Biomedical subjects

H Nogami

Publications and source records attributed to H Nogami.

At least 37 records · Page 2Linked to original sources

PubMed1998

The influence of relative body weight on toxicity of combination chemotherapy with cisplatin and etoposide.

PURPOSE: This study was conducted to determine whether there was any relationship between the adverse toxicity of combination chemotherapy and clinical values including age, sex, creatinine clearance (Ccr), body surface area and relative body weight. METHODS: Cisplatin at a dose of 80 mg/m2 on day 1 and etoposide at a dose of 100 mg/m2 on days 1, 2 and 3 were given to 42 consecutive patients with solid tumors. All patients had normal major organ function and received uniform hydration therapy. RESULTS: Body Mass Index as a measure of relative body weight was inversely correlated with the percentage decrease in white blood cells (P = 0.0681) and platelet count (P = 0.0115). Body surface area was also inversely correlated with leukopenia (P = 0.0171) and thrombocytopenia (P = 0.0058). In contrast, age, sex and Ccr had no significant relationship with adverse toxicity. CONCLUSIONS: It is concluded that dose adjustment of combination chemotherapy with cisplatin and etoposide according to age or ideal body weight is not appropriate and that a conventional dose modification method based solely on body surface area is probably not sufficient to reduce interpatient variability of cancer chemotherapy. A pharmacokinetic and pharmacodynamic study of combination chemotherapy is warranted to establish the ideal dose modification method.

Adolescent↗

PubMed1998

Bradycardia induced by irinotecan: a case report.

Irinotecan chloride (CPT-11) is a new semi-synthetic camptothecin analogue which has encouraging antitumor activity against various malignancies. The major and unique toxicity of CPT-11 is diarrhea. Cardiovascular toxicity is rare and has not been found in clinical trials performed in Japan except for a very few cases of insignificant tachycardiac arrhythmia. We report a case of a 69-year-old man with recurrent colon cancer who suffered from bradycardia induced by infusion of CPT-11. Other toxicities including hematological toxicity and diarrhea were mild. Pharmacokinetic analysis using a limited sampling model revealed that the occurrence of bradycardia did not correlate with the excess of drug exposure. Although all of the cholinergic actions reported in the literature were mild, cardiotoxicity may come to be a clinically significant problem. If the events were examined more thoroughly, the cholinergic effect may be discovered more frequently. To administer CPT-11 safely needs meticulous monitoring not only for hematological toxicity and diarrhea but also for other cholinergic actions including bradycardia.

Aged↗

PubMed1998

Differential effect of nephrectomy on renal expressions of IGF-I and IGFBPs mRNA in selective growth hormone-deficient rats.

It is known that growth hormone (GH) contributes to glomerulosclerosis and that this probably occurs via insulin-like growth factor-I (IGF-I). However, the manner by which GH and nephrectomy (Nx) alter IGF-binding protein (IGFBP) mRNA in the kidney has not been fully explained. The effects of GH on renal IGF-I and IGFBP-1, 2, 3, 4, and 5 following Nx were examined in spontaneous dwarf rats (SDRs) which have a complete and specific lack of GH among pituitary hormones. In normal Sprague-Dawley rats (SDs), Nx resulted in significant decreases in levels of IGFBP-1 mRNA and IGFBP-5 mRNA to 62.7 +/- 4.9 and 56.5 +/- 5.0% those of sham-operated kidneys, respectively. Nx did not alter the IGF-I mRNA level in SDs. The levels of IGFBP-2, IGFBP-3, and IGFBP-4 mRNAs were likewise unchanged following nephrectomy. In SDRs, Nx significantly decreased the levels of IGFBP-1, IGFBP-4, and IGFBP-5 mRNA, to 57 +/- 2.6, 46 +/- 12, and 64 +/- 8.1% of sham-operated animals. However, Nx did not alter the levels of IGF-I, IGFBP-2, and IGFBP-3 mRNA. GH injections of nephrectomized SDRs fully normalized the decreased IGFBP-4 mRNA levels, whereas levels of IGFBP-1 and IGFBP-5 mRNA were not reversed. The altered expression of IGFBP-4 mRNA following Nx of SDRs compared to that of SDs appears highly significant since it is known that, unlike SDs, glomerulosclerosis does not fully develop in SDRs following renal ablation. The change in the IGFBP-4 mRNA level might be related to the development of glomerulosclerosis in SDs.

