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Biomedical subjects

T Shoji

Publications and source records attributed to T Shoji.

At least 37 records · Page 2Linked to original sources
PubMed2001

Atherogenic lipoprotein changes in diabetic nephropathy.

Cardiovascular risk is increased in patients with diabetic nephropathy. The aim of this study was to examine the relative impacts of albuminuria and renal failure, the two important features of diabetic nephropathy, on potentially atherogenic lipoprotein changes in this condition. The subjects were 160 non-diabetic healthy controls and a total of 200 type 2 diabetes patients with various degrees of nephropathy. The diabetic patients were divided into four groups by urinary albumin/creatinine ratio (U-ACR) and serum creatinine (S-Cr) levels: DM-1 (U-ACR< 30 mg/g, N=85), DM-2 (U-ACR=30-300 mg/g, N=48), DM-3 (U-ACR > 300 mg/g, N=29) and DM-4 (S-Cr>177 micromol/l or 2.0mg/dl, N=38). Lipids in very low (VLDL), intermediate (IDL), low (LDL), and high density (HDL) lipoproteins were measured following ultracentrifugation. VLDL-cholesterol (VLDL-C) was elevated (by 73-100%) in diabetic patients and it did not differ among the stages of nephropathy. IDL-C was higher as the nephropathy stage was advanced, and the elevation was significant in the DM-3 (by 75%) and DM-4 (by 131%) groups. LDL-C was not elevated in diabetic patients and was not different among the stages of nephropathy. Reduction of HDL-C was significant in DM-1, DM-2 and DM-3 (by 12-16%) and it was more exaggerated in DM-4 (by 35%). Multiple regression analyses indicated that elevated S-Cr, but not U-ACR, was an independent factor associated with raised IDL-C and lowered HDL-C in diabetic patients. These results indicate that diabetic patients with nephropathy show multiple lipoprotein changes, and that renal failure has greater impact than albuminuria on abnormalities in IDL and HDL. These lipoprotein alterations may contribute to an increased cardiovascular risk in diabetic nephropathy, especially in diabetic renal failure.

Aged↗
PubMed2001

Femoral artery wall thickness and stiffness in evaluation of peripheral vascular disease in type 2 diabetes mellitus.

Stiffening and thickening of arterial wall are two important components of atherosclerosis. The purpose of this study was to evaluate the effects of femoral artery wall stiffness on clinical manifestation of peripheral vascular disease (PVD) in type 2 diabetes mellitus. The subjects were 315 patients with type 2 diabetes. Presence of intermittent claudication and/or leg pain at rest and reduced ankle-brachial blood pressure index (ABI<0.9) were used as a subjective and an objective index of PVD, respectively. Femoral artery intima-media thickness (FA-IMT) and stiffness parameter beta (FA-stiffness beta) were measured by ultrasound methods. Symptomatic patients (N=58) showed greater values for both FA-IMT and FA-stiffness beta than those without symptom (N=257). Similarly, patients with reduced ABI (N=56) had greater FA-IMT and FA-stiffness beta than those without (N=259). However, correlation between FA-IMT and FA-stiffness beta was not impressive, especially in the symptomatic patients. To evaluate the effect of FA-stiffness beta on PVD symptoms, the subjects were divided into three subgroups according to FA-IMT, and then FA-stiffness beta was compared between those with and without PVD symptoms in each subgroup. The symptomatic patients had greater FA-stiffness beta values than the asymptomatic subjects in all the three subgroups. Multiple logistic regression analysis indicated that the presence of PVD symptoms was associated more closely with increased FA-stiffness beta than with increased FA-IMT, whereas reduced ABI was associated more closely with FA-IMT than with FA-stiffness beta. These data suggest that stiffening of arterial wall has a significant impact on PVD manifestations, particularly on the leg symptoms, in patients with type 2 diabetes.

Adolescent↗
PubMed2001

Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC).

