Search PubMed⌕ Search

Biomedical subjects

K Yoshikawa

Publications and source records attributed to K Yoshikawa.

At least 37 records · Page 2Linked to original sources
PubMed2004

CyberKnife radiosurgery for vestibular schwannoma.

OBJECTIVE: The CyberKnife is newly developed equipment for radiosurgery and fractionated radiosurgery. The authors report on their experience using the CyberKnife in 38 patients with vestibular schwannoma who were treated between 1998 to 2002. METHODS: During this period, 38 patients with vestibular schwannoma were treated using CyberKnife fractionated radiosurgery. Before undergoing fractionated radiosurgery, 14 patients had Gardner Robertson classes I or II hearing (the serviceable hearing group), and 24 patients had classes III to V hearing (the non-serviceable hearing group). The treatment volumes of these two groups were 0.5 to 24.0 cm (3) (mean 4.7 cm (3)), and 0.5 to 41.6 cm (3) (mean 8.2 cm (3)). Target irradiation was administered in 1 - 3 fractions (mean 2.5 fractions). The total marginal radiation doses were 15.0 to 20.5 Gy (mean 17.0 Gy), and 11.9 to 20.1 Gy (mean 16.9 Gy), respectively. RESULTS: After a mean follow-up period of 31.9 months (range 12 to 59 months, median 27 months), 94 % of the tumors were controlled. Only one patient in the group with non-serviceable hearing underwent additional surgical resection for a presumed increase in tumor size. The hearing preservation rate was 93 %. Facial weakness did not develop in any of the patients in the serviceable hearing group. New trigeminal symptoms did not develop in any patients in either group. CONCLUSION: Although a longer and more extensive follow-up is needed, CyberKnife fractionated radiosurgery is considered to be safe and effective, even in patients with large tumors.

Adolescent↗
PubMed2004

Cyclooxygenase-2 is a possible target of treatment approach in conjunction with photodynamic therapy for various disorders in skin and oral cavity.

BACKGROUND: Anti-cancer effects of cyclooxygenase (COX)-2 inhibitors have been reported, but not fully investigated in skin and oral diseases. 5-aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for treating those patients with skin and oral lesions is a highly sophisticated procedure, but the incidence of disease recurrence after treatment is rather significant. OBJECTIVE: To confirm that COX-2 could be a molecular target in adjunctive therapy to ALA-based PDT, we investigated (i) COX-2 expression in various skin and oral diseases, and (ii) the inhibitory effects on cellular growth of COX-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on human oral squamous cell carcinoma (SCC) cell lines. METHODS: A total of 129 biopsy samples from the skin and oral mucosal lesions were tested immunohistochemically for COX-2 expression. Then the in vitro effects of nimesulide, ALA-based PDT, and their combination were determined on two SCC cell lines, HSC-2 and HSC-4. Three different methods (MTT assay, double-staining for annexin V and propidium iodide, caspase-3/CPP32 fluorometric protease assay) were applied for evaluation of their inhibitory effects on these two cell lines. RESULTS: Among the skin diseases, a considerable number of COX-2 high expressers were found in actinic keratosis (15 of 25, 60%), Bowen's disease (13 of 17, 76%) and extramammary Paget's disease (15 of 15, 100%). In contrast, only one of 33 (3%) basal cell carcinoma tumours was a COX-2 high expresser. Among the oral mucosal biopsies, the proportion of COX-2 high expressers increased gradually from hyperplasia (one of six, 17%) through mild dysplasia (five of eight, 63%) and moderate dysplasia (20 of 23, 87%) to severe dysplasia (two of two, 100%). Nimesulide had an inhibitory effect in vitro on HSC-2 (proven to be a COX-2 high expresser), but not on HSC-4 (a COX-2 non-expresser). While ALA-based PDT showed an inhibitory effect on both HSC-2 and HSC-4, most importantly the combination of nimesulide and ALA-based PDT demonstrated a significant synergistic effect on the cellular growth inhibition of only HSC-2, but not of HSC-4. CONCLUSIONS: Our study strongly suggests that COX-2 can be one of the molecular targets in treating various skin and oral diseases. The results from our in vitro experiments also prompt us to develop a new protocol with a combination of COX-2 selective inhibitor and ALA-based PDT for more effective treatment of those diseases.

