Biomedical subjects

A Nishikawa

Publications and source records attributed to A Nishikawa.

At least 55 records · Page 3Linked to original sources

PubMed2001

Evaluation of central nervous system involvement in nasal lymphomas.

OBJECTIVES: To clarify the usefulness of evaluating central nervous system (CNS) involvement in patients with nasal lymphomas at the initial staging procedure, and of CNS prophylaxis for patients with clinical stage I/II. PATIENTS AND METHODS: We retrospectively reviewed 43 patients with nasal lymphomas who had been treated from 1973 through 1999. The staging procedure included mainly computed tomography (CT), ultrasonography, gallium scintigraphy, upper gastrointestinal study, magnetic resonance (MR) imaging, and bone marrow biopsy. Forty-two patients received radiotherapy, and 25 patients received chemotherapy. All 38 patients with stage I/II were not subjected to CNS prophylaxis. RESULTS: Four patients demonstrated CNS involvement at the staging procedure. MR imaging demonstrated the tumor had directly infiltrated the skull base in 3 patients, but CT demonstrated CNS infiltration in only one patient. In another patient, cerebrospinal fluid (CSF) cytologic analyses demonstrated CNS involvement, but MR imaging and CT did not. These 4 patients complained of frontonasal pain and/or cerebral nerve dysfunction. No patient with stage I/II developed CNS relapse. CONCLUSIONS: MR imaging and CSF cytologic analyses should be performed at the initial staging of nasal lymphomas, especially in patients with frontonasal pain and/or cerebral nerve dysfunction. Patients with stage I/II might not need CNS prophylaxis.

Adult↗

PubMed2000

Reversible and potent uncoupling of hog gastric (H(+)+K(+))-ATPase by prodigiosins.

Prodigiosin, prodigiosin 25-C, and metacycloprodigiosin all strongly inhibited the acidification activity of (H(+)+K(+))-ATPase on membrane vesicles from hog gastric mucosa (IC(50) = 32 to 103 pmol/mg protein). But, the prodigiosins, unlike omeprazole, showed little inhibitory effect on K(+)-dependent ATPase (K(+)-ATPase) activity, although at higher concentrations they inhibited K(+)-ATPase activity with an IC(50) of 1.5 to 3.0 microM. Furthermore, the inhibitory effect of the prodigiosins was rapid and completely reversible unlike that of omeprazole, and the mode of inhibition was non-competitive with respect to ATP. Hog gastric (H(+)+K(+))-ATPase itself showed an absolute requirement of halide (effectively, chloride) for acidification activity. Prodigiosins also showed a chloride requirement for inhibition of vesicular acidification, and quickly reversed the acidification of vesicular pH to neutrality even in the presence of N, N'-dicyclohexylcarbodiimide (DCCD), showing their ionophoric nature of acidification inhibitory activity. In fact, tributyltin chloride (TBT, an OH(-)/Cl(-) exchange ionophore) also inhibited vesicular acidification, but it inhibited K(+)-ATPase activity too. Finally, the prodigiosins inhibited the acid secretion from parietal cells isolated from rabbit gastric mucosa. These results suggest that prodigiosins are potent reversible uncouplers of (H(+)+K(+))-ATPase that inhibit gastric acid secretion.

Adenosine Triphosphate↗

PubMed2000

Modifying effects of 4-phenylbutyl isothiocyanate on N-nitrosobis(2-oxopropyl)amine-induced tumorigenesis in hamsters.

