PubMed HealthSearch

Biomedical subjects

M Takizawa

Publications and source records attributed to M Takizawa.

At least 19 recordsLinked to original sources

[Radiation therapy of intracranial germinoma].

The appropriate radiation dose and field for the treatment of intracranial germinoma were investigated in 33 patients. Recurrences were observed in 4 cases treated with local field irradiation only, and all of them were recognized at the margin of the radiation field or under the dose (less than 25 Gy) area. This suggests that whole cranial irradiation (dose of 25 to 30 Gy) should be added even if the tumor is solitary. The effective dose for cerebrospinal dissemination appears to be 25-35 Gy, but prophylactic CNS irradiation seems unnecessary for patients who have not undergone surgical procedures. Changes in mental status were seen in 5 patients (26.3%). Doses of over 59 Gy may be related to this complication.

Adolescent

Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat.

Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.

Administration, Oral

The effect of a new vitamin D analog, 22-oxa-1 alpha,25(OH)2D3, on bone mineral metabolism in normal male rats.

The in vivo effects of 22-oxa-1 alpha,25 dihydroxyvitamin D3 (OCT), on bone mineral metabolism were investigated in normal male Sprague-Dawley rats. The rats were administered either vehicle (control), low-dose OCT (25 ng/100 g body weight), or high-dose OCT (250 ng/100 g body wt). High-dose OCT increased serum ionized calcium (P less than 0.05) and decreased serum parathyroid hormone (PTH) (P less than 0.05) at all time points and increased serum bone Gla protein on days 7 and 28 (P less than 0.05) compared with controls. Low-dose OCT decreased serum PTH at all the time points (P less than 0.05) compared with controls. Tibial bone histomorphometry showed no significant differences between the two doses of OCT and controls. We found that OCT has minimal direct effects on bone metabolism in normal male rats in contrast to 1,25 dihydroxyvitamin D3. This property may be advantageous in the treatment with OCT of cell-proliferative diseases.

Analysis of Variance

User and manufacturer's requirements for IMAC standardization in Japan.

Many radiologists and radiological technologists understand that Picture Archiving and Communication Systems (PACS) are useful not only for image management but also for improving the quality of patient care. However, such systems have not yet been widely installed in hospitals. In order to determine why radiologists have not installed a PACS in their hospitals, we carried out a written survey of 400 Japanese hospitals asking them to describe the current image management activities, the problems inherent in PACS and the problems related to standardization. 216 hospitals responded, and the following suggestions were compiled concerning possible improvements to PACS. (1) PACS benefit needs to be improved with respect to patient care. (2) The cost of PACS should be reduced. (3) The system should be easier to operate and should save time. (4) Standardization is needed to allow simplified, cost-effective networking. We also carried out a written survey of 25 PACS and related equipment manufacturers asking them to describe the opinions inherent in current PACs and the problems related to standardization. Ten manufacturers responded, and the various suggestions were compiled concerning possible improvements to the PAC system.

Japan

Evidence that cyclosporine G is less deleterious to rat bone in vivo than cyclosporine A.

We have previously shown that CsA administration to rats causes a high turnover bone loss with bone resorption exceeding bone formation. Similar findings have been reported in renal and cardiac transplantation patients administered CsA. Cyclosporine-G (CsG), a natural equipotent immunosuppressive analogue of CsA, has been shown to be less nephrotoxic than CsA. We therefore compared the effects of CsG and CsA on bone mineral metabolism. Sixty male Sprague-Dawley rats were divided into 3 equal groups as follows: group A (n = 20) was the control; group B (n = 20) received CsA 15 mg/kg by daily gavage; and group C received CsG 15 mg/kg by daily gavage for 28 days. Rats were bled weekly for measurement of circulating biochemical parameters of bone mineral metabolism and after sacrifice on day 28, the tibiae were removed for histomorphometric analysis. The tibial bone histomorphometry revealed that the percentage of bone volume was significantly reduced, and the osteoclast count increased in both the CsA and CsG group, but significantly less so in the CsG than the CsA group. Parameters reflecting bone formation in the CsG group were similar to controls but significantly different from the CsA group. Bone Gla protein levels in the CsA group were significantly increased compared with the control and CsG groups from day 14. Serum 1,25 dihydroxyvitamin D was increased significantly in the CsA group on days 14 and 28 compared with both control and CsG groups, and was significantly elevated in the CsG group compared with controls on the same days. We conclude that CsG is significantly less deleterious to bone mineral metabolism than CsA in the rat in vivo.

