induced NF-κB and MAPK signaling activation was also attenuated by ANG-(1-7) in the mesangial cells. These findings were related to improved mesangial expansion and to fibronectin and transforming growth factor-β1 production in response to ANG II and suggest that ANG-(1-7) may attenuate ANG II-stimulated ROS-mediated injury in type 2 diabetic nephropathy. The ACE2-ANG-(1-7)-Mas receptor axis should be investigated as a novel target for treatment of type 2 diabetic nephropathy.

Background: Although angiotensin II type 1 receptor blockers (ARB) have beneficial effects in patients with diabetic nephropathy, they may induce a compensatory increase in renin. Renin exhibits profibrotic actions independent of angiotensin II, which is regulated by extracellular signal-regulated kinase 1 and 2 (ERK1/2). Calcitriol (1,25(OH)(2)D(3)) is a negative inhibitor of the renin-angiotensin system and the present study examined the effects of combination therapy with an ARB and 1,25(OH)(2)D(3) on diabetic nephropathy in KK-A(y)/Ta mice., Methods: KK-A(y)/Ta mice were divided into four groups: ARB group, 1,25(OH)(2)D(3) group, combination group, and control group. The urinary albumin/creatinine ratio (ACR) was measured and the renal expression of renin, p-ERK1/2 and TGF-β1 protein determined., Results: The levels of urinary ACR in the combination group were significantly lower than those in the ARB or control group. Renal expression of renin in the ARB group was significantly increased compared with the control group but was significantly decreased in both the 1,25(OH)(2)D(3) and combination group. Renal expression of p-ERK1/2 in the combination group was significantly decreased compared with the control or ARB group. Expression of TGF-β1 protein in the ARB and combination groups, especially the combination group, was significantly decreased compared with those in the control group., Conclusions: These data suggest that the addition of 1,25(OH)(2)D(3) to therapy with ARB further reduced proteinuria by suppressing the compensatory increase in renin expression in type 2 diabetic nephropathy. These effects might relate to suppression of renin, ERK1/2 and TGF-β1 expression which may or may not depend on angiotensin II., (Copyright © 2010 S. Karger AG, Basel.)

Human intestinal spirochetosis is a colorectal infectious disease caused by 2 Brachyspira species. Its diagnosis is established by histology, culture, and polymerase chain reaction, but the value of cytologic examination in routine practice remains unclear. In this study, imprint cytology of biopsy specimens was examined for cytologic features specific to human intestinal spirochetosis. Specimens were obtained from 65 colorectal regions (1-3 regions from each case) in 25 ultrastructurally and/or genetically confirmed human intestinal spirochetosis cases (20 with Brachyspira aalborgi, 3 with B pilosicoli, 2 with both genotypes). In cytologic specimens, spirochetes tended to be floating freely within the mucus and intestinal fluid, whereas the "fringe formation" of spirochetes typically observed in histologic specimens was indistinct in cytologic specimens. Spirochetes were identified in 58 regions (89.2%) and 23 cases (92.0%) by cytology, against in 50 regions (76.9%) and 22 cases (88.0%) by histology (no significant differences). In 6 of 8 regions exhibiting positive cytology and negative histology, B pilosicoli was present within the mucus. Hence, B pilosicoli may tend to float in the mucus. In conclusion, cytologic examination would be useful for the routine identification of human intestinal spirochetosis, especially if B pilosicoli is involved. Further, we suggest the existence of differences in biological behavior between these spirochetes., (Copyright 2010 Elsevier Inc. All rights reserved.)

Two patients underwent uneventful total removal of convexity or trigone meningioma, but subsequently edema enlarged causing symptoms 3-4 weeks later. Gradual improvement was obtained by steroid administration in 1 patient and re-craniotomy in 1 patient. The histological findings in Case 1 were not confirmed, but inflammatory reaction against residual microfibrillar collagen hemostat (MCH) may have developed. The specimen from around the cyst in Case 2 showed moderate staining for vascular endothelial growth factor (VEGF). VEGF secreted by the tumor might have resulted in spread of inflammation due to MCH in the brain parenchyma. Furthermore, inflammatory reactions may have obstructed or formed a one-way communication in the inferior horn and residual cavity, resulting in malabsorption of cerebrospinal fluid. Postoperative edema with the timing in these cases is difficult to anticipate. However, the risk of this phenomenon can probably be minimized by ensuring that MCH is removed as effectively as possible after use, or by refraining from use in the brain parenchyma and by taking care to connect the residual cavity to the ventricular system, particularly if the tumor contacts a cerebral ventricle.

