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Biomedical subjects

T Kojima

Publications and source records attributed to T Kojima.

At least 523 records · Page 29Linked to original sources

Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol used in oral contraceptives.

OBJECTIVE: We determined the independent effects of various doses of ethinyl estradiol used in oral contraceptives or norethindrone acetate, as well as their combination, on insulin sensitivity in normal women. STUDY DESIGN: Thirty-three normal ovulatory female volunteers were recruited for this study. Insulin tolerance tests were performed after carbohydrate loading to determine the kinetic disappearance of glucose and insulin. After initial testing the women were randomized into four groups: ethinyl estradiol 20 micrograms, 35 micrograms, and 50 micrograms and norethindrone 1 mg. Insulin tolerance tests were repeated after 1 month of treatment and again after a second month, when all ethinyl estradiol groups received the addition of norethindrone 1 mg to their doses of ethinyl estradiol. Plasma glucose and insulin were measured, and insulin sensitivity (K(itt) glucose) and the disappearance of insulin (K(itt) insulin) were calculated. RESULTS: All groups were comparable at baseline, and no significant changes in fasting glucose and insulin were evident with treatment. After ingestion of 50 micrograms ethinyl estradiol the K(itt) glucose value decreased significantly (p < 0.03) and ingestion of 20 micrograms and 35 micrograms showed individual changes, but as groups the changes were not statistically significant. All ethinyl estradiol groups combined had a significant decrease in K(itt) glucose (p < 0.01). Norethindrone 1 mg alone did not change K(itt) glucose values, and after the addition of norethindrone to ethinyl estradiol, K(itt) glucose values normalized. K(itt) insulin values were also lower with treatment but were lower with ethinyl estradiol plus norethindrone compared with ethinyl estradiol alone (p < 0.04), suggesting an attenuation of insulin clearance with the progestin. CONCLUSION: Ethinyl estradiol alone decreases insulin sensitivity, and this may occur at lower doses, but norethindrone 1 mg does not appear to do so. However, progestins may alter insulin clearance.

Adult↗

Phosphoramidon-sensitive endothelin converting enzyme in cultured vascular smooth muscle cells converts big endothelin-3 to endothelin-3.

Incubation of big endothelin-3 (big ET-3, 1-41) with the membrane fraction obtained from cultured vascular smooth muscle cells (VSMCs) resulted in time-dependent increases in immunoreactive-ET (IR-ET), which were suppressed by phosphoramidon. Analysis of the incubation mixture by reverse-phase high performance liquid chromatography (RP-HPLC) confirmed that the IR-ET was due to the mature ET-3 (1-21). ET-1 (1-21) generated during incubation of big ET-1 (1-39) with the membrane fraction was markedly suppressed by the addition of big ET-3 into the incubation mixture. When the cultured VSMCs were incubated with big ET-3, a conversion to the mature ET-3 was observed. This ET-3 generation from exogenously applied big ET-3 was also suppressed by phosphoramidon. We conclude that the phosphoramidon-sensitive ET converting enzyme in VSMCs converts big ET-1 and big ET-3 to their mature form.

Animals↗

Inhibitory effect of the non-steroidal anti-inflammatory drugs, indomethacin and piroxicam on 2-acetylaminofluorene-induced hepatocarcinogenesis in male ACI/N rats.

