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Biomedical subjects

T Kagawa

Publications and source records attributed to T Kagawa.

At least 73 records · Page 4Linked to original sources
PubMed1994

Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein gene.

Myelin proteolipid protein (PLP), the major myelin protein in the CNS, has been thought to function in myelin assembly. Thus, mutations within the gene coding for PLP (Plp) cause hypomyelination, such as the jimpy phenotype in mice and Pelizaeus-Merzbacher disease in humans. However, these mutants often exhibit premature death of oligodendrocytes, which form CNS myelin. To elucidate the functional roles of Plp gene products in the maturation and/or survival of oligodendrocytes, we produced transgenic mice overexpressing the Plp gene by introducing extra wild-type mouse Plp genes. Surprisingly, transgenic mice bearing 4 more Plp genes exhibited dysmyelination in the CNS, whereas those with 2 more Plp genes showed normal myelination at an early age (3 weeks after birth), but later developed demyelination. Overexpression of the Plp gene resulted in arrested maturation of oligodendrocytes, and the severity of arrest was dependent on the extent of overexpression. Overexpression also led to oligodendrocyte cell death, apparently caused by abnormal swelling of the Golgi apparatus. Thus, tight regulation of Plp gene expression is necessary for normal oligodendrocyte differentiation and survival, and its overexpression can be the cause of both dys- and demyelination.

Animals↗
PubMed1994

Fate of jimpy-type oligodendrocytes in jimpy heterozygote.

In the jimpy mutant mouse, as well as in many other animals with mutations in the myelin proteolipid protein (PLP) gene, oligodendrocytes degenerate before their maturation. To analyze whether this degeneration is caused by the loss of function of PLP gene products related to oligodendrocyte maturation/survival acting extrinsically, expression of the PLP gene was investigated in the jimpy heterozygote, in which one-half of the cells are jimpy type and the other half are wild type due to random X-chromosome inactivation. We first showed that jimpy PLP gene expression is normally regulated at the early stages of development in brains of jimpy hemizygotes and heterozygotes, at least to day 2 after birth. However, the great increase in the level of PLP gene transcripts observed in wild-type mouse brain is suppressed in jimpy mouse brain. This increase was also suppressed in the jimpy heterozygote, and by 2 months after birth, very few jimpy-type PLP gene transcripts were detected in heterozygotes. These results indicate that jimpy-type oligodendrocytes cannot survive or are still in the immature stage in the brain of jimpy heterozygotes. Thus, degeneration of jimpy oligodendrocytes is not caused merely by the lack of trophic factors.

Animals↗
PubMed1994

Intraoperative use of Doppler ultrasound and endoscopic monitoring in the stereotactic biopsy of malignant brain tumors. Technical note.

An intraoperative monitoring tool is described that prevents mechanical injury to intracerebral vessels during stereotactic surgery. The method, which combines pulse Doppler ultrasonography and fiberendoscopy, allowed stereotactic biopsy to be performed without serious intracerebral bleeding in 25 patients with hypervascular malignant brain tumors, 13 with glioblastoma multiforme, five with anaplastic astrocytoma, five with metastatic tumor, and two with malignant lymphoma. The ultrasound apparatus has a built-in fast-Fourier transformation system analyzer and an improved filtering system that provide real-time measurement of blood flow velocity. The source of flow (arterial or venous) could be identified by both real-time sonography and acoustic signal frequencies. It was possible to measure the size and distance of a vessel by adjusting the Doppler signal gain dial from initially waxing to waning sounds, because the acoustic signal was adjusted to the axial flow of each vessel in 0.1-mm steps. Each of three Doppler probes (1 mm, 2 mm, and 3 mm in diameter) fit through the outer cannula of the biopsy needle. Vessels located within 7 mm from the tip of these probes could be detected easily and rapidly, so the biopsy needle could be advanced safely to the desired target in 7-mm steps. If sonograms revealed blood flow, indicating the presence of larger vessels in the intended stereotactic trajectory, the angle of the needle was changed slightly to avoid vascular injury. Because the fiberendoscope was connected to a video processor, the vessel could be visualized at a higher magnification on the video display, unless there was active bleeding. This technically simple and reliable system enhances operative safety while maintaining accuracy.

