Successful and long-lasting treatment of solar urticaria with ultraviolet A rush hardening therapy.

BACKGROUND: Solar urticaria (SU) is a photodermatosis that is thought to be caused through the effects of mast cell mediators released because of an altered chromophore, possibly a photoallergen recognized by IgE. Phototherapy for SU to induce a tolerant state appears to be most effective, but is often time consuming and provides only short-lived remission. Ultraviolet (UV) A rush hardening has been successful and less time consuming in serum factor-negative patients with SU. However, the mechanism of action and long-lasting effects of UVA rush hardening therapy remain unclear. OBJECTIVES: We aimed to evaluate whether UVA rush hardening exhibits long-lasting therapeutic effects in serum factor-positive patients with SU and to examine the action mechanism of tolerance. METHODS: Two serum factor-positive patients with SU were exposed to multiple UVA irradiations at 1-h intervals per day for 2 or 3 days. Intradermal injection of their in vitro-irradiated autologous serum or compound 48/80 and a prick test for histamine were performed before and after UVA rush hardening. RESULTS: The two serum factor-positive patients with SU benefited greatly from UVA rush hardening, as documented by a marked increase in minimal wealing dose, and remained symptom free without using sunscreen in their daily life. Intradermal injection of in vitro-irradiated autologous serum induced wealing before hardening, but not in tolerized skin after hardening. The responses to compound 48/80 and histamine were unaltered. CONCLUSIONS: UVA rush hardening is an effective and long-lasting treatment even in serum factor-positive patients with SU. The mechanism of tolerance may involve continued blockade of photoallergen binding to IgE on mast cells, rather than depletion of mast cell mediators or histamine tachyphylaxis.

Novel anti-idiotype antibody therapy for lipooligosaccharide-induced experimental autoimmune neuritis: use relevant to Guillain-Barré syndrome.

Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C.jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.

Dendrite-associated opioid-binding cell adhesion molecule localizes at neurosecretory granules in the hypothalamic magnocellular neurons.

Opioid-binding cell adhesion molecule (OBCAM) is a member of the immunoglobulin superfamily containing limbic system-associated membrane protein (IgLON) subgroup of glycosylphosphatidylinositol-anchored immunoglobulin cell adhesion molecules. We have previously found that OBCAM is localized preferentially to dendrites compared with somata and terminals of hypothalamic vasopressin-secreting magnocellular neurons. This localization indicates that OBCAM is one of the dendrite-associated cell adhesion molecules. In the present study, we further characterized the localization and the sorting mechanism, and activity-dependent changes of this molecule in vasopressin-secreting magnocellular dendrites. Confocal microscopic observation revealed the preferential localization of OBCAM at the neurosecretory granules in the vasopressin-positive dendrites. Electron microscopic observation using chromogen-intensified and gold-conjugated methods also demonstrated the OBCAM labeling at most of the neurosecretory granules within the dendrites, while the labeling within the somata was observed at only a few neurosecretory granules. I.c.v. colchicine administration resulted in the disappearance of OBCAM immunoreactivity from the dendrites and in its concomitant accumulation at the somata, suggesting that OBCAM is synthesized at the somata and transported to the dendrites by dendrite-associated neurosecretory granules. During the postnatal development, OBCAM immunoreactivity targeted to vasopressin-positive dendrites became clear from at least 3 weeks after birth, although it appeared at only a few somata 2 weeks after birth. Phosphatidylinositol specific phospholipase C treatment of the membrane fraction of the supraoptic homogenate solubilized OBCAM. Kilon, another IgLON member, was also shown to localize at the neurosecretory granules of vasopressin-positive dendrites via the glycosylphosphatidylinositol anchor. High K(+)-stimulation appeared to cause the diffusion of OBCAM-labeled gold particles from neurosecretory granules together with the exocytosis. These findings indicate that OBCAM is synthesized within the somata, attached to vasopressin neurosecretory granules via the glycosylphosphatidylinositol anchor, and transported to the dendrites. Moreover, the subcellular localization of OBCAM is changed in an activity-dependent manner.

