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Biomedical subjects

H Natsume

Publications and source records attributed to H Natsume.

At least 37 records · Page 2Linked to original sources
PubMed1997

A case of an iliopsoas abscess in a neonate.

The present study describes a male neonate with an iliopsoas abscess. He was born by Caesarean section at 35 weeks and 3 days gestation. At 24-days-old he had a fever and localized swelling of the groin to the femur. By ultrasonography (US) and computed tomography (CT), the swelling was diagnosed as iliopsoas abscess. We treated him through percutaneous needle drainage and antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the culture of the fluid from the abscess and the urine. US and CT were useful for the diagnosis and provided guidance for the needle puncture and follow-up of the iliopsoas abscess.

Age of Onset↗
PubMed1997

Evaluation of skin permeability of drugs by newly prepared polymer membranes.

Four polymeric membranes were prepared consisting of various ratios of 2-hydroxyethyl-methacrylate/polydimethylsiloxane-methacrylate copolymer. These membranes had both lipophilic and hydrophilic domains in their copolymer networks like skin barrier. From permeation studies of the aqueous solutions or suspensions of various lipophilic and hydrophilic drugs using these membranes, a membrane having a similar drug permeability to hairless rat and human skins was selected. Permeation of indomethacin through the selected polymer membrane from simple ointment, gel and a marketed cream were then measured. About 10(2) times higher permeability was found in the polymer membrane than through excised hairless rat skin, but the rank order of the permeability through the polymer membrane among the formulations was the same through the skin membranes. These higher permeations of indomethacin were probably related to physical and chemical properties of pharmaceutical additives in the topical formulations. It is concluded that these synthetic polymer membranes may be utilized as an alternative tool to predict human or rat skin permeability of various (hydrophilic or lipophilic) drugs as well as to screen drug candidates for transdermal drug delivery.

Administration, Cutaneous↗
PubMed1997

Long-term follow-up of a girl with the neonatal form of Bartter's syndrome.

We followed up a girl with the neonatal form of Bartter's syndrome for sixteen years and determined the sensitivity to angiotensin II before and during the indomethacin treatment. A 4-month-old girl was admitted to our hospital, because of severe hypokalemia and growth retardation. Initially we treated her with spironolactone and potassium supplements. This treatment increased plasma potassium levels and her growth. At the age of one year she was diagnosed as having Bartter's syndrome. Since then she has been treated with indomethacin at an initial dose of 3 mg/kg/day combined with spironolactone and potassium. After the start of the indomethacin treatment, her growth increased dramatically, and her final height was normal adult height. Her puberty developed normally and menarche occurred at the age of 12 years. Levels of serum sodium, chloride, plasma aldosterone and urinary prostaglandin E2 were also normalized. Levels of angiotensin I and II were improved but not within the normal range, but plasma potassium levels slightly decreased after plasma aldosterone levels were normalized and did not change during the treatment period. Plasma renin activity remained high until about the age of 8 years, after which it decreased to almost within the normal range. At 5 months after the start of indomethacin (3 mg/kg/day), her vascular sensitivity to angiotensin II had been improved, and after 2 years and 5 months, her vascular sensitivity was further improved. At this time renin activity had decreased after angiotensin II infusion, but plasma aldosterone did not change. At the age of 16 years (dose of indomethacin: 0.5 mg/kg/day), plasma aldosterone increased after angiotensin II infusion. These data suggest that indomethacin and spironolactone are effective treatments for the neonatal form of Bartter's syndrome, especially during childhood.

Angiotensin I↗
PubMed1996

Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism.

OBJECTIVE: We measured pyridinium cross-links, markers of bone resorption, by an enzyme-linked immunosorbent assay (ELISA) in hypothyroid patients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment. DESIGN AND PATIENTS: Eight hypothyroid patients, whose initial TSH levels were 268.1 +/- 87.7 mU/l (mean +/- SE), were treated with T4 (100 micrograms/day). Urinary excretion of pyridinium cross-links was assayed before and after T4 treatment. MEASUREMENTS: Pyrilinks and Pyrilinks-D kits were used. The Pyrilinks assay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks-D assay measures deoxypyridinoline (DPD) alone. The Pyrilinks reference ranges for normal subjects are 8-24nmol/mmol creatinine in males and 10-28nmol/mmol creatinine in normal premenopausal females. The DPD reference ranges obtained from normal men and women aged 40-50 years were 3.20 +/- 0.75 (mean +/- SD) nmol/mmol creatinine and 4.55 +/- 1.22 nmol/mmol creatinine, respectively. RESULTS: The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridinium cross-links were low in untreated hypothyroid patients and increased gradually as thyroid hormone status improved from hypothyroidism to euthyroidism. One month after treatment when the TSH levels in the patients were still as high as 74.4 +/- 44.5 mU/l, urinary PYD excretion has increased to 2.6 times the pretreatment level. When the TSH levels of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively. CONCLUSIONS: Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first report that urinary excretion of pyridinium cross-links is reduced in hypothyroidism and is normalized by physiological thyroid hormone replacement.

