Effect of ischemia on hydroxylase cofactor (tetrahydrobiopterin) and monoamine neurotransmitters in rat brain

Hydroxylase cofactor, monoamine neurotransmitters and their metabolites were measured in ischemic rat brain produced by four-vessel occlusion for 30 and 60 min periods. Slight reduction of hydroxylase cofactor activity was observed in the ischemic cortex after 60 min. Dopamine increased in the brainstem, and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased throughout the brain. Decrease in norepinephrine was observed in the whole brain. Decrease in serotonin and increase in 5-hydroxyindoleacetic acid, a metabolite of serotonin, was observed in the ischemic cerebral cortex. The present study has revealed that there appears to be no significant relationship between hydroxylase cofactor activity and monoamine levels in the ischemic brain. Thus, the hydroxylase cofactor does not play a main role in regulating monoamine synthesis in the acute phase of brain ischemia.     

Eosinophil cationic protein in atopic dermatitis: changes of serum levels by the anti-allergic agent ketotifen *

Background Eosinophil cationic protein (ECP) is a highly basic protein (pI over 11) with molecular weight ranging from 18.5 to 22 kDa, and is released upon eosinophil activation. ECP is stored in the eosinophil granules and has potent bactericidal, helminthotoxic, cytotoxic and neurotoxic effects. ECP levels in scrum and other body fluids are often elevated in allergic diseases and other inflammatory conditions and their measurement may give information regarding eosinophil involvement in a pathological process. Material and Methods We evaluated the scrum levels of eosinophil cationic protein (ECP), assayed using an ECP radioimmunoassay kit, and the effect of an anti-allergic agent, ketotifen, which has a potent anti-eosinophil activity, in atopic dermatitis (AD) patients. Serum ECP levels in AD patients correlated with the severity of AD as determined in clinical evaluations. Results In patients with severe and moderate AD, serum ECP levels were significantly higher (31.04 ± 3.35 μg/1, n= 32) than in non-atopic controls (4.92 ± 1.06 μg/1, n= 16) (P < 0.001). However, no significant correlation was observed between serum ECP and IgE levels, or between serum ECP levels and peripheral eosinophil count. After a 4-weck administration of ketotifen (1 mg; twice a day), in AD patients with serum ECP levels more than 20 μg/I (n= 14), serum ECP levels decreased significantly (from 44.17 ± 4.53 to 18.46 ± 3.35 μg/1, P < 0.05). Conclusion The results suggest that serum ECP levels are a useful indicator of AD activity and of the effect of anti-allergic agents on eosinophil involvement in AD.     

The prognosis of patients with gastric cancer possessing sex hormone receptors

Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissue suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.     

Mechanoenergetics of the Negative Inotropism of Isoflurane in the Canine Left Ventricle: No O sub 2 Wasting Effect

Background: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross-circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure-volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2).

Methods: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane.

Results: Emax, PVA, and VO2 dose-dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05).     

Differences in prognostic factors between leukemia and lymphoma type of adult T-cell leukemia

Prognostic factors affecting the survival of adult T-cell leukemia (ATL) patients were analyzed in three groups: total cases, leukemia type cases, and lymphoma type cases. Factors found to be important overall, i.e. for total cases, were leukocyte count, ATL cell ratio in the peripheral blood, serum calcium levels and lactate dehydrogenase (LDH) level. Of those, LDH level proved not significant when evaluated separately for leukemia type or lymphoma type cases. Leukocyte count and ATL cell ratio were significant in leukemia type patients, whereas it was serum calcium level that was significant in lymphoma type; there were mutually exclusive sets of factors for the two groups. Thus, prognostic factors for ATL patients should be considered separately for each type of the disease.     

