Expression of hypothalamic corticotropin-releasing hormone-like immunoreactivity in isolated ACTH deficiency: a report of an autopsied case.

A 77-yr-old man died of metastising adenocarcinoma of the lung. He had been treated with hydrocortisone for isolated ACTH deficiency for 9 yr. At autopsy, the pituitary and the adrenal glands were atrophic. Lymphocyte infiltration was not observed in the pituitary, the adrenal and the thyroid glands. Immunohistochemistry revealed selective loss of ACTH-like immunoreactivity in the pituitary gland whereas CRH-immunoreactive cells were found in the paraventricular nucleus of the hypothalamus. This is the first report demonstrating immunohistochemical examinations of the pituitary and the hypothalamus in isolated ACTH deficiency.

Acquisition of a gastric or duodenal phenotype on heterotropic transplantation of esophagus and bladder tissues in F344 rats.

Cell differentiation is very important but not well understood. In the present study the ability of various tissues to newly-differentiate when transplanted into the fundus or the duodenum in rats was tested. Pieces of esophagus, bladder, diaphragm and trachea from 8-week-old male F344 rats were transplanted into the gastric fundus or duodenum of females and examined after 3 or 6 months. While the diaphragm was not recognizable as a muscle layer in either the stomach or the duodenum, the esophagus and trachea persisted, the latter with the presence of cartilage. Esophagus grafts transplanted into the glandular stomach and duodenum, newly-differentiated into gastric and duodenal mucosa, respectively. Goblet cells with alcian-blue positive mucin appeared in bladder tissue implanted into the duodenum. Six months after the operation, their numbers had increased and cytoplasm alkaline phosphatase (ALP) positivity was noted. Gastrointestinal and also bladder stem cells may thus have multipotential ability for differentiation and may be able to newly-differentiate when transplanted into different environments in the gastrointestinal tract.

Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion.

It appears that PACAP has a direct action on somatotrophs to release GH. The intracellular signal transduction mechanisms for PACAP might be similar to but partly distinct from those for GRH. PACAP might play a role in GH secretion induced by serotoninergic mechanisms but not in ultradian rhythm of GH secretion in the rat. PACAP can stimulate PRL release from the pituitary in rats possibly through indirect paracrine effect. In addition, PACAP might participate in regulation of PRL secretion via hypothalamic VIP.

Serum antibodies to human pituitary membrane antigens in patients with autoimmune lymphocytic hypophysitis and infundibuloneurohypophysitis.

OBJECTIVE: Serum antipituitary antibodies were investigated by the immunoblotting method using human anterior pituitary membrane preparation as the antigen. PATIENTS: Thirteen patients with autoimmune lymphocytic hypophysitis, two patients with infundibuloneurohypophysitis, four patients with isolated ACTH deficiency, 21 patients with diabetes mellitus (type 1 and type 2) and 38 healthy subjects were studied. METHODS: Human pituitary membrane antigens were electrophoresed by sodium dodecylsulphate-polyacrimide gel electrophoresis (SDS-PAGE). The antigens were transferred to polyvinylidene difluoride membrane and reacted with the sera followed by incubation with biotinylated anti-human IgG goat serum. RESULTS: Serum antibodies to 68, 49, 43 kD human pituitary membrane antigens were detected in five of 13, one of 12 patients with infundibuloneurohypophysitis and none of four patients with isolated ACTH deficiency. These antibodies were not detectable when human thyroid, liver or rat pituitary preparations were used as the antigen. CONCLUSION: These findings suggest that serum antibodies to 68, 49, 43 kD human anterior pituitary antigen are specific but not so frequently detected in autoimmune lymphocytic hypophysitis.

Antioxidative and 5-lipoxygenase inhibiting activities of novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives.

Novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives were synthesized and evaluations were made of their inhibiting action on Fe3+-ADP induced lipid peroxidation in rat liver microsome and reducing action on alpha,alpha-diphenyl-beta-picrilhydrazyl (DPPH), a stable radical, in addition to their inhibiting action on 5-lipoxygenase (5-LO), an enzyme that synthesizes leukotrienes. We performed a structure-activity correlation study on these derivatives. A strong Fe3+-ADP induced lipid peroxidation preventing activity was observed for the derivatives with an odd number of methylene groups including 1,3-bis(4-hydroxy-2,3,5-trimethylphenoxy)propane (3b) and 3a. No change in the DPPH reducing activity was found with change in the number of methylene groups. 5-LO inhibiting activity among the derivatives was the highest for 1,6-bis(4-hydroxy-2,3,5-trimethylphenoxy)hexane (3e). MM2 calculations were performed to find a stable steric structure for the derivatives, and 1,5-bis(4-hydroxy-2,3,5-trimethylphenoxy)pentane (3d) showed a strong activity in both antioxidative action and 5-LO inhibiting action.

Reverse correlation between urine nitric oxide metabolites and insulin resistance in patients with type 2 diabetes mellitus.

