Development and application of a method to classify airborne pollen taxa concentration using light scattering data.

Although automated pollen monitoring networks using laser optics are well-established in Japan, it is thought that these methods cannot distinguish between pollen counts when evaluating various pollen taxa. However, a method for distinguishing the pollen counts of two pollen taxa was recently developed. In this study, we applied such a method to field evaluate the data of the two main allergens in Japan, Chamaecyparis obtusa and Cryptomeria japonica. We showed that the method can distinguish between the pollen counts of these two species even when they are simultaneously present in the atmosphere. This result indicates that a method for automated and simple two pollen taxa monitoring with high spatial density can be developed using the existing pollen network.

A case of central diabetes insipidus associated with cardiac dysfunction.

Central diabetes insipidus (CDI) results from a deficiency of arginine vasopressin (AVP) secretion. It is treated by replacement therapy with the synthetic AVP analogue desmopressin. To prevent heart failure in patients with CDI accompanied by cardiac dysfunction, controlling sodium and water intake is essential, using the minimum effective dose of desmopressin.

Histopathological analysis of spontaneous large necrosis of adrenal pheochromocytoma manifested as acute attacks of alternating hypertension and hypotension: a case report.

BACKGROUND: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Hypertension secondary to pheochromocytoma is often paroxysmal, and patients occasionally present with sudden attacks of alternating hypertension and hypotension. Spontaneous, extensive necrosis within the tumor that is associated with catecholamine crisis is an infrequent complication of adrenal pheochromocytoma, but its pathogenesis remains unclear. CASE PRESENTATION: A 69-year-old Japanese man developed acute-onset episodic headaches, palpitations, and chest pains. During the episodes, both marked fluctuations in blood pressure (ranging from 40/25 to 300/160 mmHg) and high plasma levels of catecholamines were found simultaneously. Radiological findings indicated a 4-cm left adrenal pheochromocytoma. These episodic symptoms disappeared within 2 weeks with normalization of plasma catecholamine levels. Two months later, the patient underwent adrenalectomy. Microscopic examinations revealed pheocromocytoma with a large central area of coagulative necrosis. The necrotic material was immunohistochemically positive for chromogranin A. Granulation tissue was adjacent to the necrotic area, accompanied by numerous hemosiderin-laden macrophages and histiocytes with vascular proliferation. Viable tumor cells, detected along the periphery of the tumor, demonstrated pyknosis, and the Ki-67 labeling index was 2 % in the hot spot. No embolus or thrombus formation was found in the resected specimen harboring the whole tumor. The Pheochromocytoma of the Adrenal gland Scaled Score was 2 out of 20. The patient's postoperative course was unremarkable for > 7 years. CONCLUSIONS: Presumed causal factors for the extensive necrosis of adrenal pheochromocytoma in previously reported cases include hemorrhage into the tumor, hypotension induced by a phentolamine administration, embolic infarction, high intracapsular pressure due to malignant growth of the tumor, and catecholamine-induced vasoconstriction. In the present case, histopathological and clinical findings suggest that under conditions of chronic ischemia due to catecholamine-induced vasoconstriction, an acute infarction occurred after sudden attacks of alternating hypertension and hypotension. Over the subsequent 2 weeks, repetitive massive release of catecholamines from the infarcts into circulation likely accelerated infarction progression by causing repeated attacks of alternating hypertension and hypotension and resulted in the large necrosis. This case highlights the need for physicians to consider acute spontaneous tumor infarction accompanying episodic catecholamine crisis as a rare but severe complication of pheochromocytoma.

Understanding the Roles of the "Two QSARs".

Quantitative structure-activity relationship (QSAR) modeling has matured over the past 50 years and has been very useful in discovering and optimizing drug leads. Although its roots were in extra-thermodynamic relationships within small sets of chemically similar molecules focused on mechanistic interpretation, a second class of QSAR models has emerged that relies on machine learning methods to generate models from large, chemically diverse data sets for predictive purposes. There has been a tension between the two groups of QSAR practitioners that is unnecessary and possibly counterproductive. This paper explains the difference in philosophy and application of these two distinct, but equally important, classes of QSAR models and how they can work together synergistically to accelerate the discovery of new drugs or materials.