Aminolevulinic Acid↗
PubMed2004

Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets.

BACKGROUND: Diabetic foot ulcers with exposed bones commonly result in amputation. OBJECTIVES: To determine whether exposure of bone marrow cells and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation. METHODS: Thirty-eight patients with chronic wounds caused by diabetes mellitus were enrolled in this study. Epidermal sheets obtained from suction blisters of each patient were grafted on to diabetic foot ulcers without exposed bones (n = 10) and were compared with the standard treatment of local wound care, debridement with a scalpel when indicated, bed rest and parenteral antibiotics (n = 8). In another group of patients, diabetic wounds with exposed bones were treated either with the standard procedure (n = 9) or with a newly developed experimental procedure (n = 11). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until fresh bleeding was observed from the exposed bone. The lesions were then immediately covered with an occlusive dressing, and finally the wound was covered with an epidermal graft of skin harvested from suction blisters. Patients in each group were matched with their counterparts by age, sex, wound size, wound infection and wound duration, to compare the time needed for total skin repair and rates of amputation. RESULTS: Epidermal grafting significantly accelerated the healing of diabetic foot ulcers (P = 0.042) without exposed bones, with site-specific differentiation. The newly developed combination therapy resulted in the healing of all diabetic ulcers with exposed bones without the occurrence of osteomyelitis or the necessity for amputation (P < 0.0001). CONCLUSIONS: Our study indicates that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation.

Adult↗
PubMed2004

Early pathological changes in the parkinsonian brain demonstrated by diffusion tensor MRI.

OBJECTIVE: To determine whether the fractional anisotropy (FA) of magnetic resonance diffusion tensor imaging is decreased in the nigrostriatal projection in parkinsonian patients. METHODS: FA values were compared in the extrapyramidal system of 12 patients with Parkinson's disease and eight age matched normal controls. RESULTS: Patients with Parkinson's disease had significantly decreased FA in the region of interest along a line between the substantia nigra and the lower part of the putamen/caudate complex, in which most of the nigrostriatal dopaminergic neurones are included. Loss of FA in this region was obvious even during the early clinical stages of Parkinson's disease. CONCLUSIONS: Assuming that the loss of FA parallels the neuronal change in the brain, the results are consistent with the view that more than half the dopaminergic neurones in the nigrostriatal projection are lost before the onset of Parkinson's disease. Close comparison of FA in the basal ganglia may contribute to the early diagnosis of Parkinson's disease.

Aged↗
PubMed2003

Competition between interchain and intrachain phase segregation.

Single-molecule observations of giant DNA have clarified that individual molecules undergo a marked discrete transition between an elongated coil state and a compact globule state. There is a relatively wide region of coexistence between the coil and the globule states, i.e., interchain phase segregation, with a change in intensive variables such as the concentration of the condensing agent, salt concentration, temperature. Very recently, the coexistence of coil and globule conformations within a single long DNA chain, i.e., intrachain phase segregation, has been reported under certain experimental conditions. In this study, we investigated general conditions for intrachain phase segregation in a single polyelectrolyte molecule, based on a simple statistical model. We consider the contribution of condensed counterions and the interaction energy of a charged coiled region. Intrachain phase segregation is stable with regard to free energy within a suitable parameter region. Our results suggest that intrachain phase segregation occurs when the electrostatic screening effect by the salt solution is negligible or when the screening effect is large and there is attractive interaction between polyelectrolyte segments.

Biophysical Phenomena↗
PubMed2003

Washout studies of 11C in rabbit thigh muscle implanted by secondary beams of HIMAC.

Heavy ion therapy has two definite advantages: good dose localization and higher biological effect. Range calculation of the heavy ions is an important factor in treatment planning. X-ray CT numbers are used to estimate the heavy ion range by looking up values in a conversion table which relates empirically photon attenuation in tissues to particle stopping power; this is one source of uncertainty in the treatment planning. Use of positron emitting radioactive beams along with a positron emission tomograph or a positron camera gives range information and may be used as a means of checking in heavy ion treatment planning. However, the metabolism of the implanted positron emitters in a living object is unpredictable because the chemical forms of these emitters are unknown and the metabolism is dependent on the organ species and may be influenced by many factors such as blood flow rate and fluid components present. In this paper, the washout rate of 11C activity implanted by injecting energetic 11C beams into thigh muscle of a rear leg of a rabbit is presented. The washout was found to consist of two components, the shorter one was about 4.2 +/- 1.1 min and the longer one ranged from 91 to 124 min. About one third of the implanted beta+ activity can be used for imaging and the rest was washed out of the target area.