The effects of intense click sounds on velocity storage in optokinetic after-nystagmus.

Vestibular evoked myogenic potentials (VEMP) occurring after click stimulation in cervical muscles are thought to be a polysynaptic response of otolith-vestibular nerve origin. In optokinetic after-nystagmus (OKAN) the direction of after-nystagmus changes and slow-phase velocity decreases with head tilt. This phenomenon may be an otolith response to the direction of gravity. We assumed that intense clicks might have some influence on OKAN via the otolith-vestibular nerve. Twelve normal subjects who showed VEMP at 75 dB normal hearing level (nHL) clicks were examined. The OKAN was recorded under four conditions: right monaural, left monaural and binaural stimulation by 75 dB nHL clicks, and absence of click stimulation. Horizontal optokinetic stimulation was applied using stepwise increasing speeds from 30 deg/s to 90 deg/s. Two seconds before the stimulus ended, clicks were sounded. The slow-phase velocity of the recorded electro-nystagmography was manually measured. There was no effect on OKAN with unilateral stimulation but binaural stimulation suppressed it. These results suggest that a velocity storage integrator is influenced by intense clicks via the otolithic area.

Increased expression of an ATP-binding cassette superfamily transporter, multidrug resistance protein 2, in human colorectal carcinomas.

The expression of ATP-binding cassette superfamily transporter genes, such as P-glycoprotein/multidrug resistance (MDR) 1 and MDR protein (MRP) 1, is often up-regulated in various tumor types and is involved in responses to some anticancer chemotherapeutic agents. Five human MRP subfamily members (MRP2-6) with structural similarities to MRP1 have been identified. The relationships between MRP2-6 mRNA levels and drug resistance are not well understood. Data on 45 patients with colorectal cancer were analyzed. Of the ATP-binding cassette superfamily genes, we asked whether mRNA levels of MDR1, MRP1, MRP2, and MRP3 correlated with drug resistance to anticancer agents. For this analysis, we used quantitative reverse transcription-PCR, and the sensitivity to anticancer agents in surgically resected colon carcinomas was determined using the in vitro succinate dehydrogenase inhibition test. MDR1, MRP1, and MRP3 were highly expressed in normal colorectal mucosa, and the relative mRNA levels of MDR1, MRP1, and MRP3 in cancerous tissues compared with noncancerous tissues were decreased or unchanged. By contrast, MRP2 mRNA expression was low in normal colorectal mucosa and specifically increased in cancer regions compared with noncancerous regions. Of the anticancer agents prescribed for patients with colorectal cancers, including doxorubicin, mitomycin C, cisplatin, 5-fluorouracil, etoposide, and a camptothecin derivative, mRNA expression of MRP2 was significantly associated with resistance to cisplatin. MRP2 may be important for resistance to cisplatin treatment in colorectal cancer.

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant bacteria expressing the PHA synthase gene phaC1 from Pseudomonas sp. 61-3.

Pseudomonas sp. 61-3 accumulated a blend of poly(3-hydroxybutyrate) [P(3HB)] homopolymer and a random copolymer consisting of 3-hydroxyalkanoate (3HA) units of 4-12 carbon atoms. The genes encoding beta-ketothiolase (PhbA(Re)) and NADPH-dependent acetoacetyl-CoA reductase (PhbB(Re)) from Ralstonia eutropha were expressed under the control of promoters for Pseudomonas sp. 61-3 pha locus or R. eutropha phb operon together with phaC1(Ps) gene (PHA synthase 1 gene) from Pseudomonas sp. 61-3 in PHA-negative mutants P. putida GPp104 and R. eutropha PHB(-4) to produce copolyesters [P(3HB-co-3HA)] consisting of 3HB and medium-chain-length 3HA units of 6-12 carbon atoms. The introduction of the three genes into GPp104 strain conferred the ability to synthesize P(3HB-co-3HA) with relatively high 3HB compositions (up to 49 mol%) from gluconate and alkanoates, although 3HB units were not incorporated at all or at a very low fraction (3 mol%) into copolyesters by the strain carrying phaC1Ps gene only. In addition, recombinant strains of R. eutropha PHB(-4) produced P(3HB-co-3HA) with higher 3HB fractions from alkanoates and plant oils than those from recombinant GPp104 strains. One of the recombinant strains, R. eutropha PHB(-4)/ pJKSc46-pha, in which all the genes introduced were expressed under the control of the native promoter for Pseudomonas sp. 61-3 pha locus, accumulated P(3HB-co-3HA) copolyester with a very high 3HB fraction (85 mol%) from palm oil. The nuclear magnetic resonance analyses showed that the copolyesters obtained here were random copolymers of 3HB and 3HA units.

