Effect of Oral Administration of A Prostacyclin Analog (Op-41483) On Pulmonary Function and Bronchial Responsiveness in Stable Asthmatic Subjects

To examine whether prostacyclin has an attenuating effect on nonspecific bronchial responsiveness in asthma, we measured provocative concentration of methacholine producing a 20% fall in forced expiratory volume in 1 second (PC₂₀-FEV₁) before and after oral administration of a chemically stable prostacyclin analog (OP-41483) (200 μg 4 times a day for 4 days) in 8 patients with stable asthma. Neither baseline pulmonary function nor PC₂₀-FEV₁ significantly improved after the treatment. These results suggest that prostacyclin may have no direct effect on bronchial responsiveness in asthmatics. Further studies using more potent and long-lasting prostacyclin mimetic will be needed to confirm the conclusion.     

Preparation and Characterization of a Murine Monoclonal Antibody (MDR3M) Reactive with mdr3 Gene Product

A murine monoclonal antibody (MDR3M) (isotype: IgM) reactive with mdr3 gene product was generated by immunizing mice with mdr3 -specific peptide (H₂N-¹²WRPTSAEGDFELGISSKQKRKKTKTVKMI⁴¹G-COOH) and hybridizing the primed mouse splenic B cells with X63-Ag8,6.5.3 mouse plasmacytoma cells. MDR3M did not cross-react with mdr1 gene product. This monoclonal antibody may be useful for analyzing the role of mdr3 gene product in cells and tissues.     

Antihypertensive effect of synthetic atrial natriuretic factor in vasopressin-infused rats

To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.     

Estrogenic Induction of NADPH- Diaphorase Activity in the Preoptic Neurons Containing Estrogen Receptor Immunoreactivity in the Female Rat

Nitric oxide and estrogen have been shown to play a critical role in the control of female reproductive function. In order to determine an anatomical relationship between nitric oxide generating neurons and estrogen target neurons, NADPH-diaphorase histochemistry was combined with estrogen receptor immunohistochemistry in the female medial preoptic area. While only a few weakly stained neurons for NADPH-diaphorase were found in ovariectomized control rats, a drastic increase in NADPH-diaphorase activity was observed in the medial preoptic nucleus of estradiol-treated ovariectomized animals. The total number of NADPH-diaphorase neurons in the estradiol-treated group increased three-fold relative to controls, and more than 80% of those neurons contained estrogen receptor-immunoreactivity in their nuclei. Since neuronal NADPH-diaphorase is nitric oxide synthase, the present result suggests that nitric oxide synthase activity can be positively regulated by estradiol in neurons containing estrogen receptor in the female medial preoptic nucleus.     

A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

A case of recrudescent groove pancreatitis, which was in remission by proximal gastrectomy with vagotomy for gastric cancer]

This report describes our experience with a 60 year old male who suffered from a recrudescence of groove pancreatitis. He had been treated by conservative medication therapy by proton pump inhibitor used for therapy of duodenal ulcer, and was in remission. During a follow-up one year later, endoscopy revealed gastric cancer, for which a proximal gastrectomy and vagotomy were performed. The patient continues to remain in remission for the groove pancreatitis. Our experience with the clinical course of this disease, in which treatment for duodenal ulcer was used effectively, offers new insights into the progression and therapy of groove pancreatitis.     

Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]

Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.     

Anal metastasis from carcinoma of the lung: Report of a case

We report herein the case of a 75-year-old man who developed anal canal metastasis from squamous cell carcinoma of the lung. Initially, he underwent a right middle and lower lobectomy combined with left atrial wall resection under cardiopulmonary bypass. He presented 3 months later with an anal polyp which had prolapsed and bled, for which he underwent a transanal polypectomy. Histologically, the polyp was classified as squamous cell carcinoma and considered to be a metastasis from the primary lung cancer. He is presently well with no signs of recurrence 9 months after his initial operation. To our knowledge, there has been no other case of anal metastasis from lung cancer ever reported.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography?

OBJECTIVES: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). BACKGROUND: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. METHODS: Follow-up (3.1 +/- 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (> or =12). RESULTS: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). CONCLUSIONS: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients.