Biomedical subjects
Publications and source records attributed to T Shimura.
A case of an intracerebral fibromyxoma in a 4-year-old female with a developing left hemiplegia is described. Primary intracranial benign fibrous tumors are rare. A review of the relevant patients in the literature revealed 12 other cases. The management of this patient and an analysis of reported cases are presented.
The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients. When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05). In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05). There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9%. In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001). The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis.
Serum soluble HLA (SHLA) class I antigens in patients with systemic lupus erythematosus (SLE) were examined by enzyme-linked immunosorbent assay. The primary antibody used was W6/32, anti-HLA class I mouse monoclonal antibody, and the secondary antibody was peroxidase-conjugated anti-mouse IgG antibody. The reactivity of SHLA class I antigens, the number of peripheral lymphocytes, and the clinical state of SLE were compared. The results were as follows; 1) Sixteen of 55 samples from SLE patients were SHLA class I antigen-positive (29%). 2) The reactivity of SHLA class I antigens was closely related to disease activity. 3) The number of lymphocytes and the reactivity of SHLA class I antigens were negatively correlated. 4) Nine of 23 samples from the active SLE patients were SHLA class I antigen-negative. Of these, 7 were from patients with a nephrotic syndrome due to lupus nephritis. It is concluded that SHLA class I antigens can be an useful marker for monitoring the clinical state of SLE.
Intraperitoneal disseminated ovarian cancer has a poor prognosis and its treatment is difficult. Recently, we undertook intraperitoneal chemotherapy (IP) of CDDP (Pt) and etoposide (Et) using an implantable reservoir. The subjects were 14 patients with advanced ovarian cancer. One hundred mg of Pt and 200 mg of Et were administered intraperitoneally through the reservoir, and the therapeutic results were evaluated. In 6 patients, levels of total platinum (t-Pt), free platinum (f-Pt) and Et were determined in the blood and intraperitoneal fluid by flameless atomic absorption spectrophotometry. 1. The 14 patients received 82 courses of IP. In 10 cases of IIIrd stage, no recurrence was detected in 5 radical operable cases, and 4 of 5 inoperable cases were able to undergo radical operation after IP. One case was inoperable even after IP. Recurrences were detected in 2 of 4 cases which subsequently became operable. In a case of IVth stage, remission was achieved, but the tumor markers began rising again 18 months after operation. No further recurrence was detected in a treated recurrence case. In 2 cases of metastatic cancer, recurrences were detected 3 and 7 months after operation, respectively. As a side effect, the incidence of gastrointestinal toxicities, anemia, leukocytopenia and alopecia was high, but the grade was almost 1 or 2. Intraperitoneal mean maximum concentrations were t-Pt: 21.98 +/- 5.78; f-Pt: 17.72 +/- 4.97; Et: 62.98 +/- 23.94 micrograms/ml. Blood mean maximum concentrations were t-Pt: 2.84 +/- 0.41; f-Pt: 0.84 +/- 0.22; Et: 11.38 +/- 2.12 micrograms/ml. Mean AUC of the blood were t-Pt: 57.76 +/- 6.62; f-Pt: 2.96 +/- 0.47; Et: 108.76 +/- 18.94 micrograms.h/ml. 2. IP is considered to be effective for advanced ovarian cancer not only as a local therapy but as a general therapy, and is feasible as maintenance therapy with the implantable reservoir and tolerable side effects.
We report two surgical cases of inflammatory conditions of the liver that, on imaging studies, closely resembled a neoplasm. Under the diagnoses of hepatic malignant neoplasms, both patients underwent hepatic resections. Histologically, one case was found to be a hepatic xanthogranuloma (an inflammatory pseudotumor) that consisted of foamy histiocytes, plasma cells, lymphocytes, and fibroblasts, while the other case was found to be an epithelioid cell granuloma with a central area of coagulative necrosis. Although their exact pathogenesis remained obscure, cholangitis in the former case and tuberculosis in the latter were assumed to be possible causal factors. Special attention should be paid to these unusual conditions in terms of the differential diagnosis of hepatic mass lesions.
