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Biomedical subjects

K Shiraki

Publications and source records attributed to K Shiraki.

At least 55 records · Page 3Linked to original sources

Prospective study of laparoscopic findings with regard to the development of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis.

BACKGROUND: The laparoscopic findings of hepatocarcinogenesis are not well defined. The purpose of this prospective study was to evaluate the predictive value of laparoscopic findings with regard to the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-associated cirrhosis. METHODS: One hundred nineteen patients with HCV-associated cirrhosis who underwent laparoscopy were enrolled in this study. Ten laparoscopic variables, including degree of development and size of regenerating nodules, irregularity of regenerating nodules, and size of both hepatic lobes, were measured. The predictive value of each finding for the development of HCC was investigated by using univariate and multivariate analyses. RESULTS: HCC developed in a total of 42 of the 119 patients (35.3%) during a mean follow-up period of 62.9 months. The degree of regenerating nodules, the presence of irregular regenerative nodules, and atrophic right lobe were significant predictive factors for HCC with univariate analysis. In particular, 67.1% of patients with irregular regenerative nodules had HCC develop within 5 years. Multivariate analysis revealed that irregular regenerative nodules (relative risk 6.32, p = 0.012), the degree of regenerative nodules (relative risk 4.78, p = 0.029), and atrophic right lobe (relative risk 3.87, p = 0.048) were independent predictive factors. CONCLUSIONS: Morphologic observation of the liver surface by laparoscopy is important and provides information on factors that are statistically significant early predictors of the development of HCC.

Adult↗

Hypovolemic intolerance to lower body negative pressure in female runners.

PURPOSE: An attenuated baroreflex response and orthostatic intolerance have been reported in endurance-trained male athletes; however, it is still unknown whether this occurs also in females. The purpose of the present study was to examine whether endurance exercise-trained women had a predisposition to orthostatic compromise, and if so, what causative factor(s) may induce orthostatic intolerance. METHODS: We studied cardiovascular and hormonal responses to graded lower body negative pressure (LBNP) (0 to -60 mm Hg) in 26 middle-distance female runners (18.6 +/- 0.1 yr) as the exercise-trained (ET) subjects and 23 age-matched untrained (UT) control subjects. On the basis of the occurrence of syncope episodes during LBNP, ET and UT subjects were further allocated to two groups; ET with presyncope (ET+syncope) and without presyncope (ET-syncope) and UT with presyncope (UT+syncope) and without presyncope (UT-syncope). RESULTS: Occurrence of presyncope episodes during LBNP was higher in ET (65.4%, P < 0.05) than that for UT (34.8%). Leg compliance was higher (P < 0.05) in ET than in UT. LBNP reduced stroke volume (SV) more (P < 0.05), increased heart rate (HR) higher (P < 0.05), and increased forearm vascular resistance (FVR) more in ET+syncope as compared with the other groups. Response of vasoactive hormones to LBNP was higher in ET+syncope (P < 0.05) than that of the other groups except for norepinephrine (NE); high in both ET+syncope and UT+syncope. The relationship between SV and NE, an index of sympathetic neuronal response, had no training-related changes during LBNP. CONCLUSION: We conclude that exercise-trained females have a high incidence of orthostatic intolerance during LBNP, with a greater reduction of SV independent of changes in baroreflex and neurohumoral function. A lower incidence of LBNP intolerance in UT may be accounted for by a lower reduction of SV during LBNP. An increase in leg compliance in the exercise-trained females may play an important role in inducing pronounced reduction of SV and hence the intolerance to LBNP.

Adolescent↗

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Acyclovir↗

Utilization of immobilized archaeal chaperonin for enzyme stabilization.

