Effects of the oral or intratumoral administration of OK432 on the immuno-reactivities of regional lymph nodes in gastric cancer patients

The effects of OK432, a streptococcal preparation, administered either orally (PO-OK432) or intratumorally (IT-OK432) on the immuno-reactivities of regional lymph nodes were investigated in gastric cancer patients. Although native lymph node lymphocytes (LNL) from untreated patients did not show any cytotoxicities against K562 and Raji cells, enhanced activities were found in LNL from patients administered OK432. Augmenting effects on the cytotoxicities of LNL byin vitro additional OK432, interleukin 2 or γ-interferon were remarkable in the patients given IT-OK432. Moreover, the cytotoxicities of peripheral blood lymphocytes were augmentedin vitro more strongly in patients given IT-OK432 than in those given PO-OK432. Flow cytometric analysis of LNL revealed a decrease in CD4⁺ cells by PO-OK432 and an increase in CD8⁺ cells by IT-OK432. An increase in CD4⁺2H4⁺ cells and a decrease in CD4⁺2H4⁻ cells were observed in the patients given OK432, though CD8⁺CD11⁺ cells decreased by PO-OK432 while CD8⁺CD11⁺ cells increased by IT-OK432. Thus, it is suggested that LNL reactive to OK432 immunotherapy may differ between PO- and IT-OK432, and that the immunoreactivities of local lymph nodes and systemical immuno-reactivities may be highly potentiated by IT-OK432 rather than PO-OK432.     

Effects of kamikihi-to, a Chinese traditional medicine, on various cholinergic biochemical markers in the brains of aged rats]

The effects of kamikihi-to (EK-49) on various cholinergic biochemical markers, muscarinic receptors, acetylcholinesterase (AChE), choline acetyltransferase (CAT) and choline uptake, in aged rat brains were examined. Administration of kamikihi-to in daily doses of 200 mg/kg, p.o. for 4 weeks to aged rats (24-months-old) significantly increased the density of muscarinic receptors (Bmax) for 3H-QNB (quinuclidinyl benzilate), but did not affect the apparent dissociation constant (Kd). After repeated administration of kamikihi-to to aged rats, AChE activity and choline uptake were not significantly different in the kamikihi-to treated aged rats as compared with the control aged rats. However, administration of kamikihi-to for 4 weeks resulted in a significant increase in Vmax values of CAT in kamikihi-to treated aged rats as compared with those of the control rats. These results indicate that long-term treatment with kamikihi-to enhances both the Bmax and Vmax for QNB binding and CAT activity in aged rats, respectively.     

Characterization of protein kinase C activities in postsynaptic density fractions prepared from cerebral cortex, hippocampus, and cerebellum

Protein kinase C (PKC) activities, especially, substrates and PKC isozymes, associated with postsynaptic density (PSD) fractions isolated from rat cerebral cortex, hippocampus, or cerebellum were investigated. The 17kM_r major substrate for PKC was associated with PSD fractions prepared from cerebral cortex and hippocampus, and several substrates including 18kM_r, protein were associated with PSD fraction isolated from cerebellum. The content of 17kM_r, substrate was extremely low in the PSD fraction prepared from cerebellum. PKCs-β and λ were associated with PSD fractions and PKC-α was virtually absent in the fraction prepared from the three different regions of the brain. All of PKCs-α, β, and λ were associated with synaptosome fractions. The 36kM_r bands immunoreactive with anti-PKC-β antibody, probably degradation products of native PKC-β, were detected in both the PSD and synaptosome fractions from the three regions, and the ratio of the degradation fragments to native PKC molecule was higher in PSD fractions than in synaptosome fractions. The results suggest postsynaptic roles of PKCs-β and λ and involvement of proteolytic activation of PKC-β in the postsynaptic signal processing.     

Characteristic Height Growth Pattern in Patients with Pseudohypoparathyroidism: Comparison between Type 1a and Type 1b

Pseudohypoparathyroidism (PHP) is a metabolic disorder characterized by organ resistance to the action of parathyroid hormone. PHP type 1 is subclassified into two apparent disorders, type 1a (PHP1a) and type 1b (PHP1b). Patients with PHP1a show Albright hereditary osteodystrophy including short stature. Patients with PHP1b have no such skeletal defects, however, literature regarding the growth of PHP1b is not currently available. We evaluated growth charts of PHP patients, including four PHP1a patients and six PHP1b patients. Growth patterns were different between PHP type 1a and 1b. Adult height was abnormally low in all PHP1a patients. The growth pattern of PHP1a was characterized by mild growth impairment in the prepubertal period, a blunted growth spurt and premature cessation of the growth spurt. The adult height of male PHP1b was slightly lower than average. An early growth spurt was observed only in male patients with PHP1b and it may reduce the adult height of male patients with PHP1b. This warrants further investigation into the growth and pubertal development of PHP1b patients.     