OBJECTIVES: To clarify prognostic factors in resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). METHODS: A total of 95 consecutive patients who underwent complete tumor resection and mediastinal dissection for pT1-2N1M0 NSCLC between 1976 and 1997 were retrospectively reviewed. p53 status and proliferative activity were evaluated immunohistochemically. RESULTS: The extent of N1 stations and p53 status proved to be significant prognostic factors. The 5-year survival rate for tumor without hilar node (#10) involvement was 66%, significantly higher than that for tumor with #10 involvement (39%, P<0.01). The 5-year survival rate for tumor with aberrant p53 expression was 37%, significantly lower than that for tumor without aberrant p53 expression (74%, P<0.01). There proved to be no significant difference in the prognosis between pT1 disease and pT2 disease; the 5-year survival rates for pT1 and pT2 diseases were 62 and 56%, respectively. Age, gender, performance status, grade of tumor differentiation, histological type, or proliferative activity were not significant factors. Multivariate analysis of prognostic factors using Cox's proportional hazard model confirmed these results. CONCLUSIONS: Involvement of the hilar node and aberrant p53 expression were significant factors to predict a worse prognosis in resected T1-2N1M0 NSCLC.

Biomarkers, Tumor↗
PubMed2001

Cromolyn sodium suppresses eosinophilic inflammation in patients with aspirin-intolerant asthma.

BACKGROUND: Although administration of cromolyn sodium is one of the most useful drugs for the treatment of aspirin-intolerant asthma (AIA), both its pharmacologic mechanism of action and association with the pathogenesis remain obscure. OBJECTIVE: This study was designed to investigate the protective effect of cromolyn sodium on airway responsiveness to the sulpyrine provocation test, and to examine whether its activity is associated with a reduction in eosinophilic inflammation. METHODS: Patients were randomly assigned to receive cromolyn sodium (20 mg/2 mL, or 1 ampoule; Fujisawa, Osaka, Japan) or matching placebo (2 mL of saline) four times daily for 1 week. We evaluated the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate AIA; those who were in stable clinical condition were allocated to this study. A double-blind, randomized, crossover design was used. Blood and sputum samples were taken in the morning on the sulpyrine provocation testing day. Eosinophil counting and measurement of eosinophilic cationic protein (ECP) were performed. RESULTS: Inhaled cromolyn sodium protect against aspirin-induced attacks of asthma through mechanisms not related to the bronchodilator property, but related to the improvement of the bronchial hypersensitivity, almost completely in all patients (P < 0.001). After 1 week's treatment with cromolyn sodium, patients' symptoms, blood and sputum eosinophils counts, and sputum ECP levels were significantly decreased compared with both placebo and baseline. CONCLUSIONS: Cromolyn sodium has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This is the first report that cromolyn sodium reduces blood and sputum eosinophils counts and sputum ECP levels in AIA.

Adult↗
PubMed2001

A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge.

BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule. While ductography has been advocated as the main procedure in patients with nipple discharge, fiberoptic ductoscopy (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast through nipple orifice exploration. METHODS: We applied ductography and FDS to 65 women who had nipple discharge, and compared their utility. RESULTS: Intraductal lesions occurred in the segmental duct and the first, second, third, fourth, fifth, and sixth branches in decreasing frequency with ductography and FDS screening. The detection rates of intraductal abnormal lesions by ductography and FDS and the their combination were 89.1 (37 patients), 97.4 (38 patients), and 97.5% (39 patients) respectively. Ductal washings performed during FDS were effective to obtain representative exfoliated ductal cells which could be evaluated (sensitivity 50%, specificity 94.3%, and diagnostic accuracy 89.7%). As a result, we diagnosed 35 cases of benign lesions and four cases of malignant lesions by cytological or/and histological examination. CONCLUSION: Ductography and fiberoptic ductoscopy are useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge.

Adult↗
PubMed2001

Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse.

Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: P(on)time 20 ms, the pulse interval: P(off) time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature.

Animals↗
PubMed2001

Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis.