Identification of human cytochrome P450 isoforms involved in the metabolism of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid.

1. To identify the cytochrome P450 (CYP) isoenzymes responsible for the major metabolic pathways of S-2-[4-(3-methyl-2-thienyl)phenyl] propionic acid (S-MTPPA) in man, the metabolism of S-MTPPA was examined using human liver microsomes and microsomes containing cDNA-expressed CYP isozymes (CYP1A2, 2A6, 2B6, 2C9-Arg, 2C9-Cys, 2C19, 2D6-Val, 2E1 and 3A4). 2. S-MTPPA was mainly oxidized to the 5-hydroxylated metabolite of the thiophene ring (MA6) with human liver microsomes in the presence of NADPH. The formation of MA6 was inhibited by SKF 525-A, suggesting that CYP plays role in the formation of MA6. 3. Eadie-Hofstee plots for the 5-hydroxylation of S-MTPPA in the range 5-100 microM were linear for all samples studied, suggesting that the formation of MA6 by human liver microsomes follows simple Michaelis-Menten kinetics. Apparent Vmax = 1.42+/-0.64 nmol/min/mg protein; Km = 12+/-5 microM. 4. Among the CYP inhibitors examined (alpha-naphthoflavone, sulphaphenazole, omeprazole, quinidine and troleandomycin), sulphaphenazole (a CYP2C9 inhibitor) showed the most potent inhibitory effect on the 5-hydroxylation of S-MTPPA by human liver microsomes. 5. When incubated with microsomes containing cDNA-expressed CYP isozymes, S-MTPPA was substantially oxidized to MA6 only by CYP2C9. 6. These results suggest that formation of the major metabolite of S-MTPPA, MA6, in human liver microsomes is catalysed predominantly by a single CYP isoenzyme, namely CYP2C9.

Transverse colonic stenosis.

A 3-year child presented with episodic lower abdominal pain; during the eighth attack, a mass was palpable in the left upper quadrant, and a barium enema revealed a stenotic area in the transverse colon. This was resected and an uneventful postoperative course followed. Subsequently, the child has remained symptom-free. instruments are no longer in use.

Sound stimulation-induced vasomotor reflex in the central artery of the rabbit ear.

Effects of sound stimulation on the central artery of the rabbit ear were studied as a somato-autonomic reflex. Vasoconstriction and dilatation, caused by metronome sound stimulation, were estimated from the temperature fluctuations in the central artery of the ear, measured by a thermistor. To enhance the detection of temperature rises, moderately high background levels of arterial tone were established by exposing the tips of the ears to water at a temperature of 10 degrees C or 5 degrees C, prior to sound stimulation. A fall in arterial temperature due to vasoconstriction was observed immediately after the start of the 1-min sound stimulation, with a subsequent temperature rise which overshot the original basal level due to vasodilatation. A positive correlation between the ear temperature before sound stimulation and the temperature fall (p < 0.01), and a negative correlation between the ear temperature and the temperature rise (p < 0.05) were obtained. The temperature fall was blocked by phenoxybenzamine (9 mg/kg, i.p., p < 0.01). The subsequent rise was not influenced by atropine (3 mg/kg, i.p.) or phenoxybenzamine, however, it was attenuated by hexamethonium (6 mg/kg, i.p., p < 0.05). The temperature fall at the beginning of sound stimulation was related to alpha-adrenergic mechanism. The subsequent temperature rise was thought to be related to parasympathetic mechanism, excluding cholinergic mechanism.