CpkA and CpkB are thermostable chaperonins from hyperthermophilic archaeon Thermococcus kodakaraensis KOD1. CpkA or CpkB was immobilized onto agarose beads by the carbodiimide coupling method. In order to investigate whether immobilized CpkA or CpkB stabilizes a foreign enzyme, their ability to stabilize enzyme was examined using beta-D-galactosidase from Escherichia coli as a model target. In the absence of chaperonin beads, 38.1% of the total soluble protein was precipitated by heat treatment at 53 degrees C for 30 min. The protein structure of the residual soluble fraction was examined by circular dichroism, indicating that beta-D-galactosidase exists as a mixture of the active folded form and the inactive unfolded form. The specific activity of the residual soluble fraction decreased to 85.1% that of the unheated level (from 149.0 U/mg to 127.0 U/mg), indicating that the active folded form in the heated soluble fraction was 85.2%. In the presence of CpkA- or CpkB-beads, 28.6% or 34.3% of beta-d-galactosidase was precipitated by the same heat treatment. However, the specific activity in the soluble fraction was almost maintained (CpkA, from 151.0 U/mg to 140.3 U/mg; CpkB, from 149.0 U/mg to 140.3 U/mg). These results indicated that CpkA- or CpkB-beads are useful for keeping the enzyme active.

Journal Article↗

Tumor cell "dead or alive": caspase and survivin regulate cell death, cell cycle and cell survival.

Cell death and cell cycle progression are two sides of the same coin, and these two different phenomenons are regulated moderately to maintain the cellular homeostasis. Tumor is one of the disease states produced as a result of the disintegrated regulation and is characterized as cells showing an irreversible progression of cell cycle and a resistance to cell death signaling. Several investigations have been performed for the understanding of cell death or cell cycle, and cell death research has remarkably progressed in these 10 years. Caspase is a nomenclature referring to ICE/CED-3 cysteine proteinase family and plays a central role during cell death. Recently, several investigations raised some possible hypotheses that caspase is also involved in cell cycle regulation. In this issue, therefore, we review the molecular basis of cell death and cell cycle regulated by caspase in tumor, especially hepatocellular carcinoma cells.

Animals↗

"Variable echo sign" (ultrasonographical alteration of echogenicity) in cavernous hepatic hemangioma.

There are few reports describing cavernous hepatic hemangiomas with alteration of ultrasonographical imaging during examinations. We performed ultrasonographic examination of 64 cavernous hepatic hemangiomas and recognized 26 cases (41%) with an alteration of echogenicity during the examinations. We refer to this alteration of echogenicity of cavernous hepatic hemangioma as a "variable echo sign". We performed angiography of the cavernous hepatic hemangiomas with variable echo sign. Most of these imaging patterns showed mild or moderate pooling, suggesting that the alteration of echogenicity might be based on a slow blood flow exchange. We suggest that a variable echo sign is specific to ultrasonographic imaging with cavernous hepatic hemangioma and may be useful to differentiate cavernous hepatic hemangioma from other tumors.

Adult↗

Combining transcatheter arterial chemoembolization with percutaneous ethanol injection therapy for small size hepatocellular carcinoma.

For patients with unresectable small size HCC, percutaneous ethanol injection therapy (PEIT) is used as a non-surgical treatment because it is difficult to achieve complete tumor necrosis by transcatheter arterial chemoembolization (TAE) alone. However, some small HCCs (<21 mm in diameter) are resistant to PEIT with incomplete tumor necrosis, which is associated with insufficient ethanol injection to the tumor. For more effective treatment for HCC, we performed a combination of TAE and PEIT on patients with small size HCC and evaluated the cumulative recurrence and survival rates. The recurrence rate in patients treated with the combination was less than that of TAE or PEIT alone. There were five patients without tumor recurrence during the follow-up period and three out of these underwent the combination treatment. The period of no recurrence was 33.4 months on average. In conclusion, we recommend combination therapy with TAE and PEIT for patients to accomplish more effective treatment of small size HCC.

Administration, Cutaneous↗

Treatment of hepatocellular carcinoma and the exacerbation of liver function.

We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), selective segmental sclerotherapy (SSS), combined TAE and PEIT, or transcatheter arterial chemo-injection (TAI). Thirteen patients showed an exacerbation of liver function after treatment. The laboratory data on admission, showed the lower levels of serum albumin and cholinesterase in this group. In comparison to patients who did not show any exacerbation of liver function, these 13 patients had undergone combined TAE and PEIT. An analysis of cases after TAE and PEIT treatment revealed that the time from TAE to PEIT was shorter in the exacerbation group than in the non-exacerbation group, however, there was no significant difference in the amount of injected ethanol between the two groups. It is assumed that the values of albumin and cholinesterase before treatment, or the period from TAE to PEIT are related to liver failure after treatment. Combining TAE and PEIT treatment may be effective for HCC, however, we should pay special attention to liver failure after treatment.

