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Biomedical subjects

H Shiomi

Publications and source records attributed to H Shiomi.

At least 19 recordsLinked to original sources

Feasibility of four-dimensional conformal planning for robotic radiosurgery.

Organ motion can have a severe impact on the dose delivered by radiation therapy, and different procedures have been developed to address its effects. Conventional techniques include breath hold methods and gating. A different approach is the compensation for target motion by moving the treatment beams synchronously. Practical results have been reported for robot based radiosurgery, where a linear accelerator mounted on a robotic arm delivers the dose. However, not all organs move in the same way, which results in a relative motion of the beams with respect to the body and the tissues in the proximity of the tumor. This relative motion can severely effect the dose delivered to critical structures. We propose a method to incorporate motion in the treatment planning for robotic radiosurgery to avoid potential overdosing of organs surrounding the target. The method takes into account the motion of all considered volumes, which is discretized for dose calculations. Similarly, the beam motion is taken into account and the aggregated dose coefficient over all discrete steps is used for planning. We simulated the treatment of a moving target with three different planning methods. First, we computed beam weights based on a 3D planning situation and simulated treatment with organ motion and the beams moving synchronously to the target. Second, beam weights were computed by the 4D planning method incorporating the organ and beam motion and treatment was simulated for beams moving synchronously to the target. Third, the beam weights were determined by the 4D planning method with the beams fixed during planning and simulation. For comparison we also give results for the 3D treatment plan if there was no organ motion and when the plan is delivered by fixed beams in the presence of organ motion. The results indicate that the new 4D method is preferable and can further improve the overall conformality of motion compensated robotic radiosurgery.

Biophysical Phenomena↗

Nitric oxide synergistically potentiates interleukin-1 beta-induced increase of cyclooxygenase-2 mRNA levels, resulting in the facilitation of substance P release from primary afferent neurons: involvement of cGMP-independent mechanisms.

We previously demonstrated that cultured rat dorsal root ganglion (DRG) cells respond to stimulation with interleukin-1 beta (IL-1 beta) by releasing substance P (SP), and this response is regulated via the cyclooxygenase (COX)-2 pathway. In this study, to ascertain the interaction between nitric oxide (NO) and prostaglandins in primary afferent neurons, we investigated the effect of NO on the IL-1 beta-induced release of SP in cultured DRG cells. An NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), did not in itself evoke SP release. However, it potentiated the IL-1 beta-induced release of SP. Similarly, while SNAP did not elicit the expression of COX-2 mRNA, it potentiated the expression induced by IL-1 beta in cultured DRG cells, and this potentiation was significantly suppressed by the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO). Moreover, SNAP also potentiated the expression of COX-2 protein induced by IL-1 beta in cultured DRG cells. The stimulatory effect of SNAP on the IL-1 beta-induced release of SP was completely inhibited on co-incubation with a selective COX-2 inhibitor, NS-398. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a potent inhibitor of soluble guanylate cyclase, did not suppress, and a membrane-permeable cGMP analogue, 8-Br-cGMP, did not mimic the stimulatory effects of SNAP in DRG cells. These results suggest that in cultured DRG cells, NO potentiates the IL-1 beta-induced increase in COX-2 expression via a soluble guanylate cyclase-cGMP-independent pathway, resulting in facilitation of SP release. The interaction between NO and COX in primary afferent neurons might contribute to the change in nociceptive perception in inflammatory hyperalgesia.

Animals↗

[Analysis for microbial contamination in production of Japanese-style confectionery "Monaka"].

Food hygiene in Japanese-style confectionery factories is hard to practice because the businesses are small. In a supporting system of voluntary-based hygienic management in this field, we microbiologically investigated the production processes of "Monaka" in a workshop in Tokyo. We microbiologically assessed the processing environments as well as the products in the workshop, then proposed some improvements in the production of the confectionery. After the improvements, microbial contamination of the processing environments was reduced and no microbial contamination was found in the sugared bean, or "An" produced, though the product "Monaka" was still contaminated, especially by molds. It was clarified that the molds came from contaminated baked wheat shells, or "Kawa" and further that the wheat shells were contaminated by molds during storage.