We present a middle-aged, heterosexual Japanese man with mixed infections including human intestinal spirochetosis, which led us to the detection of human immunodeficiency virus (HIV) infection. The patient had syphilis without related physical or neurological findings. An examination for the serum antibody for HIV performed 9 years previously was negative. In a complete medical checkup at the present time, human intestinal spirochetosis and unspecified entamebic cysts were suggested by histological examination of colonic biopsy material and parasitic examination of the intestinal fluid, respectively. Moreover, a serological test for the antibody for HIV was positive. In specimens obtained by colonoscopy, Brachyspira aalborgi was diagnosed by ultrastructural study and the polymerase chain reaction method for bacterial 16S ribosomal deoxyribonucleic acid. Although HIV infection remains at low prevalence in Japan, we recommend examination for HIV infection in patients with human intestinal spirochetosis, especially when other co-infections are apparent.

Advanced glycation end products (AGEs) contribute to the pathogenesis of diabetes-associated complications. Previously, we reported the possible effect of pyridoxamine (K-163), an AGE inhibitor, on improvement of glucose intolerance in type 2 diabetes mellitus KK-A(y)/Ta mice. Recently, AGEs and oxidative stress have been shown to induce insulin resistance. The objective of the present study is to examine the effect of pyridoxamine on glucose intolerance and oxidative stress. C57BL/6J mice were divided into 3 groups as follows: low-fat diet, high-fat diet, and high-fat diet with pyridoxamine treatment. Body and adipose tissue weight, serum insulin, hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine levels were measured. Nicotinamide adenine dinucleotide phosphate subunits, antioxidant enzymes, and adipocytokine messenger RNA expressions in the adipose tissues were evaluated. Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle were also evaluated. Body and adipose tissue weights of the pyridoxamine treatment group were significantly decreased compared with those of the high-fat diet group. Pyridoxamine attenuated serum hydrogen peroxide, malondialdehyde and AGE, and urinary 8-hydroxy-2'-deoxyguanosine and nicotinamide adenine dinucleotide phosphate oxidase expression; increased antioxidant enzyme expression; and improved dysregulation of adipocytokines in adipose tissues. Pyridoxamine improved blood glucose levels after glucose injection and fasting hyperinsulinemia. Suppressed Akt/protein kinase B activity and glucose transporter 4 translocation in skeletal muscle in high-fat diet mice were improved by pyridoxamine treatment. It appears that the antioxidative effect of pyridoxamine is associated with improvement of glucose intolerance and obesity in C57BL/6J mice fed a high-fat diet. We assume that pyridoxamine may be useful in the treatment of the obesity-associated metabolic syndrome.

Background: Adenosine monophosphate activated protein kinase (AMPK) has a protective effect on lipid peroxidation. Adiponectin and AMPK might have a role in the pathogenesis of diabetic nephropathy. Blockade of the renin-angiotensin system (RAS) increases adiponectin levels and reduces oxidative stress. The objective of the present study was to examine lipid peroxidation via adiponectin and AMPK activation in the kidneys of KK-A(y)/Ta mice by RAS inhibitors, such as enalapril and/or losartan., Methods: KK-A(y)/Ta mice were given enalapril (2.5 mg/kg/day) and/or losartan (25 mg/kg/day), or hydralazine (25 mg/kg/day) in the drinking water for 8 weeks starting at 8 weeks of age. They were divided into 5 groups as follows: enalapril 2.5 mg/kg/day treatment group (n = 5), losartan 25 mg/kg/day treatment group (n = 5), enalapril 2.5 mg/kg/day + losartan 25 mg/kg/day combination treatment group (n = 5), hydralazine 25 mg/kg/day treatment group (n = 5) and tap water group as the untreated group (n = 5). The urinary albumin/creatinine ratio (ACR), serum adiponectin and systemic blood pressure were measured as test parameters. Expressions of adiponectin, phospho-AMPKalpha (p-AMPKalpha) and phospho-acetyl CoA carboxylase(beta) (p-ACC(beta)) in the kidneys were evaluated by Western blot analyses. Pathological changes of glomeruli were evaluated by light microscopy. Accumulations of N(epsilon)-(carboxymethyl) lysine (CML), malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in glomeruli were evaluated by immunohistochemical analyses., Results: Enalapril and/or losartan improved levels of urinary ACR with activation of adiponectin, p-AMPKalpha and p-ACC(beta) in the kidneys. CML, MDA and 4-HNE expressions in glomeruli were significantly suppressed by enalapril and/or losartan, especially in the combination treatment group., Conclusions: It appears that enalapril and/or losartan, especially in combination, inhibited accumulation of CML/MDA/4-HNE in diabetic renal tissues. These effects might be related to lipid peroxidation via tissue-specific activation of adiponectin and AMPK., (Copyright 2009 S. Karger AG, Basel.)