Administration, Cutaneous↗

Susceptibility to acyclovir of herpes simplex virus isolates obtained between 1977 and 1996 in Japan.

The susceptibility of genital herpes to acyclovir (ACV) in immunocompetent women was examined, as was the frequency of ACV-resistant viruses by analyzing 56 clinical isolates in Japan between 1977 and 1996. The mean susceptibilities of herpes simplex virus (HSV) type 1 and type 2 were 0.13+/-0.74 and 0.42+/-0.14 microg/ml, respectively, assessed by the 50% inhibitory concentration of plaque formation. The susceptibility to ACV of clinical isolates did not changed since 1977, and also that of nine pairs of HSV-1 and HSV-2 isolates was not affected by ACV treatment. In order to characterize the change in the virus population, the quantitation of the ACV-resistant virus in 10(4) plaque forming units (PFU) of clinical isolates was adopted. The mean frequencies of ACV-resistant viruses per 10(4) PFU for all strains of HSV-1 and HSV-2 were 0.31+/-0.41 and 9.74+/-14.83, respectively, and were not influenced by ACV treatment. Additionally, the phenotypes of ACV-resistance were not influenced by ACV treatment, and more than 90% of ACV-resistant viruses were found to be thymidine kinase-deficient. This study characterized clinical isolates with respect to ACV susceptibility as a population and the quantitative and qualitative characterization of ACV-resistant virus in the virus population of clinical isolates was also studied. The susceptibility of isolates from genital lesions, the frequency of ACV-resistant viruses, and also the phenotypic characterization of ACV-resistant viruses was maintained between 1977 and 1996, even after the introduction of ACV treatment for genital herpes in Japan.

Acyclovir↗

Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection.

The effects of systemic and local injections of gabapentin, a novel anticonvulsant agent, were tested on nociceptive behaviors in mice with acute herpetic pain. Transdermal infection with herpes simplex virus type-1 (HSV-1) produced nociceptive hypersensitivity of the infected hind paw to innocuous (allodynia) and noxious mechanical stimulation (hyperalgesia) with von Frey filaments. Systemic administration of gabapentin (10-100 mg/kg, peroral) produced a dose-dependent inhibition of both allodynia and hyperalgesia; gabapentin (30-300 mg/kg) did not affect locomotor activity. Intrathecal injection of gabapentin (10-100 microg/animal) also attenuated dose dependently both nociceptive hypersensitivities. In contrast, intraplantar, intracisternal, and intracerebroventricular administration of gabapentin (10-100 microg/animal) had no effect on the HSV-1-induced nociceptive hypersensitivities. Pretreatment with naltrexone (1 mg/kg) inhibited antinociceptive effect of morphine (5 mg/kg), but not gabapentin (100 mg/kg). Repeated administration of morphine (5 mg/kg, four times) led to tolerance of antinociceptive action, whereas gabapentin (100 mg/kg, four times) had antinociceptive effect even after the forth administration. The present results suggest that gabapentin is effective in the treatment of acute herpetic pain without apparent adverse effects, and analgesic action of gabapentin is mainly mediated by actions on the spinal cord.

Acetates↗

Biological characterization of eugeniin as an anti-herpes simplex virus type 1 compound in vitro and in vivo.

