Pattern classification in kampo medicine.

Pattern classification is very unique in traditional medicine. Kampo medical patterns have transformed over time during Japan's history. In the 17th to 18th centuries, Japanese doctors advocated elimination of the Ming medical theory and followed the basic concepts put forth by Shang Han Lun and Jin Gui Yao Lue in the later Han dynasty (25-220 AD). The physician Todo Yoshimasu (1702-1773) emphasized that an appropriate treatment could be administered if a set of patterns could be identified. This principle is still referred to as "matching of pattern and formula" and is the basic concept underlying Kampo medicine today. In 1868, the Meiji restoration occurred, and the new government changed its policies to follow that of the European countries, adopting only Western medicine. Physicians trained in Western medicine played an important role in the revival of Kampo medicine, modernizing Kampo patterns to avoid confusion with Western biomedical terminology. In order to understand the Japanese version of traditional disorders and patterns, background information on the history of Kampo and its role in the current health care system in Japan is important. In this paper we overviewed the formation of Kampo patterns.

Reproductive experience affects parental retrieval behaviour associated with increased plasma oxytocin levels in wild-type and CD38-knockout mice.

The transition to motherhood results in a number of hormonal, neurological and behavioural changes necessary to ensure offspring growth. Once motherhood is established, further neurological and behavioural changes may result in long-term memory in mothering. Recent research has shown that postpartum motherhood enhances both nurturing behaviour and oxytocin activities. The transmembrane glycoprotein, CD38, is expressed on many neuronal cells and has been shown to play a role in social behaviours through stimulating the release of oxytocin in the hypothalamus. The present study was performed to investigate the effects of reproductive experience (primi- and multiparity, dams and sires) on the degree of parental behaviour, such as retrieval. Comparisons were performed between wild-type (Cd38 (+/+) ) and Cd38 knockout (Cd38 (-/-) ) mice of the ICR strain. Multiparous Cd38 (-/-) dams retrieved pups much faster than primiparous mice, whereas there were no significant differences between primi- and multiparous Cd38 (+/+) dams. Plasma oxytocin levels were significantly increased in multiparous dams of both genotypes. In addition, oxytocin levels in the hypothalamus and pituitary were lower in Cd38 (-/-) than in wild-type mice. ADP-ribosyl cyclase activity in the hypothalamus, but not in the pituitary, was slightly increased in Cd38 (+/+) dams. In an identical test, 40% of first-time Cd38 (+/+) sires showed retrieval. The time required to retrieval was shorter in second-time Cd38 (+/+) sires. Both first- and second-time Cd38 (-/-) sires showed only 10% retrieval behaviour. These results indicate that parental behaviour is improved by reproductive experience, especially in Cd38 (-/-) dams, and suggest that these effects may be a result of increased oxytocin levels.

Neural interactions within and beyond the critical band elicited by two simultaneously presented narrow band noises: a magnetoencephalographic study.

Neural activities elicited in the auditory system are systematically organized according to the frequency characteristics of corresponding sound inputs. This systematic frequency alignment, called 'tonotopy,' plays an important role in auditory perception. By means of magnetoencephalography (MEG) we investigated here interactions between neural groups activated by two simultaneously presented narrow-band noises (NBNs) within the human cortical tonotopic map. Auditory evoked fields indicated that the neural interactions activated by these NBNs depended on the frequency difference between them: the amplitude of the N1m-response systematically increased with increasing frequency difference between the NBNs until the critical bandwidth was reached. In contrast, the N1m decreased with frequency difference exceeding the critical bandwidth. The different N1m-response patterns within and beyond the critical band seem to result from the combination of inhibitory and excitatory neural processes in the auditory pathway and may contribute to the perception of complex sound patterns like speech and music.

Comparative study of two Japanese rhinoconjunctivitis quality-of-life questionnaires.