Animals↗
PubMed2003

Detection of circulating MN/CA9 positive renal cell carcinoma cells during operation.

Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30 % of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100 %. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.

Adult↗
PubMed2003

Physical characteristics of low and medium energy collimators for 123I imaging and simultaneous dual-isotope imaging.

Septal penetration of high energy photons may degrade 123I images obtained with a low energy collimator. We evaluated the physical characteristics of a low energy, high resolution (LEHR) collimator, special LEHR (SLEHR) collimator, and medium energy collimator for 123I studies. The cross-talk of 99mTc and 123I into the 201Tl window was also examined. Sensitivity and spatial resolution were measured with each collimator. Point sources of 99mTc and 123I were imaged at various source-collimator distances using multiple energy windows, and the effects of collimator choice on energy spectrum and spatial distribution of photopeak counts were assessed. For 99mTc, both sensitivity and resolution were similar with the low energy collimators, and higher sensitivity and lower resolution were observed with the medium energy collimator. For 123I, the full width at tenth maximum was larger for 123I than for 99mTc when using the LEHR collimator. Acquisitions with multiple energy windows revealed severe degradation due to septal penetration in imaging 123I with the LEHR collimator, especially at short distances. The degradation was reduced with the SLEHR collimator and further with the medium energy collimator. In both 99mTc and 123I imaging, cross-talk into the 201Tl window was larger at shorter distances and the largest with the LEHR collimator. In conclusion, variation in collimator geometry causes differences in the effect of septal penetration on 123I images and in cross-talk into the 201Tl window. The SLEHR collimator may be suitable for use in high resolution 123I imaging and simultaneous 99mTc/201Tl imaging. Use of the medium energy collimator appears to be preferable in quantitative 123I studies.

Equipment Failure Analysis↗
PubMed2003

A case of manganese induced parkinsonism in hereditary haemorrhagic telangiectasia.

A 44 year old right handed woman complained of difficulty in moving. She and her relatives had skin telangiectasia or recurrent epistaxis. On neurological examination, she had a mask-like facies and bradykinesia in both extremities. Laboratory examinations showed iron deficiency anaemia and mild liver dysfunction with raised serum manganese. On T1 weighted cranial magnetic resonance imaging there were hyperintense areas in the globus pallidus bilaterally, suggesting manganese deposition. Abdominal angiography confirmed multiple portal-systemic shunts in the liver, and a needle biopsy of the liver showed diffuse dilatation of the sinusoids with fatty change. Levodopa did not improve the bradykinesia. This appears to be a case of hereditary haemorrhagic telangiectasia with manganese induced parkinsonism, which may be a new type of neurological disorder in such patients.

Adult↗
PubMed2002

Cell death induced by a caspase-cleaved transmembrane fragment of the Alzheimer amyloid precursor protein.

The Alzheimer amyloid precursor protein (APP) is a transmembrane protein whose abnormal processing is associated with the pathogenesis of Alzheimer's disease. Activated caspases cleave APP and generate its carboxyl-terminally truncated fragment (APPdeltaC31). We have previously reported that overexpression of wild-type APP induces caspase-3 activation and apoptosis in postmitotic neurons. We now report that APPdeltaC31 potentially plays pathophysiological roles in neuronal death. Adenovirus-mediated overexpression of wild-type APP695 induced activation of caspase-3 and accumulation of APPdeltaC31 in postmitotic neurons derived from human NT2 embryonal carcinoma cells, whereas an APP mutant lacking the Abeta(1-20) region induced neither caspase-3 activation nor APPdeltaC31 generation. Inhibition of caspase-3 suppressed the generation of APPdeltaC31 in APP-overexpressing neurons. Forced expression of APPdeltaC31 induced apoptotic changes of neurons and non-neuronal cells, but failed to activate caspase-3. The cytotoxicity of APPdeltaC31 was also dependent on the Abeta(1-20) region. These results suggest that accumulation of wild-type APP activates neuronal caspase-3 to generate APPdeltaC31 that mediates caspase-3-independent cell death.

