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Biomedical subjects

K Kunishio

Publications and source records attributed to K Kunishio.

At least 37 records · Page 2Linked to original sources

Proliferative potential and apoptosis in rat glioma cell lines after hyperthermia.

The proliferative potential of cultured rat glioma cells (C6 and 9L) was evaluated after hyperthermia using immunohistochemical staining with bromodeoxyuridine (BrdU) and Ki-67 monoclonal antibodies. Apoptosis was assessed by in situ end-labeling of deoxyribonucleic acid breaks. Both BrdU and Ki-67 labeling indexes decreased with increasing hyperthermia time. The decrease of the Ki-67 labeling index was not as great as that of the BrdU labeling index. The number of apoptotic cells increased with time after hyperthermia. These results indicate that the antitumor effect of hyperthermia may reflect the induction of apoptosis in the cells within the cell cycle, and the resultant reduction of the proliferative potential of surviving cells, especially in the S phase.

Animals↗

[Incidence of mutation and deletion in topoisomerase II mRNA of etoposide and m-AMSA resistant cell lines].

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to ETP or m-AMSA. Subsequently, a population of cells from each subline was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. The frequency and nature of mutations in topo II in the drug selected cell lines have been evaluated. In order to screen a large number of cell lines, an RNase protection assay was developed. Fragments covering the entire coding sequence of topo II was isolated after PCR amplification and subcloned in pGEM3Z vector. Using this approach, mismatches was observed in 13.6% of resistant cell lines (12% of resistant cell lines exposed to lower drug concentrations and 18.8% of resistant cell lines exposed to higher drug concentrations). Our findings suggest that mutations of topo II gene seem to be an important and frequent mechanism of resistance to topo II inhibitors.

Amsacrine↗

New method for the evaluation of the response of cultured cell lines to continuous low-dose-rate irradiation from encapsulated iridium-192 seeds with hyperthermia.

A new method was designed to investigate and evaluate the biological effectiveness of hyperthermia combined with continuous low-dose-rate irradiation (CLDRI) from encapsulated iridium-192 seed sources on glioma cells in vitro using the MTT assay. The system consists of 10 iridium seeds contained in a catheter bent into a circle, which is placed on a culture plate containing the cells. The effects of CLDRI and CLDRI combined with hyperthermia on a cultured rat glioma cell line (C-6) were studied. The number of surviving cells decreased as the total radiation dose increased. There was no significant difference in survival rates at dose rates of 0.1 Gy/hr and of 0.2 Gy/hr (p = 0.2811). An additive effect was observed in the cells treated with hyperthermia at 41 degrees C and 42 degrees C, combined with CLDRI, and synergistic effect between the two treatment modalities was observed at 43 degrees C. This new device is less expensive, easily reproducible, and can also be performed easily enough to examine a large number of samples in a short time period for sensitivity testing.

Animals↗

[Transient mutism after resection of left frontal lobe astrocytoma in adult: case report].

We reported a case of a 32-year-old female who had a transient mutism after resection of a malignant astrocytoma in the left frontal lobe. Preoperatively magnetic resonance (MR) imaging revealed a cystic tumor in the left frontal lobe. The patient underwent surgery. She was alert but did not speak immediately after surgery. She could follow verbal commands, comprehend written language, and write letters. She had no cranial nerve or extremity paresis. Seven days postoperatively, she began to say simple words, and one month postoperatively she could talk normally. Postoperative MR imaging revealed a hypointensity area on T1 weighted image in the frontal lobe including a part of the anterior cingulate cortex and the anterior part of the corpus callosum. It appears that a dominant hemisphere lesion of both the anterior cingulate cortex and the corpus callosum may be responsible for the development of postoperative mutism.

Adult↗

[Clinical study of primary central nervous system lymphoma: the role of chemotherapy].

We conducted a retrospective study of 32 patients with histologically confirmed primary central nervous system lymphoma treated in our institute between 1971 and 1995 with an emphasis on the role of chemotherapy. Thirty of the 32 patients underwent tumor resection, whereas 2 patients had biopsies only. Twenty-eight patients received adjuvant therapy, 9 of whom received radiation therapy alone, 2 received chemotherapy alone, and 17 received both radiation therapy and chemotherapy. Chemotherapies performed were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). VEMP or VENP (vincristine, cyclophosphamide, mercaptopurine [or Natulan], and prednisolone), intravenous ACNU (nimustine), and intravenous or intra-arterial MCNU (ranimustine) and CBDCA (carboplatin). Survival data were available for 30 of the 32 patients. The median survival time of this study was 12.5 months. Twenty-seven patients died from one month through 79 months after the initiation of therapy, and 3 patients were alive for 13 to 69 months. Two patients who received the combination of radiation therapy and chemotherapy survived longer than 5 years. Although radiation therapy and chemotherapy were individually both effective and prolonged the survival time, their combination was more effective. The median survival time was significantly shorter (7.0 vs 16.5 months, p < 0.05) for the patients who received radiation therapy alone than for the patients who received the combination of radiation therapy and chemotherapy. We conclude from our results and review of previous studies that it is important for the chemotherapy of primary central nervous system lymphoma 1) to apply a combination of a variety of effective drugs, similar to that for systemic malignant lymphoma, and 2) to make a sufficient amount of anti-cancer drugs penetrate the whole central nervous system, thereby satisfying the adequate dose intensity for each drug.