CONCLUSION: Two questionnaires were used to assess quality of life (QOL) in allergic rhinitis: the Japanese translation of the Rhino-conjunctivitis Quality of Life Questionnaire (RQLQJ) and an original Japanese QOL questionnaire (JRQLQ). Either questionnaire may be used to assess QOL depending on differences in target domains. OBJECTIVES: Although pollinosis is a common disease which has a major impact on patient QOL, no internationally standardized questionnaire has been available in Japan until now. The aim of this study was to compare two currently available QOL questionnaires for allergic rhinitis in Japan-the RQLQJ and JRQLQ-in terms of their appropriateness for clinical use and their psychometric properties. MATERIAL AND METHODS: A multicenter, inter-group, cross-sectional study was conducted in 187 adult symptomatic patients with Japanese cedar pollinosis in 2003. Patient scores on the two questionnaires were compared in terms of both overall and comparable domains. We also examined the acceptability, construct and reliability of both questionnaires. RESULTS: The questionnaires were highly correlated in terms of both overall and comparable domain scores. In addition, both questionnaires had equal and satisfactory psychometric validity, demonstrating that they are both useful tools for assessing QOL in rhinitis. However, when compared with each other, the JRQLQ focuses mainly on activities of daily life and is simpler, while the RQLQJ focuses mainly on rhinitis-related health and is more responsive.

The dependence of the auditory evoked N1m decrement on the bandwidth of preceding notch-filtered noise.

The auditory evoked response is known to be changed by a preceding sound. In this study we investigated by means of magnetoencephalography how a preceding notch-filtered noise (NFN) with different bandwidths influences the human auditory evoked response elicited by the following test stimulus. We prepared white noise (WN) and four NFNs which were derived from WN by suppressing frequency regions around 1 kHz with 1/8-, 1/4-, 1/2- and 1-octave bandwidths. Stimulation for 3 s with this set of noises resulted in differences in responsiveness to a 1-kHz test tone presented 500 ms after the offset of the noises. The N1m response to the 1-kHz test tone stimulus was at a minimum when the preceding NFN had 1/4-octave stop-band frequencies as compared with 1/8-, 1/2- and 1-octave NFN and WN. This N1m decrement is explained by the imbalanced neural activities caused by habituation and lateral inhibition in the auditory system. The results contribute to understanding of the inhibitory system in the human auditory cortex.

N1m recovery from decline after exposure to noise with strong spectral contrasts.

Comb-filtered noise (CFN, derived from white noise by suppressing regularly spaced frequency regions) was presented for 3 s followed by two types of test stimuli. One test stimulus (SB) was comprised of spectra centered in the stop-band regions of the CFN and the other test stimulus (PB) of spectra centered in the band pass regions of the CFN. Magnetoencephalographically recorded N1m responses evoked by SB stimuli were decreased relative to the N1m response evoked by PB stimuli. This effect was maximal when the interval between the CFN and test stimuli was short (0.5 s) but was detected at intervals up to 2 s. The results suggest lateral inhibition in the auditory cortex and point to a decay of inhibition lasting on the order of seconds.

Chronic actinic dermatitis developed during phototherapy for psoriasis.

A patient with psoriasis vulgaris had been successfully treated with PUVA and UVB therapy. During maintenance phototherapy, he suddenly became photosensitive and developed eczematous eruption. Minimal response doses to UVB and UVA were extremely low--1.09 mJ/cm2 and 0.3 J/cm2, respectively. No chemical substances were identified as the responsible photosensitizer. The condition was diagnosed as chronic actinic dermatitis (CAD). PUVA therapy was unsatisfactory because it was not possible to administer an adequate dose of UVA. Oral cyclosporine, topical corticosteroid and sunscreen were used with beneficial therapeutic effects on psoriasis and CAD. As far as we know, the development of CAD during phototherapy has not been previously reported.

In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae.

The in vivo activity of telithromycin against erythromycin A- and penicillin G-resistant Streptococcus pneumoniae was superior to that of azithromycin, clarithromycin, cefdinir, and levofloxacin. In respiratory tract infections caused by erythromycin A-susceptible S. pneumoniae or Haemophilus influenzae in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin.

Identification of a novel Reg family gene, Reg IIIdelta, and mapping of all three types of Reg family gene in a 75 kilobase mouse genomic region.

