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Biomedical subjects

K Yada

Publications and source records attributed to K Yada.

At least 19 recordsLinked to original sources

Effects of recombinant human macrophage colony-stimulating factor on atherosclerotic lesions established in the aorta of high cholesterol-fed rabbits.

Anti-atherosclerotic effects of human macrophage colony-stimulating factor were investigated using rabbits fed a high cholesterol diet. Rabbits fed a diet containing 2% cholesterol for 59 days developed hyperlipidemia and atheromatous aortic plaques. They were then administered 80 microg/kg/day of either macrophage colony-stimulating factor or human serum albumin, as a control, for the next 12 weeks. Compared with the control group, rabbits treated with macrophage colony-stimulating factor had significantly fewer plaques on the inner surface of the thoracic and abdominal aortae, and half the sectional area of thickened intima in the aortic arch, as well as in the thoracic and abdominal aortae. Macrophage colony-stimulating factor also decreased the cholesterol content of the atherosclerotic lesions. Serobiochemical analyses revealed that macrophage colony-stimulating factor increased the levels of high density lipoprotein-cholesterol significantly, without influencing other lipid parameters such as the level of low density lipoproteins. The effects of macrophage colony-stimulating factor were evident until the fourth week of drug injection, at which time anti-human macrophage colony-stimulating factor antibodies were clearly induced in the serum. These results indicate that exogenously administered macrophage colony-stimulating factor suppresses atherosclerotic lesions induced by a high cholesterol diet by activating lipid metabolism in vivo.

Animals↗

Leptomeningeal melanomatosis with multiple cutaneous pigmented nevi: tumor cell proliferation and malignant transformation in an autopsy case.

We experienced a rare case of leptomeningeal melanomatosis. The proliferative activity and nuclear accumulation of p53 in this tumor were examined, since the relationship between this tumor type and growth has not yet been elucidated. A 33-year-old Japanese man was shown to have leptomeningeal melanomatosis with multiple cutaneous pigmented nevi. The autopsy findings showed the presence not only of benign diffuse melanosis of the leptomeninges but also of leptomeningeal melanomatosis in the subarachnoid space and brain parenchyma. In the brain parenchyma, the direct invasion of tumor cells from the subarachnoid space and Virchow-Robin spaces filled with melanoma cells were observed. Multiple hemorrhagic areas invaded by melanoma cells were also present. Immunohistochemical staining with a monoclonal antibody to melanoma cells showed positivity in the tumor cells. Proliferation analysis using the MIB-1 antibody demonstrated that the labeling index of tumor cells invading brain parenchyma (2.54%) was higher than that in other lesions of the inner (0.89%) and outer layer (0.76%) of the subarachnoid space. Nuclear accumulation of p53 protein was rarely seen in the tumor cells. We reported a case of leptomeningeal melanomatosis. Higher proliferative activity was found in invading cells of the brain parenchyma. Malignant transformation of the tumor did not appear to be associated with p53 gene mutation.

Adult↗

[Identification of a sulfhydryl-reducing agent-inducible protein highly homologous to protein synthesis elongation factor Tu in Bacillus subtilis].

It was examined that the effect of beta-mercaptoethanol and dithiothreitol treatments, which should affect disulfide bond formation of proteins, on cellular protein components of Bacillus subtilis. In LB medium, the treatments induced the synthesis of a 50 kD protein (P50), which is synthesized constitutively under normal growth condition and is a major cytoplasmic protein. P50 was also induced by heat shock, but not by sporulation. In Schaeffer's sporulation medium, however, P50 was not induced by the sulfhydryl-reducing agents. This suggests that the sulfhydryl-reducing agent-inducibility of P50 might depent on specific physiological condition(s). The amino terminal sequences of two of the four main V8 protease fragments of P50 were determined. A search in databases revealed that P50 was highly homologous to protein synthesis elongation factor Tu of B. subtilis.

Amino Acid Sequence↗

Effect of recombinant human macrophage-colony stimulating factor on marrow, splenic, and peripheral hematopoietic progenitor cells in mice.