Fulminant type 1 diabetes mellitus and fulminant viral myocarditis. A case report and literature review.

A 35-year-old Japanese woman was admitted with coma following flu-like symptoms. She was diagnosed with diabetic ketoacidosis and fulminant type 1 diabetes (FT1D) and received intravenous infusion of insulin and saline. The next day, the ketoacidosis disappeared, and she recovered consciousness. However, extensive ST-segment elevations in the electrocardiogram appeared with a positive troponin test, and the patient developed pulmonary edema on day 3. An echocardiogram showed globally reduced wall motion of the left ventricle and mild pericardial effusion. Despite medical therapy with intravenous furosemide, carperitide, and catecholamines, her cardiac function deteriorated rapidly, with the left ventricular ejection fraction decreasing to 26% within 7 hours, and progressed to cardiogenic shock that afternoon. The patient received mechanical circulatory support for 4 days with intra-aortic balloon pumping and percutaneous cardiopulmonary support, and recovered fully from circulatory failure. A paired serum antibody test showed a significantly elevated titer against parainfluenza-3 virus, indicating a diagnosis of fulminant viral myocarditis. She was discharged on multiple daily insulin injection therapy, and her subsequent clinical course has been uneventful. In summary, we present a case of concurrent FT1D and fulminant viral myocarditis. Parainfluenza-3 viral infection was confirmed serologically and was considered to be a cause of both the FT1D and fulminant myocarditis.

Scavenger receptor A index and coronary thrombus in patients with acute ST elevation myocardial infarction.

To examine the relationship between the scavenger receptor A (SRA) index (the number of SRA+ cells observed in 10 high power fields of peripheral blood (PB) smear samples; normal upper limit <30) and coronary thrombus, 389 thrombi obtained from 393 patients with acute ST elevation myocardial infarction were examined. Thrombi were classified into platelets (PT), mixed (MT), fibrin-rich (FT) and organizing thrombi (OT); 387, 269, 57 and 29 cases were detected, respectively. Patients were divided into group A (PT only, 89 cases), B (containing MT and PT but not FT, 243 cases), and C (containing FT, 57 cases). SRA+ cells had infiltrated into all FT cases and 147 of the 269 MT, but no PT. At hospitalization, the SRA index exceeded 30 in 276 patients. PT was observed in 274 cases, and MT and FT (residual mural thrombus; RMT) observed in 230. Infarct-related coronary artery was thought to be totally and rapidly occluded by PT that had formed as a result of severe stenosis due to extrusion of plaque content or growth of RMT. An abnormal increase of SRA+ cells is considered to be a useful finding to detecting the presence of PT and, probably, RMT.

Bepotastine besilate OD tablets suppress nasal symptoms caused by Japanese cedar pollen exposure in an artificial exposure chamber (OHIO Chamber).

OBJECTIVE: To investigate the efficacy and safety of bepotastine, we conducted a randomized, investigator-blind, placebo-controlled and parallel study to evaluate the allergic symptoms and the cognitive function of the subjects with Japanese cedar (JC) pollinosis in response to JC pollen exposure in an artificial exposure chamber. METHODS: Twenty-four volunteers with JC pollinosis were enrolled in this study. The subjects were randomly divided into two groups: a bepotastine group and a placebo group (12 subjects each). Subjects received either a 10-mg bepotastine OD (orally disintegrating) tablet or a placebo 10 min before entering the chamber for a 3-h exposure. The nasal and ocular symptoms were evaluated by each patient at regular intervals. The amount of nasal discharge was measured and the number of sneezes recorded. To evaluate the cognitive function, a digit cancellation test (D-CAT), in which the subjects have to eliminate certain numbers within a fixed time, was conducted. RESULTS: Twelve subjects in the placebo group developed nasal and/or ocular symptoms, whereas six subjects in the bepotastine group showed none of the symptoms during exposure. Mean secretion weights and number of sneezes were significantly lower in the bepotastine group than in the placebo group. In D-CAT, no deterioration of work performance was observed in the bepotastine group. No adverse effects were observed in either group. CONCLUSION: Bepotastine treatment is effective and well tolerated in patients with allergen-induced symptoms exposed to JC pollen in an exposure chamber.

