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Biomedical subjects

K Shiraki

Publications and source records attributed to K Shiraki.

At least 127 records · Page 7Linked to original sources

Childhood bacterial meningitis in Japan.

Haemophilus influenzae type b (Hib) vaccines currently are not used in Japan, but interest in preventing H. influenzae disease by immunization has grown. We performed a retrospective survey for bacterial meningitis in 6 prefectures of Japan. Questionnaires requested the age, sex, clinical outcome and identity of the etiologic organism, if known, of all patients with meningitis younger than 16 years of age who were admitted during calendar year 1994. Of 876 hospitals within the 6 study prefectures, 363 (41.4%) returned a completed questionnaire. There were 1769 cases of meningitis reported, of which 160 (9%) were considered bacterial in origin. H. influenzae was the most common cause of bacterial meningitis, accounting for 68 cases (43%). Sixty-six cases (97%) of H. influenzae meningitis occurred in children 4 years of age or younger, and 27 (40%) occurred in children <1 year of age. Calculated incidence rates based on the population of children 4 years of age or less for each prefecture ranged from 3.4 to 9.9 cases per 100000 (mean, 4.7 cases/100000). H. influenzae is the most common cause of meningitis in Japan, and the estimated incidence rates from this study are very similar to those previously reported from Japan. More comprehensive, prospective surveillance studies will be needed to define better the incidence of Hib meningitis and to aid in making rational decisions regarding the use of Hib vaccination in Japan.

Adolescent↗

Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus-infected mice.

Gingyo-san is composed of 10 crude drugs and used as a traditional antipyretic medicine for the treatment of the common cold and influenza virus infection. In a murine intranasal influenza infection model, fever produced by the infection has been demonstrated to be reduced by suppressing interferon-induced interleukin (IL)-1 alpha production. Thus, we focused on the serum level of IL-1 alpha which produces such novel antipyretic activity, and evaluated the relationship between defervescence and the suppression of IL-1 alpha production by Gingyo-san in influenza virus-infected mice. Fever was produced in the infected mice 33-44 h after infection. Oral administration of a hot water-extract of Gingyo-san (8.9-12.5 mg/0.25 ml/mouse x 3 per day) significantly reduced fever production and suppressed the rise in IL-1 alpha production to the level in uninfected mice. No apparent toxicity by Gingyo-san was observed in infected mice. When the hot water-extract of each 10 of the crude components of Gingyo-san (an unknown amount extracted from 6.25 mg/0.25 ml/mouse x 3 per day for Saigae Tataricae Cornu and 3.5 mg/0.25 ml/mouse x 3 per day for the other 9) was orally administered to infected mice, 6 showed significant antipyretic activity. Of these 6, Saigae Tatricae Cornu significantly suppressed the rise in IL-1 alpha production to the basal level while the other 5 did not affect serum IL-1 alpha. Thus, of the 10 crude components of Gingyo-san, Saigae Tataricae Cornu simultaneously exhibited antipyretic and IL-1 alpha-regulatory activities. The novel antipyretic action of Gingyo-san may be mainly mediated by Saigae Tataricae Cornu which regulates the elevated serum IL-1 alpha level produced by influenza infection.

Analgesics, Non-Narcotic↗

[Development of antiviral therapeutic agents from traditional medicines].

Traditional medicines contain various metabolites derived from nucleic acid, protein, and lipid metabolism. Some of these specific metabolites may recognize the differences between viral and host metabolism resulting in anti-viral activity; hence traditional medicines may be useful sources for new antiviral agents. Traditional medicines can be cheaply obtained and have been orally administered as hot-water extracts. Therefore, they may be used for the prophylactic and therapeutic treatment of viral infection by drinking them, such as coffee or tea. Here we describe how the antiviral activity of traditional medicines was screened in vitro and how their therapeutic antiviral activities were verified in vivo, to obtain traditional antiviral medicines that can be clinically used. Therefore, we have selected 12 herbal extracts, from more than 250 herbal medicines, that exhibit therapeutic activities against cutaneous herpes simplex virus (HSV) type 1 (HSV-1) infection in mice. Four of the 12 augmented the therapeutic efficacy of acyclovir (ACV) in mice and showed potent anti-HSV activity against infection with ACV-resistant HSV-1 mutants in mice. These herbal extracts selectively inhibited viral DNA synthesis and showed a different mode of anti-HSV-1 action from that of ACV. They were also effective against both recurrent HSV and cytomegalovirus infections, without toxicity. Such prophylactic and therapeutic antiviral activities of the traditional medicines were verified by the purification of major active compounds. We could show new indications of traditional medicines as antiviral agents. Thus, the drinking of the extracts, in a daily tea or coffee, may be used for prophylaxis and therapy of diseases caused by herpes virus infection and improve the quality of life.