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The internalization of a neuromodulatory adrenocorticotropic hormone (ACTH) analogue, [125I]ebiratide (H-Met(O2)-Glu[125I]His-Phe-D-Lys-Phe-NH(CH2)2NH2), was examined in cultured monolayers of bovine brain capillary endothelial cells (BCEC). HPLC analysis of the incubation solution showed that [125I]ebiratide was not metabolized during the incubation with BCEC. The acid-resistant binding of [125I]ebiratide to BCEC increased with time for 120 min and showed a significant dependence on temperature and medium osmolarity. Pretreatment of BCEC with dansylcadaverine or phenylarsine oxide, endocytosis inhibitors, and 2,4-dinitrophenol, a metabolic inhibitor, decreased significantly the acid-resistant binding of [125I]ebiratide. The acid-resistant binding of [125I]ebiratide was saturable in the presence of unlabeled ebiratide (100 nM-1 mM). The maximal internalization capacity (Bmax) at 30 min was 7.96 +/- 3.27 pmol/mg of protein with a half-saturation constant (Kd) of 15.9 +/- 6.4 microM. The acid-resistant binding was inhibited by basic peptides such as poly-L-lysine, protamine, histone, and ACTH but was not inhibited by poly-L-glutamic acid, insulin, or transferrin. These results confirmed that ebiratide is transported through the blood-brain barrier via an absorptive-mediated endocytosis.
The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.
The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Platinum pyrimidine greens inhibited the deoxyribonucleic acid (DNA) synthesis of tumor cells in the S phase of the cell cycle and exerted antitumor activity. Clear differences were observed in the activity between the samples prepared at 40 degrees C and at 75 degrees C. Using 3H-thymidine incorporation assay and cell cycle analysis we confirmed that the former had much stronger and more specific inhibitory activity against DNA synthesis than the latter. Reactivity of the 40 degrees C sample with deoxyguanosine monophosphate (dGMP) and deoxyadenosine monophosphate (dAMP) was, respectively, two and three times larger than that of the 75 degrees C sample.
This paper reports clinicopathological findings concerning an enlarged bulky cyst and the tumor cavity following local administration of an anticancer agent combined with radiotherapy in two patients suffering from malignant glioma. Case 1: This 69 year-old man who had been diagnosed as having glioblastoma in the right parietal lobe had received local chemotherapy after the first operation. Simultaneously radiotherapy of 69 Gy in total dose was performed. At the second operation for the tumor, cyst formation was clinically confirmed and necrotomy as well as evacuation of the large cyst was performed after adjuvant therapy. The patient died at a time ten months after the first surgical operation. Case 2: This is the case of a 48 year-old man who was diagnosed as having gemistocytic astrocytoma in the left frontal lobe. The first surgical operation was performed and was followed by local chemotherapy as well as radiotherapy (total dose of 90 Gy in two sessions). The second surgical operation of the recurrent tumor, with necrotomy and evacuation of the large cyst were performed after adjuvant therapy. The patient expired at a time sixty-five months after the first surgical operation. Relevant to the chemotherapy, adriamycin (ADM) (0.5mg) and methotrexate (MTX) (1mg) were administered through the Ommaya's reservoir into the tumor bed at craniotomy. The usual doses of ADM and MTX amounted to 5.0mg respectively. Through conventional CT and MRI, formation of a cyst including abundant membranous debris or septi was identified in both cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of electrical stimulation of the lateral midbrain tegmentum (LMT) on the copulatory behavior of male rats were examined in our investigation of the role of the LMT in this behavior. Sexually experienced male rats (n = 15) that had been implanted with chronic electrodes under sodium pentobarbital anesthesia were individually tested for copulation with a receptive female under a 30 s on, 30 s off pattern of stimulation. The ejaculation latency, and mount and intromission frequencies decreased significantly during the stimulation tests, indicative of facilitation of copulation. In contrast, a strong stimulus-bound inhibition of copulation was found in 12 males (80%). Six animals who showed accelerated copulation also depressed the lever for self-stimulation at an identical current during the copulation tests. These results suggest that the LMT functions in ejaculation, in the normal expression of intromission and in sexual reward, thereby regulating the copulatory behavior of male rats.
Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.
The binding and internalization of a novel adrenocorticotropic hormone (ACTH) analog having a potent neuromodulating effect, ebiratide (H-Met(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8NH2), by isolated bovine brain capillaries, were examined. Metabolism of [5-125I-His]ebiratide occurred during a 30-min incubation with bovine brain capillaries at 37 degrees C. In the presence of 20 mM EDTA, added to inhibit this metabolism, the medium, after 30 min of incubation, contained 82.3 +/- 0.5% of the unchanged ebiratide. The total binding and acid-resistant binding of [125I]ebiratide increased with time and reached an equilibrium at about 15 min. The total binding and acid-resistant binding at 30 min (as the cell/medium ratios corrected with [14C]sucrose) were 13.07 +/- 0.86 and 5.00 +/- 0.18 microliters/mg of protein, respectively. The acid-resistant binding showed significant dependence on temperature and medium osmolarity. The [125I]ebiratide binding was significantly inhibited by dansylcadaverine, an endocytosis inhibitor. The saturable acid-resistant binding was obtained by the addition of unlabeled ebiratide (100 nM-5 mM), and the maximal internalization capacity (Bmax) at 30 min was 144.2 pmol/mg of protein, with the half-saturation constant (KD) of 62.1 microM. The nonsaturable acid-resistant binding [cell/medium ratio in the presence of the unlabeled compound (1 mM or more)] was 2.2 microliters/mg of protein. The acid-resistant binding was significantly inhibited by human ACTH, poly-L-lysine, protamine and E-2078, a basic peptide, but was not inhibited by poly-L-glutamate, insulin or transferrin. These results demonstrate that ebiratide is transported through the blood-brain barrier via a basic peptide-specific absorptive-mediated endocytosis.