Biopsy↗
PubMed1993

A randomized, controlled trial of weekly administration of lymphoblastoid interferon in patients with chronic hepatitis C.

To evaluate the efficacy of a treatment of weekly interferon administration in patients with chronic hepatitis C, 36 patients were randomly assigned to two groups. In one group lymphoblastoid interferon was given at a dose of 6 million units, intramuscularly, once per week for 24 weeks, and no treatment was given to the other. Serum alanine aminotransferase levels in the treated group were significantly lower during therapy than in the control group, although there was no significant difference between these two groups before therapy. The normalization of serum alanine aminotransferase levels at the end of therapy was observed in 50% of the treated group, and in 11.1% of the control group. This difference was statistically significant (p < 0.03). Response to interferon was better in patients with chronic persistent hepatitis or with chronic active hepatitis than in patients with chronic active hepatitis with cirrhosis. Relapse after the end of therapy was observed in 83.3% of the responders. These results indicate that the weekly administration of 6 million units of lymphoblastoid interferon is effective in decreasing serum alanine aminotransferase levels in patients with type C chronic persistent hepatitis or chronic active hepatitis.

Alanine Transaminase↗
PubMed1993

Bone mineral density of the radius in patients with ossification of the cervical posterior longitudinal ligament. A longitudinal study.

Radial bone mineral density (BMD) in the distal one sixth and distal one third of the left radius was measured by single-photon absorptiometry (SPA) in patients with ossification of the cervical posterior longitudinal ligament (OPLL). Twenty-three OPLL patients (15 men and 8 women) with mean initial age of 60.1 years were studied longitudinally for mean follow-up period of 3.9 years. Based on roentgenologic findings, the patients were divided into two groups, those with advancing OPLL and those with non-advancing OPLL. The final value of distal 1/6th BMD in the advancing group was significantly lower than its initial value, but no change of the value of the distal 1/3rd BMD was observed in either group. The final value of distal 1/6th BMD/distal 1/3rd BMD ratio in the advancing group was significantly decreased compared with its initial value. These results suggest that, in the advancing OPLL group, trabecular bone mass decreased while cortical bone mass remained unchanged.

Absorptiometry, Photon↗
PubMed1993

Novel isoforms of mouse myelin basic protein predominantly expressed in embryonic stage.

Myelin basic protein (MBP), a major protein of myelin, is thought to play an important role in myelination, which occurs postnatally in mouse. Here we report that the MBP gene is expressed from the 12th embryonic day in mouse brain and that most of the predominant embryonic isoforms are not those reported previously. These isoforms have a deletion of a sequence encoded by exon 5 from the well-known isoforms. These isoforms show a unique developmental profile, i.e., they peak in the embryonic stage and decrease thereafter. In jimpy, a dysmyelinating mutant, the level of these isoforms remains high even in the older ages. These results suggest that MBPs have heretofore unknown functions unrelated to myelination before myelinogenesis begins. The possible presence of 18 isoforms of MBP mRNA, which are classified into at least three groups with different developmental profiles, is also reported here.

Animals↗
PubMed1993

Effects of extracorporeal circulation on blood ketone body ratio reflecting hepatic energy metabolism during cardiac operation.

To examine the effects of extracorporeal circulation using an artificial heart and lung machine on hepatic energy metabolism in patients with cardiac operation using hypothermia, the arterial blood ketone body ratio (AKBR) reflecting the hepatic mitochondrial redox state was determined in 12 patients who had undergone cardiac operation using extracorporeal circulation from March to August 1991. Changes in AKBR were compared with those before and after extracorporeal circulation. AKBR decreased significantly after the beginning of extracorporeal circulation (p < 0.001) and remained at a lower level throughout extracorporeal circulation. On termination of extracorporeal circulation, the initial level was immediately resumed. The extent of decrease in ketone body ratio at ten minutes before termination of extracorporeal circulation was correlated with short term postoperative hepatic insufficiency. The patients whose ratio decreased below 0.4 showed increased levels in glutamic-pyruvic transaminase at the end of the first and second week after operation. Changes in AKBR were significantly associated with those in blood pressure (r = 0.433; p < 0.005) and body temperature (r = 0.472; p < 0.005). It was concluded that blood pressure and body temperature influence the blood ketone body ratio during extracorporeal circulation.