Animals↗

Renal function in hyperbaric environment.

During mixed gas saturation diving (to 3-49.5 ATA) daily urine flow increases by about 500 ml/day, with no changes in fluid intake and glomerular filtration rate. The diuresis is accompanied by a significant decrease in urine osmolality and increase in excretion of such solutes as urea, K+, Na+, Ca2+ and inorganic phosphate (Pi). The fall in urine osmolality is mainly due to a reduction of free water reabsorption which is associated with a suppression of insensible water loss and the attendant inhibition of antidiuretic hormone (ADH) system. The increase in urea excretion may be associated with a reduction of urea reabsorption at the collecting duct as a consequence of ADH suppression. The rise in K+ excretion is due to a facilitated K+ secretion at the distal tubule as a result of increased aldosterone, urine flow and excretion of impermeable anions such as Pi. The activation of aldosterone system is partly attributed to a transient dehydration induced by early hyperbaric diuresis. The increase in Na+ excretion in the face of enhanced aldosterone secretion indicates that the Na+ transport in the proximal tubule is markedly inhibited (by unknown mechanism). The Pi excretion increases with no changes in plasma level of parathyroid hormone (PTH), thus it may be due to an inhibition of Na(+)-Pi cotransport in the proximal tubule. The increase in Ca2+ excretion may be secondary to the inhibition of Na+ transport at the proximal tubule. Precise information on the proximal tubular Na+ transport is important to understand the mechanisms of impaired solute transport under hyperbaric conditions.

Diuresis↗

[Intravenous immunoglobulin (GB-0998) for prophylaxis of recurrent acute otitis media and lower respiratory tract infection in infancy with IgG 2 deficiency].

The prophylactic effect of intravenous immunoglobulin (GB-0998) on the recurrent acute otitis media, bronchitis and bronchopneumonia in IgG 2 deficient infants was investigated in a multicenter trial. GB-0998 was administered 6 times every 4 weeks. The doses were 300 mg/kg wt. during the first treatment, followed by 5 doses of 200 mg/kg wt. The results indicated that GB-0998 was effective in the prophylaxis of the recurrent infection of acute otitis media, bronchitis and bronchopneumonia in infancy with IgG 2 deficiency and/or IgG 2 antibody deficiency specific for Streptococcus pneumoniae.

Acute Disease↗

Cytotoxicities of alkaloids from processed and unprocessed seeds of Strychnos nux-vomica.

AIM: To examine the cytotoxicities of 6 crude Strychnos alkaloid fractions from the seeds of Strychnos nux-vomica unprocessed or processed with various traditional processing methods and 13 pure Strychnos alkaloids from the fractions. METHODS: Using cell culture, their inhibitory effects on Vero cell growth-inhibition assay, and host cell DNA synthesis by [3H]thymidine ([3H]TdR) uptake assay. RESULTS: The IC50 of processed seeds were 155% and 212% of unprocessed ones in cell growth-inhibition assay and in [3H]TdR uptake assay, respectively. The IC50 of 13 compounds were 0.45-0.80 mmol.L-1 and 0.50-12 mmol.L-1, respectively. The processing method with sand bath exhibited a wide safety margin compared with other traditional processing methods or no processing. The isomers of Strychnos alkaloids and their N-oxides showed much lower cytotoxicities among these alkaloids. Isobrucine N-oxide showed the lowest cytotoxicity. The contents of isomers and N-oxides of Strychnos alkaloids were the highest in the sand processing. CONCLUSION: Processing of nux vomica plays a critical role in its toxicity.

Alkaloids↗

Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum.