Food Handling↗

[Clinical experience of new stereotactic radiotherapy system named CyberKnife].

The CyberKnife is a small linear accelerator mounted on a robot. The CyberKinfe has the IPS(Image Processing System) that evaluates the patient position during the treatment. If there is any movement of the patient, the robot chases the tumor. Invasive flame to fix the patient skull is not needed. From April 1998 through July 2000, we applied the CyberKnife treatment for 136 sites in 94 patients. Sixty-seven of 136 sites were metastatic brain tumors. Progression-free rate of tumors treated with 24-27 Gy at 3 months after treatment was 89%. There was no severe adverse effects except epilation. The CyberKnife treatment was applied for tumors in the body in USA. It will be available in Japan in near future.

Brain Neoplasms↗

High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial.

PURPOSE: To improve results for localized prostate cancer, a prospective clinical trial of hyperfractionated Iridium-192 high-dose-rate (HDR) brachytherapy as a monotherapy was initiated. METHODS AND MATERIALS: Between May 1995 and September 1998, 22 implants were performed on 22 patients with localized prostate cancer (T1:T2:T3:T4 = 4:6:9:3) at Osaka University Hospital. Nineteen patients, who had T3-T4 tumors or pretreatment PSA >/= 20.0 ng/mL, received hormone therapy. No patient had external beam radiation. Transperineal needle implants using real-time ultrasound guidance were performed, followed by dose optimization program. Patients were irradiated twice a day, with a time interval of more than 6 h. Total dose was 48 Gy/8 fractions/5 days or 54 Gy/9 fractions/5 days. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Median follow-up time was 31 months. RESULTS: HDR brachytherapy as a monotherapy was well-tolerated. No significant intra- or peri-operative complications occurred. No patient experienced acute toxicity of grade 3 or more. PSA levels normalized in 95% of patients within 20 months after irradiation. Four-year clinical and biochemical relapse-free rates were 95% and 55%, respectively. CONCLUSION: Acute toxicity with this method was acceptable. Further patient accrual and longer follow-up will allow comparison to other techniques.

Aged↗

Cellular distribution and clinical value of urokinase-type plasminogen activator, its receptor, and plasminogen activator inhibitor-2 in esophageal squamous cell carcinoma.

To assess the participation of the plasminogen activation system in the invasiveness of esophageal squamous cell carcinoma, we performed immunohistochemistry and in situ hybridization to study the distribution of a urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR), and plasminogen activator inhibitor-2 (PAI-2). u-PA and PAI-2 were expressed heterogeneously in cancer cells, and restricted expression was found in stromal cells, especially fibroblasts, that were located in the immediate proximity of the cancerous cells. u-PAR was found only in cancer cells located at the periphery of tumors. Compared with patients with u-PA-negative cancer cells, patients with u-PA-positive cancer cells more frequently showed a neoplastic invasion beyond the muscularis propria and lymph node metastases. They also showed a significantly shorter 5-year overall survival. Patients with PAI-2-positive fibroblasts showed significantly lower levels of local invasiveness, represented by a neoplastic invasion beyond the muscularis propria, than those who were PAI-2 negative. Our results suggest that the expression of u-PA in esophageal squamous cell carcinoma is predictive of poor survival, whereas the expression of PAI-2 in the fibroblasts surrounding them is protective. An analysis of u-PA and PAI-2 expression in cancer cells and their surrounding fibroblasts may be useful for predicting the prognosis of patients with esophageal squamous cell carcinoma.

Adult↗

Occult breast cancer presenting axillary nodal metastasis: a case report.

We report a case of a 42-year-old female with occult breast cancer presenting axillary nodal metastasis. She complained of a swelling of the right axillary lymph node, but no breast mass was palpable. Biopsy of the lymph node was performed and histological examination showed a metastatic ductal carcinoma with papillotubular formation. Estrogen receptor of the lymph node was positive. No pathological findings were obtained by mammography and ultrasonography and systemic examinations revealed no extramammary primary lesion. All these data suggested an occult carcinoma of the breast and modified radical mastectomy was performed. Pathological findings of the removed specimen failed to find the primary breast cancer lesion. The patient has been treated with hormonal therapy and she is well without evidence of disease 5 years after surgery.