We report 3 cases of solitary papillomas located in peripheral regions of the lung that are extremely rare in the literature. The patients were 75-year-old and 72-year-old men and a 53-year-old woman. One patient complained of recurrent hemoptysis. The other 2 had no symptoms, but abnormal nodular shadows were revealed by chest radiographs during a health check. The maximum diameters of the tumors were 1.0, 1.4, and 1.1 cm, respectively. The 3 tumors gave almost the same histologic findings. Papillomatous fronds lined by a stratified columnar epithelium were seen in the lumens of peripheral bronchi, bronchioles, or alveoli. The stratified columnar epithelium consisted of ciliated, mucous, and basal cells. The neoplastic epithelium extended to the alveolar region and showed a similar appearance to bronchioloalveolar or papillary type adenocarcinomas. For differential diagnosis, it is noteworthy that endobronchiolar papillomatous fronds constantly exist and spreading along alveolar walls is limited in adjacent alveoli in peripheral papillomas. The presence of ciliated cells and basal cells is considered an important finding to suggest benign character of the lesion.

Background: There are few reports on the clinical, radiologic, and pathologic features of pure mica pneumoconiosis., Methods: A case of definite pure mica pneumoconiosis in a rubber factory worker is reported with the clinicopathological findings., Results: Chest HRCT demonstrated subpleural and peribronchovascular interstitial thickening. The characteristic histologic features were pulmonary fibrosis accompanied by prominent histiocytic granulomas containing giant cells., Conclusions: Pure mica pneumoconiosis can be identified by specific radiologic and pathologic findings., (Copyright 2004 Wiley-Liss, Inc.)

To determine correlations among the levels of urinary MMP-9 and type-IV collagen, hyperglycemia, urinary protein excretion, and renal injuries in patients with type 2 diabetic nephropathy, we measured levels of urinary MMP-9 and protein, blood urea nitrogen (BUN), serum creatinine (s-Cr), fasting plasma glucose (FPG), and glycohemoglobin A1c (HbA1c) in 47 diabetic patients and 14 healthy adults. Urinary type-IV collagen was also measured in 28 diabetic patients and seven healthy adults. Patients with diabetic nephropathy were divided into two groups: 1). patients with normoalbuminuria or microalbuminuria (0-299 mg/g.Cr; n=27), and 2). patients with macroalbuminuria (>300 mg/g.Cr; n=20). The mean level of urinary MMP-9 in group 2 was significantly higher than those in healthy adults (P<0.05), and the levels of urinary MMP-9 in patients with diabetic nephropathy increased in accordance with the clinical stage of the disease. The levels of urinary MMP-9 tended to be correlated with HbA1c in these patients, but the correlation was not statistically significant. The mean level of urinary type-IV collagen in group 2 of patients with diabetic nephropathy was significantly higher than that in group 1 and healthy adults. Levels of urinary type-IV collagen in patients with diabetic nephropathy also increased in accordance with the clinical stage of the disease. The results suggest that measurements of urinary MMP-9, as well as urinary type-IV collagen, may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy, especially in the early stage., (Copyright 2004 Wiley-Liss, Inc.)

A 58-year-old woman was admitted because of bilateral diffuse nodular shadows on chest radiograph. Video-assisted thoracoscopic lung biopsy specimens showed marked lymphocytic infiltration into the bronchiolar wall. HTLV-1 antibody was examined because the patient's parents were born in Okinawa Prefecture. The patient turned out to be an adult T-cell leukemia-lymphoma (ATLL) carrier with positive HTLV-1 antibody. Therefore, HTLV-1 associated bronchiolitis was diagnosed. Although no dry symptoms appeared, it became clear by the saxon test that she was also complicated with Sjögren syndrome. Generally, it is reported that there is coherence with HTLV-1 infection and Sjögren syndrome. So the HTLV-1 infection might have accounted for the pathogenesis of these three disorders (HTLV-1 infection, bronchiolitis, Sjögren syndrome).