Validation study of the OHIO Chamber in patients with Japanese cedar pollinosis.

BACKGROUND: An artificial exposure chamber (OHIO Chamber), which allows dispersal of a fixed concentration of Japanese cedar (JC) pollen under stable conditions, was constructed. This study was conducted to identify the exposure conditions assuring validity of the clinical tests conducted using this chamber. METHODS: Twenty-four adult patients with JC pollinosis were exposed to different concentrations of JC pollen: 0 (only during the summer period), 4,000, 8,000 and 12,000 grains/m3, and the nasal and ocular symptoms were self-assessed during a 4-hour period of exposure. The amount of nasal discharge was measured and the sneezing frequency was recorded. This study was conducted twice during the summer and winter periods, i.e. non-pollen seasons. The reproducibility of the symptoms between the two seasons was assessed. RESULTS: None of the subjects developed any symptom at the pollen concentration of 0 grains/m3. No significant differences in the time to the onset of symptoms were found between the summer and winter study, regardless of the pollen concentration. There were no significant differences between the summer and winter study in the total symptom score and total nasal symptom score at any pollen concentration, suggesting the very favorable reproducibility of symptoms. CONCLUSIONS: Efficient and reproducible results are obtained in patients exposed to JC pollen in the OHIO Chamber. The results suggest the conditions of JC pollen exposure have scientific validity and the OHIO Chamber has the potential to contribute significantly to basic and clinical studies of JC pollinosis.

[Vertical distribution of formaldehyde concentration and simulated temperature and wind velocity from computational fluid dynamics in a gross anatomy laboratory].

Cadavers for gross anatomy laboratories are typically embalmed in formaldehyde. Thus, medical students and instructors are exposed to formaldehyde vapors emitted from cadavers during dissection. In an attempt to improve the dissection environment, we examined indoor formaldehyde concentrations in a gross anatomy laboratory. Air samples were taken from 20, 110, 160, and 230 cm above the floor between dissection beds to represent areas near the floor, in the breathing zone of sitting students, in the breathing zone of standing students, and near the ceiling, respectively. Formaldehyde vapors were thoroughly diffused from the floor to the ceiling, suggesting that medical students are exposed to similar concentrations of formaldehyde based on distance from the floor. Computational fluid dynamics showed that cadavers are warmed by overhead fluorescent lights and the body heat of anatomy students, and indicated that the diffusion of formaldehyde vapors is increased by lighting and the body temperature of students. Computational fluid dynamics showed that gentle convection from anatomy students and cadavers carry formaldehyde vapors upward; downward flow near admission ports diffuse formaldehyde vapors from the ceiling to the floor in the anatomy laboratory.

Increase of scavenger receptor A-positive monocytes in patients with acute coronary syndromes.

To evaluate the utility of the scavenger receptor A (SRA) index (no. SRA(+) monocytes observed in 10 high-power fields of peripheral blood (PB) smear samples, normal upper limit <30) as the indication of disrupted, fissured, or eroded plaque, 225 patients with acute myocardial infarction (AMI), 79 with unstable angina (UA) and 91 with stable angina (SA) were examined. Thrombus was gathered from 95 of 205 sequential AMI patients (46.3%), and classified into platelets, mixed, and two kinds of residual mural thrombus (RMT). RMT was observed in 56 of 169 (33.1%) AMI patients with SRA index > or =30 at hospitalization. The SRA index of 82.4% of AMI, and 75.9% of UA, and 70.3% of SA patients was > or =30 at hospitalization. For 36 AMI patients who initially had an SRA index of <30 at hospitalization, it exceeded 30 within 2 days, and the SRA index rapidly increased in most AMI patients after hospitalization. SRA(+) monocytes were considered to differentiate from SRA(-) monocytes in PB. An abnormally high SRA index is considered to be a useful indication of disrupted or fissured or eroded plaque.