The modifying effects of dietary 4-phenylbutyl isothiocyanate (PBITC), given during the initiation stage of carcinogenesis, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). A total of 120 female 5-week-old hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were given BOP by two subcutaneous injections, 1 week apart, at a dose of 20 mg/kg body weight, plus 0, 10 or 100 micromol/animal of PBITC in corn oil by gavage 2 h prior to each carcinogen treatment. Ten animals in group 4 served as a vehicle control, and animals in groups 5 and 6, each consisting of ten hamsters, were given 10 and 100 micromol of PBITC alone in corn oil. Sacrifice was 52 weeks after the first BOP injection. The PBITC treatments significantly (P<0.05) inhibited the development of pancreatic ductal dysplasias and adenocarcinomas. Also, lung tumors (adenomas and adenocarcinomas) were significantly (P<0.05) reduced in a dose-dependent manner. In contrast, both hepatocellular and cholangiocellular tumors (adenomas and carcinomas) tended to be or were significantly increased by PBITC. These results, taken together with our previous findings, indicate that the natural isothiocyanate, phenethyl isothiocyanate (PEITC), has a more potent chemopreventive action against BOP-induced tumorigenesis than synthetic isothiocyanates with longer alkyl chains, such as 3-phenylpropyl isothiocyanate (PPITC) and PBITC. Thus, their lipophilicity does not necessarily reflect the chemopreventive potential because the strength of lipophilicity is PEITC<PPITC<PBITC.

Adenocarcinoma↗

PubMed2000

Identification of a conserved motif in the yeast golgi GDP-mannose transporter required for binding to nucleotide sugar.

Glycoproteins and lipids in the Golgi complex are modified by the addition of sugars. In the yeast Saccharomyces cerevisiae, these terminal Golgi carbohydrate modifications primarily involve mannose additions that utilize GDP-mannose as the substrate. The transport of GDP-mannose from its site of synthesis in the cytosol into the lumen of the Golgi is mediated by the VRG4 gene product, a nucleotide sugar transporter that is a member of a large family of related membrane proteins. Loss of VRG4 function leads to lethality, but several viable vrg4 mutants were isolated whose GDP-mannose transport activity was reduced but not obliterated. Mutations in these alleles mapped to a region of the Vrg4 protein that is highly conserved among other GDP-mannose transporters but not other types of nucleotide sugar transporters. Here, we present evidence that suggest an involvement of this region of the protein in binding GDP-mannose. Most of the mutations that were introduced within this conserved domain, spanning amino acids 280-291 of Vrg4p, lead to lethality, and none interfere with Vrg4 protein stability, localization, or dimer formation. The null phenotype of these mutant vrg4 alleles can be complemented by their overexpression. Vesicles prepared from vrg4 mutant strains were reduced in luminal GDP-mannose transport activity, but this effect could be suppressed by increasing the concentration of GDP-mannose in vitro. Thus, either an increased substrate concentration, in vitro, or an increased Vrg4 protein concentration, in vivo, can suppress these vrg4 mutant phenotypes. Vrg4 proteins with alterations in this region were reduced in binding to guanosine 5'-[gamma-(32)P]triphosphate gamma-azidoanilide, a photoaffinity substrate analogue whose binding to Vrg4-HAp was specifically inhibited by GDP-mannose. Taken together, these data are consistent with the model that amino acids in this region of the yeast GDP-mannose transporter mediate the recognition of or binding to nucleotide sugar prior to its transport into the Golgi.

Alleles↗

PubMed2000

Effects of octreotide, a somatostatin analogue, on initiation of pancreatic carcinogenesis in hamsters with N-nitrosobis(2-oxopropyl)amine.

The modifying effects of octreotide acetate, a somatostatin (SMS) analogue shown to inhibit secretion of digestive enzymes, bicarbonate and pancreatic juice, on the initiation phase of pancreatic carcinogenesis were investigated in hamsters simultaneously treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups 1-3, each consisting of 20 animals, were given BOP subcutaneously once a week three times at a dose of 10 mg/kg body weight during administration of octreotide acetate for 28 days via osmotic pumps implanted subcutaneously at doses of 6 microg/day (group 1), 3 microg/day (group 2) or 0 microg/day (saline) (group 3). Group 4-6 animals (each group ten animals) were similarly administered octreotide acetate for the same period with five subcutaneous injections of saline. At the termination of experimental week 40, the incidences and multiplicities of pancreatic ductal adenocarcinomas and dysplastic lesions did not significantly differ among groups 1-3. No neoplastic lesions were found in groups 4-6. Subcutaneous administration of octreotide acetate resulted in obviously increased plasma octreotide levels. Our results thus suggest that this SMS analogue may not modulate the initiation of BOP-induced pancreatic carcinogenesis, regardless of its pharmacological action.