Involvement of α-adrenoceptors in the endothelium-dependent depression of noradrenaline-induced contraction in rat aorta

The involvement of endothelium-derived nitric oxide (NO) in the depressant action of the endothelium on noradrenaline-induced contractions and characterization of the receptor involved in the release of NO were studied using rat aorta. The noradrenaline-induced contraction was significantly potentiated by endothelium removal and in the presence of N^G-nitro-L-arginine (L-NNA) or N^G-monomethyl-L-arginine (L-NMMA). The contraction induced by phenylephrine was also potentiated in the presence of L-NNA. Clonidine could induce contraction only in endothelium-denuded preparations or in the presence of L-NNA. The potentiating action of L-NNA on noradrenaline-induced contractions could also be observed in the presence of yohimbine or rauwolscine, although dose-response curves were shifted to the right. The depression of noradrenaline-induced contractions observed in the presence of the endothelium was increased by repeated stimulation. The depression was prevented by L-NNA and this effect was reversed by L-arginine. These results indicate the possibility that NO can be released through stimulation of α₁- and α₂-adrenoceptors on the endothelium and depresses noradrenaline-induced contractions of smooth muscle, although the contribution of the respective adrenoceptors remains to be investigated. The release of NO was increased when the stimulation was applied repeatedly.     

Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study.

BACKGROUND: Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS: Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS: After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS: After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.     

Optimization and safety of the intra-aortic balloon pumping balloon catheter

Tokai Medical Products developed an intra-aortic balloon pumping (IABP) balloon catheter with the following unique characteristics: the balloon can be applied to any patient irrespective of their physical size, and is therefore suitable for Japanese patients of small stature; a long soft tip is used, which is designed to avoid damage to blood vessels; the size of the catheter is reduced to 7 Fr, and the catheter can be used as a multifunctional balloon catheter, such as the Yoshioka type, that allows simultaneous percutaneous coronary intervention (PCI). The safety of this catheter has been proven in scientific studies. In this review, we report the development of our IABP balloon catheter and give an outline of its characteristics.     

Goldmann-Favre syndrome in a four-year-old-girl

We report a suspected early stage of Goldmann-Favre syndrome in a four-year-old girl complaining of poor visual acuity in both eyesOphthalmological examinations were performed including fundus examination, fluorescein angiography, and electrophysiological studies. However, dark adaptation and visual field testing were not performed because of her age.Ophthalmoscopic examinations revealed peripheral retinoschisis in the superior temporal retina, diffusely abnormal retinal pigment epithelium, and lack of macular and foveal reflexes in both eyes. Foveal retinoschisis was not observed and the vitreous did not show severe degeneration. Fluorescein angiography showed many leaking points posterior to the retinoschisis. Scotopic electroretinogram (ERG) was almost non-recordable. Photopic electroretinogram showed a marked reduction of the b-wave with a negative shape and delayed peak time. Flash visual evoked potentials were within normal range.It is very difficult to distinguish this case from X-linked juvenile retinoschisis by ophthalmological findings. However, Goldmann-Favre syndrome is most suspected from the fact that the patient is female and her parents and brothers are normal.     

Localization of GTPase-activating protein-(GAP) like immunoreactivity in mouse cerebral regions

GTPase-activating protein is known to regulate the conversion between ras-GTP and ras-GDP. We studied the basal expression of GTPase-activating protein-like immunoreactivity in mouse cerebral regions using a polyclonal anti-GTPase-activating protein antibody. Cells with GTPase-activating protein-like immunoreactivity were distributed in frontal cortical layers IV and V, and in the parietal cortex, piriform cortex, amygdaloid area, septum, lateral thalamus, and hypothalamus. The GTPase-activating protein-like immunoreactivity was also observed in fiber-like structures in the caudate putamen, stria terminalis, internal capsule, and medial forebrain bundle, and around CA2 pyramidal cells in Ammon’s horn. These results imply that GTPase-activating protein is constitutively expressed in mouse brain regions and may have physiological functions in specific neuronal pathways in the brain.