Adult↗
PubMed1996

Introducing a point mutation identified in a patient with pituitary resistance to thyroid hormone (Arg 338 to Trp) into other mutant thyroid hormone receptors weakens their dominant negative activities.

Clinical resistance to thyroid hormone (RTH) has been classified into generalized resistance to thyroid hormone (GRTH) and pituitary resistance to thyroid hormone (PRTH) types. Since similar mutations have been identified in tri-iodothyronine (T3) receptor (TR) beta gene in GRTH and PRTH, and since considerable overlap has been seen in the clinical manifestations in patients with GRTH and PRTH, two subtypes of RTH are now considered to be a continuous spectrum with the same genetic defect. A point mutation at amino acid Arg 338 to Trp (R338W) which we identified in a patient with PRTH is very interesting, since R338W has been found in several other patients with PRTH, raising the possibility that this mutation may tend to associate with a phenotype of PRTH. In our previous study, we found that R338W had relatively less impaired transcriptional potency, weaker dominant negative activity on various T3 response elements and poor homodimer formation, as compared with another GRTH mutant. In this study, to investigate the functional properties of R338W further, especially in terms of the relation between transcriptional activity and dimer formations, we introduced the R338W mutation into the mutant receptors, K443E and F451X, constructing the double mutants, R338W/K443E and R338W/ F451X. Both R338W/K443E and R338W/F451X showed negligible T3 binding and transcriptional activities. The dominant negative activities of K443E and F451X were, however, significantly weakened by introducing the R338W mutation. As a control, a double mutant G345R/K443E was constructed by introducing a point mutation, G345R, located in the same exon 9 as R338W, into the K443E mutant. Dominant negative activity did not differ between G345R/K443E and K443E. Homodimer formation was significantly reduced in the double mutants containing R338W, but not G345R. In summary, introducing the R338W mutation, but not G345R, into the mutant TR significantly weakened the dominant negative activity, despite further impairment of the T3 binding and transcriptional activities.

Cells, Cultured↗
PubMed1995

Dual regulation of 21-hydroxylase activity by sex steroid hormones in rat hepatocytes.

In the rat liver, cytochrome P450 catalyzes the hydroxylation of steroid hormones. The expression and activity of some P450 isozymes are regulated by sex steroid hormones. Steroid 21-hydroxylase activity in rat liver is provided mainly by CYP2C6. We studied the regulation of 21-hydroxylase activity by sex steroid hormones in rat primary hepatocyte culture. We added estrogens (estrone, estradiol, estriol) and androgens (testosterone, dihydrotestosterone), (ranging from 10(-9) to 10(-5)M) to the culture. The 21-hydroxylase activity was stimulated by estrogens and was suppressed slightly by androgen in a dose-related manner. The results of our studies demonstrated that sex steroid hormones act differently on 21-hydroxylase activity in rat hepatocytes and, thus, support the hypothesis that the extra-adrenal production of deoxycorticosterone from circulating progesterone is increased during pregnancy by the massive presence of estrogens.

Androgens↗
PubMed1995

A boy with atrophic thyroiditis of prepubertal onset, who was positive for TSH-binding inhibitor immunoglobulins.

A 12 year old boy was admitted to our hospital because of short stature. From the age of 7, his growth velocity decreased and he manifested intolerance to low temperatures, hoarseness, dry skin, and slowness of thought and physical movement. On admission, his height was 129.8 cm (-3 s.d.) and his body weight was 43.2 kg (-0.5 s.d.). His clinical features also included relaxation phase of tendon reflexes, periorbital puffiness and cold skin but no struma. His bone age was 9 years. His serum thyroxine (T4), triiodothyronine (T3), free T4 and free T3 were low, while his thyrotropin was high. He was positive for antithyroglobulin antibodies, antimicrosomal antibodies, and TSH-binding inhibitor immunoglobulins. He was diagnosed as having atrophic thyroiditis. We also determined the HLA haplotypes of his family members. His father's HLA haplotypes were A2, BW61(a) and A24, BW52(b), while his mother's haplotypes were A24, BW52(c) and A30, BW60(d). The HLA haplotypes of both the patient and his younger brother showed a and d, while the patient's elder brother's HLA haplotypes showed b and c. His family members all had normal thyroid function, but his father was positive for antimicrosomal antibodies. In summary, we describe a rare case where the onset of hypothyroidism was prepubertal, where the pathogenesis may have involved TSH-receptor blocking antibodies, and where the inheritance of the disease may have been from the paternal side of the family.