Animals↗

PubMed1998

Effect of nitric oxide synthase inhibitor on allergen- and hyperventilation-induced bronchoconstriction in guinea-pigs.

To elucidate the role of endogenous nitric oxide (NO) in allergen- (AIB) and hyperventilation-induced bronchoconstriction (HIB), the effects of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on AIB and HIB were studied in guinea-pigs. In the AIB group, 21 anaesthetized guinea-pigs, actively sensitized with 1% ovalbumin, were challenged with aerosolized 0.1% ovalbumin solution under mechanical ventilation. In the HIB group, 14 guinea-pigs were challenged with hyperventilation (tidal volume of 12 mL x kg(-1) at 150 breaths x min(-1) with 21% O2 and 5% CO2 dry gas) for 5 min. In both groups, lung resistance (RL) was measured using a pressure-volume-sensitive body plethysmograph, with or without L-NAME pretreatment (8 mg x kg(-1) i.v. followed by 2 mg x kg(-1) x min(-1) i.v.). The NO precursor, L-arginine was injected at a rate of 15 mg x kg(-1) x min(-1) after L-NAME injection (10 mg x kg(-1)) in the AIB group. The results were as follows. In the AIB group, the maximal RL change was significantly potentiated by pretreatment with L-NAME. This potentiating effect of L-NAME was reversed by L-arginine. In the HIB group, the pretreatment with L-NAME had no effect on increases in RL. These findings suggest that endogenous nitric oxide may play an important role in the modulation of allergen-, but not hyperventilation-induced bronchoconstriction in guinea-pigs.

Airway Resistance↗

PubMed1998

[A case of neurologic type of Wilson's disease with increased aluminum in liver: comparative study with histological findings to metal contents in the liver].

Histological findings and metal contents in the liver were studied in a patient with neurologic type of Wilson's disease. Copper and aluminum contents in the biopsied liver of the patient with Wilson's disease were measured simultaneously by neutron activation analysis at Research Reactor Institute, Kyoto University. Four cases of adult cirrhosis were selected as the control for cirrhosis and five cases of adult liver as the control for neurologically normal. The biopsied liver showed markedly increase in the copper content (814.4 micrograms/g: dry weight) and extremely high content of aluminum (479.4 micrograms/g: dry weight), compared to those of the controls. On the other hand, macroscopically no cirrhosis was observed and the characteristic appearances of macronodular cirrhosis failed to detect histologically. Interestingly the fibrosis or inflammation of the liver was seen faintly. It is likely that toxic metals in the liver such as aluminum, copper and manganese might be implicated in the pathogenesis of neurologic type of Wilson's disease.

Adult↗

PubMed1997

Congenital anterolateral bowing of the tibia with ipsilateral polydactyly of the great toe.

We report on two cases of congenital unilateral anterolateral bowing and focal defect of the tibia associated with ipsilateral polydactyly of the great toe. Computed tomographic examination showed an unusual partial cleft of the tibia at the site of bowing. A long follow-up of one patient showed spontaneous resolution of the bowing without progression to pseudoarthrosis. These anomalies should be considered as a new entity related to the tibial developmental field.

Adolescent↗

PubMed1997

Sp1 protein contributes to airway-specific rat MUC 2 mucin gene transcription.