Adult↗

[Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle].

Hibernation in mammalians such as hamsters is a physiological state characterized by an extreme reduction of various functions such as body temperature and metabolism. Under such severe conditions, the central nervous system (CNS) activity is maintained at a functionally responsive level. Although hibernation is an interesting behavioral state, the physiological mechanisms of the introduction to and/or the arousal from hibernation have not been clearly defined. Intracerebroventricularly (i.c.v.) injected adenosine produces hypothermia in various animals. The effect of adenosine is generated by A1-receptors and is caused by the suppression of the thermogenesis center of the posterior hypothalamus. At on ambient temperature of 5, i.c.v. injected N6-cyclohexyladenosine (CHA) adenosine A1-receptor agonist induces profound hypothermia in hamsters. Although the time course of the descent of body temperature coincided with that of entry into natural hibernation, the effect was not antagonized by 8-cyclopentyltheophyllin (CPT), an adenosine A1-receptor antagonist. However, i.c.v. injection of CPT elevated the body temperature and interrupted hibernation, albeit the deep-phase (post-entry 30 h) was unaffected. This result suggests that a different system may suppress the thermogenesis center in the deep hibernation phase. Interestingly, i.c.v. injected thyrotropin releasing hormone (TRH) elevated the body temperature in both hibernation phases in hamsters. These findings suggest that the central adenosine and TRH play important roles in thermoregulation and that the new thermogenesis system, activating in low-body temperature, is induced in naturally hibernating animals.

Adenosine↗

Radiotherapy of early tongue cancer in patients less than 40 years old.

PURPOSE: To evaluate the results of treatment for early mobile tongue cancer in patients less than 40 years. METHODS AND MATERIALS: Between January 1967 and September 1992, 70 patients less than 40 years old (young age group) with early tongue cancer (T1-2N0M0) were treated with low-dose-rate (LDR) interstitial radiotherapy at the Osaka University Hospital (OUH). All patients had a minimum 2-year follow-up (median: 13 years). External radiotherapy (median: 30 Gy) was combined in 25 cases. The treatment results were compared with those for two older age groups (middle age: 40-64 years old; old age: 65 years old or more). RESULTS: The 5-year probability of cause-specific survival (CSS) rate for the young age group was 80%, which was not significantly different from the two older groups: 81% for middle age and 71% for old age. However, male patients of young age showed significantly worse rates than those of middle and old age (p = 0.02). The 5-year local control rate for the young age group was 78%. It was not significantly different from the two older groups: 81% for middle age and 70% for old age. The incidence of regional lymph node metastasis was 32% for T1, 48% for T2, 56% for males, and 24% for females. The regional failure rate of young males was significantly higher than those of the two older groups: 32% for middle and 22% for old age (p = 0.001). CONCLUSION: The overall treatment results for patients with early tongue cancer less than 40 years old were not worse than those of older age groups. However, male gender was a risk factor for lymph node metastasis and CSS.

Adult↗

Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons.

The effects of pituitary adenylate cyclase activating polypeptides (PACAPs: PACAP27, PACAP38) on glutamate-induced neurotoxicity were examined using cultured retinal neurons obtained from 3- to 5-day old Wistar rats. Cell viability was evaluated by double staining with fluorescein diacetate and propidium iodide. Effects of PACAPs on the increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in retinal neurons was investigated using the Ca(2+) image analyzing system with fura-2. The cAMP contents and the mitogen-activated protein (MAP) kinase activity in retinal cultures were measured by radioimmunoassay. Concomitant application of PACAPs (10 nM-1 microM) with glutamate (1 mM) for 10 min inhibited the delayed death of retinal neurons, which was observed 24 h after glutamate (1 mM) treatment in a dose-dependent manner. Protection by PACAPs (100 nM) against glutamate-induced neurotoxicity was antagonized by PACAP6-38 (1 microM), a PACAP antagonist, and H-89 (1 microM), a protein kinase A (PKA) inhibitor. However, PACAPs did not affect the glutamate-induced increase in [Ca(2+)](i), but PACAPs (1-100 nM) increased the cAMP levels in a dose-dependent manner. In addition, activation of MAP kinase by PACAP38 (1 microM) was inhibited by simultaneous application with H-89 (1 microM). These findings suggest that PACAPs attenuate glutamate-induced delayed neurotoxicity in cultured retinal neurons by activating MAP kinase through the activation of cAMP-stimulated PKA.