Adenocarcinoma↗

PubMed2000

In vivo genotoxicity of 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline in lacI transgenic (Big Blue) mice.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a heterocyclic amine found in cooked meat, is a strong mutagen in the Salmonella/microsome assay and was proven to be a hepatocarcinogen in rodents. We used the lacI transgenic (Big Blue(R)) mouse to investigate MeIQx genotoxicity in vivo. lacI mutant frequencies were examined in liver and colon after single intragastric administration of MeIQx (males) or 12 weeks of feeding in the diet (males and females). Micronucleus induction was monitored in the peripheral blood and cell proliferating activity was monitored by proliferating cell nuclear antigen (PCNA) immunostaining, but only after the intragastric administration. Intragastric treatment with MeIQx (100 mg/kg) did not increase mutant frequency (MF) in liver or colon but it did induce a slight but statistically significant increase in the incidence of micronucleated reticulocytes 48 h after the treatment. No apparent increase in PCNA-positive foci was observed in any of tissues analyzed 14 days after the treatment. Administration of MeIQx (300 ppm) in diet for 12 weeks, however, caused MF increases in liver and colon in male and female mice, with greater increases in the females. An increase was also obvious after 4 weeks, but only in females. The sex difference in MF is consistent with the fact that female mice are more susceptible to MeIQx carcinogenesis. These results demonstrated that in the transgenic mouse mutation assay, long-term feeding of MeIQx was more effective than single gastric exposures in revealing the compound's mutagenicity in the target organs of carcinogenicity and that sex differences in susceptibility can also be observed.

Administration, Oral↗

PubMed2000

Concurrent administration of fish meal and sodium nitrite does not promote renal carcinogenesis in rats after initiation with N-ethyl-N-hydroxyethylnitrosamine.

The modifying effects of concurrent administration of fish meal and sodium nitrite on the development of renal tumors after initiation with N-ethyl-N-hydroxyethylnitrosamine (EHEN) were investigated. A total of 120 male 6-week-old Wistar rats were divided into six groups. Groups 1-3 (30 animals each) were given 1000 ppm EHEN in their drinking water for 3 weeks as an initiation treatment for renal cancer induction and thereafter fed respective diets containing 64, 32, and 8% (original concentration in the basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in the drinking water for 33 weeks. Groups 4-6 (ten animals each) were similarly treated without the prior application of EHEN. At the end of the 37th experimental week, all surviving animals were autopsied and examined histopathologically for the existence of renal proliferative lesions. The incidences of dysplastic lesions, adenomas or adenocarcinomas of the kidney were not significantly different among groups 1-3. No renal proliferative lesions were found in groups 4-6. Chronic nephropathy was slightly but significantly enhanced in the 64 and 32% fish meal-treated groups as compared with group 3. Our results suggest that concurrent administration of fish meal and sodium nitrite does not affect the post-initiation phase of EHEN-induced renal carcinogenesis in the rat.

Adenocarcinoma↗

PubMed2000

Organ-dependent modifying effects of oltipraz on N-nitrosobis(2-oxopropyl)amine (BOP)-initiation of tumorigenesis in hamsters.