The effects of human macrophage colony-stimulating factor (M-CSF) on marrow, splenic, and peripheral progenitor cells (CFU-M, CFU-GM, and CFU-G) were investigated in mice administered recombinant human M-CSF (8-4,000 micrograms/kg). Single injection of 4,000 micrograms/kg of M-CSF resulted in a decrease in the number of marrow progenitor cells (CFU-M, CFU-GM, and CFU-G) on day 2 followed by a gradual increase, returning to the original level on day 4 or 5. In contrast, each type of splenic progenitors tested for started to increase markedly on day 2, reaching a level 4- to 15-fold higher than that of the basal value on day 3 or 4. Peripheral CFU-M, CFU-GM, and CFU-G also increased on day 2. In addition, administration of 800 micrograms/kg of M-CSF in mice caused a decrease in marrow CFU-G, as well as an increase in splenic CFU-G. The present results indicate that treatments of mice with pharmacological concentrations of human M-CSF affect the number of progenitor cells not only of monocyte/macrophage lineage but also of granulocyte lineage. Also, the coincidence between decrease of marrow progenitor cells and increase of splenic and peripheral progenitor cells suggests that the progenitor cells are released from bone marrow to peripheral blood and reseeded to the spleen by the action of M-CSF.

Animals↗

Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica.

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250-500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and beta-lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, umcommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.

Adolescent↗

A source of haemorrhage in adult patients with moyamoya disease: the significance of tributaries from the choroidal artery.

This study concerns 19 patients over 16 years of age with Moyamoya disease. Ten cases of intracranial haemorrhage, as the initial haemorrhagic event in patients aged from 21 to 55 (haemorrhagic group) and 9 cases of ischaemic events in 18- to 53-year-old patients (ischaemic group) were included. All haemorrhages were associated with intraventricular haemorrhages (IVH); and all but one case of thalamic haemorrhage were thought to be primary IVH (2 cases of small paraventricular haemorrhage; 2 of small haemorrhages in the splenium; 5 with no intracerebral haematoma). In the 9 patients of the ischaemic group, there were 2 cases of transient ischaemic attacks and 7 of cerebral infarction. Angiographic evaluations demonstrated that the abnormal basal vessel formation and the collateral supplies from the external carotid arteries were poorly developed in both groups. In contrast, the collateral circulation via the choroidal and posterior pericallosal arteries was well demonstrated. Furthermore, marked enlargement of the choroidal arteries and the medullary arteries derived from them was seen more frequently in the haemorrhagic group. These findings suggested that the haemodynamic load in the vessels supplying the walls of the posterior parts of the ventricles and the periventricular region was increased, especially in the haemorrhagic group. Those vessels were considered to be important sites of IVH in adult patients with Moyamoya disease.

Adult↗

Stump pressure as a guide to the safety of permanent occlusion of the internal carotid artery.

Does the absolute value of the stump pressure (post-occlusion back pressure) become a useful index of a good collateral circulation? The authors continuously monitored the mean arterial pressure before, during and after 20-minute balloon test occlusion in 24 patients. The stump pressure was then compared with the results of 99mTc-hexa-methyl propyleneamine (99mTc-HMPAO) single photon emission computed tomography (SPECT) performed after 20 minutes of test occlusion. Patients who failed to tolerate even brief periods of carotid occlusion and showed asymmetric decreases in cerebral blood flow (CBF) on SPECT were divided into high and moderate risk groups. Those with no significant change in CBF on the occluded side formed the minimum risk group. Mean stump pressure was over 50 mmHg in three of a total of 13 patients in the high and moderate risk groups, and below 50 mmHg in two of the 11 patients in the minimum risk group. The ratios of the initial mean stump pressure to the pre-occlusion mean arterial pressure (%) and of the final mean stump pressure at the end of occlusion to the post-opening mean arterial pressure (%) did not exceed 58% in any patient in the high and moderate risk groups, and were at least 60% in all patients of the minimum risk group. Maintenance of a mean stump pressure of 60% or more of the mean systemic pressure during test occlusion may be a more useful index of a good collateral circulation than the absolute value of mean stump pressure.

Adult↗

Effects of macrophage colony-stimulating factor (M-CSF) on lipopolysaccharide (LPS)-induced mediator production from monocytes in vitro.