The hot-water extract of Geum japonicum has been shown to exhibit prophylactic and therapeutic anti-herpes simplex virus (HSV) activity in murine infection models. Eugeniin was purified as an anti-HSV compound from the extract and also was isolated from another herbal extract (Syzygium aromaticum) that had exhibited anti-HSV activity in mice. Thus the anti-HSV action of eugeniin was characterized. The effective concentration (5.0 microg/ml) for 50% plaque reduction of eugeniin for wild HSV type 1 (HSV-1) on Vero cells was 13.9-fold lower than its 50% cytotoxic concentration determined by a yield-reduction assay. Eugeniin also inhibited the growth of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1 and wild HSV type 2. Eugeniin as well as phosphonoacetic acid inhibited viral DNA and late viral protein syntheses in their infected Vero cells, but not cellular protein synthesis at its inhibitory concentrations. Purified HSV-1 DNA polymerase activity was inhibited by eugeniin noncompetitively with respect to dTTP. Its apparent Ki value for euginiin was 8.2- and 5. 8-fold lower than the Ki values of purified human DNA polymerases alpha and beta, respectively. Thus one of the major target sites of inhibitory action of eugeniin is viral DNA synthesis; the inhibitory action for viral DNA polymerase activity was novel compared with anti-HSV nucleoside analogs.

Animals↗

[Cytomegalovirus infection and its possible treatment with herbal medicines].

Medicinal herbs, Geum japonicum, Syzygium aromaticum, Terminalia chebula, and Rhus javanica, with anti-herpes simplex virus therapeutic activity, inhibited replication of human cytomegalovirus(CMV) and murine CMV(MCMV) in vitro. These anti-CMV activities were examined in an MCMV infection model using immunosuppressed mice. Geum japonicum, Syzygium aromaticum, and Terminalia chebula significantly suppressed MCMV yields in lungs of treated mice compared with water treatment. Efficacy of oral treatment with 750 mg/kg/day of Geum japonicum-extract was similar to that of the intraperitoneal administration with 2 mg/kg/day of ganciclovir in increasing the body weight of infected mice and reducing the virus yield in the lungs. These herbs may be beneficial for the prophylaxis of CMV diseases in immunocompromized patients.

Animals↗

Assessment of cardiac autonomic nervous activities during heliox exposure at 24 atm abs.

BACKGROUND: This experiment was designed to examine the involvement of the autonomic nervous system in the production of hyperbaric bradycardia. METHODS: Four male divers were exposed to a He-O2 (heliox) environment at 24 atmosphere absolute (atm abs) for 7 d. The heart rate (HR) and respiratory rate were recorded at rest in the morning (0700 h) and at night (2230 h) on 1 d during a 5-d predive control, 2 d during a 7-d saturation dive at 24 atm abs, 2 d during decompression, and on 1 d during a 4-d postdive period. Cardiac sympathetic and parasympathetic activities were estimated by using a spectral analysis of the variability of R-R intervals. RESULTS: The morning HR did not fluctuate throughout the experimental days. The night time HR decreased (p < 0.05) by 11.8% on the first day at 24 atm abs compared with that of the predive control. The bradycardia diminished gradually and returned to the predive level with continued exposure at 24 atm abs. The high-frequency power of the cardiac variability, an index of cardiac parasympathetic activity, increased (p < 0.05) only in the first night at 24 atm abs, whereas the low-frequency power and a ratio of low- to high-frequency power, an index of cardiac sympathetic activity, were unchanged. CONCLUSIONS: The present results suggest that an increased parasympathetic activity rather than a decrease in the sympathetic activity is responsible for the bradycardia on exposure to heliox dry saturation dive at 24 atm abs. The mechanism of the gradual disappearance of the bradycardia is unknown, but perhaps it may be related to the development of cardiovascular deconditioning.

Adult↗

Expression of Fas ligand in liver metastases of human colonic adenocarcinomas.

Fas ligand (FasL) plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis. Since FasL has been implicated in the existence of immunologically privileged body sites by inducing apoptosis of activated T lymphocytes, we investigated the expression of FasL in human colon cancers. We found that two out of seven primary tumors and all four hepatic metastatic tumors of surgically obtained colonic adenocarcinoma expressed FasL mRNA and protein, detected by reverse transcription-coupled PCR and by immunohistochemical staining, respectively. Expression of FasL was not detected in normal colonic epithelial cells. FasL mRNA was also expressed in some human colonic adenocarcinoma cell lines including SW480, SW1116, and LS180 cells. Cell-surface-associated FasL was detected in these human colon cancer cells by fluorescence immunocytochemical staining. In addition, the expressed FasL was demonstrated to be functional, since coculture experiments using FasL-expressing SW480 cells resulted in apoptosis of Jurkat T leukemia cells that are sensitive to Fas-mediated apoptosis, and this process was specifically inhibited by the neutralizing anti-human FasL antibody. Thus, our findings and other data suggest an alternative mechanism that enables tumors to evade immune destruction by inducing apoptosis in activated T lymphocytes. Furthermore, constitutive expression of FasL in hepatic metastatic tumors suggests that FasL may also be important in their colonization in the liver through induction of apoptosis in the surrounding Fas-expressing hepatocytes.