Thermal damage threshold of brain tissue--histological study of heated normal monkey brains.

The thermal damage threshold of normal brain tissue was evaluated from immediate and delayed histological changes caused by hyperthermia treatment of normal monkey (Macaca fuscata) brains. A 2450 MHz microwave antenna and an antenna cooling system devised by our group were used for interstitial hyperthermia treatment. The antenna within the cooling system was inserted through a small craniectomy under general anesthesia. The temperature at a reference point, 4 mm radially away from the surface of the cooling system, was maintained at 42, 43, 44, 45, or 46 degrees C for 60 minutes. Eighteen animals were treated and sacrificed immediately after the treatment, while nine animals were treated and sacrificed 7 days after the treatment. The histological changes were studied microscopically on sections stained with HE or Kluver-Barrera's method. The non-survival experiment demonstrated that areas heated at 44 degrees C or below showed no obvious irreversible changes. The survival experiment showed areas heated at 44 degrees C or above developed coagulative necrosis. These histological findings indicate that thermal damage occurs in normal brain tissue after heating at 44 degrees C or above for 60 minutes, suggesting that the safety limit for brain hyperthermia is 43 degrees C for 60 minutes.

[Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin].

Anti-inflammatory activities of quercitrin (Qu) were studied using various experimental models in mice, rats and guinea pigs. Qu (50, 100 and 200 mg/kg, p.o.) inhibited the rat hind paw edema induced by various phlogistics (carrageenin, dextran, histamine, serotonin and bradykinin) in a dose-dependent manner, and 200 mg/kg of this compound also inhibited the scald edema induced by hot water (54 degrees C). Qu did not show any significant inhibition of the ultraviolet light-induced erythema in guinea-pigs and of the increase of vascular permeability induced by acetic acid in mice. Qu did not affect the granuloma formation in a cotton pellet and the development of adjuvant arthritis in rats. These results indicate that Qu might have an inhibitory effect on acute inflammation.

Time dependent effects of selenium on cadmium-induced acute mouse testicular damage.

Twenty-four hr after a single subcutaneous injection of Cd (0.024 mmol/kg), the testis showed severe and widespread degeneration. The damage was accompanied by an increase of lipoperoxide and a decrease of glutathione in the testis. Se (0.048 mmol/kg) injections 2 hr before, at the same time, and 1 hr after the Cd injection, decreased the damage. In these groups, the level of glutathione and lipoperoxides was restored to the control level. With a Se injection 6 hr after the Cd injection, the preventive effect of Se was no longer found. In the testis in which Se injection alleviated the damage caused by Cd, the changes in Ca, Mg and Zn were also restored to the control level. Uptake of Cd into the testis was stimulated by the Se injection. However, the uptake still remained at a low level in the testis in which the Se preventive effect was not found. These results suggest that the preventive effect of Se against testicular Cd toxicity is dependent on the interval between Cd and Se injections.

[Pharmacological studies on Zingiber mioga (ZM) (1). General pharmacological effects of water extracts (author's transl)].

In the central nervous system, ZM decreased locomotor activity and potentiated hypnosis of hexobarbital-Na in mice. ZM had little hypothermic action and there were no anticonvulsive effects on chemoconvulsion and electroconvulsion shock. ZM, 3 mg/kg i.v. produced a sleep-like pattern in the spontaneous EEG activity of cat; from 20 to 30 min. after injection, spindle burst-like waves (12-13 Hz) appeared in the cortex and subcortex. These EEG activities were antagonized by atropine sulfate. In the respiratory and cardiovascular system, ZM, 1 mg/kg or over produced a fall in blood pressure and stimulated respiration in dogs. This hypotensive action was antagonized by atropine sulfate and diphenhydramine hydrochloride, and tachyphylaxis was observed in blood pressure. This compound inhibited cardiomotility in isolated toad heart, had little effect on peripheral blood flow, and produced contractions of isolated guinea pig ileum which were inhibited by atropine by sulfate. Regarding inflammatory response, ZM showed inhibitory effects on the acute edema induced serotonin and dextran. These results indicate that water extracts of ZM have cholinergic actions and in peripheral tissues, histaminergic-like actions.