Eugeniin exhibits antiviral activity against acyclovir and phosphonoacetic acid (PAA)-resistant herpes simplex virus type 1 (HSV-1) as well as the wild-type HSV-1 in vitro. In this study, we characterized the biological activity of eugeniin in cutaneously HSV-1-infected mice and its interaction with HSV-1 DNA polymerase. The oral and intraperitoneal administrations of eugeniin at 0.3 mg/kg showed similar therapeutic efficacy in retarding the development of skin lesions of HSV-1-infected mice. The two routes of administration at 6 or 50 mg/kg significantly prolonged the mean survival times and/or reduced mortality without toxicity. The oral administration of eugeniin at 50 mg/kg reduced virus yields in the skin and brain of infected mice. Thus, the therapeutic efficacy of oral administration at the various doses of eugeniin was similar to that of intraperitoneal administration, suggesting that the oral bioavailability of eugeniin was high with respect to absorption. Furthermore, the anti-HSV-1 activity of eugeniin was characterized by isobolograms analyzing its combined effects with acyclovir or PAA in HSV-1-infected Vero cells. Eugeniin enhanced the anti-HSV-1 activity of acyclovir but was suggested to be antagonistic with PAA. The interaction of eugeniin and PAA on the activity of partially purified HSV-1 DNA polymerase suggested that eugeniin interacted with the polymerase in the vicinity of PAA-binding site. Thus, eugeniin showed different anti-HSV-1 action from acyclovir and PAA and therapeutic anti-HSV-1 activity in mice.

Acyclovir↗

Early augmentation of interleukin (IL)-12 level in the airway of mice administered orally with clarithromycin or intranasally with IL-12 results in alleviation of influenza infection.

The protective role of interleukin (IL)-12 against influenza infection was assessed by analyzing the efficacies of orally administered clarithromycin (CAM) as an immunomodulator and intranasal administration of recombinant IL-12 in intranasally influenza virus-infected mice. In infected mice, CAM at 20 mg/mouse/day significantly elevated the levels of IL-12 and interferon-gamma on days 2 and 3, respectively, after infection in the bronchoalveolar lavage fluid (BALF), but the levels in the sera were not affected. The levels of IL-4, -6, and -10 were not significantly affected in the sera and BALF. Corresponding with the local elevation of IL-12 level, CAM reduced virus yield and the number of infiltrated cells in the BALF, the severity of pneumonia, and mortality of the treated mice. The potential activity of CAM as an experimental immunomodulator was verified at a dose of 20 mg/mouse/day. Intranasal administration of the optimal dose (20 ng/mouse) of IL-12 on day 2 significantly reduced virus yield in the BALF after infection. The loss of body weight was significantly suppressed by IL-12 administration. The local elevation of IL-12 level at the optimal dose and timing in influenza infection was confirmed to be effective in alleviating the influenza infection in mice treated with the two different ways. Thus, the augmentation of IL-12 production or administration of supplementary IL-12 in the respiratory tract was essential in reducing virus yield in the early phase of influenza and may be crucial for recovery from influenza infection.

Administration, Intranasal↗

Prolonged herpes zoster in a patient infected with the human immunodeficiency virus.

In 1983, varicella zoster virus (VZV) disease was first recognized in the context of infection with the human immunodeficiency virus (HIV). Since that time, there have been many reports discussing the occurrence and clinical manifestations of hepes zoster in HIV-infected patients. We describe the development of prolonged herpes zoster in a patient with acquired immunodeficiency syndrome (AIDS) over the course of 104 days. Viral isolates at the three different clinical stages of the skin lesions were sensitive in vitro to acyclovir, and supposed to be a same strain by polymerase chain reaction (PCR) analysis. We also discuss an effective treatment for prolonged cases of zoster.

AIDS-Related Opportunistic Infections↗

Radioprotective effects of miso (fermented soy bean paste) against radiation in B6C3F1 mice: increased small intestinal crypt survival, crypt lengths and prolongation of average time to death.

The radioprotective effect of miso, a fermentation product from soy bean, was investigated with reference to the survival time, crypt survival and jejunum crypt length in male B6C3F1 mice. Miso at three different fermentation stages (early-, medium- and long-term fermented miso) was mixed in MF diet into biscuits at 10% and was administered from 1 week before irradiation. Animal survival in the long-term fermented miso group was significantly prolonged as compared with the short-term fermented miso and MF cases after 8 Gy of 60Co-gamma-ray irradiation at a dose rate of 2Gy min(-1). Delay in mortality was evident in all three miso groups, with significantly increased survival. At doses of 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1), the treatment with long-term fermented miso significantly increased crypt survival. Also the protective influence against irradiation in terms of crypt lengths in the long-term fermented miso group was significantly greater than in the short-term or medium-term fermented miso and MF diet groups. Thus, prolonged fermentation appears to be very important for protection against radiation effects.