Adolescent↗
PubMed1993

A case of sellar chordoma mimicking a non-functioning pituitary adenoma with survival of more than 10 years.

A rare case of sellar chordoma occurring in a 67-year-old woman who survived for more than 10 years is presented. Clinical signs and symptoms masqueraded as a non-functioning pituitary adenoma with visual disturbance and hypopituitarism. Initial computed tomography (CT) showed an intrasellar mixed dense mass with suprasellar extension, accompanied by non-homogeneous contrast enhancement. Partial removal of the mass was accomplished via right fronto-temporal craniotomy. Histological examination revealed a typical chordoma with no malignancy. After postoperative irradiation, the patient was discharged with clinical improvement. Serial CT and magnetic resonance imaging 8 years after treatment disclosed a regrowth of the intrasellar lesion, which extended to the sphenoid sinus and clivus, accompanied by non-homogeneous contrast enhancement. The patient underwent subtotal removal of the recurrent tumor through a sublabial transsphenoidal approach. Histological examination confirmed the previous diagnosis. Immunohistochemical study demonstrated positive cytoplasmic expression of vimentin, epithelial membrane antigen, keratin and S-100 protein, in contrast with a lack of appearance of carcinoembryonic antigen. After reoperation, she completely recovered and has survived for more than 10 years with good quality of life.

Adenoma↗
PubMed1993

[Empty sella syndrome].

An empty sella is defined as a sella which, regardless of its size, is completely or partly filled with cerebrospinal fluid (CSF). Empty sella is occasionally found as a normal anatomical variation, which is referred to as primary empty sella. On the other hand, empty sella is also seen after surgery, irradiation or medical treatment of pituitary adenoma, which is called secondary empty sella. Magnetic resonance imaging (MRI) is useful in diagnosing empty sella. Primary empty sella is usually free from clinical symptoms but sometimes associated with headache, obesity, visual disturbance, non-traumatic CSF rhinorrhea and pituitary insufficiency. These associated findings constitute the empty sella syndrome. CSF rhinorrhea, visual disturbance and severe increased intracranial pressure are the indications for surgical treatment. Non-symptomatic cases require no treatment but periodical follow up is necessary.

Adenoma↗
PubMed1993

A pilot study of long-term weekly interferon-beta administration for chronic hepatitis B.

Interferon-beta was given weekly for 24 wk, at a dose of 3 million units, intravenously, to 10 patients with chronic hepatitis B who were serologically positive for HBsAg and HBeAg. Their condition was followed for 6 months after the end of therapy. Both serum hepatitis B virus-associated DNA-polymerase activity and alanine aminotransferase level became significantly lower during therapy and during the 6 months after the end of therapy than at the beginning of therapy. In five of 10 patients, the seroconversion from HBeAg positive to anti-HBe positive had occurred by 6 months after the end of therapy, and in four of these five patients, serum alanine aminotransferase level became normal. Weekly interferon-beta administration over 6 months seems effective in inducing seroconversion and in normalizing serum alanine aminotransferase level.

Adolescent↗
PubMed1993

[Measurements of bone mineral density of lumbar vertebrae in the lateral projection by dual-energy X-ray absorptiometry--comparison with anteroposterior spinal and radial bone mineral measurements].

