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Biomedical subjects

M Tomonaga

Publications and source records attributed to M Tomonaga.

At least 289 records · Page 16Linked to original sources

Aneurysm of the lenticulostriate artery--report of four cases.

Four rare cases of aneurysm of the lenticulostriate artery (LSA) are presented. LSA aneurysms were located at the origin in three patients and distally in one. Two cases were of multiple aneurysms, one was associated with hypertensive intracerebral hematoma (putaminal hemorrhage), and the other with moyamoya disease. Two patients were successfully treated by microsurgical procedures. The occurrence of LSA aneurysm suggests that aneurysm formation and growth are accentuated by hemodynamic alteration and stress.

Adult↗

Emergence of symmetry in a visual conditional discrimination by chimpanzees (Pan troglodytes).

In Exp. 1, three young chimpanzees were trained to match red to a cross and green to a circle in an arbitrary matching-to-sample task. After acquisition of this task, they were tested for the emergence of associative symmetry of these conditional relations using the trials on which shapes were presented as samples and colors as comparisons. One of the three chimpanzees showed statistically significant accuracy on these test trials. This successful subject served in Exp. 2, in which an auditory-visual stimulus appeared contingent upon red and a cross while another auditory-visual stimulus was contingent upon green and a circle. This subject showed higher accuracies in symmetry tests than in Exp. 1, which suggested the facilitative effects of these events common to sample and correct comparison on the development of symmetry. In Exp. 3, subsequent tests in which only these stimuli were presented as samples indicated that these stimuli might have become the members of equivalence classes.

Animals↗

[Mouse fetal brain specific protein "GP68" is expressed in human tumor cells].

It is well known that some fetal antigens are expressed in malignant tumor cells. Likewise, brain tumors, especially histologically malignant cases, may have any antigenic relationships with fetal brain. So, we investigated the relationship by immunohistochemical technique, utilizing a polyclonal antibody to mouse fetal stage-specific polypeptide "GP68". We prepared GP68 from homogenate of head part of embryos at the 14th day of gestation mice by RCA-1 agarose column chromatography. And immunized it to Japanese white rabbits and the titer was measured by enzyme-linked immunosorbent assay. We analyzed operatively resected brain tumors and autopsy brain tissues. Frozen tissues were fixed in cold acetone and immunostained with anti-GP68 serum according to biotin-streptavidin peroxidase method. Remained tissues were homogenized in Laemmli's sample buffer and electrophoresed. The proteins were transferred to nitrocellulose membrane and immunostained with anti-GP68. Normal brain tissues were not positively stained, except for capillary endothelium which showed a weak staining. On the other hand, brain tumors of neuroectodermal origin were positively stained in varying degrees, and other tumors were negative. It is especially noteworthy that, in astrocytoma cases, there exists a definite correlation between the intensity of stain and the degree of histological malignancy. Immunoblot studies demonstrated a very weak band at 68 KD in normal brain and meningioma. In contrast, very strong band at the same position was seen in malignant astrocytomas. These results suggested that in brain tumors, especially those of neuroectodermal origin, GP68 antigen is expressed and the degree of expression is related to their histological malignancy. So this fetal antigen may be useful for evaluation of biological malignancy of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinicopathological study of meningiomas of the tentorium and its surrounding structures].

We report the clinical features, radiological studies, operative procedures and results, and follow-up data in 29 patients with meningiomas of the tentorium and its surrounding structures. The cases represented 22.5% of all the intracranial meningiomas operated on in a 15 year period and were divided into three groups, depending on their main attachments, tentorial, cerebellopontine angle (dorsal aspect of the petrous ridge) and others. Tumor size was generally large and 13 cases were larger than 5 cm. The most common tumor site was along or near the superior petrosal sinus and transverse-sigmoid junction in cases involving the tentorium, and medial to the porus acousticus in cases involving the cerebellopontine angle. Different operative approaches to these tumors were carried out, depending on their location. The tumors in the lateral or medial petrous ridge were approached mainly with a suboccipital craniectomy using a retromastoid incision. Total removal was carried out in 80% of the tentorial cases, in 46.2% of cerebellopontine angle cases, and in the 83.3% in the others. Total operative mortality rate was zero. Follow-up periods ranged up to 5 years 5 months in the tentorial cases, 4 years 6 months in cerebellopontine angle cases, and 7 years 1 month in the others. Long-term results were good in 21 cases (72.4%), fair in 3 cases (10.3%) and poor in 2 (6.9%). Three patients died due to tumor recurrence. One of them suffered lung metastasis, and two of them suffered extensive local recurrences. We recommend the retromastoid approach combined with the petrosal approach, if the CPA tumor is large enough and extends to the retroclival region.

Adult↗

[No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia].

We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML.