5-(2-Pyrazinyl)-4-methyl-1,2-dithiole-thione (oltipraz), a substituted 1,2-dithiole-3-thione, is known to inhibit tumorigenesis induced by variety of carcinogens in several animal model systems. In the present experiment, the modifying effects of dietary oltipraz, given during N-nitrosobis(2-oxopropyl)amine (BOP) initiation of carcinogenesis, were investigated in Syrian hamsters. A total of 120 six-week-old females were divided into six groups. Groups 1-3 (30 animals each) were thrice given subcutaneous injections of BOP (10 mg/kg, body weight) at 1 week intervals and fed diets supplemented with 400 or 200 ppm of oltipraz or basal diet alone, starting 1 week prior and finishing 1 week after the carcinogen exposure. Groups 4-6 (10 animals each) were similarly treated without application of BOP. At the end of the 52nd experimental week, all surviving animals were autopsied and examined histopathologically for proliferative lesions of the major target organs for BOP tumorigenicity, including pancreas, liver, kidney, and lung. The incidences and multiplicity of adenocarcinomas of the pancreas were higher in groups 1 and 2 than in group 3 although without statistical significance. The incidence of pancreatic duct dysplasias was significantly (P<0.05) increased in group 2 (62.0%) but not in group 1 (50.0%) as compared with group 3 (46.6%). While the incidences of alveolar adenomas and carcinomas were significantly (P<0.05) decreased by the high dose, the multiplicities of hepatocellular adenomas, cholagiocellular carcinomas and gall bladder adenomas were elevated in the BOP/oltipraz groups (P<0.05). The results of the present study suggest that oltipraz exerts organ-dependent modifying effects on BOP-induced carcinogenesis in hamsters when given in the initiation stage.

Animals↗

PubMed2000

Inhibition by methionine of pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl) amine.

The modifying effects of dietary L-methionine in the post-initiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups consisting of 20 and 30 animals, respectively, were given BOP subcutaneously, once a week five times at a dose of 10 mg/kg body wt. and then continuously fed diet supplemented with 2% (group 1) or 0% (group 2) methionine (weeks 5-32). After five subcutaneous injections of saline, group 3 animals were similarly fed diet supplemented with 2% methionine for the same period. The incidence of pancreatic ductal adenocarcinomas was significantly lower in group 1 (36.8%, P<0.05) than in group 2 (71.4%). Multiplicity of adenocarcinomas was also significantly lowered (0.52 and 1.28/hamster, P<0.05). Similarly, total numbers of combined adenocarcinomas and dysplastic lesions were significantly decreased in group 1 (2.05, P<0.05) as compared with group 2 (3.67). Methionine enhanced atrophic change of pancreatic acinar cells in hamsters given BOP, indicating that the inhibitory effects on the post-initiation stage of BOP-induced pancreatic carcinogenesis in hamsters could be generally linked to suppression of growth.

Adipose Tissue↗

PubMed2000

Deoxyguanosine adducts of t-4-hydroxy-2-nonenal are endogenous DNA lesions in rodents and humans: detection and potential sources.

t-4-Hydroxy-2-nonenal (HNE) is a free radical-mediated oxidation product of polyunsaturated fatty acids. As an electrophile, HNE readily binds to proteins and yields diastereomeric cyclic 1,N2-propano adducts with deoxyguanosine (dG). Here, we report the detection and identification of the HNE-derived cyclic 1,N2-propano-dG adducts as endogenous DNA lesions in tissues of untreated rats and humans using a highly sensitive 32P-postlabeling method in conjunction with high-performance liquid chromatography. These adducts were first verified by their comigration with the synthetic UV standards of HNE-dG adducts. Subsequently, their identities were unequivocally established by two independent reactions. An approximately 37-fold increase in the levels of HNE-dG adducts was observed in the liver DNA of F344 rats after treatment with CCl4, suggesting that tissue lipid peroxidation is a likely source of their formation. Our studies in vitro further indicate that omega-6 polyunsaturated fatty acids are likely a unique class of fatty acids involved in HNE-dG adduct formation.

Aldehydes↗

PubMed2000

Trans-4-hydroxy-2-nonenal, an aldehydic lipid peroxidation product, lacks genotoxicity in lacI transgenic mice.