Animals↗

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors.

PURPOSE: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. CONCLUSION: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases.

Adolescent↗

Handlebar hernia with intra-abdominal extraluminal air presenting as a novel form of traumatic abdominal wall hernia: report of a case.

An 18-year-old male was admitted to our Emergency Department with a traumatic abdominal wall hernia (TAWH) of the left lower quadrant (LLQ) after suffering hypogastric blunt injury and urogenital lacerations in a motorcycle accident. Upright chest X-ray showed a small amount of right infradiaphragmatic free air, and a computed tomographic (CT) scan demonstrated an abdominal wall hernia. At surgery, no impairment was found in the digestive tract, and an abdominal herniorrhaphy was performed. It is suggested that the free air had passed through a connection between the scrotal laceration and the contralateral abdominal defect via the subcutaneous space and was palpated as emphysema. This is a new type of TAWH, which suggests that blunt abdominal trauma may result in negative pressure in the subcutaneous and peritoneal cavity, and this could reflect the pathophysiology of TAWH.

Abdominal Muscles↗

Functional analysis of the heterologous NSP1 genes in the genetic background of simian rotavirus SA11.

Function of rotavirus NSP1 was analyzed by using single-NSP1 gene-substitution reassortants, SKF, SDF, and SNF which have the NSP1 gene derived from human rotaviruses KU, DS-1, and canine rotavirus K9, respectively, in the genetic background of simian rotavirus SA11. The NSP1 genes from KU, DS-1, K9, and SA11 exhibited 58-76% nucleotide sequence identity to one another. No substantial difference in viral growth was observed among the reassortants and SA11. However, production of NSP1 was not detected in SNF when viral proteins were labelled with 35S-methionine during replication in MA104 cells, in contrast to SA11, SKF and SDF which exhibited evident expression of NSP1. Difference in reassortant formation was examined among the reassortant clones generated between human rotavirus strain 69M and either of SA11, SKF or SNF. Although reassortant formation rate was significantly lower in the cross 69M x SNF than the other crosses, selection rates of RNA segments from parent strain 69M in the resultant reassortants was similar among the crosses. Selectivity of homologous and heterologous NSP1 genes in SA11 background was also analyzed by mixed infection and multiple passages among the single-NSP1 gene-reassortants and/or SA11, KU NSP1 gene was selected most frequently, whereas homologous (SA11) NSP1 gene was least efficiently segregated. These results indicated that viral growth and genome segment reassortment with other viruses may not be influenced by the presence of heterologous NSP1 and its expression level, while genomic diversity of NSP1 genes might have been associated with the relative adaptability to the genetic background of SA11.

Animals↗

Recent advances in neuropharmacology of cutaneous nociceptors.

Cutaneous nociceptors are peripheral receptive endings of primary sensory neurons activated by noxious stimuli. Nociceptors detect and signal the presence of tissue-damaging stimuli or the existence of tissue damage. In this short review, we will focus on the molecular mechanism of maintenance, activation, inhibition and sensitization in cutaneous nociceptors. Neurotrophic factors are essential to the development of nociceptors during embryogenesis. Recent evidences have indicated that nociceptors in the adult are maintained by either nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF). A selective activator of nociceptors is capsaicin, natural product of capsicum peppers. Recently, the receptor for capsaicin (the vanilloid receptor 1: VR1) has been cloned, identified and characterized. VR1 seems to play an important role in the activation and sensitization of nociceptors. In contrast, peripheral endogenous cannabinoids such as anandamide are novel candidates for mediators that inhibit the excitation of nociceptors. Intracellular messengers and the mechanisms of signal transduction in nociceptors have also been studied. Our recent findings provide evidences demonstrate that an activation of both cAMP- and cGMP-second messenger systems is required to induce the sensitization of nociceptors. Such emerging evidences reviewed here would make a significant contribution to further understanding of the molecular mechanism of nociceptors.