Adolescent↗

[Topographic organization of the ventral striatum afferent projection from amygdaloid complex and hippocampal formation].

The organization of the striatal afferent fibers from the amygdaloid complex and hippocampal formation was studied in the monkey with particular emphasis on specific projections of the ventral striatum. Retrograde tracers were injected into the different regions of the ventral (limbic) striatum and dorsolateral (sensorimotor) striatum. Labeled neurons were observed in the various regions of the amygdaloid complex and hippocampal formation. The medial ventral striatum received dense projections from the amygdala (the basal nucleus and the magnocellular division of the accessory basal nucleus), and the hippocampus (subiculum, CA1 and CA3). The shell of the nucleus accumbens (calbindin-D28k negative region) also received dense projections from the amygdala (the basal nucleus and the magnocellular division of the accessory basal nucleus), and the hippocampus (subiculum). The injections into the core of the nucleus accumbens showed scattered labeled neurons in the amygdala, and only a few labeled neurons in the hippocampus. The lateral ventral striatum received few inputs from the amygdala and hippocampus. In contrast to the ventral striatum, the dorsolateral striatum received no projection from the amygdala or the hippocampus. The connectional similarities between the medial ventral striatum and the shell of the nucleus accumbens suggest that although the medial ventral striatum is not calbindin-D28k negative, it may be regarded as a transitional zone between the shell and the rest of the ventral striatum.

Amygdala↗

Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices.

p16 is involved in a cell-cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1 and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/ p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma, 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25%) and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%) than in those without deletions (10%; p = 0.0001). These results suggest that homozygous CDKN2/p16 deletions in high-grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4-cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.

Adult↗

The orbital and medial prefrontal circuit through the primate basal ganglia.

The ventral striatum is considered an interface between limbic and motor systems. We followed the orbital and medial prefrontal circuit through the monkey basal ganglia by analyzing the projection from this cortical area to the ventral striatum and the representation of orbitofrontal cortex via the striatum, in the globus pallidus and substantia nigra. Following injections of Lucifer yellow and horse radish peroxidase into the medial ventral striatum, there is a very densely labeled distribution of cells in areas 13a and 13b, primarily in layers V and VI, and in medial prefrontal areas 32 and 25. Injections into the shell of the nucleus accumbens labeled primarily areas 25 and 32. The reaction product in the globus pallidus and the substantia nigra supports previous studies demonstrating that efferent projections from the ventral striatum are represented topographically in the ventral pallidum and nontopographically in the substantia nigra, pars compacta. Tritiated amino acid or PHA-L tracer injections into orbitofrontal cortex produce dense patches of terminal labeling along the medial edge of the caudate nucleus and the dorsal part of the nucleus accumbens. These results demonstrate that the orbital prefrontal cortex projects primarily to the medial edge of the ventral striatum and to the core of the nucleus accumbens. The arrangement of terminals in the globus pallidus and substantia nigra show two different patterns. Thus, the orbital and medial prefrontal cortex is represented in a confined region of the globus pallidus but throughout an extensive area of the dorsal substantia nigra. Terminals are extensive throughout the region of the dopaminergic neurons, suggesting that this input may influence a wide area of both the striatum and frontal cortex.

Animals↗

Primate cingulostriatal projection: limbic striatal versus sensorimotor striatal input.