We have shown increases in the abundance of airway mucin mRNA during the pathogenesis of chronic obstructive pulmonary disease in rat models (Jany et al., 1991) and now seek to determine the underlying mechanisms. As transcriptional modulation may be involved, we provide here a functional analysis of the 5' flanking region of a rat mucin gene (MUC 2). Using deletion mutants to bp -859, we constructed expression cassettes in CAT vectors and transfected them into two MUC 2-expressing cell lines, SPOC 1, a rat airway epithelial cell line and IEC-6, a rat intestinal epithelial cell line, and into one MUC 2 non-expressing cell line, FR, a rat skin fibroblast cell line. Results indicated that nucleotides -59 to -40 mediated high level expression in SPOC 1, but not in the other cells. Used as a probe in gel shift assays, fragment -59/-40 formed complexes of differing mobilities when incubated with nuclear protein extracts from the three cell types. Mutation of the putative Sp1 binding site in the probe sequence interfered with protein binding in all three cell types, but anti-Sp1 antibody supershifted a band formed only by airway cell extracts. A model of airway cell-specific MUC 2 transcription is proposed.

Animals↗

PubMed1997

Involvement of glucocorticoid-induced factor(s) in the stimulation of growth hormone expression in the fetal rat pituitary gland in vitro.

The mechanism by which glucocorticoids induce GH expression between embryonic days 18 and 19 (E18-19) in the fetal rat pituitary gland was examined with an in vitro organ culture system. Twenty-four hour incubation of E18 pituitary glands in serum-free medium containing either dexamethasone (DEX, 5-50 nM) or corticosterone (0.55 microM) resulted in a conspicuous accumulation of GH messenger RNA (mRNA), whereas no spontaneous expression of GH mRNA was noted without glucocorticoid. Triiodothyronine (1 nM) alone weakly induced GH mRNA but increased the effect of DEX 2-fold. The GH mRNA accumulation was not observed after 5 or 10 h incubation with DEX. However, a 10-h incubation with DEX followed by 14 h chase incubation without DEX resulted in apparent induction of GH mRNA. The induction of GH mRNA by DEX was completely inhibited by puromycin. These data, taken as a whole, suggest that the induction of GH mRNA by DEX in the fetal pituitary gland is not a direct effect of DEX on the GH gene but is mediated by a factor that is synthesized in the pituitary gland in response to DEX. Both immunoblot and RNase protection assays suggested that this factor is not pit-1, which is known to be required for GH mRNA expression.

Animals↗

PubMed1996

Immunoreactive luteinizing hormone (ir-LH) cells in the lung and stomach of chick embryos.

Luteinizing hormone (LH) immunoreactivity was detected in the lung and stomach of chick embryos by the immunoperoxidase staining technique using specific antiserum to chicken LH. Immunoreactive LH (ir-LH) cells first appeared in the primordial cells of the epithelial layer of lung bud and foregut as well as of Rathke s pouch in the 3-day-old embryo, Hamburger and Hamilton stage 21. Ir-LH cells increased in number with advancing age of embryos in the lung, stomach, and pituitary gland. In the lung of 7-day-old embryos, stage 31, the ir-LH cells were distributed in the epithelium of primary, secondary, and tertiary bronchi, and their shapes were pseudostratified columnar, simple columnar, and simple cuboidal, depending on their sites in the intrapulmonary airway. Ir-LH cells were more numerous in the median part than in the lateral part of the lung, and the population in the epithelial layer of entobronchi of the secondary bronchi was 4 times higher than that in ectobronchi and laterobronchi of the secondary bronchi and in the primary bronchi. The immunoreactive products were found, either in the entire cell or in the apical part, facing the lumina of bronchi. In the stomach, ir-LH cells were found in the epithelial layer of gastric glands. No ir-LH cells were observed in interstitial regions, which consisted of mesenchymal cells and blood vessels, in the lung and stomach tissues. With advancing age, ir-LH cells changed their shapes to flat or squamous, coincident with the formation of parabronchi. Other pituitary hormones were not observed immunohistochemically in either the lung or stomach before hatching. Preabsorption of the antiserum against avian LH with the purified chicken LH or the extract of pituitaries from 10-day-old embryos completely destroyed the immunoreactivity to the cells in the lung and the pituitary. A single band of the immunoreaction products, whose molecular weight was around 25 K daltons, was shown by the immunostaining of nitrocellulose membrane transblotted after sodium dodecylsulphate-polyacrylamide gel electrophoresis of the purified pituitary LH, extracts of pituitaries from 10-day-old embryos, and the extracts of lungs from 7-, 10-, and 14-day-old chick embryos. These results demonstrated that ir-LH cells are present in extrapituitary tissues, and may play an important role during the development of chick embryonic lung and stomach.