New procedure for the measurement of pancreatic lipase activity in human serum using a thioester substrate.

BACKGROUND: Definitive substrates for the measurement of pancreatic lipase activity in human serum have not been conclusively identified owing to poor aqueous solubility and nonspecific susceptibility of substrates with existing methods. Thus, it is still important to propose new substrates for robust lipase measurements. METHODS: Reaction conditions were studied for a lipase method using newly synthesized 2,3-dibutyrylthio-1-propyl oleate as the substrate and 5,5'-dithio-bis-(2-nitro-benzoic acid) as the chromogen. RESULTS: Optimum conditions, using colipase and Mg(++) in aqueous hexamethyl phosphoric triamide medium at pH 9.2, were defined. The substrate was highly selective to pancreatic lipase. The reaction increased linearly with lipase concentrations up to 500 U/l. The reference interval of serum lipase concentrations was 21.5-65 U/l. Using the Passing-Bablok regression analysis, the present assay shows a slope of 0.414, an intercept of -2.4 U/l, and r-value of 0.992 in the comparison with the chromogenic method using the 6-methylresorufin ester of 1-O,2-O-dilauryl-rac-glycero-3-glutaric acid as the substrate. CONCLUSION: Because of the simple composition of the reagents, the proposed procedure may represent a significant advancement in the commercially available methods for pancreatic lipase determination.

Preliminary study on Japanese cedar pollinosis in an artificial exposure chamber (OHIO Chamber).

BACKGROUND: A pollen exposure chamber (OHIO Chamber) was built in central Tokyo, Japan, in order to study seasonal allergic rhinitis (SAR). Since satisfactory outcomes were obtained from the controlled pollen exposure at the chamber, we conducted preliminary studies in volunteers with SAR. METHODS: Ten volunteers with SAR sensitive to Japanese cedar (JC) pollen were enrolled in this study. In order to investigate the intranasal and intraocular pollen number, volunteers were initially exposed to a low concentration of JC (2500 grains/m3) for at most 1 hour in this chamber. Before and after the exposure, nasal cavities and eyes were washed with 100ml and 25 ml of saline, respectively. Nasal and eye washing solutions were collected and the number of JC pollen was counted. After 3 hours the volunteers were subsequently exposed to a moderate concentration of JC (4500 grains/m3) for 2 hours. Subjective nasal and ocular symptoms were recorded and the amount of nasal secretion was measured during the allergen exposure periods. RESULTS: During the initial exposure, all volunteers except one stayed in the chamber for 1 hour without any nasal or ocular symptoms. The number of pollen in the nose and eyes was 249.2 +/- 120.9 and 13.6 +/- 13.6 grains, respectively. During the subsequent 2-hour exposure to JC pollen, nasal and ocular symptoms developed gradually in a time dependent manner in all the volunteers except one. CONCLUSIONS: This is the first clinical study using Japanese cedar pollen under well-controlled conditions in the OHIO chamber in which the induction of allergic symptoms was observed. The OHIO chamber will be useful for studying allergic rhinitis in Japan.

Enhanced hit-to-lead process using bioanalogous lead evolution and chemogenomics: application in designing selective matrix metalloprotease inhibitors.