Psoriasis is a chronic inflammatory skin disease in which epidermal proliferation is closely associated with excessive microvascular expansion within the papillary dermis. Angiopoietins have recently been identified as the major ligands of the endothelial- specific receptor Tie2. Angiopoietin 1 induces Tie2 signaling as a receptor activator and maintains blood vessel formation, whereas angiopoietin 2 destabilizes vessels by blocking Tie2 signaling as an antagonist of angiopoietin 1 and acts with vascular endothelial growth factor to initiate angiogenesis. In this study we examined the potential role of angiopoietins and the Tie2 receptor in vascular changes of psoriasis. Angiopoietin 1, angiopoietin 2, and Tie2 were upregulated in involved psoriasis skin compared to uninvolved psoriasis skin, healthy skin, and chronic spongiotic dermatitis skin. Angiopoietin 1 was expressed by stromal cells in the highly vascularized papillary dermis of involved psoriasis skin. Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor. Vascular endothelial growth factor and basic fibroblast growth factor, which were overexpressed in involved psoriasis skin, enhanced angiopoietin 2 and Tie2 expression in dermal microvascular endothelial cell cultures. Thus, our findings suggest that upregulation of angiopoietin 1, angiopoietin 2, and Tie2 is closely associated with the development of microvascular proliferation in psoriasis, and that the angiopoietin-Tie2 system may act coordinately with vascular endothelial growth factor and basic fibroblast growth factor to promote neovascularization in psoriasis. Moreover, successful antipsoriatic treatment was accompanied by noticeable reduction of angiopoietin 2 expression, suggesting that alteration of angiopoietin 2 expression may be particularly important in controlling vascular proliferation in the treatment of psoriasis.

Angiopoietin-1↗
PubMed2001

Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia?

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.

Arteriosclerosis↗
PubMed2001

Atherogenic lipoproteins in end-stage renal disease.

Cardiovascular mortality is substantially higher in patients with end-stage renal disease (ESRD). Lipoprotein abnormality in ESRD is one of the possible risk factors for advanced atherosclerosis. Uremic dyslipidemia is characterized by increased plasma triglycerides due to elevated very low density lipoprotein (VLDL) and decreased high-density lipoprotein (HDL). Plasma total or low-density lipoprotein (LDL) cholesterol is rarely elevated in hemodialysis patients. The "LDL" by standard assay methods consists of intermediate-density lipoprotein (IDL) and LDL devoid of IDL. Although "LDL" is not increased, IDL is markedly elevated in uremic plasma. We previously showed that aortic stiffness of hemodialysis patients was associated positively with VLDL, IDL, and LDL devoid of IDL and that IDL is the best lipoprotein predictor of aortic stiffness. The IDL level is correlated positively with plasma total cholesterol, triglyceride, and "LDL" levels. Importantly, increased IDL is found in ESRD patients with "normal" "LDL"cholesterol levels, indicating that the target "LDL" level should be lower than that for the general population. More than 40% of hemodialysis patients exceeded the upper limit (15 mg/dL, 95th percentile level) of IDL cholesterol in healthy subjects. Based on a linear relationship between IDL and "LDL," the normal range of IDL cholesterol (<15 mg/dL) corresponds to "LDL" cholesterol by the Friedewald equation below 100 mg/dL in hemodialysis patients. Statins effectively and safely reduce "LDL," including IDL in patients treated with hemodialysis or peritoneal dialysis. The effect of lipid-lowering therapy on cardiovascular mortality in ESRD, however, awaits the results of ongoing prospective trials.

Cardiovascular Diseases↗
PubMed2001

Renal insufficiency accelerates atherosclerosis in patients with type 2 diabetes mellitus.