To review the pulmonary CT findings in sarcoidosis at diagnosis, and to analyze the change in each finding at follow-up in cases without corticosteroid treatment. The study included 21 cases of pulmonary involvement of sarcoidosis. We analyzed the presence or absence and grade of each HRCT finding: bronchial wall thickening, enlargement of vascular shadows, pleural involvement, septal thickening, small nodules, ground-glass opacities, centrilobular opacities, consolidation, nodules, and volume loss. Afterwards, we compared the initial CT with the follow-up CT, and described the change of each finding as "improved" or "not improved". Furthermore, we decided if each case as a whole was improved or not after considering all of the pulmonary CT findings. Twelve of the 21 cases were improved. Small nodules, ground-glass opacities, centrilobular opacities, and nodules had improved in more than 50% of the cases since the initial CT. However, pleural involvement (10/11) and volume loss (6/9) were not improved. Pleural involvement and volume loss correlated the radiological irreversibility (p < 0.05). Of the several pulmonary CT findings in sarcoidosis, pleural involvement and volume loss show the highest rates of irreversible pulmonary changes.

The effect of taste stimulation on serum free-amino acid concentrations and amylase and trypsin activities in fasting rats was studied. Following an acclimation period of 5 d, male Sprague-Dawley rats were fasted for 4 d and sacrificed after taste stimulation with a palatable sodium saccharin or unpalatable quinine sulfate flavored diet. Blood was collected from the portal vein and inferior vena cava at 0, 5, 10, 20 and 30 min after taste stimulation. Intestinal contents were also collected at the same time intervals as the blood collections. Total amino acid concentrations in the saccharin stimulated group increased significantly at 5 and 20 min following taste stimulation in comparison with the control of 0 time in the portal vein, and a significant difference between the saccharin and quinine stimulated groups was also observed at 5 min. No difference was found in the inferior vena cava. A high level of alanine and low level of glutamine were depicted in the portal vein as compared to that of the inferior vena cava. The elevation of alanine that is gluconeogenic amino acid was remarkable in the saccharin group at 20 min in the portal vein. Moreover, amylase and trypsin activities in the saccharin group reached peak values promptly and kept constant throughout the experiment as compared to the quinine group. The results suggest that taste stimulation originates changes in the cephalic phase amino acid concentrations in the portal vein and that taste information, overcoming a hunger, plays an important role in amino acid metabolism and digestive enzyme activities. Therefore, eating with gusto is significant for the maintenance of body functions even under starvation conditions.

Objective: The present study investigated the effect of timing of protein feeding on taste preference, serum zinc concentration and morphological changes of tongue epithelia., Methods: Weanling rats were fed one of three diets: protein-free and 2.5 or 8% purified egg protein (PEP) diets for 14 days (first feeding period). Rats in each group were further subdivided into three dietary treatments, totaling nine groups and fed one of the same three diets for 14 days (second feeding period). Preference tests between 3 or 6 mmol/L NaCl vs. deionized water were conducted in both feeding periods. At the end of each period, blood and tongue were collected for the measurement of serum zinc concentrations and morphological observations., Results: The rats fed the protein-free diet in the first feeding period did not discriminate 3 mmol/L NaCl from deionized water in both feeding periods, even though adequate protein was administered in the second feeding period. The rats fed the 2.5 or 8% PEP diet in the first feeding period discriminated 3 mmol/L NaCl from deionized water regardless of the protein levels in the diet during the second feeding period. Serum zinc concentration was proportionate to protein content in the diet at the end of each feeding period (p < 0.001), and low serum zinc concentration was restored by protein feeding. Abnormal changes of tongue epithelia were observed only in the rats fed the protein-free diet throughout the two feeding periods., Conclusions: The results suggest that protein nutrition immediately after weaning is important to maintain normal taste function.

The influence of dietary protein levels on the preference for sodium chloride was studied in juvenile rats fed diets containing 0, 25 or 50 g purified egg protein/kg and 20.0 mg zinc/kg diet. Preference tests between aqueous solution of NaCl (2-51 mmol/L) or deionized water were conducted. Blood samples were collected for measuring the serum zinc concentration. Scanning electron microscopy was performed to observe the rats' tongue epithelia. Only the rats fed 50 g purified egg protein/kg diet preferred the lowest concentration of 2 mmol/L NaCl solution to deionized water, whereas the rats fed protein-free diet did not discriminate diluted NaCl solution until the concentration was 9 mmol/L. The filiform papillae of the protein-free diet fed group showed significantly less development than the 25 g purified egg protein/kg and the 50 g purified egg protein/kg diet-fed groups. The more protein the diets contained, the higher was the serum concentration of zinc. Significant correlations were observed between protein intake and discriminated NaCl concentration (r = -0.93, P < 0.001), serum zinc (r = 0.90, P < 0.001) or length of filiform papillae (r = 0.93, P < 0.001). The present study suggests that taste preference is impaired by protein malnutrition and this may be related to zinc status.