The organization of the projections from the cingulate cortex to the striatum in the monkey was studied using the retrograde tracers Lucifer Yellow conjugated to dextran amines and horseradish peroxidase conjugated to wheat germ agglutinin. These tracers were injected into the different regions of the ventral (limbic) striatum and the dorsal (sensorimotor) striatum. The shell region of the nucleus accumbens was defined using calbindin-D28K immunohistochemistry. Following injections into the ventral striatum, there are numerous retrogradely labeled neurons in the various regions of the primate cingulate cortex, most of which are derived from layer V. The cytoarchitectural subdivisions of cingulate cortex include the anterior cingulate cortex, areas 25, 24a-c, and 24a'-c', and the posterior cingulate cortex, areas 23a-c, 29, 30, and 31. There is a topographical organization of the projections from these different cingulate areas to the ventral and dorsal striatum. The medial ventral striatum receives input from the rostral part of the anterior cingulate cortex (areas 25 and 24a,b). The shell region of the nucleus accumbens receives fibers from areas 25, 24a,b, and 24a',b'. Projections to the central ventral striatum including the core of the nucleus accumbens are derived primarily from areas 25, 24a, 24b, and the medial part of area 24c. However, few labeled cells are detected in areas 24c and 24c'. The lateral ventral striatum receives input primarily from areas 24b, 24b' and 23b and medial portion of area 24c. The medial ventral striatum and the shell of the nucleus accumbens have a similar distribution of labeled cells, such that these regions derive their input almost entirely from the rostral anterior cingulate cortex. In contrast to the ventral striatum, the dorsal sensorimotor striatum receives projections from areas 24c, 24c' 23c and 31. These arise primarily from the lateral portion of lower bank and the fundus of the cingulate sulcus. Our results demonstrate that areas 24c, 24c' and 23c, the lateral portion of the lower bank and the fundus of the cingulate sulcus project to the dorsal sensorimotor striatum. The medial portion of the lower bank of the cingulate cortex projects to the ventral striatum including the core of the nucleus accumbens. Different projections to striatum from discrete subdivisions of cingulate cortex indicate that these areas are heterogeneous and have different functions such that the fundus of the cingulate sulcus is related to skeletomotor function, whereas the medial portion of the lower bank of the cingulate sulcus is associated with the limbic-related and association cortical function.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The significance of nucleolar organizer region (AgNOR) score in predicting meningioma recurrence.

BACKGROUND: Argyrophilic nucleolar organizer region (AgNOR) has been demonstrated in recent studies of human brain tumors, including meningiomas. The authors used this technique in meningiomas to analyze whether the mean numbers of AgNOR per nucleus (AgNOR score) are related to the recurrence rate or the proliferative potential of meningiomas. METHODS: AgNOR staining technique was applied to paraffin-embedded sections of 60 meningiomas. Twenty of these specimens also were investigated immunohistochemically with monoclonal antibody (MoAb) against DNA polymerase alpha (Pol.alpha) and with MoAb Ki-67 to compare the AgNOR score with the proliferative potential. RESULTS: There was a statistically significant difference between the AgNOR score in nonrecurrent meningiomas (2.48 +/- 0.73) and recurrent histologically benign meningiomas after gross total resection (3.20 +/- 0.96) (P < 0.02). The recurrence rate of tumors after gross total resection with an AgNOR score of 3.0 or more was significantly higher than that with an AgNOR score of less than 3.0. The AgNOR score did not always correlate with Pol.alpha or Ki-67 score; the AgNOR score of malignant meningioma that had high proliferative score was not always high. CONCLUSIONS: This study indicates that AgNOR staining appears to be a simple and useful method for estimating the probability of histologically benign meningioma recurrence even after gross total resection.

Adult↗

Extracranial vertebral artery aneurysm causing spinal subarachnoid hemorrhage--case report.

A 48-year-old female presented with spinal subarachnoid hemorrhage (SAH) due to the rupture of an extracranial vertebral artery (VA) aneurysm. The aneurysm arose from the junction of the third and the fourth segments of the left VA just inside the dura mater, and was partially coated with Biobond. This is only the second such case reported. We recommend complete four-vessel angiography in evaluating patients with SAH, with special attention given to the extracranial VA if spinal SAH is suspected.

Aneurysm, Ruptured↗

Factors influencing the recurrence rate of intracranial meningiomas after surgery.

The postoperative recurrence rate was examined in 242 patients with intracranial meningiomas to identify correlations with age, location, histology, or extent of surgery (Simpson's grade). There was no significant difference in the recurrence rate among the histological subtypes, but malignant meningiomas and hemangiopericytomas tended to recur earlier. Anterior basal meningiomas demonstrated a higher recurrence rate, but this depended on the feasibility of complete surgical removal. The recurrence rates significantly decreased in the order Simpson's grade I surgery, grade II or III surgery, and grade IV surgery (p < 0.001). These results indicate that the most important factor to influence recurrence is the extent of surgical removal.

Adolescent↗

Evaluation of MRI score in the differentiation between glioblastoma multiforme and metastatic adenocarcinoma of the brain.