M-CSF is a macrophage-lineage-specific growth factor that causes proliferation and differentiation of progenitor cells in the bone marrow. To investigate the effects of M-CSF on more matured cells, human monocytes were cultured in the presence or absence of M-CSF for 6 days. Addition of M-CSF at more than 10(2) U/ml resulted in higher viability and caused morphological differentiation to large macrophage-like cells. LPS-induced mediator production was also compared between M-CSF-treated and control cell. Monocytes were incubated with or without M-CSF for 3 days, and were stimulated with 1 microgram/ml of LPS for 2 days. IL-1 beta was not detected in the both culture supernatants, and PGE2 production was not influenced by M-CSF. However, amounts of G-CSF, GM-CSF, IL-6, and TNF-alpha produced in response to 1 microgram/ml of LPS were 1.5 to 2 times greater from monocytes treated with 10(4) U/ml of M-CSF than from control cells. The priming effect of M-CSF on LPS-induced cytokine production was found to require 3-day preincubation, and reached a maximum at the concentration of 10(4) U/ml. M-CSF-treated cells responded to a 10 times lower concentration of LPS than control cells in terms of cytokine production. M-CSF was also shown by flowcytometric analysis to influence the expression of CD14, a receptor for LPS, which might render monocytes more sensitive to LPS.

Cells, Cultured↗

Impaired autoregulation in an experimental model of chronic cerebral hypoperfusion in rats.

BACKGROUND AND PURPOSE: To verify the hypothesis that impaired autoregulation may contribute to cerebral swelling or hemorrhage after a sudden recovery of perfusion pressure, we studied the chronic effects of cerebral hypoperfusion on the autoregulatory responses of the pial arterioles in situ. METHODS: Eight to 12 weeks after a carotid-jugular fistula was created in rats, experiments were performed under alpha-chloralose and urethane anesthesia. Regional cerebral blood flow (rCBF) was determined by the hydrogen clearance method, and carotid pressure was measured. Using a closed cranial window, we determined the autoregulatory responses of the arterioles (30 to 50 microns) to both hypertension induced by norepinephrine and sudden fistula closure at various mean arterial pressures (MAPs). RESULTS: rCBF on the fistula side was reduced by 27%. Carotid pressure was significantly lower than normal but was immediately increased by fistula closure. The pial arterioles showed marked elongation and enlargement. During induced hypertension, the arterioles in the fistula group started to dilate at an MAP lower than that of the control group (130 versus 180 mm Hg, respectively). The arterioles constricted when the fistula was occluded at normal MAP. However, when the fistula was occluded at an MAP higher than 130 mm Hg, the vessels dilated. CONCLUSIONS: It was demonstrated that (1) chronic hypoperfusion induced impairment of the upper limit of autoregulation and (2) sudden fistula closure under hypertensive conditions caused vasodilation of the arterioles. These findings suggest that rapid restoration of perfusion pressure is possibly followed by a pressure breakthrough phenomenon in a chronically hypoperfused cerebrovasculature.

Animals↗

Diagnostic significance of serum neuron-specific enolase and myelin basic protein assay in patients with acute head injury.

BACKGROUND: Neuron-specific enolase (NSE) and myelin basic protein (MBP) in the peripheral venous blood (PVB) have been reported to be sensitive markers for judging the prognosis of patients with head injury. However, to our knowledge, the levels of NSE and MBP in the internal jugular venous blood (IJVB) have never been studied. METHODS: In 25 patients with acute head injury, blood samples were taken from the internal jugular vein and the peripheral vein at the same time before any medical or surgical procedure was performed. The levels of NSE and MBP in the both venous blood samples were measured. The time interval between injury and sampling was 1.5-8.0 hours (mean 4.3 hours). The levels of NSE and MBP in the IJVB were compared to those in the PVB. The relationship between the clinical outcome and the serum levels of those was evaluated. RESULTS: The levels of NSE and MBP in the IJVB were almost equal to those in the PVB. The levels of NSE and MBP were significantly higher in the patients who died than in those who survived. In the survivors, the levels of NSE and MBP in the IJVB were 17.6 +/- 11.4 ng/ml and 1.4 +/- 1.5 ng/ml, whereas in the patients who died, both levels were elevated to 51.3 +/- 27.3 ng/ml (p < 0.005) and to 11.3 +/- 9.5 ng/ml (p < 0.01), respectively. CONCLUSIONS: The assay of serum NSE and MBP levels provides a reliable laboratory indicator of the degree of brain damage and allows early prediction of the prognosis in patients with acute head injury.

