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Biomedical subjects

M Kishikawa

Publications and source records attributed to M Kishikawa.

At least 55 records · Page 3Linked to original sources
PubMed1996

Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides but exhibit only subtle defects in their nervous system.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in the vertebrate (mammalian) nervous system. Their composition is spatially and developmentally regulated, and gangliosides have been widely believed to lay essential roles in establishment of the nervous system, especially in neuritogenesis and synaptogenesis. However, this has never been tested directly. Here we report the generation of mice with a disrupted beta 1,4-N-acetylgalactosaminyltransferase (GM2/GD2 synthase; EC 2.4.1.92) gene. The mice lacked all complex gangliosides. Nevertheless, they did not show any major histological defects in their nervous systems or in gross behavior. Just a slight reduction in the neural conduction velocity from the tibial nerve to the somatosensory cortex, but not to the lumbar spine, was detected. These findings suggest that complex gangliosides are required in neuronal functions but not in the morphogenesis and organogenesis of the brain. The higher levels of GM3 and GD3 expressed in the brains of these mutant mice may be able to compensate for the lack of complex gangliosides.

Animals↗
PubMed1996

Quantitative age-related changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among senescence accelerated mice (SAMP1TA/Ngs).

SAMP1TA/Ngs, a substrain of senescence accelerated mouse, is a useful animal model for research on brain dysfunction due to senescence. In a previous study it was reported that the age-related changes in basal dendrites and spines of CA1 pyramidal neurons coincide with the behavioral characteristics found in SAMP1TA/Ngs. The goal of the present study was to investigate morphological changes in apical dendrites and dendritic spines of CA1 pyramidal neurons among 3-, 5-, 7-month-old SAMP1TA/Ngs. Pyramidal neurons of the hippocampus were stained by the rapid Golgi method, and the number of apical dendrites, the number of their spines and the density of the dendritic spines were evaluated. The number and density of the spines of apical dendrites were significantly higher at 5 months than at 3 or 7 months of age. We propose that the low number of dendritic spines in 3-month-old animals was caused by immaturity, while the changes in the density and number of dendritic spines in 7-month-old mice were due to accelerated aging. The data on the morphology of apical dendrites are a useful complement to the results reported previously. The findings of the present study also support the hypothesis that this model mouse demonstrates changes in respective developmental stages, i.e. immaturity, adulthood and senescence. This pattern of postnatal growth has special meaning because it indicates the usefulness of the strain in the study of geriatric disorders in humans.

Aging↗
PubMed1996

A histopathologic and immunohistochemical study of small nodules of renal angiomyolipoma: a comparison of small nodules with angiomyolipoma.

Small mesenchymal nodules (SNs) are observed in some cases of renal angiomyolipoma (AML), with or without tuberous sclerosis. They are composed of blood vessels and/or nonvascular smooth muscle cells (SMCs) and/or fat cells. We examined 20 cases of AML, performed detailed histopathologic and immunohistochemical studies of SNs, verified the histologic relationship between SNs and AMLs, and compared the SNs of the tuberous/nontuberous sclerosis groups. Seventy-seven SNs were observed in five cases of AML. The SNs were 0.11 mm to 20.0 mm in diameter. The location of small-sized SNs in the kidney was variable; almost all of the SNs larger than 3.25 mm were in the renal capsule. The small-sized SNs contained mainly epithelioid-type nonvascular SMCs. Blood vessels and fat cells were not observed in the small-sized SNs but appeared gradually in the large-sized SNs. Almost all of the SNs were rounded lesions, and no fusion was observed between the SNs. Nonvascular SMCs of all of the SNs and AMLs were positive for vimentin, alpha-SM actin, and S-100 protein. The SNs less than 1.13 mm in diameter were negative for HMB-45; the nonvascular SMCs of AMLs and of SNs greater than 1.13 mm in diameter were positive for HMB-45. Nonvascular SMCs of SNs and AMLs showed a neurogenic phenotype. The SNs of the nontuberous sclerosis group contained only SMC components, whereas the same-size SNs of the tuberous sclerosis group contained SMCs, fat cells, and blood vessels. The SNs of the nontuberous sclerosis group may not increase in size or may grow slowly. Some of the SNs of patients with tuberous sclerosis grow to become AML. Although the SNs in patients with nontuberous sclerosis do not contain any blood vessels or fat cells, their SMCs show the histologic and immunohistochemical characteristics of AMLs; this indicates that SNs are the "buds" of AML.