Female↗

Treatment of myelodysplastic syndromes with orally administered N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex).

N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6-16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease.

Acute Disease↗

[HSP 70 is associated with abnormal cytoplasmic inclusions characteristic of neurodegenerative diseases].

Several degenerative diseases of the central nervous system are characterized by the presence of neuronal inclusions. One of these inclusions, neurofibrillary tangles in Alzheimer's disease, has been shown to contain ubiquitin that belongs to a group of proteins known as heat shock proteins. Subsequent studies revealed that ubiquitin is also associated with various neuronal inclusions including Lewy bodies, Pick bodies and hyaline inclusions. Very recently, ubiquitin has been found also to be associated with glial inclusions that are unique to multiple system atrophy. The close association of ubiquitin with varying cellular inclusions, together with its function in the proteolytic process, raised the hypothesis that ubiquitin may be involved in the degradation of abnormal proteins appearing in the damaged neurons and glial cells. In central nervous system, a group of heat shock proteins collectively known as HSP 70 is also present which is constitutive and/or inducible. Since HSP 70 has been suspected to play a crucial role degradation and repair of abnormal intracellular proteins, we hypothesized that HSP 70 may be associated with those inclusions, as the case with ubiquitin. To test this we performed immunohistochemical studies on brain tissues from patients with various neurodegenerative conditions by using specific polyclonal antibody to HSP 70. Brain tissues were obtained at autopsy from each three patients with Alzheimer's disease, Pick's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and multiple system atrophy. Tissues were fixed in buffered formalin and embedded in paraffin. Immunostaining was performed by the standard ABC method using diaminobenzidine as a chromogen. Sections were lightly stained with hematoxylin. Polyclonal antibodies were raised in rabbits against mouse HSP 70.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia.

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.

Acute Disease↗

Alzheimer's disease amyloid precursor protein is present in the myelin sheath of central nervous system in rat.

By using polyclonal antibodies to C- and N-terminal portions of beta-amyloid precursor protein (APP), we immunohistochemically examined postnatal and adult rat brains. Immunoreactivity was observed in myelin of nerve fibers in myelination and of mature myelinated fibers, as well as in various brain cells. In trigeminal nerve roots, the immunoreactivity was observed in central myelin but not in peripheral myelin. The results strongly suggest that APP is a component of central myelin in rat.

Alzheimer Disease↗

Astrocytic localization of the immunoreactivity for protein kinase C isozyme (type III) in human brain.

The localization of 3 major types of protein kinase C (PKC) was immunohistochemically studied in human brain using monoclonal antibodies raised against each of the types. Immunoreactivity for type I was observed in neuronal cells in cerebrum and Purkinje cells in cerebellum. Immunoreactivity for type II was mainly observed in neuropil of cerebral cortex and in the molecular and granular layers of cerebellum. Occasional neurons in cerebrum were also stained. Immunoreactivity for type III was almost exclusively localized in astrocytes in gray and white matter, subpial astrocytes, and cerebellar Bergmann's glia. The present study suggests that the type III of PKC is preferentially expressed in astrocytes in human brain.

Antibodies, Monoclonal↗

Immunocytochemical and ultrastructural studies of lower motor neurons in amyotrophic lateral sclerosis.

Neuronal inclusions in lower motor neurons in 23 cases of adult-onset sporadic amyotrophic lateral sclerosis were studied immunocytochemically and ultrastructurally. Monoclonal and polyclonal antiubiquitin antibodies recognized four structures in the neuronal perikarya: (1) all Lewy body-like inclusions in 6 cases with a relatively short clinical course, (2) a small percentage of Bunina bodies in 4 cases with abundant Bunina bodies, (3) ill-defined structures closely associated with Bunina bodies (Bunina body-related structures) in 15 cases, and (4) a focally aggregated meshwork of fine filamentous structures not associated with Bunina bodies in all cases. These four structures were not recognized by the antibodies raised against cytoskeletal proteins (neurofilament, tubulin, microtubule-associated protein 2, and phosphorylated tau). Electron microscopy revealed Lewy body-like inclusions to be accumulations of randomly oriented filaments, approximately 15 nm in diameter, covered by fine granules. Bundles of coated filaments 12 nm in diameter that sometimes formed Bunina body-like structures were also observed in the perikarya. Immunoelectron microscopy showed the reaction product with antiubiquitin to be on the filaments, 15 nm in diameter, of Lewy body-like inclusions. Our study revealed the existence of two types of filaments in lower motor neurons of patients with amyotrophic lateral sclerosis: (1) ubiquitin-positive, granule-associated filaments, approximately 15 nm in diameter, that form Lewy body-like inclusions; and (2) 12 nm coated filaments that may be a candidate for another ubiquitin-positive structure and possibly a precursor of Bunina bodies. These two types of filaments may represent early pathological changes of lower motor neurons in amyotrophic lateral sclerosis.