Animals↗

Protective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina.

The effects of vasoactive intestinal peptide (VIP) on glutamate-induced delayed death were examined using the primary cultures of rat retinal neurons. Effects of VIP on glutamate-induced neurotoxicity were evaluated by double staining with fluorescein diacetate and propidium iodide. Glutamate (1 mM) was applied to the culture for 10 min in the presence and absence of VIP, and visible cells enumerated 24 h after culture in normal medium. Effects of VIP on increase in the intracellular Ca2+ concentration and currents induced by glutamate in retinal neurons were investigated using the Ca2+ image analyzing system with fura-2 and whole-cell patch-clamp recording, respectively. The cAMP contents in retinal cultures were measured by radioimmunoassay. VIP (10 nM-1 microM) dose-dependently protected against glutamate-induced neurotoxicity in cultured retinal neurons. Protection by VIP (100 nM) against glutamate (1 mM)-induced neurotoxicity was antagonized by VIP6-28 (1 microM), a VIP antagonist, and H-89 (100 nM and 1 microM), a protein kinase A inhibitor. However, VIP had no effect on glutamate-induced inward currents nor glutamate-induced increase in the intracellular Ca2+ concentration. A 10-min exposure of VIP (100 nM) with glutamate (1 mM) resulted in an increase in the cAMP level to 446+/-58 from 22+/-1 pmol/mg protein. These findings suggest that VIP protects against the glutamate-induced neurotoxicity in retinal cultures by elevating the cAMP level via VIP receptors and thereby activating protein kinase A.

8-Bromo Cyclic Adenosine Monophosphate↗

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth.

PURPOSE: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. METHODS AND MATERIALS: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. CONCLUSION: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.

Adult↗

Optical high-precision three-dimensional position measurement system suitable for head motion tracking in frameless stereotactic radiosurgery.

Head motion is a significant source of therapy-effect degradation in frameless stereotactic radiosurgery (SRS). In this study, a three-dimensional (3-D) optical head motion measurement system and a coordinate transformation algorithm were used to track patient head motion. With this system, head motion in frameless SRS was carefully investigated with a precision of < 0.1 mm. Head motions without any restraint (three cases) and with a Laitinen adapter (four cases) were measured with a data sampling rate of once per second for 30 min. Positions of IR light emission diode markers attached to the head were analyzed by two statistical methods. From these data, mathematically simulated head motions were obtained in each of the three coordinate directions for nonrestraint and Laitinen-adapter SRS. The results show that segmenting a frameless SRS procedure into a sequence of short intervals and repeating registration of the target position for each interval is a good strategy for better therapy precision. This optical 3-D position measurement system is suitable for high-precision head motion tracking in frameless SRS.

Adult↗

Involvement of adenosine in vanadate-stimulated release of lipoprotein lipase activity.

A short-term incubation of isolated rat fat pads with vanadate showed the stimulated release of lipoprotein lipase (LPL) activity and suppression of the rise in extracellular adenosine level. The addition of adenosine to the medium showed inhibition of both the stimulated release of LPL activity and an increase in intracellular cAMP content by vanadate. A progressive increase in 5'-nucleotidase activity in the particulate fraction containing plasma membrane was suppressed by vanadate in a time- and dose-dependent manner, suggesting that vanadate inhibits, in part, the production of adenosine based on a dephosphorylation of AMP. In adipocytes, the inhibition of adenylate cyclase via A1 adenosine receptor is more predominant than the stimulation of adenylate cyclase via A2 adenosine receptor (Londos C. et al., Proc. Natl. Acad. Sci. U.S.A., 75, 5362-5366 (1978)). Therefore, vanadate may stimulate the release of LPL activity from the fat pads by suppressing the rise in extracellular adenosine level, accompanied by the activation of adenylate cyclase activity.

5'-Nucleotidase↗