Single unit activity was recorded from the lateral mesencephalic tegmentum (LMT) during free copulatory activity by male rats. Twenty-four (89%) of 27 units showed changes in the firing rate during at least one of the three phases of copulatory behavior: pursuit of the female, pelvic thrusting and genital grooming. The activity of 16 units (59%) increased during pursuit of the female, and the activity of 3 units (11%) increased markedly during pelvic thrusting accompanied by intromission. In contrast, 6 units (22%) were suppressed during thrusting with intromission. Whereas the activity of 10 units (37%) increased during genital grooming, 7 units (26%) were suppressed below the baseline during this behavior. The specific firing patterns of the LMT units that are correlated with the particular copulatory movements are a strong indication that the LMT may have an important function in the execution of male copulatory behavior. Some LMT units may mediate sensory information from the genitals that is needed to display a series of copulatory movements. Other units may be more directly related to reflex-like copulatory movements.
A 59-year-old female was hospitalized because of disturbance of consciousness and convulsive seizures. She had taken a hormonal drug for 15 months after breast cancer surgery. A computed tomography scan revealed multiple high-density areas in the left temporal and frontal and the right parietal lobes. Angiography showed a dural arteriovenous malformation (AVM) in the posterior fossa fed by the occipital and the middle meningeal arteries and draining into the transverse sinus. It also demonstrated occlusion of the left sigmoid sinus in the venous phase. She complained of headache in the occipital region and dizziness. On day 13, the left occipital artery was ligated and cut, and then abnormal arterial anastomoses around the lesion were coagulated. After surgery, clinical symptoms disappeared. The etiology of dural AVM is controversial, but in this case it is suspected that sinus thrombosis due to the drug caused the dural AVM. The authors discuss the etiology and treatment of dural AVM in the posterior fossa.
Though meningiomas are usually well demarcated from the brain, their interfaces with the brain take various forms. Based on 27 nonoperated supratentorial meningiomas from autopsies, the interfaces were classified into four types, that is, smooth, lobular, finger-like expansion, and invasive. Relationships between the types of interfaces and the so-called capsule of the tumor and subarachnoid vessels are discussed. Additionally, three surgical cases which showed more or less the invasive form are presented with neuroradiological findings.
A form of disseminated necrotizing leukoencephalopathy and the shaping process of calcification was observed by CT scan in a 9-year-old boy with intracranial germ cell tumor who had received systemic combined chemotherapy, brain radiation, and intraventricular administration of methotrexate and bleomycin for the meningeal involvement of tumor cells. He was admitted to our hospital complaining of hemiparesis and gait instability. Hormonal examination revealed abnormality of high serum HCG and testosterone. An initial CT scan showed a ring enhancing lesion in the right side of the caudate head. He received a course of irradiation, which was 5,000 rads locally, and combined chemotherapy using cisplatin, vinblastine and bleomycin for ectopic germ cell tumor. Unfortunately, consecutive CT examinations revealed that the tumor recurred with hormonal abnormality and ventricular seeding of tumor cells. Therefore, the patient received two courses of irradiation, which were each 3,000 rads locally, and intraventricular administration of methotrexate and bleomycin via an Ommaya tube at about one year intervals. However, 23 months after the first irradiation, a serial CT scan revealed an abnormal diffuse low density area in the deep white matter of the frontal lobe, predominantly the paraventricular region. Furthermore, 31 months after the first irradiation, a serial CT scan revealed fine and granular calcification in the above mentioned lesion. The Hounsfield number of high density areas was 103.00 in the round calcification of the left parietotemporal lobes. Finally, 34 months after the first irradiation, a serial CT scan revealed large round calcifications in the left temporal lobe and right occipital lobe. The patient died three years and six months after the initial symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)