Value of endoscopic color doppler ultrasonography in endoscopic injection sclerotherapy‐resistant esophageal varices

A 72‐year‐old man with type C cirrhosis was admitted to our hospital for refractory esophageal varices. Prophylactic endoscopic injection sclerotherapy (EIS) was performed twice in August 2000 for high‐risk esophageal varices at an outside hospital. However, a therapeutic effect was not attained. Endoscopic ?nding revealed F1, Cb, RC (–) at the gastroesophageal junction to approximately a 5‐cm oral site, and F3, Cb, RC (+) varices at the upper site from the 5‐cm oral site of the gastroesophageal junction. Color ?ow images were obtained of the posterior branch of the left gastric vein and revealed an in?ow‐type perforating vein about a site 5 cm oral from the gastroesophageal junction. Color ?ow images of esophageal varices were detected with endoscopic color Doppler ultrasonography. Color ?ow images of out‐?owing‐type perforating veins were discerned in the middle esophagus. The vessel images of intramural esophageal varices were clearly delineated via an ultrasonic microprobe and showed a perforating vein with a diameter of 4 mm. We performed EIS with an attached balloon to occlude the out‐?owing‐type perforating veins with 5% ethanolamine oleate with iopamidol. Seven days after the ?rst EIS, thromboses were observed in the intramural esophageal varices and in the in?ow type‐perforating veins via ultrasonic microprobe. We exchanged the hemodynamics of this esophageal variceal case with blockade of the in?ow‐type perforating vein. Next, we successfully performed EIS, and achieved the blockade of passageways, including the palisade veins. Forty days after EIS, endoscopic ?ndings revealed disappearance of the esophageal varices.     

Contractility to minimize oxygen consumption for constant work in dog left ventricle

Summary We studied whether an optimal E_max (contractility index) to minimize myocardial O₂ consumption (MVo₂) for a constant external work (EW) and, hence, maximize mechanical work efficiency exists as a nadir of MVo₂ within the physiological range of E_max. MVo₂ and E_max were measured in the left ventricles (LV) of 10 dogs. In each experiment, heart rate, cardiac output, and mean aortic pressure were kept constant by pacing, bypassing the right heart, and adjusting the inflation of an intra-aortic balloon, respectively, to maintain a constant EW. MVo₂ was determined as the product of coronary arteriovenous O₂ difference, and coronary blood flow drained from the right heart. E_max was obtained by an abrupt aortic occlusion method. We changed E_max over 1.4–16.1 mmHg·ml^–1·100 g) by dobutamine, propranolol, and sodium pentobarbital. The obtained MVo₂-E_max relationship showed that MVo₂ correlated positively with E_max in 9 of the 10 dogs (correlation coefficients=0.68–0.96). In one of the 9 dogs and the remaining dog, MVo₂ slightly increased with decreases in E_max below 7–8 mmHg·ml^–1·100 g. We conclude that the optimal E_max to minimize MVo₂ for a constant EW does not generally exist as a nadir of MVo₂ in the physiological range of E_max in dog hearts.     

Cardiac muscle fiber force versus length determined by a cardiac muscle crossbridge model

Summary A mathematical model incorporating Huxley's sliding filament crossbridge muscle model coupled with parallel and series elastic components was simulated to examine force-length relations under different external calcium concentrations. Several researchers have determined experimentally in both papillary muscle preparations and in situ heart experiments that the calcium concentration (or effective concentration from inotropic agents) will affect the strength and convexity of the cardiac muscle fiber force-length relations. Simulations were performed over a several-order-of-magnitude range of calcium concentrations in isometric contractions and these showed that the force-length curve convexity was changed. Simulation results demonstrated that increasing the stiffness in the model contractile element or series elasticity element did not change the force-length convexity. Increasing the series elasticity element stiffness did slightly change the shape of the force-length curve. The model predicts that the curve convexity changes as a result of the calcium-troponin interactions.On leave from the Yale School of Medicine 367 Cedar St., New Haven, CT 06510 USA     

Evidence for the existence of substance P-like immunoreactive neurons in the human cerebral cortex: an immunohistochemical analysis

Cellular localization of substance P-like immunoreactive (SP-IR) structures in the pre- and postcentral gyri of the human cerebral cortex was examined by indirect immunofluorescence. SP-IR was localized mostly in bipolar and partly in multipolar cells in layers II and IV. SP-IR fibers were also noted in these gyri, especially in layers II and IV.