Animals↗

PubMed1996

Immunoelectron microscopy of corticotropes and melanotropes in the pituitary gland of the European ferret, Mustela putorius furo.

The superimposition technique and protein A-gold method of immunoelectron microscopy were employed to study the ultrastructure of corticotropes as well as melanotropes in the ferret pituitary gland. This is the first study ever elucidating the ultrastructural heterogeneity of melanotropes in mammalian pars intermedia on an immunocytochemical basis. Morphological heterogeneity of pars distalis corticotropes has also been elucidated. It is suggested that the different subtypes may represent stages of development (histogenesis), or functional phases of a single cell type. In addition, the occurrence and distribution of both corticotropes and melanotropes in different hypophyseal components have been studied by light-microscopic immunocytochemistry.

Adrenocorticotropic Hormone↗

PubMed1996

Role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin in guinea-pigs.

To elucidate the role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin (Bk), we studied the effects of FK224, a neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonist, on the bronchoconstriction induced by intravenous (i.v.) administration of Bk (5-100 micrograms.kg-1) in guinea-pigs. Total pulmonary resistance -(RL) was measured using a pressure-volume sensitive body plethysmograph in anaesthetized artificially ventilated guinea-pigs pretreated with atropine (1 mg.kg-1) and propranolol (1 mg.kg-1). In the control group, i.v. administration of Bk produced a dose-dependent increase in RL. In animals pretreated with FK224, bronchoconstriction induced by higher doses of Bk (10, 50 and 100 micrograms.kg-1) was significantly reduced, whilst the bronchoconstriction caused by lower doses of Bk (5 and 7.5 micrograms.kg-1) was not. Pretreatment with a combination of FK224 and indomethacin markedly inhibited the bronchoconstriction induced by each dose of Bk compared with the groups pretreated with FK224 alone. Although pretreatment with indomethacin alone significantly reduced RL at a high dose of Bk (50 micrograms.kg-1), the reduction was significantly lower than that produced by a combination of FK224 and indomethacin. These results suggest that intravenous administration of a high dose of bradykinin causes bronchoconstriction both by cyclo-oxygenase products and by release of tachykinins.

Animals↗

PubMed1996

BAY u3405, a thromboxane A2 antagonist, reduces bronchial hyperresponsiveness in asthmatics.

OBJECTIVE: Thromboxane A2 (TXA2) is reported to induce bronchial hyperresponsiveness along with the well-documented bronchoconstrictor action on smooth muscles. We examined the effect of the TXA2 antagonist, BAY u3405, on bronchial hyperresponsiveness to methacholine (MCh) in asthmatics. PATIENTS: Twelve adult asthmatics were studied in a randomized, double-blind, placebo-controlled, crossover fashion. DESIGN: Following a 2-week run-in period, the subjects were administered 75 mg of BAY u3405 or placebo orally, twice a day for 2 weeks each in a crossover design, interposing a 2-week washout period. Bronchial hyperresponsiveness was measured by the astograph method. Briefly, the respiratory resistance (Rrs) was measured by the forced oscillation method during continuous inhalation of MCh in stepwise incremental concentrations, until Rrs reached twice the baseline value. Bronchial hyperresponsiveness was evaluated as the minimum cumulative dose (Dmin) of MCh that induced an increase in Rrs. Dmin was calculated so that 1 U of Dmin equals to 1 min of inhalation of aerosol solution at 1.0 mg/mL during quiet breathing. RESULTS: Three subjects were withdrawn from the evaluation because they had asthmatic attacks or wheezing during the study. The Dmin value of 0.533 U (GSEM 1.675) after the BAY u3405 treatment was significantly greater than that of 0.135 U (GSEM 1.969) after the placebo treatment (p = 0.0139). There were no safety concerns in either treatment group. CONCLUSION: We conclude that BAY u3405 may be a useful drug for attenuating bronchial hyperresponsiveness in bronchial asthma.