Adenocarcinoma↗

Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan.

Limited information is available regarding the histology of hepatitis C virus infection in children. The aim of this study was to determine the histological pattern of chronic hepatitis C (CHC) in children, and liver biopsy specimens from 109 pediatric patients with CHC were examined. Each biopsy specimen was evaluated based on a numerical scoring system for the stage of fibrosis (1-4), the grade of portal/periportal necroinflammation (0-4), the grade of lobular necroinflammation (0-4), and their sum (final grade). The histological lesions considered to be characteristic of chronic hepatitis were also evaluated. None of the children had liver cirrhosis, and 105 cases (97%) were stage 1 or 2. Only 4 children were stage 3. Two of these 4 cases showed hemosiderosis. A significant correlation was observed between the staging score and the final grade in the pediatric patients (r = .59; P < .0001). The histological characteristics of adult CHC, such as lymphoid aggregate, bile duct injury, and fatty changes, were also observed in the children. In conclusion, the majority of children with CHC presented with mild fibrosis, but a few showed CHC with lobular distortion and hemosiderosis. Frequent blood transfusion may aggravate hepatic lesions in pediatric CHC.

Adolescent↗

Effects of acute hyperthermia on the carotid baroreflex control of heart rate in humans.

The purpose of this study was to examine the effect of hyperthermia on the carotid baroreceptor-cardiac reflexes in humans. Nine healthy males underwent acute hyperthermia (esophageal temperature -38.0 degrees C) produced by hot water-perfused suits. Beat-to-beat heart rate (HR) responses were determined during positive and negative R-were-triggered neck pressure steps from +40 to -65 mm Hg during normothermia and hyperthermia. The carotid baroreceptor-cardiac reflex sensitivity was evaluated from the maximum slope of the HR response to changes in carotid distending pressure. Buffering capacity of the HR response to carotid distending pressure was evaluated in % from a reference point calculated as (HR at 0 mm Hg neck pressure-minimum HR)/HR range x 100. An upward shift of the curve was evident in hyperthermia because HR increased from 57.7 +/- 2.4 beats/min in normothermia to 88.7 +/- 4.1 beats/min in hyperthermia (P < 0.05) without changes in mean arterial pressure. The maximum slope of the curve in hyperthermia was similar to that in normothermia. The reference point was increased (P < 0.05) during hyperthermia. These results suggest that the sensitivity of the carotid baroreflex of HR remains unchanged in hyperthermia. However, the capacity for tachycardia response to rapid onset of hypotension is reduced and the capacity for bradycardia response to sudden hypertension is increased during acute hyperthermia.

Acute Disease↗

Evaluation of mean skin temperature formulas by infrared thermography.

To study the reliability of formulas for calculating mean skin temperature (Tsk), values were computed by 18 different techniques and were compared with the mean of 10,841 skin temperatures measured by infrared thermography. One hundred whole-body infrared thermograms were scanned in ten resting males while changing the air temperature from 40 degrees C to 4 degrees C. Local, regional average and mean skin temperatures were obtained using an image processing system. The agreement frequency, defined as the percentage of the calculated Tsk values which agreed with the corresponding infrared thermographic Tsk within +/- 0.2 degree C, ranged for with the various formulas from 7% to 80%. In many sites, the local skin temperature did not coincide with the regional average skin temperature. When the local skin temperatures which showed the highest percentage similarity to the regional average skin temperature within +/- 0.4 degree C were applied to the formula, the agreement frequency was markedly improved for all formulas. However, the agreement frequency was not affected by changing the weighting factors from specific constants to individually measured values of regional surface area. By applying the physiologically reliable accuracy range of +/- 0.2 degree C in the moderate and +/- 0.4 degree C in the cool condition, agreement frequencies of at least 95% were observed in formulas involving seven or more skin temperature measurement sites, including the hand and foot. We conclude that calculation of a reliable mean skin temperature must involve more than seven skin temperature measurement sites regardless of ambient temperature. Optimal sites for skin temperature measurement are proposed for various formulas.