Animals

17 beta-estradiol prevents osteopenia in the oophorectomized rat treated with cyclosporin-A.

Cyclosporin-A (CsA) administered to the oophorectomized rat exaggerates the high turnover osteopenia associated with oophorectomy alone. This study investigated whether 17 beta-estradiol replacement could influence the development of osteopenia in the oophorectomized rat treated with CsA. Ninety female Sprague-Dawley rats, approximately 300 g in weight, were divided into 6 groups of 15 each and treated according to the following protocol: group A were sham operated (control), group B underwent oophorectomy (Ox), group C underwent Ox and received CsA (15 mg/kg, by daily gavage) for 28 days (Ox and CsA), group D underwent Ox and received CsA and a 0.1 mg 17 beta-estradiol pellet (EP) implanted sc (Ox, CsA, and EP), group E underwent Ox and received EP (Ox and EP), and group F, which was intact and nonoperated, received CsA (CsA). Rats were weighed and bled on days -7, 0, 7, 14, 21, and 28 for measurement of blood ionized calcium, bone Gla protein (BGP), 17 beta-estradiol, and PTH. Bone histomorphometry was determined after double tetracycline labeling. On day 28, serum 17 beta-estradiol was undetectable in groups B (Ox) and C (Ox and CsA), and similar to group A (control) in groups D (Ox, CsA, and EP), E (Ox and EP), and F (CsA). Oophorectomy resulted in a significant gain in weight in groups B (Ox) and C (Ox and CsA), which was prevented by 17 beta-estradiol in groups D (Ox, CsA, and EP) and E (Ox and EP). On day 28, serum BGP levels were higher in groups B (Ox; 73.58 +/- 3.63 ng/ml), C (Ox and CsA; 85.05 +/- 9.88), and F (CsA; 81.35 +/- 3.4) compared to group A (control; 46.07 +/- 5.52; P less than 0.05), while 17 beta-estradiol in groups D (Ox, CsA, and EP; 38.65 +/- 2.85) and E (Ox and EP; 41.89 +/- 1.89) prevented this rise (P = 0.01). BGP levels in group C (Ox and CsA) were higher on days 14 and 21 compared to group B (Ox). Groups D (Ox, CsA, and EP) and E (Ox and EP) had elevated blood ionized calcium levels from day 7 onward. Serum PTH levels were unchanged. Histomorphometric analyses of tibial metaphyses revealed increased parameters of bone formation and resorption, with significant loss of bone volume, in groups B (Ox; 12.03 +/- 1.40%) and C (Ox and CsA; 11.43 +/- 2.20) vs. group A (control; 24.36 +/- 2.37; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29,852) in conscious hypertensive dogs.

The hypotensive efficacy of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29,852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI) was examined in conscious two-kidney, one-clip Goldblatt hypertensive dogs. The acute hypotensive effect of SQ 29 852 was compared with that of captopril or enalapril at 3 mg/kg, p.o., for each, and the potencies were ranked as follows, enalapril greater than SQ 29,852 greater than captopril. On the other hand, the hypotension caused by repetitive dosing with SQ 29,852 (3 mg/kg, p.o./d for 7 d followed by another 7-d treatment with 10 mg/kg, p.o./d) was somewhat more marked than that by enalapril at the same dosage. Blood urea nitrogen (BUN) increased in all the animals given enalapril, while that in all of the SQ 29,852-treated animals did not increase. These results indicate that SQ 29,852 is a potent, and long-lasting ACEI with a possible low incidence of side effects.