The modifying effects of the non-steroidal anti-inflammatory drugs, indomethacin (IMC) and piroxicam (PC) on hepatocarcinogenesis induced by 2-acetylaminofluorene (AAF) were investigated in male ACI/N rats. Rats were divided into 6 groups: group 1 was fed a diet containing 200 ppm AAF for 16 weeks, starting at 6 weeks of age; group 2 was fed an AAF together with 130 ppm PC-containing diet; group 3 received an AAF diet and IMC (10 ppm) in their drinking water; group 4 was fed a PC diet alone; group 5 was given IMC alone; and group 6 served as controls. The PC diet, or the drinking water containing IMC, was given to the rats starting at 5 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 36), the incidences of iron-excluding altered liver cell foci (24.2 +/- 5.2/cm2) and liver cell tumors (1/10, 10%), and the tumor multiplicity (0.10/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 42.6 +/- 6.7/cm2; tumor incidence, 10/10, 100%; and multiplicity, 4.00/rat) (P < 0.05). Similarly, the incidence of iron-excluding hepatocellular foci (27.4 < 1.2/cm2) and liver cell tumors (1/10, 10%) and the tumor multiplicity (0.10/rat) in rats of group 3 were significantly lower than those of group 1 (P < 0.05). There were no liver cell lesions (foci and neoplasms) in rats of groups 4, 5 and 6. Thus, PC and IMC inhibited the hepatocarcinogenesis induced by AAF when administered concurrently with the carcinogen and the results may indicate possible involvement of altered arachidonic metabolism in the initiation phase of AAF-induced liver carcinogenesis.

2-Acetylaminofluorene↗

An anatomic study of the innervation of the wrist joint and Wilhelm's technique for denervation.

Innervation of the wrist joint has been clarified in this study by loupe dissection and histologic examination. The posterior interosseous nerve, the lateral antebrachial cutaneous nerve, the superficial branch of the radial nerve, and the dorsal branch and the perforating branches of the ulnar nerve innervate the wrist joint from the dorsal side. The anterior interosseous nerve, the palmar cutaneous branch of the median nerve, and the deep branch and the main trunk of the ulnar nerve innervate it from the palmar side. The findings indicate that surgical denervation of most of the articular nerves of the wrist joint is possible with the use of Wilhelm's procedure, but denervation of the palmar side of the intercarpal and carpometacarpal joints, which are innervated by the deep branch of the ulnar nerve, is not included in Wilhelm's technique.

Denervation↗

Urinary endothelin-1-like immunoreactivity excretion in the newborn period.

Urinary endothelin-1-like immunoreactivity (ET-1-LI) excretion was determined in 31 neonates, six sick infants with renal dysfunction secondary to neonatal asphyxia and 25 healthy infants, during the first week of life to clarify its evolutional change and the origin of the urinary ET-1-LI in the newborn period. Urinary ET-1-LI concentrations in the healthy infants maintained the same level during the first week of life (n = 35, 36 +/- 22 pg/mg creatinine, mean +/- SD). There was no difference in urinary ET-1-LI excretion in infants between 30 and 41 weeks of gestation. Urinary ET-1-LI concentrations in the sick infants were significantly elevated through the first week of life when compared with those of healthy infants. Fractional excretion of sodium and endothelin clearance were more elevated in the sick infants than in the healthy infants. A good correlation was observed between urinary ET-1-LI concentrations and urinary N-acetyl-beta-D-glucosaminidase index (r = 0.72, p < 0.01). These results suggest that the origin of urinary endothelin-1 may be the renal tissue and that ET-1 may be a nonspecific marker of renal injury in neonates.

Acetylglucosaminidase↗

Production and secretion of progesterone in vitro and presence of platelet activating factor (PAF) in early pregnancy of the marsupial, Macropus eugenii.