Adult↗

Immunocytochemical and ultrastructural studies of Pick's disease.

Cerebral cortical changes in 10 cases with Pick's disease were studied immunocytochemically and ultrastructurally. All cases contained Pick's argentophilic bodies and ballooned neurons. The antibodies against phosphorylated tau proteins that intensely stained all Pick bodies recognized numerous neuronal processes around Pick body-bearing cells and focal portions in the perikarya of ballooned neurons. Monoclonal and polyclonal anti-ubiquitin antibodies stained not only some Pick bodies with variable intensity, but also the perikarya of all ballooned neurons. Ultrastructurally, Pick bodies consisted of accumulation of randomly oriented, approximately 15-nm straight filaments and paired twisted profiles with a minimal diameter of 13 nm, maximal diameter of 26 nm, and twist periodicity of 120 nm. These Pick body-type filaments were also observed in the perikarya of ballooned neurons and neuronal processes around Pick body-bearing cells. Our studies demonstrate, for the first time, the characteristic pathological feature of neuropil in Pick's disease. Pick body-bearing cells and ballooned neurons show unique immunocytochemical and ultrastructural properties that may be a clue to the pathogenesis of Pick's disease.

Aged↗

Intraventricular craniopharyngioma: its characteristics in magnetic resonance imaging and successful total removal.

We experienced a craniopharyngioma in the third ventricle which was removed totally by a staged operation through the lamina terminalis and then through the foramen of Monro using a transventricular approach. In magnetic resonance imaging, chiasmal thickening with pot-belly expansion and bilobed shape of the mass were found, and postoperative magnetic resonance imaging showed indentation of the chiasm and flattening of the floor of the third ventricle.

Adult↗

Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia.

To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.

Adult↗

Paraneoplastic encephalomyelitis. An autopsy case with encephalitis principally confined to the thalamus and associated with pulmonary and gastric cancers.

We report an autopsy case of encephalitis principally confined to the bilateral thalamus and associated with pulmonary and gastric cancers. An 81-year-old man exhibiting behavioral abnormalities and progressive somnolence died of pneumonia 11 months after onset. Because the patient had lung cancer and no definite cause of the encephalitis was found, this case was categorized as one of paraneoplastic encephalomyelitis. This may be the first reported case of this condition in which the central nervous system (CNS) lesion was located predominantly in the thalamus.

Aged↗

Fructose 2,6-bisphosphate changes in rat brain during ischemia.

Brain ischemia was produced by bilateral ligation of the common carotid arteries of spontaneously hypertensive rats. The concentrations of fructose 2,6-bisphosphate and other glycolytic intermediates as well as of pyridine and adenine nucleotides were measured in frozen brain samples. In contrast to the decrease reported in hepatocytes under anoxic conditions, the fructose 2,6-bisphosphate content was increased by 20-30% during the early stages of ischemia. Elevation in fructose 1,6-bisphosphate level and lactate formation followed the rise in fructose 2,6-bisphosphate content, a finding suggesting that this compound plays a key role in the compensatory acceleration of glycolysis under ischemic conditions in vivo.

Animals↗

Pineocytoma with neuronal differentiation--case report.

The authors describe a case of pineocytoma studied by light and electron microscopy and the immunoperoxidase method. The tumor consisted of two types of cells bearing either chromatin-rich or pale nuclei. These cells were arranged in rosettes and contained pale, eosinophilic material at the center, or in lobular patterns with thin connective tissue and a few blood vessels. Bodian silver staining disclosed a delicate tangle of argyrophilic fibers and processes with small, club-like terminations. These findings are characteristic of pineocytoma. On ultrastructural examination, the tumor cells were found to be closely packed, in clumps separated by numerous fine or expanded, interlacing processes, some of which contained microtubules. A few dense core vesicles and clusters of clear vesicles similar to synaptic vesicles were seen, the latter being aggregated around desmosome-like thickenings in the cellular membrane, suggestive of a synaptic complex. Some tumor cells were positive for neuron-specific enolase and S-100 protein. Only a few cells positive for glial fibrillary acidic protein were distributed in the tumor tissue, but it was not ascertained if they were tumor cells or normal, pre-existing astrocytes. The tumor was diagnosed as a pineocytoma with neuronal differentiation.

Adult↗

A new neurosurgical ventriculoscope--technical note.

A new, flexible fiberoptic ventriculoscope for observation of the ventricles and major cisterns is reported. This device has been safely used to examine patients with obstructive hydrocephalus due to lesions within the lateral and third ventricles or to congenital aqueductal stenosis. With this instrument, a pineal tumor protruding into the third ventricle was successfully observed and photographed in situ.

Adult↗