The authors describe an innovative approach for designing novel inhibitors. This approach effectively integrates the emerging chemogenomics concept of target-family-based drug discovery with bioanalogous design strategies, including privileged structures, molecular frameworks as well as bioisosteric and bioanalogous/isofunctional modifications. The authors applied this method in the design of selective inhibitors of matrix metalloproteases (MMPs), also referred to as matrixins, on the basis of a unique analysis of the ligand-target knowledge base, the 'matrixinome'. For this analysis, the authors created an annotated MMP database containing ∼ 300 inhibitors with their published activity profile. The ligand space was then arranged into a lead evolution tree, where the substructural transformations in each virtual step led to marked changes in the activity pattern. This allowed subtype-specific privileged fragments to be extracted as well as modifications, which improve activity and/or selectivity. Furthermore, the compounds with the preferred activity profile were correlated with sequence homology as well as binding site similarity within the target family, thereby leading to the identification of substructural modifications that turn non-selective, biohomologous structures into selective inhibitors. The matrixinomic application of the authors' approach, therefore, provides an example of how the combination of ligand space knowledge with sequence-related data can radically improve the outcome of the lead optimisation process to achieve higher selectivity within a given target family.

Clinical utility of 2',5'-oligoadenylate synthetase activity measurement: using whole blood as a highly sensitive method to detect the effects of IFN.

Research progress on the pleiotropic effects of interferons (IFN) has thus far required detecting responses by weak IFN signals. The activity of 2',5'-oligoadenylate synthetase (2-5OAS) is a valuable indicator in the prognosis and IFN treatment of patients with viral diseases such as hepatitis B and C. Although serum samples generally are used to measure enzyme activity, their values depend on the exact conditions under which blood is stored and the degree of haemolysis that occurs during blood drawing or serum separation. This study presents an improved method of evaluating 2-5OAS activity by using whole blood samples containing heparin, which are frozen and then thawed, instead of serum samples. This method is more reliable, convenient, and 50-100 times more sensitive than the conventional methods of measuring serum 2-5OAS activity. The reliability and sensitivity of this improved method enables detection of the effects of low doses of oral IFN administration or changes in the IFN and cytokine system by infection or autoimmune diseases.

[A case of chronic inflammatory demyelinating polyneuropathy presenting with acute pain and SIADH followed by weakness of all four limbs 2 month after the first symptoms].

We report a 73-year-old man who presented symptoms of low back pain and SIADH followed by weakness of all four limbs and sensory disturbance of the lower legs 2 month after the first symptoms. He was referred to our department because of the evolution of weakness. Neurological examination on admission revealed weakness of the arms and legs, areflexia, and hypoesthesia of the lower legs. The straight leg raising test induced prominent radiating pain bilaterally. The level of sodium was 114 mEq/l, the plasma osmolality was 239 mOsm/kg, and the level of plasma antidiuretic hormone was 3.45 pg/ml. Other blood chemical values were unremarkable. The urine osmolality was 527 mOsm/kg. T1-weighted MR image with gadolinium showed thickening and enhancement of the nerve root. Nerve conduction study revealed compromised conduction with demyelinating features, and somatosensory evoked potential study could not show any potentials. He was diagnosed as having CIDP complicating with SIADH. An association between SIADH and AIDP has been much reported previously. To our knowledge, however, there has been no report of SIADH complicating with CIDP.

Analyses of the partition coefficient, log P, using ab initio MO parameter and accessible surface area of solute molecules.

To analyze the log P(sol/w) values (sol: n-octanol or chloroform, w: water) in the framework of the molecular orbital (MO) procedure, we selected solute descriptors such as the solvation energy difference between aqueous and organic solvent phases and the "surface" area of solute molecules to which water molecules are accessible. The solvation energy of solute molecules in their minimum free-energy conformation was calculated using the ab initio self-consistent reaction field-MO method with the conductor-like screening model. The experimentally measured log P(sol/w) value of various solutes except for those of amphiprotics was shown to be analyzable reasonably well by the MO model with additional descriptors for the hydrogen-bonding patterns in the solute-solvent interactions.