The authors statistically analyzed the MR configurations of 14 glioblastoma multiformes (GBMs) and 15 metastatic adenocarcinomas (MACs) of the brain in order to distinguish these two histological types on MR images. MR configurations were classified and scored upon the 9 criteria of heterogeneity, cyst or necrosis, haemorrhage, crossing of the midline by the tumour, oedema or mass effect, border definition, flow void sign, degree and heterogeneity after contrast enhancement. The mean value of GBMs was 1.47 +/- 0.22, and that of MACs was 0.91 +/- 0.37 (P < 0.001). GBMs had significantly higher values in five out of the nine criteria: border definition, heterogeneity, crossing of the midline of the tumour, flow void sign, and degree of the contrast enhancement (P < 0.001-0.05). Border definition was the best criterion for distinguishing two histological types. Six cases of MACs displayed hypo-intense lesions on T2 weighted images in contrast to GBMs which showed hyperintense lesions in all cases. In 4 out of the 6 MACs which were shown as hyperintensities on T2 weighted images, a hypo-intense peritumoural rim was noticed between the tumour parenchyma and the surrounding oedema. These data strongly suggest that GBMs and MACs can be distinguished on MR image by using MRI score.

Adenocarcinoma↗

Neuropsychological outcome and social recovery of head-injured patients.

The Wechsler Adult Intelligence Scale and Yatabe-Guilford personality test were administered to 123 patients hospitalized for head injury who had made a relatively good recovery. Intelligence quotient (IQ) was correlated with clinical condition based on the Glasgow Coma Scale and duration of coma. More severely injured patients tended to show a greater decline in IQ. The type of lesion, as described by computed tomography, was also an important factor in predicting the outcome of intellectual function. The mean IQ of patients with diffuse injury, such as diffuse axonal injury and diffuse brain swelling, and intracerebral hematoma, was significantly lower than that of the control subjects, especially performance IQ (PIQ). Several patients demonstrated improved IQ level during the initial year. In particular, PIQ improved more than verbal IQ. The difference between the IQ of patients achieving social recovery and not was significant (p < 0.001). Causes of difficulty in returning to previous work were decreased IQ and personality change, such as lack of cooperativeness. Neuropsychological evaluation is important in predicting social recovery and selecting necessary neuropsychological rehabilitation.

Adolescent↗

Choroid plexus papilloma in an infant.

A case of choroid plexus papilloma (CPP) associated with overproduction of cerebrospinal fluid (CSF) in an infant is reported. The tumor was totally resected. Histologically, it was diagnosed as CPP with several mitosis, however, there were no other features indicating malignancy. Transthyretin immunoreactivity was found in the tumor cells on CSF cytological examination as well as in surgical specimens. Though the percentage of PCNA was high (10.8%), it was not higher than other benign CPPs (mean score: 18.2%). There was no recurrence or dissemination on follow-up CT or MRI 1 year after surgery. The patient has grown normally after surgery without a shunting procedure.

Antigens, Neoplasm↗

[Neuropsychological outcome of head injury in children].

Wechsler Intelligence Scale for Children-Revised (WISC-R) and Yatabe-Guilford personality test were administered to 31 children who had been hospitalized for head injury and made a GR or MD by the Glasgow Outcome Scale (GOS). The type of lesion, as defined by CT scan categories, was an important factor to prognosticate the outcome of intellectual function. The IQ, especially performance IQ, of acute subdural hematoma (EDH) or severe diffuse brain injury (DBI) was lower than that caused by other types of lesion. Several children demonstrated improvement in IQ level during the initial year. The difference between the IQ of the children who could return to previous school life and that of the children who could not was significant. One of the causes of difficulty in returning to previous school life is decreasing IQ and personality change such as social disadaptability. Neuropsychological evaluation is important in predicting school recovery and deciding proper neuropsychological rehabilitation.

Child↗

[Analysis of long-term social rehabilitation of brain contusion].

164 patients with brain contusion were evaluated with respect to social rehabilitation. 70 out of 134 patients (66.7%), said to have had good recovery or moderate disability by the Glasgow Outcome Scale (GOS), returned to full or partial employment. Factors such as age, Glasgow Coma Scale (GCS) at admission, duration of unawareness, fibrin and fibrinogen degradation product (FDP) were the most important in predicting social recovery. The Wechsler Adult Intelligence Scale (WAIS) was applied in 33 patients. The IQs of the patients who returned to their job fully tended to be higher than those who could not. In the majority of patients, impaired capacity for work was caused not only by physical deficits, but by mental retardation described as such as IQ score.

Adolescent↗