Bone mineral density (BMD) of lumbar vertebral bodies in the lateral projection were evaluated using dual-energy X-ray absorptiometry (DEXA) with respect to reproducibility of spinal bone measurements in two projections in healthy men, age-related bone mass changes in healthy women, and the bone mass in osteoporotic women. The BMD of the third lumbar vertebral body in the lateral projection (L3-LAT-BMD) and of the entire third lumbar vertebra in the anteroposterior projection (L3-AP-BMD) were measured with DEXA. The BMD of the distal metaphysis and distal diaphysis of the left radius were measured by single photon absorptiometry. The coefficient of variation in six men aged from 24 to 28 years was 1.7% for L3-LAT-BMD and 1.8% for L3-AP-BMD. In 82 healthy women ranging from 26 to 69 years of age (mean 50 years), BMD decreased rapidly after 50 years of age and above at all measured sites. However L3-LAT-BMD value showed wide distribution and decreased at an earlier age. Correlations within the two BMD values in the same bones were high (r = 0.799 for the vertebra and 0.803 for the radius), while those for any two BMD parameters for different bones were relatively low, with r values varying from 0.456 to 0.560. In 22 women with involutional osteoporosis ranging from 54 to 75 years of age (mean 65), values for L3-LAT-BMD and BMD of the distal metaphysis of the radius were lower than values predicted based on BMD of healthy women.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line, HCC-M.

Human neutrophil-mediated oxidative processes against a human hepatoma cell line, HCC-M, was visualized at the cellular level by using a silicon-intensified target camera and subsequently processing with a computer-assisted digital-imaging processor. Neutrophils were activated by a streptococcal preparation, OK-432. A hydroperoxide-sensitive tracer, dichlorofluorescein diacetate, was loaded in HCC-M and temporal and spatial changes of lipid peroxides in this cell after addition of stimulated neutrophils were analyzed. The luminol-dependent chemiluminescence activity of neutrophils was significantly enhanced and continued for at least 2 hr by stimulation with OK-432, and its activity was shown to be accumulated at the site where a neutrophil attached with HCC-M. The intensity of dichlorofluorescein fluorescence in HCC-M rapidly increased after adding stimulated neutrophils, and their reaction was significantly attenuated by superoxide dismutase. The number of non-viable cells was increased as the dichlorofluorescein fluorescence increase. It is suggested that oxidative stress may play an important role in neutrophil-mediated tumor-cell damage.

Carcinoma, Hepatocellular↗
PubMed1992

Radial bone mineral changes in pre- and postmenopausal healthy Japanese women: cross-sectional and longitudinal studies.

Healthy premenopausal and postmenopausal Japanese women were evaluated by longitudinal and cross-sectional studies to assess changes in radial bone mineral density. A total of 300 healthy Japanese women were enrolled in the cross-sectional study, and 126 of them were chosen for the longitudinal study. In the cross-sectional study significantly lower bone mineral density was found in the women over 50 years old. In the longitudinal study, premenopausal women aged 45-54 years showed rate of change of -0.61%/year at the distal radius and 0.49%/year at the radial shaft. The perimenopausal changes were -1.95 and -0.93%/year and the postmenopausal changes were -1.88 and -1.37%/year at the distal radius and at the radial shaft, respectively, in the women aged 45-54 years. These rates of premenopausal and postmenopausal change were similar to those reported for whites in the United States. The strength of the relationship between the rate of change in radial bone mineral density and the anthropometric values, biochemical data, and menopausal status was evaluated by multiple linear regression analysis. Menopausal status had the greatest influence on the rate of change in radial bone mineral density. It is concluded that menopausal status was the most important variable related to bone loss in our longitudinal study and the rate of bone loss was greatest during the early postmenopausal period in healthy Japanese women.

Adult↗
PubMed1992

Characterization of male meiotic germ cell-specific antigen (Meg 1) by monoclonal antibody TRA 369 in mice.