Actins↗
PubMed1995

Age-related changes in basal dendrite and dendritic spine of hippocampal pyramidal neurons (CA1) among SAMP1TA/Ngs--quantitative analysis by the rapid Golgi method.

It has been confirmed that a substrain of the senescence-accelerated mouse SAMP1TA/Ngs develops learning disturbance-like behavior at 3 months of age, exhibits almost normal behavior at 5 months, and manifests learning disturbance at 7 months. The changes with age in basal dendrites and dendritic spines of CA1 pyramidal neurons were quantitatively evaluated by the Golgi method using male SAMP1TA/Ngs. The correlation between the change in learning ability and the morphometry was examined. The number of dendritic spines in the 3- and 7-month-old groups was significantly lower than that in the 5-month-old group. It is presumed that the disturbance in acquisition of learning ability at 3 months of age is secondary to the immaturity of neurons, while the learning disturbance at 7 months of age is due to neuronal aging. This substrain, which is characterized by the impairment of acquired learning ability due to senescence, is useful as a model for studies on human brain dysfunction associated with senescence.

Age Factors↗
PubMed1995

Immunohistochemical expression of the estrogen receptor-related antigen (ER-D5) in human intracranial tumors.

BACKGROUND: Expression of the estrogen receptor-related antigen (ER-D5) has been reported in some normal and neoplastic tissues. The authors evaluated the expression of ER-D5 in 143 intracranial tumors of different histologic types. METHODS: Formalin fixed, paraffin embedded tumor sections were stained with the monoclonal D5 antibody by avidin-biotin complex immunohistochemistry. RESULTS: Eighty-eight (62%) of the 143 brain tumors showed positive ER-D5 immunoreactivity. ER-D5 expression was observed in 9/30 low grade astrocytomas, in 6/13 anaplastic astrocytomas, in 16/27 glioblastomas, in 2/5 ependymomas, in 5/8 medulloblastomas, in 10/15 meningiomas, in 20/23 schwannomas, in 11/11 hemangioblastomas, in 9/9 germ cell tumors, in 0/2 oligodendrogliomas, and in 17/28 pediatric and childhood brain tumors. The mean percentage of ER-D5-positive cells varied in different tumor types, was lowest in the meningotheliomatous meningiomas, and was highest in the hemangioblastomas. ER-D5 immunoreactivity was also observed in the microvascular endothelial proliferations and in tumor blood vessels. ER-D5 expression in tumors was not related to the overall tumor grades, but a statistically significant higher percentage of ER-D5-positive cells was noted in the glioblastomas compared with the low grade astrocytomas (P < 0.05) and in the combined high grade tumors compared with the low grade tumors (P < 0.005) if vascular-origin tumor hemangioblastomas are considered a separate entity from other brain tumors. CONCLUSION: The current study suggests that the ER-D5 antigen may participate in the growth of the intracranial tumors and tumor angiogenesis. ER-D5 in embryonal and germ cell brain tumors suggests that ER-D5 may be a developmentally regulated protein.

Adolescent↗
PubMed1995

A long surviving case of amyotrophic lateral sclerosis with atrophy of the frontal lobe: a comparison with the Mitsuyama type.

A female patient with amyotrophic lateral sclerosis (ALS) showing psychiatric symptoms during her last 2 years of life is reported. Although pseudobulbar signs were seen at the onset of ALS and no respirator was used, the period from onset to death was rather long (9 years). The spinal lesions showed features common to ordinary ALS, while the marked atrophy with destructive changes throughout the frontal lobe seemed to be considerably more severe than that seen with either ordinary ALS or the Mitsuyama type of ALS. Since the clinical manifestations and histological characteristics are apparently different from those of the Mitsuyama type, our case may be a new nosological variant of ALS with psychiatric manifestations.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Expression of the small heat shock protein (hsp) 27 in human astrocytomas correlates with histologic grades and tumor growth fractions.