Diabetes mellitus is a strong risk factor for the progression of atherosclerosis. In patients with chronic renal failure on hemodialysis, advanced atherosclerosis is reported to be present. We examined how renal insufficiency affects intima-medial thickness (IMT) of the carotid and femoral arteries in patients with type 2 diabetes mellitus. IMT was measured by B-mode ultrasonography in 115 patients with type 2 diabetes mellitus (65 men, 50 women; 58 +/- 13 years old). The IMT of the carotid and the femoral artery of patients with creatinine clearance less than 80 mL/min (n = 55) were significantly greater than those of patients with creatinine clearance 80 mL/min or greater (n = 60; P < 0.01 and P < 0.05). Linear regression analyses showed that there was a significant negative correlation between creatinine clearance and IMT of the carotid artery (r = -0.330; P < 0.001) and femoral artery (r = -0.336; P < 0.001). Multiple regression analyses revealed that age and creatinine clearance significantly and independently affected the IMT of the carotid artery (R(2) = 0.176; P < 0.0001), and age, duration of diabetes, and smoking affected the IMT of the femoral artery (R(2) = 0.287; P < 0.0001). These findings show that decreased renal function accelerates atherosclerosis in patients with type 2 diabetes mellitus and that chronic renal failure is a significant, independent risk factor for carotid atherosclerosis in these patients.

Age Factors↗
PubMed2001

Non-penetrating vascular clips anastomosis inhibited intimal thickening under poor runoff conditions in canine autogenous vein grafts.

OBJECTIVE: Late graft failure is still a significant problem, particularly in cases with poor runoff vessels. The main cause of late graft failure is intimal thickening of the anastomotic region. Vascular closure system (VCS) clips may provide ideal anastomosis, since they do not penetrate the wall. Therefore, we examined whether the VCS clips affect intimal thickening under poor runoff conditions in the canine autogenous vein grafts. METHODS: A canine poor runoff model was prepared at both femoral veins. Four weeks after the first surgical procedure, two groups were established according to the two different methods of anastomosis employed. The right femoral vein graft was performed using polypropylene sutures, conventional surgical anastomosis (control group), while the left femoral vein graft was performed using VCS clips anastomosis (VCS group). Four weeks after grafting, the vein grafts were removed and the intimal thickening of proximal, distal anastomosis and midportion of the vein grafts were examined histologically. RESULTS: In the control group, flow rate and variation were 26+/-8 ml/min and 51+/-10 dynes/cm(2), respectively. In the VCS group, the flow rate and variation were 23+/-11 ml/min and 44+/-14 dynes/cm(2), respectively. There were no significant differences between the two groups. The average value of intimal thickening of both the anastomotic region and the midportion of the vein graft in the VCS group was significantly inhibited compared to that of the control group. The number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group. CONCLUSIONS: These experiments indicate that VCS clips significantly inhibit intimal thickening under poor runoff conditions in canine autogenous vein grafts to a greater extent compared to suture-constructed anastomosis. One mechanism that may account for the decreased intimal thickening is the inhibition of the expression of transforming growth factor-beta (TGF-beta), because the number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group.

Animals↗
PubMed2001

Effect of insulin resistance on serum paraoxonase activity in a nondiabetic population.

Paraoxonase is a high-density lipoprotein (HDL)-bound esterase that hydrolyzes various organophosphorus compounds and protects low-density lipoprotein (LDL) against accumulation of lipid peroxides. Paraoxonase activity is strongly affected by the polymorphism of the paraoxonase gene (PON1) at position 192. In addition, the enzyme activity shows a great variation within each genotype, although the underlying mechanism is unknown. Because paraoxonase activity is decreased in subjects with type 2 diabetes mellitus who have insulin resistance, we investigated the association between paraoxonase activity and insulin resistance in a nondiabetic population. The subjects were 237 healthy Japanese adults with fasting plasma glucose less than 7.0 mmol/L. Paraoxonase activity was measured using paraoxon as a routine substrate. Insulin resistance was assessed by homeostasis model assessment index (HOMA index). Paraoxonase activity was affected by HDL level. To reduce the effect of HDL on paraoxonase, paraoxonase activity/HDL ratio was used. When the subjects were divided into tertiles by HOMA index, the subjects with higher HOMA values had higher paraoxonase/HDL ratios, although the 3 groups were comparable in age, gender and the PON1 genotype distribution. Paraoxonase/HDL ratio showed significant positive correlations not only with HOMA index, but also with body mass index, waist-to-hip ratio (WHR), whereas it correlated inversely with age at borderline significance. Multiple regression analysis indicated that the association between HOMA index and paraoxonase/HDL ratio was significant and independent of PON1 genotype, age, and adipocity. The positive association between HOMA index and HDL-corrected enzyme activity was again significant when the enzyme activity was measured with diazoxon as an alternative substrate. These results suggest that insulin resistance or hyperinsulinemia is a factor contributing to the intragenotype variability of paraoxonase activity in a population without overt hyperglycemia.