In order to cast light on the significance of lipid peroxidation products for carcinogenesis, the lacI mutant frequency (MF), micronucleus induction and cell proliferation were analyzed in lacI transgenic mice treated with trans-4-hydroxy-2-nonenal (HNE), a typical example. Male mice were ip injected with HNE at doses of 0, 5 or 50 mg/kg bw and 48 h thereafter, peripheral blood was collected for analyzing micronucleus induction. After 14 days, the mice were sacrificed to allow tissue sampling for examination of lacI MF and cell proliferative activity. Sixty percent of the mice given 50 mg/kg HNE died within 5 days after the treatment, but no other mortalities were observed. Histopathologically, marked pulmonary hemorrhage was found in the 50 mg/kg HNE group mice that survived until day 14. Immunohistochemically, HNE-modified proteins were detected in their alveolar macrophages. The HNE treatment did not increase lacI MF in the liver, kidney and lung and no significant increase in micronucleus induction or cell proliferation in major organs was found in either treatment. Moreover, no tumors developed in the 5 mg/kg HNE-treated mice which survived until week 78. Our results thus indicate that HNE lacks in vivo genotoxicity in lacI transgenic mice even when lethal doses are applied.

Aldehydes↗

PubMed2000

Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity.

The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.

Adult↗

PubMed2000

Expression of various matrix proteases and Ets family transcriptional factors in ovarian cancer cell lines: correlation to invasive potential.

OBJECTIVES: The aim of our study was to determine the important molecules responsible for the invasive activity of ovarian cancer cells. METHODS: We compared the biological characteristics, that is, growth rate, motility, and invasive activity, of five ovarian cancer cell lines with the gene expression of various matrix proteases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, MT3-MMP, urokinase plasminogen activator [uPA]), their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1], TIMP-2, plasminogen activator inhibitor type 1, [PAI-1], and PAI-2), and the potential transcriptional regulators E1AF and Ets-1. RESULTS: There was no clear correlation in the growth rate, motility, and invasion, suggesting that there are independent properties for malignant potential in ovarian cancer cells. However, HTBOA, a poorly differentiated cancer cell line, exhibited highly invasive activity, rapid growth, and increased motility. This cell line also expressed both Ets transcriptional factors, E1AF and Ets-1, and many matrix-degrading enzymes. Three cell lines that expressed E1AF showed rapid cell growth. The highly invasive cell lines, HTBOA and HTOA (well-differentiated serous cystadenocarcinoma), produced either MMP-2 or MMP-1, and both cell lines expressed MT1-MMP and uPA. Furthermore, the active forms of pro-MMP-2 and pro-MMP-1 were detected in HTBOA and HTOA by zymography. CONCLUSION: We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.

Adenocarcinoma↗

PubMed2000

Lack of carcinogenicity of gardenia blue colour given chronically in the diet to F344 rats.

The carcinogenicity of gardenia blue colour was examined in Fischer 344 (F344) rats. Groups of 50 males and 50 females were given the material at dietary doses of 0 (control), 2.5 or 5% for 104 weeks and then sacrificed. The doses were selected on the basis of results from a 13-week subchronic toxicity study. A slight increase in relative organ weights of the left lung was observed in male rats of the 5% group. However, no significant differences between the control and treated groups were noted with regard to clinical signs, mortality and haematological findings. A variety of tumours developed in all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any type of neoplastic lesion was found for either sex in the treated groups. Thus, it was concluded that, under the present experimental conditions, gardenia blue colour is not carcinogenic in F344 rats.

Administration, Oral↗

PubMed2000

Larval-to-adult conversion of a myogenic system in the frog, Xenopus laevis, by larval-type myoblast-specific control of cell division, cell differentiation, and programmed cell death by triiodo-L-thyronine.

For the clarification of larval-to-adult muscle conversion, the authors established primary culture methods for adult- and larval-type myoblasts in the frog, Xenopus laevis, and examined the hormonal response in each case. The cell types were enzymatically dissociated from adult frog leg and tadpole tail muscles, respectively. The cells became attached to culture plates, proliferated, and fused with each other to form multinucleated myotubes within one week. Five significant differences between the two cell types were noted. (1) Adult cells showed greater proliferation activity than larval cells, the former increasing 5.5-fold over 6 days while the latter increase only 2.5-fold. (2) Differentiation (fusion) of larval type myoblasts started earlier. Cell fusion began on day 2 or 3 in larval cells and on day 4 in adult cells. (3) The metamorphic hormone, triiodo-L-thyronine (T3) decreased larval cell numbers to 56% of that of control-cultures on day 7 but had no effect on adult cell number. DNA synthetic activity (3H-thymidine incorporation) in larval cells decreased under T3 (10(-8) M) to 45% of the control level on day 7. (4) Differentiation of adult myoblasts into myotubes was promoted by T3, whereas that of larval cells diminished by half. (5) Myotube death was induced by T3 specifically in larval but not in adult cultures. In addition to the myotube death, double staining with TUNEL (in situ DNA nick end labeling) and anti-desmin antibody indicated that T3 induces myoblast (desmin+ cell) death specifically in larval but not in adult cells. It is thus evident that the conversion of a larval-type myogenic system during metamorphosis becomes possible through nearly totally specific control of cell division, cell differentiation, and programmed cell death at a precursor cell level by T3.