1. Cellular expression and distribution of the stress response small heat shock protein 27 (hsp27) in 39 high-grade astrocytomas (27 glioblastoma multiformes, 12 anaplastic astrocytomas) and in 27 low-grade astrocytomas (grade I-II) were analyzed immunohistochemically. 2. The correlation between hsp27 expression and tumor growth fractions of the astrocytomas was examined following Ki-67 immunostaining. 3. The hsp27 staining was cell cytoplasmic. The hsp27 immunopositive rate was significantly higher in high-grade astrocytomas; the rates was 74% for glioblastomas, 58% for anaplastic astrocytomas, and 37% for low-grade astrocytomas. The small and large tumor cells, especially in glioblastomas, multinucleated tumor giant cells, tumor cells in the pseudopalisading and necrotic areas, cells of the microvascular endothelial proliferations, and tumor vascular smooth muscles were usually hsp27 positive. The mean percentage of hsp27-positive cells was significantly higher in the glioblastomas alone and in the combined high-grade astrocytomas, compared to the low-grade, and in recurrent rather than in primary high-grade astrocytomas. 4. The high-grade astrocytomas had a highly statistical significant Ki-67 labeling index. The Ki-67 labeling indices were significantly higher in the hsp27-positive than the hsp27-negative astrocytomas, irrespective of the histological grade. In the high-grade astrocytomas with a Ki-67 labeling index of five and above, 81% of those tumors were hsp27 positive. 5. Thus, a large number of human astrocytomas express hsp27, and hsp27 expression correlates with histological grades of astrocytoma and with tumor growth fractions. This being the case, hsp27 is likely to have a role in the growth of human astrocytomas.

Adolescent↗
PubMed1995

Minigemistocytic astrocytoma with frequent apoptoses: analysis of tumor growth.

A rare glial tumor known as 'minigemistocytic astrocytoma (gliofibrillary oligodendroglioma)' is reported in a 73 year old Japanese male. A low-density area found by computed tomography and thought to be an operative scare remaining after hematoma in the right frontal lobe of the cerebrum had been followed for 10 years. This area, however, had been accompanied by a cyst for 2 years and had developed gradually for 1 year prior to dissection. The tumor was poorly demarcated from the surrounding normal tissue macroscopically at operation. Microscopically, the tumor consisted of small gemistocytic cells in uniform sheets intersected by a small vascular stroma with frequent eosinophilic granular bodies, mitoses and apoptotic bodies. Immunohistochemical examination for glial fibrillary acidic protein (GFAP) revealed remarkable positive reactivity in the perinuclear cytoplasm, but no immunoreactivity for vimentin or Leu 7 was found. Electron microscopically, rich filaments arranged in parallel bundles were found in the neoplastic cells. These histological findings are closely consistent with those of previously reported minigemistocytic astrocytoma cases. The GFAP-rich minigemistocytic astrocytoma with granular bodies and frequent mitoses in the present case is considered to indicate a higher degree of astrocytic differentiation and malignant potential than previous cases. The frequent apoptoses, however, might inhibit tumor growth in this case.

Aged↗
PubMed1995

Primary adrenal lymphoma with chromosomal abnormalities.

Lymphomas developing in the adrenal glands are rare. Twenty-one cases of primary adrenal lymphomas have been reported in the English literature, but no cytogenetic data were given. We had the opportunity to examine three cases of primary adrenal lymphoma characterized by the B cell phenotype. Samples for histologic and immunohistologic diagnosis were obtained from postmortem examination in cases 1 and 2, and with an ultrasound-guided needle biopsy in cases 2 and 3. In all 3 cases, histologic examination of adrenal masses showed diffuse medium-sized cleaved lymphoma cells, which were positive for L-26, an immunohistochemical B cell marker. Endocrine studies showed adrenal insufficiency in 1 case. Cytogenetic examination showed clonal abnormalities, including 8q24 in case 1 and 14q32 in case 2, similar to those observed in nodal B cell lymphoma.

Adrenal Gland Neoplasms↗
PubMed1995

New isolates of pneumonia virus of mice (PVM) from Japanese rat colonies and their characterization.

Two virus strains were isolated from the lungs of athymic rats and mice used as sentinel animals in 2 colonies of laboratory rats in Japan in which antibodies to the pneumonia virus of mice (PVM) had been detected. The new isolates were identified as PVM by the following characteristics: RNA virus, susceptibility to ether treatment, long filamentous viral structure in the cytoplasm of infected cells, and hemagglutinating activity in various erythrocytes, including those of mice and rats. In addition, cross neutralization with the prototype of PVM (No. 15 strain) was observed. This is the first report of the isolation of PVM from laboratory animals in Japan.

Animals↗
PubMed1995

Infantile digital fibromatosis: a study of the development and regression of cytoplasmic inclusion bodies.