The corpus luteum (CL) of the tammar is suppressed by lactation. Removal of the sucking pouch young induces reactivation of the CL which produces a peak in plasma progesterone concentration on Day 5, 6 or 7; reactivation of the embryo after diapause precedes by one day this transient peak of progesterone. This study examines progesterone production and secretion in vitro by the CL and the production of platelet activating factor (PAF) by the endometrium during this stage of pregnancy (Days 0 and 3-8). Blood samples were collected twice daily to determine for each animal (n = 28) at autopsy the relationship of PAF production to the day of the progesterone peak. Significant changes in basal plasma progesterone concentrations were used to define four groups according to the time the animals were killed: Group A, Day 0; Group B, other animals showing no significant change; Group C, peripheral progesterone concentration increasing; Group D, peripheral progesterone concentration decreasing after the peak. At autopsy on successive days, blood samples were taken from the heart, caudal vein and uterine branch of the ovarian vein, and CL and endometria were prepared for explant culture. Progesterone contents of pre- and post-incubation luteal tissues and of medium were determined at 4, 12 and 24 h to estimate production and secretion rates. The values for all progesterone parameters from animals in Group C were significantly higher than in the other groups. It is concluded that the progesterone peak results from a change in rate of production and secretion of progesterone by the CL, one day before the peak in peripheral plasma, and that this change could provide the first signal to the uterus. Endometrium was incubated for 24 h and the medium assayed for PAF. High concentrations of PAF were detected in half the animals in Groups B and C, that is, before or at the time progesterone was increasing. This is the first measurement of PAF in any marsupial and the first demonstration of the release of PAF by the endometrium. The detection of PAF provides a candidate for an endometrial signal that is responsive to the rising progesterone concentration in the utero-ovarian vein draining the CL-bearing ovary and that may stimulate reactivation of the blastocyst.

Animals↗

Acute and subacute toxicity tests of onion coat, natural colorant extracted from onion (Allium cepa L.), in (C57BL/6 x C3H)F1 mice.

The toxicity test of onion coat colorant (OC), a food colorant extracted from onion (Allium cepa L.), was undertaken using (C57BL/6 x C3H)F1 mice of both sexes for the safety assessment of this product. The acute toxicity test was performed by administration of OC suspended in corn oil by gavage at doses of 2500, 5000, 7500, and 10,000 mg/kg body weight to groups of 5 or 6 males and 6 or 7 females, maintained for 14 d. Six of 12 females dosed at 10,000 mg/kg body weight and 3 of 11 females dosed at 7500 mg/kg body weight were dead before the end of the study, indicating that the tolerated dose of OC was between 7500 and 5000 mg/kg body weight. The subacute toxicity test of OC was examined using 123 mice of both sexes (62 males and 61 females) by feeding a diet mixed with OC at concentrations of 5, 2.5, 1.25, 0.6, and 0.3% for 90 d. All mice tolerated these doses of OC well. The body weight gains of male and female mice were not affected by the treatment. Histopathological examinations showed that hyperplastic changes in the esophagus, forestomach, pancreas, cervix, and endometrium of mice were found in treated and control mice. However, their incidences were not related to the dose of OC. Moreover, only a spontaneous ovarian teratoma was found in an OC-treated mouse. These results suggest that OC has no acute and subacute toxic effects in mice.

Administration, Oral↗

Inhibition of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by the naturally occurring plant phenolics caffeic, ellagic, chlorogenic and ferulic acids.

The modifying effects of dietary administration of the plant phenolic antioxidants caffeic acid (CA), ellagic acid (EA), chlorogenic acid (CGA) and ferulic acid (FA) during the initiation phase on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and on the number and area of silver-stained nucleolar organizer region proteins (AgNORs), a new cell proliferation marker, of the tongue squamous epithelium were investigated in male F344 rats. Rats were fed the diet containing 500 p.p.m. CA, 400 p.p.m. EA, 250 p.p.m. CGA or 500 p.p.m. FA for 7 weeks. One week after the commencement of the diets, 4-NQO (20 p.p.m.) was administered in the drinking water for 5 weeks. Feeding of four phenolic compounds significantly reduced the incidences of tongue neoplasms (squamous cell papilloma and carcinoma) and preneoplastic lesions (hyperplasia and dysplasia) by 32 weeks, and rats fed CA or EA had no tongue neoplasms. The number and area of AgNORs per nucleus were decreased significantly by dietary treatment with these four phenolics. Thus, CA, EA, CGA and FA inhibited the tongue carcinogenesis induced by 4-NQO when they were administered concurrently with the carcinogen. These results might suggest possible application of these natural substances for cancer chemoprevention in tongue in addition to other tissues (skin, lung, liver and esophagus).