Adenoviridae↗
PubMed2002

Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples.

AIMS: The expression of human neuropsin (KLK8) mRNA in normal and pathological skin samples was analysed and the results compared with those for tissue plasminogen activator (tPA) mRNA. METHODS: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed. RESULTS: A weak signal for KLK8 mRNA and no signal for tPA mRNA was seen in normal skin on northern blot analysis. Weak signals for KLK8 were localised to the superficial cells beneath the cornified layer in normal skin on in situ hybridisation. Psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma skin samples, which show severe hyperkeratosis, displayed a high density of KLK8 mRNA on northern and in situ hybridisation analyses. The signals were localised in granular and spinous layers of lesional skin in all hyperkeratic samples, including the area surrounding the horn pearls of squamous cell carcinoma. To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures. When keratinisation proceeded in high calcium medium, a correlative increase in the expression of KLK8 mRNA was observed. CONCLUSION: The results are consistent with a role for this protease in the terminal differentiation of keratinocytes.

Adult↗
PubMed2002

False positive uptake of metaiodobenzylguanidine in hepatocellular carcinoma.

We present the case of a patient who showed increased accumulation of (123)I-metaiodobenzylguanidine (MIBG) in hepatocellular carcinoma, leading to a false presumptive diagnosis of intrahepatic neuroendocrine tumour. The increase in uptake was not seen on images obtained 4 h after tracer injection but was evident on those taken after 24 h, suggesting slower washout from the liver tumour than from non-tumoural liver parenchyma. Our observations indicate that a non-neuroendocrine malignant tumour may exhibit high accumulation of MIBG associated with prolonged retention.

3-Iodobenzylguanidine↗
PubMed2002

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.

Adult↗
PubMed2001

Controlling the higher-order structure of giant DNA molecules.

Giant DNA molecules of size greater than several kbp adopt an elongated coil conformation in aqueous solution. On addition of various kinds of condensing agents, the giant DNA molecules fold into a compact state. With multivalent cations, individual DNA molecules show large discrete transitions between the elongated and compact states. Similarly, with the addition of polymers such as PEG, DNA molecules also switch conformation in an all-or-none manner. In contrast, DNAs fold into a loose compact state with cationic surfactants. The experimental conditions necessary to generate stable soluble particles from single DNA molecules and also to obtain multiple DNA molecular assemblies are outlined. The relationship between the higher-order structure and the efficiency of gene transfection is discussed.

Animals↗
PubMed2001

Neurotoxic and neuroprotective effects of glutamate are enhanced by introduction of amyloid precursor protein cDNA.

The physiological role of amyloid precursor protein (APP), whose anomalous metabolite is a putative pathogen for Alzheimer disease, remains unclear. From the enhanced responsiveness to glutamate in cultured hippocampal neurons after the introduction of cDNA of APP695 (an isoform of APP dominant in human brain) using an adenovirus vector, we have recently raised the hypothesis that APP modulates neuronal sensitivity to glutamate. To test this hypothesis, we utilized here the unique effects of glutamate on the survival of different types of neurons. It is known that hippocampal neurons undergo deterioration in 24 h after application of glutamate in a dose-dependent manner. This vulnerability was increased in the cells transfected with adenovirus carrying cDNA of APP695. By contrast, it is known that cerebellar granule neurons require for their survival the supplementation of NMDA to the medium. The dose of NMDA required for survival was reduced after the transfection of the APP-adenovirus to cerebellar granule neurons. These enhancing effects of APP on the glutamate-induced vulnerability in hippocampal neurons and the glutamate (NMDA)-dependent survival in cerebellar neurons were blocked by glutamate receptor inhibitors, and were not seen after application of a control adenovirus carrying cDNA of beta-galactosidase. Since the effects of glutamate were enhanced in both directions, the hypothesis became more likely that one of the physiological functions of cellular APP is the regulation of glutamate receptors.

Amyloid beta-Protein Precursor↗