Adult↗

PubMed1996

[Mucin gene--regulation of the expression of MUC2 and MUC3 mucin gene in the airway].

Mucus hypersecretion is a characteristic feature of several human airway diseases, including chronic bronchitis, cystic fibrosis and asthma. Analysis of rat disease models has suggested that mucin synthesis is up-regulated as part of the disease process. To understand the primary structure of secretory mucins, several cDNAs encoding airway mucin have been isolated. In most cases, full-length sequences have not been obtained. In this review, we focused on the MUC2 and MUC3 mucin gene. MUC2 mucin has been reported to be expressed in the human lung with airway disease and in the rat lung with infection and exposure to irritant such as SO2. MUC3 is also expressed in the bronchus. Less is known about the structure and the expression pattern of the MUC3 mucin gene. Recent findings show that the expression pattern of the MUC2 and MUC3 mucin genes differ strikingly, suggesting that they play distinct functional roles in the airway and intestine. Functional analysis of mucin gene promoter will provide better understanding of the regulation of its expression in the airway under both normal and pathological conditions.

Amino Acid Sequence↗

PubMed1995

Tubular hypertrophy due to work load induced by furosemide is associated with increases of IGF-1 and IGFBP-1.

We have examined the expression of insulin-like growth factor 1 (IGF-1), IGF binding protein-1 (IGFBP-1), and IGF binding protein-3 (IGFBP-3) in the rat distal nephron during increased cell work load and hypertrophy, induced by the diuretic, furosemide. Furosemide was given for six days to increase distal sodium delivery and uptake. To mitigate salt loss, the animals drank 0.8% NaCl and 0.1% KCl. Control rats were infused with vehicle (0.9% saline) and drank tap water. Furosemide increased urinary volume (13-fold) and sodium excretion (eightfold), and decreased urine osmolarity (fourfold). By immunocytochemistry, staining for IGF-1 and IGFBP-1 was markedly increased in distal convoluted tubules and cortical collecting ducts; both segments also underwent hypertrophy. Increased staining for the peptides was evident early (1 hr, 18 hr) after furosemide, prior to hypertrophy of cells. Whereas transcripts of IGF-1 and IGFBP-3 mRNA showed little or no increase in extracts from furosemide-treated kidney cortices, IGFBP-1 mRNA was increased threefold 18 hours after furosemide. Alterations of IGF-1 and IGFBP-1 were independent of changes in plasma aldosterone, glucocorticoids or arginine vasopressin. That IGFBP-1 mRNA increased threefold without significant changes in IGF-1 mRNA suggests that hypertrophic stimuli might initially induce the synthesis of IGF binding protein followed by the trapping of extracellular IGF-1. The present study raises the possibility of IGF-1 and IGFBP-1 being involved in processes that lead to tubular hypertrophy. IGFBP-1 may regulate these effects by binding to and interaction with IGF-1.

Animals↗

PubMed1995

Growth hormone and nutrition interact to regulate expressions of kidney IGF-I and IGFBP mRNAs.