4-Nitroquinoline-1-oxide↗

Pulsatility index of uterine artery in pregnant and non-pregnant women.

In 60 infertile women, 73 uterine arterial pulsatility indices (PI) were measured by transvaginal colour Doppler sonography. The aims were to assess uterine perfusion response in infertile women during spontaneous ovarian cycles, and to analyse the change of uterine perfusion in pregnant cases. The mean PI values (+/- SD) of 67 non-pregnant cycles were 2.30 (+/- 0.78) in the follicular phase, 2.51 (+/- 1.05) in the ovulatory phase and 2.50 (+/- 0.97) in the mid-luteal phase. The mean PI values (+/- SD) of six pregnant cycles were 1.67 (+/- 0.22), 1.89 (+/- 0.41) and 2.23 (+/- 0.69) in the corresponding phases respectively. The difference between the PI values in the follicular phase for the pregnant and non-pregnant groups was significant (P < 0.05), as well as that between the follicular and mid-luteal phase for the pregnant group (P < 0.05). There was no significant difference between the PI values in the ovulatory or mid-luteal phase of the two groups.

Arteries↗

Site dependence of methamphetamine concentrations in blood samples collected from cadavers of people who had been methamphetamine abusers.

Various blood samples were collected from heart cavities and blood vessels in eight autopsy cases of people who had been methamphetamine abusers. Methamphetamine and its metabolite, amphetamine, were determined by gas chromatography-mass spectrometry-selected ion monitoring. In four cases where left and right heart blood samples were collected, methamphetamine concentrations in the left heart blood samples were 1.9-2.6 times higher than those in the right heart blood samples. In three cases where pulmonary vein blood samples were collected, methamphetamine concentrations in the pulmonary vein blood samples were higher than those in other blood samples sites. To interpret the blood methamphetamine concentrations, site dependence should be taken into consideration.

Adult↗

A combination surgical method for preaxial polydactyly of the foot.

A combination procedure was performed on the medial two toes in a 6-month-old child with preaxial polydactyly of the left foot. The first toe had the appearance of a cosmetically intact great toe, but the second toe had better function. A method to combine the advantages of these two toes was therefore applied, with favorable results seen at 1.5 years after surgery.

Follow-Up Studies↗

Eisenin (L-pyroGlu-L-Gln-L-Ala), a new biological response modifier.

Eisenin (L-pyroGlu-L-Gln-L-Ala), a tripeptide extracted from a brown marine alga (Eisenia bicyclis Setchell) showed the immunological activity to augment natural cytotoxicity of peripheral blood lymphocytes (PBLs) in humans. This activity could be seen when it was added directly to 51Cr release assay, and also when PBLs alone were incubated with this compound for 0.5-1 h before addition to the 51Cr release assay. The resulting augmented cytotoxicity can be attributed to natural killer cells because treatment of eisenin-stimulated PBLs with anti-Leu 11b monoclonal antibody (mAb) plus complement completely abolished the augmented cytotoxicity, and, moreover, deletion of Leu 19-positive cells with anti-Leu 19 mAb (mouse IgG1) and anti-mouse IgG-coated magnetic beads showed the same effect. Eisenin could not augment natural cytotoxicity of Sephadex G-10 column-eluted cells. Eisenin rendered K-562 target cells resistant to lysis by PBLs stimulated by eisenin. Both amino acids, L-pyroglutamic acid and L-alanine, as well as a mixture of the three component amino acids of eisenin could augment the natural cytotoxicity. Therefore, it is considered that the structure responsible for the augmentation of natural cytotoxicity by eisenin may be that of the amino acids.

Alanine↗

Clam nail deformity of the little finger.

A case of a 2-month-old infant who had an extremely rare congenital nail deformity of the right little finger was reported. The nail looked like a clam, wrapping three-quarters of the distal phalanx. A neurovascular pedicle island flap was transposed to reconstruct the pulp and lateral nail fold with good results. Early surgery is justifiable to avoid growth disturbance of the fingertip.