Regenerating gene (Reg), first isolated from a regenerating islet cDNA library, encodes a secretory protein with a growth stimulating effect on pancreatic beta cells that ameliorates the diabetes of 90% depancreatized rats and non-obese diabetic mice. Reg and Reg-related genes have been revealed to constitute a multigene family, the Reg family, which consists of three subtypes (types I, II, III) based on the primary structures of the encoded proteins of the genes. We have isolated three types of mouse Reg family gene (Reg I, Reg II, Reg IIIalpha, Reg IIIbeta and Reg IIIgamma) [Unno et al. (1993) J. Biol. Chem. 268, 15974-15982; Narushima et al. (1997) Gene 185, 159-168]. In the present study, by Southern blot analysis of a mouse bacterial artificial chromosome clone containing the five Reg family genes in combination with PCR cloning of every interspace fragment between adjacent genes, the Reg family genes were mapped to a contiguous 75kb region of the mouse genome according to the following order: 5'-Reg IIIbeta-Reg IIIalpha-Reg II-Reg I-Reg IIIgamma-3'. In the process of ordering the genes, we sequenced the 6.8kb interspace fragment between Reg IIIbeta and Reg IIIalpha and encountered a novel type III Reg gene, Reg IIIdelta. This gene is divided into six exons spanning about 3kb, and encodes a 175 amino acid protein with 40-52% identity with the other five mouse Reg (regenerating gene product) proteins. Reg IIIdelta was expressed predominantly in exocrine pancreas, but not in normal islets, hyperplastic islets, intestine or colon, whereas both Reg I and Reg II were expressed in hyperplastic islets and Reg IIIalpha, Reg IIIbeta and Reg IIIgamma were expressed strongly in the intestinal tract. Possible roles of Reg IIIdelta and the widespread occurrence of the Reg IIIdelta gene in mammalian genomes are discussed.

The clinical and photobiological characteristics of solar urticaria in 40 patients.

Forty patients with solar urticaria, 16 male and 24 female, were examined personally during the past 25 years. The median age at onset of symptoms was 32 years, ranging from 13 to 76 years. Most commonly (45%) solar urticaria first appeared during the third decade. The mean duration of the disease was 3.6 years at presentation. The action spectrum was found in the visible light range in 24 patients (60%), in the ultraviolet (UV) A range in four, in the UVB in four, from the UVA to UVB in three, from the UVA to visible light in one and in a broad range from UVB to visible light in four patients. An inhibition spectrum was detected in 13 of 19 patients (68%), occurring at longer wavelengths than the action spectrum in 12 of these cases. The augmentation spectrum was found in only four of 14 patients (29%) examined. Twenty-four of 31 patients (77%) developed an urticarial reaction to autologous serum, which had been previously irradiated in vitro at the action spectrum for that patient. In a single patient, solar urticaria was caused by a drug, namely chlorpromazine. In two patients, polymorphic light eruption occurred in association with solar urticaria. No single modality of treatment was satisfactory, but combined use of antihistamines, sunbathing, psoralen UVA photochemotherapy and/or sunscreening agents partially suppressed the symptoms.

Identification of a receptor for reg (regenerating gene) protein, a pancreatic beta-cell regeneration factor.

Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem. 263, 2111-2114). Rat and human Reg gene products, Reg/REG proteins, have been demonstrated to stimulate islet beta-cell growth in vitro and in vivo and to ameliorate experimental diabetes. In the present study, we isolated a cDNA for the Reg protein receptor from a rat islet cDNA library. The cDNA encoded a cell surface 919-amino acid protein, and the cells into which the cDNA had been introduced bound Reg protein with high affinity. When the cDNA was introduced into RINm5F cells, a pancreatic beta-cell line that shows Reg-dependent growth, the transformants exhibited significant increases in the incorporation of 5'-bromo-2'-deoxyuridine as well as in the cell numbers in response to Reg protein. A homology search revealed that the cDNA is a homologue to a human multiple exostoses-like gene, the function of which has hitherto been unknown. These results strongly suggest that the receptor is encoded by the exostoses-like gene and mediates a growth signal of Reg protein for beta-cell regeneration.

Effects of thromboxane synthetase inhibitor (RS-5186) on experimentally-induced cerebral vasospasm.

RS-5186, which inhibits thromboxane A2 (TXA2) synthetase activity, ameliorated delayed cerebral vasospasm in a canine two-hemorrhage model. Subarachnoid hemorrhage was induced in 15 dogs, which were divided into two groups. In the RS-5186-treated group (9 dogs), 50 mg kg-1 of RS-5186 was administered twice a day for seven days. The remaining six dogs without administration of RS-5186 were used as a control group. In the RS-5186-treated group, the angiographic diameter of the basilar artery on Day 7 after subarachnoid hemorrhage was constricted to 60.9% +/- 11.6% (n = 9, mean +/- SD) of that on Day 0, before subarachnoid hemorrhage. The corresponding value was 42.8% +/- 6.1% (n = 6) in the control group. There was a statistically significant difference between these percentages. In the RS-5186-treated group, plasma thromboxane B2 level on Day 7 was 144.3 +/- 28.1 pg ml-1 (n = 4), which was lower than the 815.5 +/- 162.0 pg ml-1 (n = 4) in the control group (p < 0.0005). The plasma 6-keto-prostaglandin F1 alpha level on Day 7 was 180.5 +/- 66.5 pg ml-1 (n = 4) in the RS-5186-treated group, and higher than 107.3 +/- 12.4 pg ml-1 (n = 4) in the control group (p = 0.0734). Thus, administration of RS-5186 reduced TXA2 plasma level and had a beneficial effect on angiographically-detected delayed vasospasm.