Animals↗

Adjuvant action of Escherichia coli enterotoxin for delayed-type hypersensitivity to Oka vaccine virus on pernasal co-administration in mice.

The usefulness of a mutant of Escherichia coli enterotoxin for the induction of cellular immunity to varicella-zoster virus as a mucosal adjuvant is assessed in mice. When a commercially available live varicella vaccine (the Oka strain) and toxin were once administered simultaneously via the nasal route, delayed-type hypersensitivity to Oka vaccine virus was significantly induced and detected by footpad test in mice. Moreover, when spleen cells from mice immunized with the vaccine and toxin were re-stimulated with live vaccine in vitro, they showed more thymidine uptake and produced more IL-2 than those from mice immunized with the vaccine alone. These results suggest that mutant enterotoxin has adjuvant action to induce a specific delayed-type hypersensitivity to Oka vaccine virus on nasal co-administration with live vaccine virus.

Adjuvants, Immunologic↗

Prospective reevaluation of risk factors in mother-to-child transmission of hepatitis C virus: high virus load, vaginal delivery, and negative anti-NS4 antibody.

Of 21,791 pregnant women screened in Tottori Prefecture, Japan, 127 (0.58%) were positive for anti-hepatitis C virus (HCV) antibody and 84 (0.39%) were positive for HCV RNA. Of 84 children followed up for at least 6 months, 7 (8%) were infected. All of them were born to 26 mothers with a high virus load (HVL; >/=2.5x106 RNA copies/mL [27%]), compared with 0 of 58 children born to non-HVL mothers (P<.001). Because all the infected children were vaginally delivered, the infection rate among 16 vaginally delivered children born to the HVL mothers was as high as 44%. The prevalence of anti-NS4 antibody in the mothers with an infectious HVL was significantly lower than that in the mothers with a noninfectious HVL (P=.048). Analysis of our results suggests that maternal HVL, vaginal delivery, and negative anti-NS4 antibody are significant risk factors for the mother-to-child transmission of HCV.

Delivery, Obstetric↗

Frequency of choroidal abnormalities in neurofibromatosis type 1.

BACKGROUND: Choroidal neurofibromatosis is thought to be a rare form of neurofibromatosis that involves the eyes. The development of infrared light examination with a scanning laser ophthalmoscope (SLO) and indocyanine-green fundus angiography has allowed examination of the choroid. We studied choroidal abnormalities in patients with neurofibromatosis 1 and compared their frequency with that of other ocular abnormalities. METHODS: We examined 33 eyes of 17 consecutive patients diagnosed with neurofibromatosis 1 by conventional ophthalmoscopy and by non-invasive infrared monochromatic light with confocal SLO. 76 eyes of 39 age-matched controls were examined similarly by confocal SLO. 21 digital fluorescein and indocyanine-green angiographies were obtained from 11 adult patients, and 77 angiograms were obtained from age-matched controls. FINDINGS: Infrared monochromatic light examination by confocal SLO showed bright multiple patchy regions at and around the entire posterior pole of all 33 eyes examined. All bright patchy regions seen in adult patients corresponded to hypofluorescent areas on their indocyanine-green angiograms. However, no abnormalities were noted in any patient at corresponding areas under conventional ophthalmoscopic examination or fluorescein angiography. In SLO and indocyanine-green studies, controls and control angiograms showed no choroidal abnormalities. Iris nodules were noted in 25 eyes (76%) of 14 patients (82%) and eyelid neurofibroma in five patients (29%). INTERPRETATION: The bright patchy regions noted under infrared fundus examination and the corresponding hypofluorescent areas seen on indocyanine-green angiograms are probably of choroidal origin. The high frequency (100%) of these abnormalities suggests that the choroid is one of the structures most commonly affected by neurofibromatosis 1.

Adult↗