Adult↗

Functions of purified gB, gE:gI, and gH:gL, and their sialyl residues in varicella-zoster virus infection.

Varicella-zoster virus glycoproteins were purified by using monoclonal antibodies and analyzed for their effects on cell-free virus infection. Preinfection treatment of cells with gH:gL reduced the infection efficiency and increased the number of unadsorbed virus. Postinfection treatment of cells with gB increased the infection efficiency, but that with gE:gI reduced it. Treatment of gE:gI and gH:gL with neuraminidase (NA) abolished their inhibitory activity and the plaque formation was enhanced by NA treatment of glycoproteins and cells. Glycoproteins exhibited their diverse activities despite their common role in viral penetration, and sialyl residues were responsible for their function in cell-free virus infection.

Animals↗

Detection of maternofetal transfusion by placental alkaline phosphatase levels.

We investigated the volume of maternofetal transfusion by measuring placental alkaline phosphatase (PLAP) as an indicator of placental passage. PLAP levels were measured in 135 pairs of maternal-neonatal sera. Estimated volumes of maternofetal transfusion were calculated with the following formula: Volume of transfusion (in milliliters) = 85 ml/kg x BW (in kilograms) x (PLAPAB-PLAP1MO)/ PLAPMA, where BW is the birth weight, PLAPAB is the PLAP level in neonatal serum at birth, PLAP1MO is the PLAP level in neonatal serum at 1 month of age, and PLAPMA is the PLAP level in maternal serum at delivery. The mean PLAPMA, PLAPAB, and PLAP1MO levels were 276.95 +/- 159.74 IU/L, 3.83 +/- 2.17 IU/L, and 0.25 +/- 0.22 IU/L, respectively. The mean volume of maternofetal transfusion was estimated to be 3.33 +/- 1.68 ml. The mean estimated volume of maternofetal transfusion per kilogram of birth weight was significantly lower in cases of scheduled cesarean delivery (0.74 +/- 0.35 ml/kg) than in cases of vaginal delivery (1.18 +/- 0.54 ml/kg; p < 0.001) and emergency cesarean delivery (1.73 +/- 1.00 ml/kg; p < 0.01). In scheduled cesarean delivery a significant positive correlation between gestational age and the estimated volumes of transfusion per kilogram of birth weight was observed. In cases of vaginal delivery, the estimated volume of transfusion per kilogram of birth weight was significantly lower in the group with short labor (< 5 hours: 0.92 +/- 0.32 ml/kg) than in the group with prolonged labor (> or = 5 hours: 1.29 +/- 0.61 ml/kg; p < 0.001). PLAP was considered to be useful for estimating the volume of maternofetal transfusion. The transfer volume appeared to relate to uterine contractions and to histologic changes in the placenta with aging.

Adult↗

Prophylactic efficacy of traditional herbal medicines against recurrent herpes simplex virus type 1 infection from latently infected ganglia in mice.

Traditional herbal medicines with anti-herpes simplex virus type 1 (HSV-1) activity in vivo were examined for their prophylactic effects on recurrent HSV-1 infection in mice. Mice were intradermally infected with HSV-1 in the pinna and recurrent HSV-1 disease was induced by ultraviolet irradiation. Herbal extracts arrested the progression of recurrent HSV-1 disease, reduced the incidence of severe erythema and/or vesicles in the pinna, and/or shortened the period of severe recurrent lesions compared with water-administered mice (P < 0.01 or 0.05). Similarly, the prophylactic treatment of herbal extracts limited the development of recurrent skin lesions induced by stripping with cellophane tape physically. The prophylactic efficacy on recurrence was confirmed by the absence of HSV DNA in the skin lesions. HSV-1 genome was revealed to exist in the trigeminal ganglia but not in the pinna of latently infected mice before stimuli by a nested-polymerase chain reaction assay. After stimuli, HSV-1 genome was detected in both pinna and trigeminal ganglia of latently infected mice administered with water. However, prophylactic treatment decreased the rate of detection of HSV-1 genome in the stimulated pinna. Thus, the herbal extracts exhibited prophylactic efficacy against recurrent HSV-1 disease in mice and modulated the recurrent HSV-1 infection.

Animals↗