Prevalence of anti-hepatitis C antibodies in a rural community without high mortality from liver disease in Niigata prefecture.

The prevalence of hepatitis C virus (HCV) infection and factors relating to the HCV transmission were evaluated in a community without high mortality from chronic liver disease in Niigata prefecture. A total of 2,231 subjects were examined to detect anti-HCV core antibodies by enzyme-linked immunosorbent assay with synthetic peptides CP14 and CP9. The prevalence was 1.66% (95% CI; 1.17% to 2.29%) and tended to increase with age. The values were lower than those reported from districts with hepatic disease endemic. Histories of blood transfusion (relative risk (RR) 5.51; 95% CI 2.90 to 10.48) and surgery with hospital admission (RR 4.43; 95% CI 2.04 to 9.65) were significantly associated with the anti-HCV core antibodies positive. Multiple logistic analysis corroborated independency of these factors. Among 188 subjects who experienced surgery and/or blood transfusion after 1990, only one (0.5%) had HCV infection. By contrast, 8 (3.5%) were positive in subjects who experienced first acupuncture therapy after 1990. The acupuncture therapy in alternative medicine could be still related to the HCV transmission.

Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment.

Oral linomide, (quinoline-3-carboxamide), has been shown to prevent autoimmune insulitis, islet destruction, and diabetes in NOD mice treated at an early stage of the disease, but confers only partial protection in animals with advanced disease. Reg protein, the gene product of a complementary DNA isolated from a regenerating rat islet library, has been previously shown to induce expansion of beta-cell mass in pancreatectomized rats. To determine the effect of treatment combining immunomodulation and Reg protein on advanced autoimmune diabetes, we treated female NOD mice with oral linomide and i.p. Reg protein injections. In 14-week-old animals with less severe disease (glucose tolerant), treatment with each agent alone resulted in amelioration of diabetes, as did treatment with Reg alone in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease (glucose intolerant), only treatment with the combination of both agents, but not that with each separately, resulted in amelioration of diabetes. Our study suggests that treatment aimed at abrogation of autoimmunity combined with expansion of beta-cell mass constitutes a potential therapeutic approach for treatment of insulin-dependent diabetes mellitus.

[Seasonal changes of laboratory data in patients with Japanese cedar pollinosis].

Japanese cedar pollen (JCP) causes a significant seasonal allergic rhinitis in Japan during the early spring. Blood samples were collected monthly from October 1993 through October 1994 from 11 patients with Japanese cedar pollinosis. The patients were segregated into two categories based on specific IgE (RAST): single positive RAST to JCP only and multiple positive RAST to JCP, house dust (H1) and mite (D1). These two populations differed in levels of total serum IgE, numbers of eosinophils, basophils and neutrophils in peripheral blood and clinical symptoms. Seasonal increase of JCP-specific IgE was observed after pollen season in both groups. In the single positive group, but not in the multiple positive group, seasonal increase of the number of eosinophils in peripheral blood was observed with post seasonal fall and the level of total serum IgE was increased in the same manner as that of the JCP specific IgE. Although it was not significant, there was a broad seasonal increase of serum nitrate anion, a metabolite of nitric oxide.

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis.

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.

Natural course of serum-specific immunoglobulin E and immunoglobulin G4 for a span of eight years in untreated patients with perennial allergic rhinitis.