Age of Onset↗
PubMed1994

Effect of sodium taurodihydrofusidate on nasal drug delivery: differences in its concentration and penetrant molecular weight.

The effect of sodium taurodihydrofusidate (STDHF) on drug permeation across nasal mucosa was studied in vitro using Ussing type diffusion chamber. Disodium cromoglicate (DSCG, M.W. 512.3) and fluorescein isothiocyanate-dextran (FD) of different molecular weights (M.W. 4400-71200) were used as model drugs. Permeation profiles of DSCG and FDs showed a typical pseudo steady-state curve with short lag time. The permeability coefficient of FD (M.W. 9400) sigmodially increased with increasing STDHF concentration. It also enhanced the DSCG permeation. Interestingly the enhancement efficacy was independent of molecular weight of penetrants.

Adjuvants, Pharmaceutic↗
PubMed1994

Evaluation of enhancers to increase nasal absorption using Ussing chamber technique.

The effects of eight prospective absorption enhancers on the nasal mucosa in rabbit have been assessed using an in vitro Ussing chamber technique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence of these enhancers. Their enhancement ratio was found to be in the order of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leaching and enhancement ratio dependent on the magnitude of change of membrane resistance (delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. delta Rm thus appears to be a useful indicator by which one can estimate nasal mucosa damage by the enhancers.

Absorption↗
PubMed1993

The structural barrier of absorptive mucosae: site difference of the permeability of fluorescein isothiocyanate-labelled dextran in rabbits.

The permeability of fluorescein isothiocyanate-labelled dextran (FD, M.W. 4400-71,200) across nasal, buccal, duodenal, jejunal, ileal, colonic, and rectal mucosae excised from rabbits has been measured to estimate the structural barrier of absorptive mucosae using Ussing-type diffusion chambers. The permeability coefficient of FD in all these mucosae decreased with increasing molecular weight. The rank order of FD permeability did not always correlate with the electrical resistance of the mucosae. Among components of the small intestine (duodenum, jejunum, ileum) and the large intestine (colon, rectum), however, the rank order of FD permeability corresponded to the magnitude of the electrical resistance in each instance; the upper colonic mucosa showed the highest permeability, especially in FD of low molecular weight, and permeability of the rectal mucosa was lowest except for the duodenal mucosa. The nasal mucosa showed the lowest electrical resistance and the highest permeability of those studied, suggesting that it has a leaky structural barrier.

Animals↗
PubMed1993

A case of Goldenhar syndrome associated with growth hormone deficiency.

We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency.

Child↗
PubMed1993

Regulation of steroid 21-hydroxylation by 17 beta-estradiol in rat liver: in vivo and in vitro study.

In various extraadrenal organs, progesterone (P4) is converted to deoxycorticosterone (DOC) by steroid 21-hydroxylation. To investigate the regulation of extraadrenal 21-hydroxylase activity by 17 beta-estradiol (E2), the following two experiments were performed. Exp. 1). Three-week-old male SD rats were testectomized (TX) and injected with E2 (1 mg) or sesame-oil s.c. Sham rats were treated with sesame-oil. In these groups the serum concentration of DOC and corticosterone (B), microsomal 21-Hydroxylase activity and the expression of P450c21 mRNA of the liver and the adrenals were analyzed. Exp. 2). Isolated rat hepatocytes were cultured and stimulated by E2, 10(-9) approximately 10(-5) M. 21-Hydroxylase activity of these cells was analysed by the rate of production of DOC in the medium containing P4. The results of experiment 1 showed that both serum DOC concentration and 21-hydroxylase activity in the liver microsomal fraction were increased by E2 injection, but the expression of P450c21 mRNA was not detected in the liver even after E2 injection. In experiment 2, the activity of steroid 21-hydroxylase in isolated rat hepatocytes was stimulated by E2 in a dose dependent manner. These data provided evidence that: in rats the liver was one sites of the extraadrenal steroid 21-hydroxylase activity which had been stimulated by E2. The results also suggested that this hepatic enzyme was a different enzyme from the steroid 21-hydroxylase P450c21 expressed in the adrenal gland.

Adrenal Glands↗
PubMed1993

Selective accumulation and tumoricidal effect of cisplatin suspended in viscous ethyl oleate on hepatic cancers in animals after intraarterial infusion.