Vasculogenesis depends on autocrine secretion of basic fibroblast growth factor (bFGF) from capillary endothelial cells. Retinoic acid (RA) induced avascular yolk sac (AVY) of mouse embryos of dams given 60 mg/kg of RA orally on Day 8 of gestation and sacrificed 3 days later. We studied the localization and transcriptional expression of bFGF and FGF-receptor (flg), heparin-binding growth factor (HBGF) activity, localization of lysosomal enzymes and alpha 1-antitrypsin (AAT), and electron microscopy of the normal mouse visceral yolk sac (VYS) and AVY. bFGF, which is normally present in the endoderm of the VYS of 8-day-old embryos and in all components of the VYS by Day 11 of gestation, was reduced in the AVY. However, in the presence of bFGF in vitro capillary nets were restored in the AVY. The mRNA for bFGF was not detectable in either VYS or AVY, while flg mRNA was detected equally in both organs in Northern blotting. The characteristic distribution pattern of lysosomal enzymes, acid phosphatase, lysozyme, and cathepsin D, and AAT was altered in the AVY. The level of acid phosphatase and AAT was reduced to 10% in the AVY. Electron microscopy revealed a partial or total loss of lysosomal membranes where the contents of lysosomes fused with adjacent lysosomes and the external organelles. These results suggest that vitelline blood vessels are not developed by endogenous autocrine bFGF but by exogenous transcellular bFGF from absorptive endodermal cells. Retinoic acid does not affect the angiogenic capacity of the VYS mesenchyme but destroys lysosomes, which release hydrolytic enzymes, leading to degradation of AAT in the endodermal cells and then digestion of endocytosed bFGF.

Studies in the taste system of mammals indicate that monosodium glutamate (MSG) produces a unique taste sensation termed umami. As a derivative of glutamic acid, MSG is a naturally occurring nutrient in many foods; its commercial use to improve food palatability for humans is well documented. Behavioral studies with experimental animals have revealed that preference for MSG in solutions and selection of MSG-flavored diets can be explained by sensory means with no appreciable effects on preference by postingestive consequences. However, preference for umami-flavored fluids is reduced by feeding rats low-protein diets or low quality protein. MSG-flavored diets, initially unpreferred, were subsequently highly selected. However, the adulteration of diets by MSG either did not or only slightly increased food intake. In light of the significant contribution of MSG to diet taste, apparently as a signal coupled to dietary proteins, physiological studies have been initiated to reveal its role as a stimulator of the cephalic phase of pancreatic exocrine secretion. Modified sham-feeding experiments with dogs have shown that oral stimulation by MSG produced significant stimulation of both pancreatic flow and protein output in conscious dogs.

The purpose of this study was to determine effects of oral stimulation of sucrose on the diurnal output of pancreatic secretion in conscious dogs. Male beagle dogs weighing 9-11 kg were prepared with gastric and duodenal fistulae. Once a day at 14:00 the animals were trained to eat a sufficient amount of a commercial stock diet to maintain their body weight. Gustatory receptors were stimulated at 9:00, 13:00, 15:00, and 18:00 for 5 min with 100 ml of 0.5% agar solutions containing 0.3 M sucrose. Pancreatic juice was collected every 5 min before and after stimulation, and volume flow and protein output were measured. As a result, we demonstrated daily fluctuations timed by feeding not only in the pancreatic basal secretions but also in pancreatic responses to the gustatory stimulation. These results suggest the significant role of taste stimuli in the nutrition of, at least digestion in, animals.

We carried out experimental and clinical studies with low-power laser to perform the surgical application. The developed device for microvascular anastomosis with semiconductor laser diode made of In-Ga-As-P was used to perform 15 end-to-end laser assisted microvascular anastomoses of carotid arteries in rabbits. In four of 7 cases which were irradiated with power output 50mW showed patency immediately after surgery with no wound disruption. A new medical device with Ga-A1-As semiconductor laser diode was developed for pain relief. A double-blind evaluation of the test was initiated in 124 patients suffering from chronic inflammatory pain. Result is that of 63 patients irradiated laser, 45(71%) were effective and of 61 cases not irradiated laser, 8(13%) were relieved pain. The data were analyzed statistically by chi square, and criterion for statistical significance was the 0.01 level. The spectral properties of laser-excited fluorescence of three photosensitizers, namely tetracycline, hematoporphyrin free base and chlorin e6Na, taken up in human arterial intima were detected. Photosensitizers were administrated to resected human arteries for 2 hours in vitro. The main results are following: 1) Photosensitizers are confirmed to be taken up in arterial intima and the fluorescence intensity decreases as the time goes on. 2) The fluorescence intensity from atheromatous plaque is usually stronger than that from normal region.