Adult↗
PubMed2001

A case of repetitive intrapleural cancer chemotherapy using INFUSE-A-PORT for malignant mesothelioma.

A 57-year-old man was diagnosed as having malignant pleural mesothelioma. We placed an implantable reservoir (INFUSE-A-PORT) into his pleural cavity to administer repetitive intrapleural chemotherapy. We administered intrapleural chemotherapy 7 times over a period of 10 months. The progression of the disease was very gradual; he could continue working during this time. INFUSE-A-PORT may be useful for repetitive intrapleural chemotherapy in outpatient treatment of malignant mesothelioma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Two cases of Kaposi's sarcoma mimicking Stewart-Treves syndrome found to be human herpesvirus-8 positive.

Although angiosarcoma is the most frequent tumor arising in the clinical setting of chronic lymphedema, as in Stewart-Treves syndrome, Kaposi's sarcoma has also been reported in this setting, although rarely. We describe two women who developed Kaposi's sarcoma in the lymphedematous arm many years after surgery for breast cancer. Case 1 is a 92-year-old and Case 2 is an 81-year-old; they underwent left total mastectomy and axillary node dissection for infiltrating breast carcinoma in 1981 and 1982 respectively. At that time, neither patient received further treatment. Except for persistent lymphedema, both women did well until over fourteen years later when each noted the development of several purple asymptomatic plaques on the edematous arm. In both, the clinical diagnosis at the time of biopsy was angiosarcoma. However, histologic findings in both cases were typical for Kaposi's sarcoma. In addition, a nested polymerase chain reaction (PCR) for the detection of a 233bp segment of KSHV/HHV8 was performed on DNA extracted from the paraffin-embedded specimens and both cases were positive for this sequence. Histologic sections of both cases were also tested for KSHV by in situ hybridization and demonstrated a positive signal in the lesional cells in each case.

Aged↗
PubMed2001

Inhibitory effect of prostaglandin E 1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts.

The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E 1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction.

Alprostadil↗
PubMed2001

Parallel induction of nitric oxide and tetrahydrobiopterin synthesis in alveolar macrophages.

BACKGROUND: Nitric oxide (NO) and an essential cofactor for both constitutive and inducible NO synthase (NOS) activity, tetrahydrobiopterin (6R-L-erythro-1',2'-dihydroxypropyl-2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine; BH4), are thought to be important modulators of function in normal and inflamed airways. However, the exact pathologic roles of NO and BH4 remain obscure. Even less is known about the effects of cytokines on alveolar macrophages. OBJECTIVE: This study was designed to determine whether NO and BH4 are induced by cytokines in mouse alveolar macrophages and to investigate whether NO synthesis is affected by changes in intracellular BH4 levels in alveolar macrophages. METHODS: We compared the induction by lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) of NO production and BH4 synthesis in alveolar macrophages. To determine whether NO synthesis is affected by changes in intracellular BH4 levels in alveolar macrophages, we used inhibitors of BH4 biosynthesis. RESULTS: Activation of alveolar macrophages induced parallel increases in NO and intracellular BH4 levels, although induction of the latter appears to be somewhat more sensitive than that of the latter to diverse cytokines. Inducible NO production in alveolar macrophages was blocked by inhibitors of BH4 biosynthesis. IL-2, an important component of the immunomodulatory system, was only a weak activator of alveolar macrophages by itself but potently synergized with IFN-gamma to stimulate the production of both NO and BH4. CONCLUSION: Our results suggest that BH4 synthesis in alveolar macrophages is a potential target for therapeutic intervention in airway inflammatory diseases, such as asthma, cystic fibrosis, and acute bronchial infections whose pathology may be mediated by overproduction of NO.

Animals↗