The selective accumulation and tumoricidal effects of cisplatin after intra-arterial infusion suspended in viscous ethyl oleate (VEO) on hepatic cancers of AH 272 tumor-bearing rats and VX-2 tumor-bearing rabbits were compared with those of cisplatin suspensions in ethyl oleate (EO) and Lipiodol Ultra Fluide (LP). The viscosities of VEO, EO and LP were 120, 4, and 21 centipoise (cp) respectively. Complete in vitro release of cisplatin from EO and LP occurred within 24 h, whereas only about 25% of cisplatin was released from VEO over the same period. When EO or VEO containing 3H-oleic acid were infused into the hepatic artery of rat liver inoculated with AH 272 tumor cells, radioactivity in the tumor site was higher than that in normal liver. In the case of cisplatin, concentration ratios after the infusion of EO and VEO were almost the same as those of oily carriers. Similar results were obtained in rabbit liver inoculated with VX-2 tumor cells. Cisplatin concentration in the tumor site seven days after intra-arterial infusion of VEO suspension was 5- and 1.7-fold higher, respectively, than that after EO and LP suspensions. The tumoricidal effect of cisplatin in VEO suspension on AH 272 tumor-bearing rats was higher than that after cisplatin solution and EO and LP suspensions, while VX-2 tumor growth was inhibited by the infusion of all cisplatin-containing oily carriers. VEO suspension thus appears very promising in intra-arterial infusion therapy.

Animals↗
PubMed1992

Oily drug carriers in cancer chemotherapy. II. Preparation of viscous ethyl oleate for intraarterial infusion therapy and its disposition in rats and hamsters.

Viscous ethyl oleate (VEO) was prepared as an oil drug carrier by the addition of aluminum stearate or ethyl cellulose. Since the rate of shear of VEO containing aluminum stearate was greatly and nonlinearly changed against the shearing stress compared to that containing ethyl cellulose, the latter was used for subsequent microvascular and organ distribution experiments in rats and hamsters. For infusion into the carotid artery in hamsters, neat ethyl oleate (EO, 4cP) or VEOs of various apparent viscosities (40, 80, 120 cP-VEOs) embolized the vascular system in the cheek pouch, although arrival time to the site where the embolization was observed and the embolization period differed depending on the type of oily drug carrier. For infusion into the hepatic artery in rats, however, only 120 cP-VEO embolized the vascular system in the liver. After infusion of the oily drug carrier containing 3H-oleic acid into the artery of hamster cheek pouch and rat liver, 30-50% of the radioactivity was gradually eliminated within 48 h, whereas about 80% of the dose was rapidly eliminated after infusion to rat stomach and kidney. In addition, the amount of 120 cP-VEO remaining in each organ 48 h after infusion was higher than those of EO and 40 and 80 cP-VEOs. Histological observation after infusion in rat liver revealed that 120 cP-VEO slowly migrated from the artery or arteriole to the sinusoidal capillary region. These results suggest that 120 cP-VEO can be used as a drug carrier because of its function of vascular embolization and high retention in a targeted tissue.

Animals↗
PubMed1991

In vitro release profile of mitomycin C from albumin microspheres: extrapolation from macrospheres to microspheres.

To analyze the in vitro release profiles of mitomycin C from albumin microspheres prepared by chemical denaturation in a multiparticulate system, a method to calculate the total cumulative amount of mitomycin C released from a batch of microspheres was developed. Mitomycin C-loaded albumin macrospheres (diameter in mm range) were prepared, and the in vitro release kinetics of mitomycin C from individual macrospheres were determined. Then the relationship between the kinetic parameters and the physical parameters (e.g., diameter, weight) was investigated under the assumption that macrospheres and microspheres behave identically. Further, the size distribution of microspheres was measured, and the total cumulative amount of mitomycin C released from albumin microspheres was calculated. The release profiles of mitomycin C from individual macrospheres fitted first-order release kinetics better than spherical matrix kinetics. The calculated initial mitomycin C contents and first-order release rate constants for individual macrospheres were correlated with the weight and reciprocal of surface area of the macrospheres, respectively. The observed in vitro release profile for the microspheres agreed with the calculated values. These results suggest that this method is valid for calculating drug release from albumin microspheres.

Albumins↗
PubMed1987

[A case of congenital unilateral multicystic kidney with renal matrix calculi].

A forty-two-year-old man was seen with right lumbar pain. Physical examination revealed a right flank mass. Conventional excretory urography showed lack of right renal function, whereas left kidney was visualized. Right nephrectomy was performed. A cluster of several different sized cysts was disclosed in the right renal region. The renal surface was smooth. The removed kidney weighed 1,150 g. The ureter was completely obstructed at the ureteropelvic junction. Cysts were filled with matrix calculi. Pathological examination showed dysplastic glomeruli and primitive tubules within loose embryonic mesenchyme between two cysts whose walls consisted of smooth muscle strands and connective tissue. The final diagnosis was a congenital unilateral multicystic kidney with renal matrix calculi. The multicystic kidney is the most common form of renal cystic disease in infancy. However, few cases in adults have been reported. The diagnostic approach, treatment and outcome of a congenital unilateral multicystic kidney are discussed.

Adult↗