Experiments were designed to compare the nutritive values of L-, DL- and D-tryptophan in rats and chicks. Growing rats and chicks were fed for 19 and 21 days, respectively, diets containing amino acid mixtures with graded levels of either L-, DL- or D-tryptophan so that the regression of weight gain or protein retention on tryptophan intake could be established. After the end of the experiments, plasma free L-tryptophan was estimated by a microbiological method. The nutritive values of DL- and D-tryptophan relative to the L-isomer were 47 and 21%, respectively in chicks and close to 100% in rats. In chicks, plasma free L-tryptophan concentration increased with the increase of L- and DL-tryptophan levels in the diet, but remained at a low level regardless of the D-tryptophan level in the diet. In rats, however, a good correlation was observed between plasma free L-tryptophan and tryptophan level in the diet.

The effects of oral contraceptives on human offspring have not been established. This study shows the long-term effects of prenatal exposure to ethinyl estradiol, a common estrogenic component of oral contraceptives, on the testes and epididymides of aged mice. Five (83%) of the six aged male mice examined showed atrophy of seminiferous tubules, four (67%) had Leydig's cell hyperplasia, and one (17%) had precancerous changes in the epididymis. These phenomena may be results of decreases in testosterone content and its drastic conversion into estradiol-17 beta in the fetal testes at critical periods induced by ethinyl estradiol.

Kallikrein and urokinase were used successively in dogs and patients with peripheral vascular disturbance. It was found that kallikrein showed similar pattern of peripheral dye solution curve with that of urokinase. However, its action was slower than urokinase.

The present study was undertaken to determine the nutritive value of L-, DL- and D-tryptophan in chicks. Day-old chicks were fed commercial chick starter ration for one week and then they were given an experimental diet containing zein as a protein source for three weeks. The experimental results were analyzed by a slope ratio technique (weight gain vs. tryptophan intake). The relative biological utilization of DL- and D-tryptophan compared to L-tryptophan was approximately 55 and 15%, respectively. At the end of the experiment, the chicks were sacrificed and the concentration of free tryptophan in plasma was measured. The free tryptophan concentration in plasma corresponded closely with the increment level of tryptophan in diet when there was a normal level of dietary protein. But there was less correspondence when chicks were fed a diet low in protein.

Various kinds of drugs are used to improve the lymphedema of the extemities. In this report, a dye transducer was applied on the site of edema of the leg, foot, or hand and indocyanine green was injected intravenously. The change of circulating dye was recorded by means of dye densitometer. The edematous tissue showed higher dye concentration with lapse of time, while drugs, i.e., Esberiven, urokinase, kallikrein, etc., accelerated the dye dilution. These drugs have the effect to correct the stagnant microcirculation to a more steady flow in the region of edema.

The behavior of D-tryptophan in the blood plasma and the pattern of tryptophan excretion in the urine were studied in the rat and the chick. When D-tryptophan was administered orally to rats and chicks, both showed D-tryptophan in the plasma. Conversion of D-tryptophan to the L-isomer in the rat was found by an examination of plasma from the posterior vena cava and the portal vein, following stomach intubation of 100 micromoles D-tryptophan/100 g of body weight. The peak in the increase of L-tryptophan was approximately 150 nmoles/ml plasma when measured at 30 minutes after administration and the peak was 200 nmoles when measured 2 hours after administration. No conversion of D-tryptophan to the L-isomer was found in chicks. Under similar conditions, D-tryptophan was measured in the urine of rats and chicks. In rats the D-tryptophan excreted was at most 1% of the amount administered; while in chicks most of the D-tryptophan was excreted.

In order to study the effect of hematocrit (Ht) on the photoelectric plethysmograms of fingers and toes, an experimental model study and a clinical study were carried out. Experimentally, it was found that the height of the plethysmograms increased when the values of Ht were lowered. In the clinical study, 3 groups of patients with different HT values ranging from 27 to 55% were examined. A reverse relationship was found between the Ht value and pulse height of the plethysmogram. The physical effects of the blood flow and contents upon the plethysmograms were discussed.