An 8-yr-old Japanese boy developed infantile digital fibromatosis in the right ring finger with recurrence and another lesion in the right middle finger. Histologic investigation of the tumor disclosed that the size and frequency of inclusion bodies were inversely proportional to the degree of fibrosis. Electron microscopic study revealed a variety of stages in the development of inclusion bodies, ranging from small, dense aggregates of filaments into bundles with dense bodies traversing the cytoplasm to typical inclusion bodies that also contained cytoplasmic organelles. In areas of dense fibrosis, the cytoplasm of the tumor cells showed areas of constriction and compression by adjacent bundles of collagen. The tendency for a decrease in the number of inclusion bodies in these areas necessitated a differential diagnosis from other fibrous or fibro-histiocytic lesions. Our findings suggest that the tumor may undergo a decrease in the numbers of inclusion bodies and spontaneously may become fibrotic with time. Thus, even as a form of fibromatosis featuring both recurrence and multiple lesions, it may not have a consistently aggressive nature. These findings support the concept that infantile digital fibromatosis should be managed by limited excision rather than by immediate aggressive surgical treatment.

Child↗
PubMed1994

Age-related accumulation of lipofuscin in three different regions of rat brain.

The rate of accumulation of auto-fluorescent granules (lipofuscin) in three different regions of rat brain was investigated at various ages from very young to old animals (1, 2, 3, 6, 12 and 30-34 months of age. The accumulation of lipofuscin increased with age in the three brain regions. The first appearance of lipofuscin granules was at 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found in 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x - 0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, a slower rate of lipofuscin accumulation was observed (y = 0.072x - 0.14, r = 0.797 for cerebral cortex; y = 0.067x - 0.14, r = 0.953 for thalamus). It was noted that the most abundant accumulation and the highest rate of lipofuscin accumulation was in the hippocampus. But the rate and magnitude of lipofuscin accumulation in the hippocampus were low compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs.

Aging↗
PubMed1994

Sequence heterogeneity of HTLV-I proviral DNA in the central nervous system of patients with HTLV-I-associated myelopathy.

The nucleotide sequence of human T-lymphotropic virus type I (HTLV-I) in central nervous system tissue was determined in 3 autopsy cases with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and 1 seropositive carrier without HAM/TSP but with multiple sclerosis. All HAM/TSP samples (3 spinal cords and 2 brains) and the sample from the seropositive carrier without HAM/TSP (brain) were positive for HTLV-I env (5146-6681), pX5' (6549-7494), and pX3' (7354-8276) regions by the two-step polymerase chain reaction method. A nucleotide sequence analysis of the pX5' and pX3' polymerase chain reaction products from nucleotides 6631 to 8259 revealed heterogeneity of the HTLV-I genome in all cases. It is notable that 13 of 50 clones derived from the pX3' polymerase chain reaction products were defective in the tax open reading frame while 7 were defective in the rex open reading frame in the HAM/TSP samples. All 17 clones from 1 HAM/TSP case were defective in the pX open reading frame II. One nucleotide insertion at 7784 creating a frame shift in both tax and rex was seen in all 3 HAM/TSP cases but not in the HTLV-I carrier without HAM/TSP. The pX-defective mutants found frequently in the central nervous system may contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication.

Aged↗
PubMed1994

Intravascular leiomyomatosis with uterine lipoleiomyoma.

A very rare case of uterine lipoleiomyomata with intravascular leiomyoma in a 48-year-old woman is described. Located in the corpus of the uterus, the lipoleiomyomata showed proliferation of leiomyocytes intermingling with mature adipocytes. Intravascular leiomyoma was present in the broad ligament. It exhibited only spindle cells, and was reactive for HHF35 actin, without adipocytes. No continuity was detected between these tumors. Immunohistochemical studies revealed that the same portion of the intravascular leiomyoma was positive for S-100 alpha protein, NSE, factor VIII-related antigen, and HHF35 actin. These findings suggest that the leiomyomatous tumor components arise from multipotent undifferentiated mesenchymal stem cells.

Adipose Tissue↗
PubMed1994

The effect of blood volume replacement on the mortality of head-injured patient.

In 77 head-injured and transfused patients, the amount of blood volume replacement (BVR) and patient outcome were retrospectively analyzed. They were divided into four groups of intracranial lesion by initial CT; acute subdural hematoma (SDH) with or without other lesions, traumatic subarachnoid hemorrhage only, epidural hematoma only and all other lesions. Result shows SDH is the most vulnerable to massive transfusion and BVR more than 5000 ml was fatal. Patients with other lesions have high possibility of survival even if BVR amounts to 7000ml. It is concluded, for patients resuscitated with excessive amount of transfusion (> 5000 ml), follow up CT and some vigorous treatment such as administration of hypertonic solutions should be scheduled.

Adolescent↗