Acute Disease↗

Experimental model of chronic tonsillar herniation associated with early stage syringomyelia.

This report describes an experimental model of chronic tonsillar herniation and its effects on the spinal cord. In ten rats, a small piece of chemically induced mammary cancer was transplanted to the supraoccipital bone. In all cases, the transplanted cancers grew into the posterior fossa, destroying the supraoccipital bone and compressing the cerebellum extradurally. In six of the ten rats, tonsillar herniation was observed at 8-14 weeks after transplantation. Transdural infiltration of the tumor cells was not apparent in any animal. In those rats with tonsillar herniation (n = 6), the spinal cord from the C5 to the T8 segments showed enlargement of the central canal without exception. Histological examination revealed the following changes: stretching and thinning of the ependymal cells; swelling of the astrocytic processes; and extra-cellular edema, predominantly in the dorsal gray matter, but also in the ventral inner portion of the dorsal column. In the control group (n = 4) and those rats without tonsillar herniation (n = 4), such histological changes of the spinal cord were not observed. Although the lesions can not be regarded as representing mature syringomyelia, they most likely constitute an earlier evolutionary stage.

Animals↗

[Protective effect of human macrophage colony-stimulating factor on fungal infection (2). In vitro effect of human macrophage colony-stimulating factor on systemic aspergillosis and in vitro effect on the activities of macrophage].

We studied the protective effect of human macrophage colony-stimulating factor (M-CSF) of fungal infection due to systemic aspergillosis in normal mice. We also examined the effect of M-CSF against the activities of mouse peritoneal macrophage which were relating to the phagocytosis, the killing, the production of superoxide after contacting with phorbol myristate acetate and the production of nitric oxide after contacting with interferon-gamma in vitro. M-CSF improved the median survival time and the survival rate of systemic aspergillosis. Combination therapy with M-CSF and amphotericin-B (AMPH-B) showed the therapy with either M-CSF or AMPH-B alone. M-CSF enhanced the activities of phagocytosis and the killing of ingested Candida albicans H and spores of Aspergillus fumigatus K by macrophage. Furthermore, M-CSF promoted the production of superoxide and nitric oxide in macrophage. These results indicate that M-CSF can enhance the fungicidal activity of macrophages by activation in vivo, thereby preventing the dissemination of fungal infection.

Amphotericin B↗

[Protective effect of human macrophage colony-stimulating factor (hM-CSF) on fungal infection (1). In vivo effect of hM-CSF on systemic candidiasis and in vitro effect of hM-CSF on macrophages activities].

We studied the protective effect of human macrophage colony-stimulating factor (hM-CSF) on fungal infection due to systemic candidiasis in vivo and the activities of macrophages in vitro, in order to demonstrate the usefulness of M-CSF on fungal infection. The effect of hM-CSF on systemic candidiasis was examined by using normal and immunosuppressed mice. In addition, the effects of hM-CSF on the activity of reticuloendothelial system (RES) organ and on the phagocytic activity and NBT reduction activity of mouse macrophage were also examined in vitro. HM-CSF improved the survival rate of systemic candidiasis in both normal and immunosuppressed mice. Combination therapy with hM-CSF and fluconazole showed higher survival rate more than in the therapy with either hM-CSF or fluconazole alone. Furthermore, hM-CSF enhanced the activity of RES organ, phagocytosis by macrophages and NBT reduction by macrophages, significantly. These results indicate that hM-CSF enhances the phagocytic cactivity and candicidal activity by macrophages in vivo, thereby preventing dissemination of fungal infection.

Animals↗

Basic fibroblast growth factor increases regional cerebral blood flow and reduces infarct size after experimental ischemia in a rat model.