[Pharmacological studies on Zingiber Mioga (2). Effects of water extracts on the central nervous system (author's transl)].

Effects on the cat central nervous system of water extracts of Zingiber Mioga (ZM) were studied by electroencephalography (EEG). ZM had little effect on the EEG arousal response to electrical stimulation of mid-brain reticular formation. ZM (3 approximately 5 mg/kg, i.v.) suppressed the recruiting response and the augmenting response recorded from the posterior sigmoid gyrus, respectively. ZM (1 approximately 3 mg/kg, i.v.) decreased the photic driving response, while 5 mg/kg, i.v., tended to enhance the response. In the chronic experiments, ZM(1 approximately 3 mg/kg, i.v.) induced a drowsy pattern in the cortex and subcortex, and shortened the lasting time of the EEG arousal response to sonic stimulation. After 5 to 10 minutes, behavior showed a drowsy to light sleeping state, and electromyogram recorded from the platysma showed a decreased amplitude and frequency, but, did not have an inhibitory effect on the motor system, (ataxia). ZM (5 mg/kg, i.v.) induced desynchronization in the cortex and subcortex, arousal wave appeared in hippocampus, midbrain reticular formation, nucl. ventralis postero-lateralis and amygdala, and behavior tended toward the awake stage. After 10 minutes, EEG transferred to a drowsy pattern and behavior showed a drowsy to light sleeping state. The animal could be readily awakened by sonic stimulation, at every time. ZM appears to have an inhibitory effect on the central nervous system.

Reliability of slow vertex response audiometry in young children with sensorineural hearing loss.

In order to supplement our previous report on the reliability and validity of slow vertex response (SVR) audiometry, the detectability of the response, the agreement among scorers and test-retest reliability were studied in 6 children aged 2-4 years who have sensorineural hearing loss of 60-75 dB for the test frequency (1 000 Hz). Mean percentage of positive response increased from 20.6 to 62.2% as stimulus intensity was increased from 60 to 80 dB. Such a sharp increase in the detectability of the response at a level of stimulus intensity close to the auditory threshold of the subjects was not observed in normal children. The results indicate that SVR audiometry is more reliable and valid in children with sensorineural hearing loss than in normal children.

Neonatal meconium obstruction in the ileum without mucoviscidosis.

Two newborns with intestinal obstruction of the terminal ileum without mucoviscidosis were cured by Gastrografin enema. A further case of a premature infant showed, at autopsy, a large intestine containing normal meconium, but an ileum which was plugged with tenacious meconium containing PAS-positive and alcian blue-negative mucus. Our 3 cases were similar to cases of "meconium disease" reported by Rickham and of "meconium plug in the small intestine" reported by Emery. The primary cause of this disease lies in the large amount of PAS-positive mucus secreted from goblet cells of the ileal mucosa and the hypertrophy of lymph nodules in the ileal submucosa.

Reliability and validity of late vertex-evoked response audiometry.

In order to evaluate the current visual scoring technique in the late vertex-evoked response audiometry (ERA), the detectability of the response, errors in judgment, consistency between scorers and test-retest reliability were studied in adults and young children in waking and sleeping states. In waking adults, ERA proved to be a quite reliable and valid method for testing hearing objectively. On the contrary, a marked inconsistency was found in the appearance of the response in children during sleep. From a clinical standpoint, ERA in waking adults and sleeping children should be regarded as two substantially different methods.

Gastrocolic fistula complicating benign gastric ulcer: case report and review of literature.

A review of the literature and report of a case of benign gastrocolic fistula indicate that epigastric pain is the most frequent early symptom. Later, the predominant symptoms are diarrhea, weight loss and feculent vomiting. Patients suffering from rheumatoid arthritis and taking steroids appear to be particularly at risk of developing a gastrocolic fistula. Barium enema is the most reliable method of demonstrating the fistula. Preferred management is a one-stage gastrocolic resection and primary anastomosis.