Animals↗

PubMed2000

Isolation of Trichosporon asahii from environmental materials.

Trichosporon asahii is the most clinically important pathogenic yeast in the genus Trichosporon, as this species causes both deep-seated infection and summer-type hypersensitivity pneumonitis. We isolated 29 T. asahii colonies from environmental samples using the polymerase chain reaction (PCR) and dichloran rose bengal chloramphenicol (DRBC) medium. Our results suggest that T. asahii is common in nature.

Culture Media↗

PubMed2000

Cell wall components of Staphylococcus aureus induce interleukin-5 production in patients with atopic dermatitis.

Lipoteichoic acid (LTA) and peptidoglycan (PEG) from Staphylococcus aureus induced interleukin-5 (IL-5) production in human peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) but not in PBMC from healthy donors. The production of IL-5 induced by LTA or PEG was correlated with the expression of IL-5 mRNA in PBMC. Furthermore, the level of IL-5 production induced by treatment with both LTA and PEG from S. aureus was higher than that induced by the addition of each alone. These results suggest that LTA and PEG have an additive effect on IL-5 production in PBMC from AD patients and may explain the role of colonization with nontoxin-producing strains of S. aureus in these patients.

Adjuvants, Immunologic↗

PubMed2000

Dramatic synergism between excess soybean intake and iodine deficiency on the development of rat thyroid hyperplasia.

The effects of defatted soybean and/or iodine-deficient diet feeding were investigated in female F344 rats. Rats were divided into four groups, each consisting of 10 animals, and fed basal AIN-93G diet in which the protein was exchanged for 20% gluten (Group 1), iodine-deficient gluten (Group 2), 20% defatted soybean (Group 3) and iodine-deficient defatted soybean (Group 4). At week 10, relative thyroid gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 2 (15.5 +/- 1.3) and 4 (81.7 +/- 8.6) than in Group 1 (8.4 +/- 2.0) and pituitary gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 3 (9.1 +/- 0. 6) and 4 (9.7 +/- 1.5) than in Group 1 (6.5 +/- 1.5). Serum biochemical assays revealed thyroxine to be significantly (P < 0.05) lower in Groups 2 and 4 than in Group 1. On the other hand, serum thyroid-stimulating hormone (TSH) was significantly (P < 0.01) higher in Groups 3 and 4 than in Group 1. This was particularly striking for TSH (ng/ml) at week 10 in Group 4 (126 +/- 11) as compared with Groups 1 (4.36 +/- 0.30), 2 (4.84 +/- 0.80) and 3 (5. 78 +/- 0.80). Histologically, marked diffuse follicular hyperplasia of the thyroid was evident in Group 4 rats. Proliferating cell nuclear antigen labeling indices (%) were significantly higher (P < 0.05) in Groups 2 (4.8 +/- 2.5) and 4 (13.2 +/- 1.1) than in Group 1 (0.4 +/- 0.5). Ultrastructurally, severe disorganization and disarrangement of mitochondria were apparent in thyroid follicular cells of Group 4. In the anterior pituitary, dilated rough surfaced endoplasmic reticulum and increased secretory granules were remarkable in this group. Our results thus strongly suggest that dietary defatted soybean synergistically stimulates the growth of rat thyroid with iodine deficiency, partly through a pituitary-dependent pathway.

Animals↗