BACKGROUND AND PURPOSE: The aim of this study was to ascertain whether basic fibroblast growth factors (bFGF) caused reduction in size of cerebral infarcts in Sprague-Dawley rats with experimental ischemia. METHODS: In the first experiment we induced permanent occlusion of the left middle cerebral artery (MCA). Within 5 minutes after MCA occlusion, we infused bFGF (100 ng in 0.1 mL of saline) in the bFGF-treated group (n = 14) and 0.1 mL of saline alone in the control group (n = 7) into the common carotid artery ipsilateral to MCA occlusion. We harvested the brains 24 hours after MCA occlusion and determined infarct size planimetrically as a percentage of hemisphere size. In the second experiment cerebral blood flow (CBF) was continuously measured for 120 minutes after MCA occlusion in the bFGF-treated group (n = 9) and in the control group (n = 8) with the use of laser-Doppler flowmetry. RESULTS: Infarct size in the bFGF-treated group decreased significantly in comparison with that in the control group (repeated-measures ANOVA, P < .0001). CBF in the transitional areas between the MCA and the anterior cerebral artery significantly increased in the bFGF-treated group in comparison with that in the control group (repeated-measures ANOVA, P < .005). An approximate 58% decrease in infarct size and a 40% increase in regional CBF were seen on bFGF treatment. CONCLUSIONS: The present study suggested that intracarotid administration of bFGF (100 ng) can reduce infarct size after MCA occlusion. It was speculated that the increased CBF in the penumbral areas of MCA may contribute to contraction of infarct size.

Animals↗

[Characteristic neurological signs in patients with cervical disc disease].

In cervical radiculopathy, neurological findings for the upper extremities and the responsible level of the radices have been precisely detailed. However, in cases of cervical spondylotic myelopathy, it is not always easy to determine the responsible level of the cervical spine solely based on neurological findings. To disclose characteristic neurological lesions of the upper extremities, if any, for different locations of disc disease, 49 patients with cervical disc protrusion at single levels, confirmed by magnetic resonance imaging, were analyzed. Thirty-six patients demonstrated long tract signs (LTS) concomitant with segmental signs in the upper extremities, and 13 patients had no LTS. Except for deep tendon reflexes and the extent of dysesthesia in the upper extremities, there were no characteristic neurological findings, such as muscle atrophy, loss of muscle strength, extent of hypalgesia, or hypesthesia, pointing to the responsible compression site. In the 13 patients without LTS, the extent of dysesthesia and diminution of deep tendon reflexes proved to be completely in agreement with results for radiculopathy: 9 had protruded discs at the C56 level and described dysesthesia in the thumb and the index finger with deep tendon reflexes in the biceps and brachioradialis being diminished. The remaining 4 had protruded discs at the C67 level and described dysesthesia in the middle finger. Their deep tendon reflexes in the triceps were diminished. A clear contrast was observed for the patients with LTS. Four out of 36 patients had C34 protruded discs and did not complain of dysesthesia in any digits. Their deep tendon reflexes were exaggerated in all muscles in the upper extremities.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Epidemiology of syringomyelia in Japan--the nationwide survey].

The nationwide epidemiological survey of syringomyelia was carried out in Japan by sending inquiries to neurologists, child neurologists, neurosurgeons and orthopedic surgeons for the period of 1991 and 1992. A total of 1,243 cases of syringomyelia were ascertained. Among them, 622 were men and 619 women, and the average age of onset was 28 years old. The classification by Barnett et al was used, presenting syringomyelia with Chiari malformation in 684 cases (51.2%), dysraphism in 47 (3.7%), post traumatic syringomyelia in 139 (11%), post-spinal arachnoiditis in 76 (6%), spinal cord tumor in 132 (10.5%) and others in 204. Its predominant clinical course was slowly progressive, but 202 cases (17.9%) showed rather stable course including spontaneous resolution in 29 cases. The main initial symptoms were numbness in 522 cases (42%), motor disturbance in 504 (40.5%), and pain in 296 (23.8%). Neurologic signs noted in the abnormality of deep tendon reflexes in 836 cases (67.3%), motor disturbance in 763 (60.4%) and positive pathological reflexes in 383 (30.1%). Sensory disturbance was found in 942 cases (75.8%) and the dissociated type were 559 out of them (59.3%). It is noteworthy that 982 out of 1,243 were documented by MRI and surgical operations such as foramen magnum decompression, syringo-subarachnoid shunt and others were performed in 829 cases. Syringobulbia was confirmed on MRI in 101 cases of syringomyelia in which spinal cord tumors were most frequently associated.

Adolescent↗