During the past two decades, considerable attention has been devoted to the clinical role of serum-specific IgE and IgG4 following immunotherapy. To definitely discuss the clinical role of serum-specific IgG4, we should know the natural course of serum-specific IgG4 in the untreated patient with allergic rhinitis. To our knowledge, however, no such kind of study can be found in the literature. Our present study focused on the long-term follow-up of serum-specific IgE and IgG4 in patients who were not treated with immunotherapy for perennial allergic rhinitis. They were scheduled to take no medication for their perennial nasal symptoms for 8 years. Serum-specific IgE and IgG4 in untreated patients with perennial allergic rhinitis never significantly change during the observation period. These data will be of great value for studies in serologic changes following active treatment for atopic diseases. Additionally, our study suggests that a reduction in serum-specific IgE and an increase in serum-specific IgG4 following immunotherapy are not the result of an immunotherapy-independent and age-related phenomenon but the result of active immunologic modulation by immunotherapy.

Lysine 129 of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) participates in the binding of ATP to inhibit the cyclic ADP-ribose hydrolase.

CD38 catalyzes not only the formation of cyclic ADP-ribose (cADPR) from NAD+ but also the hydrolysis of cADPR to ADP-ribose (ADPR), and ATP inhibits the hydrolysis (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). In the present study, using purified recombinant CD38, we showed that the cADPR hydrolase activity of CD38 was inhibited by ATP in a competitive manner with cADPR. To identify the binding site for ATP and/or cADPR, we labeled the purified CD38 with FSBA. Sequence analysis of the lysylendopeptidase-digested fragment of the labeled CD38 indicated that the FSBA-labeled residue was Lys-129. We introduced site-directed mutations to change the Lys-129 of CD38 to Ala and to Arg. Neither mutant was labeled with FSBA nor catalyzed the hydrolysis of cADPR to ADPR. Furthermore, the mutants did not bind cADPR, whereas they still used NAD+ as a substrate to form cADPR and ADPR. These results indicate that Lys-129 of CD38 participates in cADPR binding and that ATP competes with cADPR for the binding site, resulting in the inhibition of the cADPR hydrolase activity of CD38.

Molecular cloning and analysis of the cDNA for an auxin-regulated calmodulin gene.

An auxin-regulated calmodulin cDNA (arCaM) were isolated by differential screening from a mung bean (Vigna radiata) cDNA library. The expression of the arCaM transcript in the etiolated mung bean hypocotyl was examined by RNA gel blot analysis. The arCaM transcript was induced depending on indole-3-acetic acid (IAA) concentrations. An increase in level of the arCaM transcript upon treatment of hypocotyl segments with 10 microM IAA was detected after 1 h and a maximum level was detected at 2 h. Induction of the arCaM transcript occurred upon treatment with 10 microM 2,4-dichlorophenoxyacetic acid (2,4-D) or naphthalene-1-acetic acid (NAA) as well as with IAA, while treatment with 10 microM p-chlorophenoxyisobutyric acid (PCIB) as an anti-auxin, prevented the induction. Ethylene did not have any effect. Other stress conditions, such as exposure to salt stress, heavy metal ions and heat shock, also had no effect on the induction. The levels of the arCaM transcript in leaves of light-grown mung bean plants treated with IAA showed steady but small increases with time.

The effect of ultrasonic irrigation before and after citric acid treatment on collagen fibril exposure: an in vitro SEM study.

The surface characteristics of periodontally diseased human teeth after two treatments were compared both before and after partial demineralization with citric acid. Thirteen teeth were obtained from patients with advanced periodontal disease. Three teeth were selected for control groups and 10 were used for experimental groups. All diseased root surfaces were identified and outlined. The roots were cut longitudinally into two sections. They were then scaled and root planed and the paired sections were separately classified into two control or two experimental groups. Three sections in control group 1 were rinsed by syringe with saline solution. The three sections in control group 2 were treated with ultrasonic irrigation. The 10 sections in experimental group 1 were rinsed by syringe with saline solution before and after citric acid application; the 10 sections in experimental group 2 were irrigated ultrasonically before and after citric acid application. The concentration of the citric acid was 25% (pH 1.62) and the immersion time was 3 minutes. The root samples were examined by scanning electron microscope. A significant amount of grinding debris covered on all the root surfaces in control group 1, whereas smear was removed in control group 2. The features of root surfaces of the two experimental groups differed considerably. All specimens in experimental group 2 exhibited collagen fibrils exposed as a consequence of citric acid etching. On the other hand, the smear layer was not thoroughly removed from the root surface in experimental group 1, which meant that few collagen fibrils were exposed after partial demineralization. From these results, ultrasonic irrigation before and after citric acid application improves exposure of collagen fibrils, which may be desirable for clinical success in periodontal regenerative therapy.