We have identified a male meiotic germ cell-specific antigen (Meg 1) with monoclonal antibody (mAb) TRA 369 in mice. The Meg 1 antigen was strongly expressed in specific steps of meiotic germ cells from pachytene spermatocyte to early spermatid, and not in other germ cells or somatic cells. Immunohistochemical examination revealed that the antigen was localized to the cytoplasm and was not distributed in the nucleus or on the cell surface. This antigen was demonstrated to have a molecular weight of 93 kDa and an isoelectric point of 5.2 by Western blotting. This molecule was first detected in the testis of 13-day-old mouse when pachytene spermatocytes first appeared. Thus this is a differentiation-specific antigen in male meiotic germ cells, and mAb TRA 369 is a useful tool to study the regulation of germ cell differentiation and to define germ cell development in a molecular level.

Animals↗
PubMed1992

Relationship among serum levels of luteinizing hormone, estradiol, and progesterone during follicle stimulation and results of in vitro fertilization and embryo transfer (IVF-ET).

Eighty-eight IVF-ET cycles were classified into four groups according to the results of IVF-ET (Group A-conceptional cycles, 10 cycles; Group B-cycles with cleaved oocytes, 58 cycles; Group C-cycles with fertilized oocytes, 9 cycles; Group D-cycles without fertilization, 11 cycles). Serum luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels during follicle stimulation were studied in these groups. Patients participated in our IVF-ET program due to irreparable tubal damage. Follicle development was stimulated with a clomiphene-human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) regimen. Group C showed a low E2 response to follicle stimulation. Groups B and D showed significantly higher serum P levels on day 0 (the day of hCG injection) than Group A (Group A, 0.73 +/- 0.11, vs Groups B and D, 1.43 +/- 0.15 and 2.17 +/- 0.42 ng/ml; P less than 0.01). The effects of serum P and LH levels on the fertilization and pregnancy rates were studied. The pregnancy rate was not affected by the serum LH level but was only 2.7% in cycles in which serum P was 1.2 ng/ml on day 0, which was significantly lower than that in cycles in which serum P was less than 1.2 ng/ml on day 0 (19.1%) (P less than 0.05). The fertilization rate was significantly lower in the cycles with higher levels of serum P and/or LH than in cycles in which serum P was less than 1.2 ng/ml and serum LH was normal (50.5 vs 78.8%; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clomiphene↗
PubMed1992

Retrovirus-mediated gene transfer targeted to malignant glioma cells in murine brain.

A murine model for meningeal metastasis of malignant glioma was developed to study selective gene transfer into tumor cells and to establish a reliable means of determining the rate of tumor cell infection. A murine ecotropic retroviral vector was created in which the Escherichia coli beta-galactosidase gene served as a marker for gene expression from the integrated retrovirus. This retrovirus exhibited a high rate of infectivity in RSV-M mouse glioma cells in vitro. The recombinant retrovirus was injected directly into the cisterna magna of the mice. Staining of beta-galactosidase showed that the rate of gene integration was high in the disseminated glioma cells. These results suggest the possibility of retrovirus-mediated gene therapy for meningeal dissemination of malignant glioma.

Animals↗
PubMed1992

Selective expression of DM-20, an alternatively spliced myelin proteolipid protein gene product, in developing nervous system and in nonglial cells.

Mutations within the gene for myelin proteolipid protein (PLP), a major myelin structural protein, result in abnormal glial differentiation, suggesting that the PLP gene products play some other functional roles. Transcripts from the PLP gene were analyzed in the developing mouse brain by a sensitive method using polymerase chain reaction. The mRNA for DM-20, an alternatively spliced transcript from the PLP gene, was detected in the embryonic mouse brain as early as embryonic day 11, long before the appearance of oligodendrocytes, which were considered to be responsible for PLP production. PLP gene expression was analyzed in various cell lines to determine whether synthesis of the DM-20 mRNA is restricted to those of glial cell lineage. All of the nervous system cell lines examined, including nonglial cell lines, produced DM-20 mRNA but no or very little PLP mRNA. Peripheral sciatic nerve from adult Wistar rats also produced mainly DM-20 mRNA. These results indicate that DM-20 is not only a myelin structural protein, but it also plays other roles in the nervous system that seem to relate, at least in part, to glial differentiation.

Animals↗