The effects of growth hormone (GH) and fasting on renal insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBP)-1, -2, -3, -4, -5 were examined in spontaneous dwarf rats (SDR) which have a complete and specific lack of GH among pituitary hormones. Renal expression of the mRNA which encodes IGF-I was reduced in these rats, and IGFBP-1 and IGFBP-4 were found to be elevated. Administration of GH restored expression of IGF-I and IGFBP-1 mRNA, suggesting that GH is, among other pituitary hormones, more specifically associated with renal expression of these genes. The elevation in the IGFBP-4 mRNA level, however, was not attenuated by GH administration, indicating that this hormone may not be directly related to the regulation of expression of this gene. Fasting for 48 hours resulted in a reduction of IGF-I mRNA and an increase in IGFBP-1 mRNA in SDRs as well as in normal rats, suggesting that a cause other than a reduced serum GH is responsible for these fasting-induced changes. Fasting resulted in little change in levels of other IGFBP-2, -3, -4, -5 mRNAs. When these results were compared with those obtained using liver, IGFBP mRNA expression was shown to be regulated differently in different tissues. Based on our finding that IGFBP-1 modulates the mitogenic action of IGF-I, a full understanding of nutrition-related growth processes in the kidney must take this relationship into consideration as well as that which exists between GH and IGF-I.

Animal Nutritional Physiological Phenomena↗

PubMed1995

Regulation of growth hormone expression in fetal rat pituitary gland by thyroid or glucocorticoid hormone.

The regulation of growth hormone (GH) cell development by thyroid and glucocorticoid hormones in the fetal rat pituitary gland was examined. Dexamethasone (Dex) treatment of dams induced GH and GH mRNA accumulation in the fetal pituitary gland on day 17 or 18 of gestation when substantial GH expression has not yet occurred in the control fetus. The additional thyroxine injections apparently enhanced the effect of Dex, whereas it exhibited no effect when given alone. The reduction of fetal thyroid hormone level by methimazole suppressed either the Dex induction of GH expression on day 18 or the spontaneous onset of GH expression on day 19 of gestation. The results suggest that 1) thyroid hormone exerts its stimulatory action on fetal GH gene expression only in the presence of glucocorticoid, 2) this synergistic action of these two hormones is evident as early as day 17 of gestation, and 3) rapid maturation of GH cells seen on day 19 in the normal fetus is considered to be induced by concomitant increase in both serum thyroid and glucocorticoid hormone levels.

Animals↗

PubMed1995

Intrauterine growth retardation due to growth hormone deficiency in rats.

The effect of growth hormone (GH) on fetal growth was examined in the spontaneous dwarf rat (SDR) with the isolated GH deficiency. A 328-bp GH gene fragment containing the site of SDR mutation was amplified from fetal liver genomic DNA using PCR and digested with restriction enzyme SauI to distinguish the fetal genotype. When heterozygote (dr/+) males and females were crossed, a significant reduction in body weight of dr/dr fetuses was observed on days 20 and 21 (92 and 89% that of +/+ fetuses, respectively). Body weight reduction was also noticed on day 21 in dr/dr fetuses (80%) in comparison with that of dr/+ fetuses crossed from dr/dr females and dr/+ males. Unexpectedly, the body weight of dr/+ fetuses was found to be significantly less than that of +/+ fetuses on days 19 (94%) and 20 (97%), which reached the level of +/+ fetuses by day 21 of gestation. The fetal tail length was not affected by the GH status. These results provide direct evidence for the involvement of pituitary GH in the regulation of fetal body weight during late gestation, but not in fetal skeletal growth.

Animals↗

PubMed1995

The fine structure of dexamethasone-induced growth hormone cells in the anterior pituitary gland of the rat fetus.

The effect of synthetic glucocorticoid, dexamethasone (DEX), on the fine structure of the fetal growth hormone (GH) cell was examined in rats on Days 17-19 of gestation by the protein A-gold method of immuno-electron microscopy. GH cells appeared on Day 19 in the control fetuses. The DEX-induced GH cells of Day 17 fetuses displayed more immature features than those of Day 18, which closely resembled GH cells found in the control fetus on Day 19. Cytological changes which indicate increased secretory activity such as the development of the rough endoplasmic reticulum or enlargement of the Golgi complex, and an accumulation of secretory granules were evident only in the DEX-treated fetuses on Day 19. It is concluded that DEX not only accelerates the development of GH cells, as observed on Day 17 or 18, but also brings them to a functionally stimulated state by Day 19.

Animals↗