Fingers↗

Transplantation of long-term cryopreserved allocutaneous tissue by skin graft or microsurgical anastomosis: experimental studies in the rat.

A step-wise method of freezing cutaneous soft tissue containing vessels to -196 degrees C for permanent preservation was developed. The methods of embryo cryopreservation were modified for soft-tissue preservation. Cutaneous tissue obtained from the abdominal wall of a Lewis rat was preserved for more than 3 weeks by this method and was then transplanted to a Brown Norway rat with the largest difference in major histocompatibility complex. Rejection reaction against the epidermal layer was markedly delayed, followed by a decrease in antigenicity of the dermis, with survival of the majority of the tissue for more than 6 months. A concept of artificial skin was formed based on these experimental results. A skin flap from the abdominal wall with a vascular pedicle consisting of the femoral artery and vein was similarly preserved and transplanted by vascular anastomosis. This transplant was made viable over a long period through the additional use of an immunosuppressant. Replantation of a rat hindleg also was successfully accomplished by using a skin flap from the abdominal wall with a vascular pedicle consisting of the femoral artery and vein, which had been cryopreserved for more than 3 weeks. These results with 65 pieces in five different treatment groups indicate the reliability of this method of preservation in maintaining the tissue in a state adequate for transfer without loss of viability over a long period. The applicability of this method of allograft preservation to the field of free-tissue transfer combined with microsurgical technique may introduce a new concept to the field of reconstructive surgery in the future. According to the results of the present experiment, the great potential for clinical application is described for the deepithelialized cryopreserved allocutaneous flap transfer.

Abdominal Muscles↗

Complete congenital duplication with incomplete separation of a lower extremity.

A case of a boy with complete duplication of the lower extremity and separation below the lower leg was described. Although x-ray examination revealed no femur, operation revealed a cartilage expected to become the femur in the future. A classification of duplication and separation of the lower extremity is proposed. The method and course of treatment in the present case were described in detail, including the application of tissue expanders on the deformity of the knee joint accompanied by a shortening of the sciatic nerve.

Congenital Abnormalities↗

Cyclosporin A rapidly inhibits epidermal cytokine expression in psoriasis lesions, but not in cytokine-stimulated cultured keratinocytes.

To better understand the cellular target(s) of cyclosporin action in psoriasis, we have studied the effects of systemic short-term (7 d), low-dose (3-7.5 mg/kg) cyclosporin A administration on the expression of the cytokines interleukin (IL)-8 and IL-1 beta in psoriatic lesions. RNA blot hybridization analysis of pretreatment keratome biopsies revealed that expression of both cytokine mRNAs was highly variable from patient to patient. Significant covariation of both cytokine mRNA levels was noted (r = 0.86, p < 0.0001). However, there was no significant correlation between expression of either cytokine and clinical severity, as measured by the pretreatment Psoriasis Area and Severity Index (PASI). IL-1 beta protein levels measured by enzyme-linked immunosorbent assay (ELISA) were highly correlated with IL-1 beta mRNA levels, indicating that the differences in transcript levels accurately reflect differences in epidermal cytokine protein. Significant reductions in both cytokine transcripts and in IL-1 beta immunoreactive protein were noted in the high expression subgroup after 1 week of cyclosporin A therapy, prior to detectable clinical improvement. In contrast to its pronounced effects on epidermal cytokine expression in vivo and the allogeneic mixed lymphocyte reaction in vitro, cyclosporine A did not inhibit the induction of intercellular adhesion molecule (ICAM)-1 or IL-8 mRNAs by cultured keratinocytes in response to IL-1 beta or the combination of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. These data suggest that epidermal keratinocytes respond to signals produced by activated T cells by coordinate expression of multiple cytokines, and that cyclosporin A acts primarily through blockade of T cells, rather than through keratinocyte activation.

Blotting, Northern↗