Administration, Oral

Histological study of atelocollagen infused into the human vocal cords.

There have been only three case reports of histological study on injection of atelocollagen into the human vocal cords, and none of these have indicated foreign body reaction. We histologically examined the larynx of a 70-year-old man, which had to be excised 44 days after infusion of atelocollagen into the vocal cords. The atelocollagen infused was found to have been replaced with the collagen of host cells, but no foreign body reaction was observed. As in conventional reports, the histoaffinity of atelocollagen was confirmed.

Aged

Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse.

We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase

Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss.

Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.

Animals

Cholesterol-free diet with a high ratio of polyunsaturated to saturated fatty acids in heterozygous familial hypercholesterolemia: significant lowering effect on plasma cholesterol.

We have studied the effect of diet therapy on plasma lipoprotein metabolism in heterozygous familial hypercholesterolemia. Seven patients with a mean plasma cholesterol concentration of 323 +/- 67 mg/dl were hospitalized and kept on a cholesterol-free diet for as long as 11 days without any medication. The content of dietary cholesterol was approximately 1.4 mg a day, and dietary fat, carbohydrate and protein comprised 18.0, 69.2 and 12.8% of calories, respectively. The ratio of polyunsaturated to saturated fatty acids (P/S) was 3.1. At the end of the study period, plasma cholesterol was lowered by 14.2%, from 323 to 277 mg/dl, and low density lipoprotein (LDL) cholesterol by 17.5% from 229 to 189 mg/dl. Using density gradient ultracentrifugation, the major change in LDL cholesterol was found to be in those fractions with a mean density between 1.034 and 1.042, where cholesterol concentrations decreased from 132 to 87 mg/dl (34%). These results indicate that diet therapy with free-cholesterol and a high ratio of P/S is highly effective in controlling plasma cholesterol levels in heterozygous familial hypercholesterolemia.

Adult

TAN-999 and TAN-1030A, new indolocarbazole alkaloids with macrophage-activating properties.

Two new indolocarbazole alkaloids, TAN-999 and TAN-1030A, were isolated from culture broths of Nocardiopsis dassonvillei C-71425 and Streptomyces sp. C-71799, respectively. Their structures were elucidated on the basis of their reactions, spectroscopic analyses and in particular, comparison of spectral data with that of staurosporine. These metabolites induced spreading of a murine macrophage cell line, Mm 1. They also augmented the phagocytic activity, Fc gamma receptor expression and beta-glucuronidase activity of murine macrophage cell lines, Mm 1 and J774A.1. When proteose-peptone elicited peritoneal macrophages from mice were incubated with these metabolites for 2 days, the phagocytosis-dependent respiratory burst of these cells was enhanced. Similar enhancement was also observed when the peritoneal macrophages in mice were modulated by intraperitoneal administration of these metabolites. These results reveal that TAN-999 and TAN-1030A can activate macrophage functions in mice.

Alkaloids

A new pyrrole-amidine antibiotic TAN-868 A.

A new pyrrole-amidine antibiotic TAN-868 A was isolated from the culture broth of Streptomyces idiomorphus sp. nov. Its chemical structure was determined by spectroscopic analyses and degradation studies to be 4-[(2S,4R)-4-hydroxy-5-iminoprolyl]amino- N-(2-amidinoethenyl)-2-pyrrolecarboxamide. The antibiotic is active against bacteria, fungi and a protozoan, and has cytotoxic activity against murine tumor cells. DNA thermal denaturation studies suggest that TAN-868 A preferentially interacts with AT rich regions of double-stranded DNA.

Anti-Bacterial Agents

Two sulfur-containing ansamycin antibiotics from Streptomyces albolongus.

Two sulfur-containing ansamycin antibiotics were isolated from the culture broth of Streptomyces albolongus C-46366; the major one was identical with awamycin and the minor one was a new ansamycin antibiotic, ansathiazin. Their structures were elucidated from their reactions and spectroscopic analyses. These antibiotics were active against gram-positive bacteria, acid-fast bacteria and a protozoan.

Anti-Bacterial Agents