We studied the possible relationship between nitric oxide (NO) production and insulin resistance in patients with type 2 diabetes mellitus. Urine NO metabolites (NOx) were measured as an index for NO production by HPLC combined with a Cd column, Griess reaction and a spectrophotometer in 403 healthy control subjects and 102 hospitalized patients with type 2 diabetes. Glucose infusion rate (GIR) was measured as a reverse index for insulin resistance by euglycemic glucose clamp study using an artificial pancreas in 20 of 102 diabetic patients. Urine NOx was lower in the patients with type 2 diabetes than in healthy control subjects (mean+/-SE: 3.18 +/-0.02 versus 3.25 +/-0.01 log[-micromol/gCr], p<0.01). Urine NOx was correlated with body mass index (BMI) in 102 diabetic patients (r= -0.372, p<0.001), but not related to either age, sex, fasting plasma glucose, HbA1c or blood pressure. Urine NOx was correlated with GIR independent of BMI in 20 diabetic patients (r=0.774, P<0.0001). These findings suggest that NO production is closely related with insulin resistance in patients with type 2 diabetes.

Beta-cyclodextrin-linked chitosan beads: preparation and application to removal of bisphenol A from water.

Water-insoluble and highly porous chitosan beads having an ability to form inclusion complexes have been synthesized by treatment of a solution of chitosan in aqueous acetic acid with aqueous NaOH followed by crosslinking and reductive alkylation with 2-O-formylmethyl-beta-cyclodextrin. Preliminary experiments for its application to removal of endocrine disrupting chemicals were carried out using a column of the resulting beads and bisphenol A as the model substrate.

Inflammatory action of 8-methoxypsoralen-spermine photoproduct (8-MOP-Spm-P(GFC)) and effects of various drugs on rat paw edema induced by 8-MOP-Spm-P(GFC).

The photoproducts produced by irradiating 8-methoxypsoralen (8-MOP) in the presence of spermine (Spm) were fractionated using gel filtration chromatography (GFC) on a Sephadex G-25 column. As a result, two bands which were characterized by the effects on hyaluronidase activity were obtained. The first band strongly activated the hyaluronidase, but a second band did not exhibit any effect on the enzyme activity. The first and second bands contained photoproducts with molecular weights (MW)>2700 and MW<728, respectively, determined by the GFC method. The photoproducts, 8-MOP-Spm-P(GFC) obtained from the first band, but not the photoproducts with lower MW from the second band, showed enzyme activating action. 8-MOP-Spm-P(GFC) induced paw edema, which was stronger in the first phase than the second one in rats, differing from that induced by carrageenin. This photoproduct was a substance with lower cell toxicity because it did not cause hemolysis on red blood cells or the release of lactic dehydrogenase from mast cells in rats. The effects of various drugs on 8-MOP-Spm-P(GFC)-induced edema were investigated. As a result, edema formation was inhibited by drugs with an anti-histaminic action, such as alimemazine, dl-chlorpheniramine, promethazine, ketotifen and azelastine, and with anti-serotonin action such as cyproheptadine. On the other hand, tranilast did not show significant inhibition and indomethacin showed a tendency to increase its formation. These results suggested that 8-MOP-Spm-P(GFC) is a new inflammatory substance and is very useful as an agent to develop new anti-inflammatory drugs without cyclooxygenase inhibitory action.

Analysis of urinary nitric oxide metabolites in healthy subjects.

Nitric oxide (NO) has divergent actions under physiological and pathological conditions. NO is rapidly decomposed to nitrite (NO2-) and nitrate (NO3-). Since these metabolites are stable, they are good indices of NO production under various conditions. In the present study, we measured NO2- and NO3- concentrations in the urine collected from 62 hospital controls and 504 healthy subjects by means of a new HPLC system combined with Griess reaction. NOx was the sum of NO2- and NO3-. There was no considerable inter-day variation in urinary NO metabolite levels, and there was close correlation between NO2-, NO3- and NOx values in spot urine obtained in the early morning and those in 24-h stored urine in hospital controls. Urinary NO metabolite levels, which were corrected by creatinine (Cr) excretion and expressed on a logarithmic scale, showed normal distribution and were independent of sex and age in healthy subjects. The normal ranges of urinary NO2-, NO3- and NOx levels were estimated as 17-72 micromol/g Cr, 1,023-2,818 pmol/g Cr, and 1,071-2,951 micromol/g Cr, respectively. We also found that urinary NO metabolite levels were lower than normal range in patients with various diseases.

Renal expression of insulin-like growth factor-l in acute renal failure: a preliminary report.

Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.

[Usefulness of low dose 5'-DFUR (5'-deoxy-5-fluorouridine) for advanced or recurrent breast cancer].

The usefulness of low dose (600 mg/day) 5'-DFUR for advanced or recurrent breast cancer was evaluated. Eight patients out of 38 showed a partial response (response rate 21.1%), 22 patients had no change, and 8 patients had progressive disease. The response rate was 31.0% in soft tissue and 9.1% in bone, both of which were slight. In both one-shot (200 mg) and continuous (1-4 months) administration of 5'-DFUR (600 mg/day), the concentration of 5'-DFUR of 5-FU in sera reached a plateau from 30 minutes to 2 hours after administration of 5'-DFUR, and disappeared after 3 hours. There were no significant differences in the concentration of 5'-DFUR of 5-FU in sera between one-shot and continuous administration. It is concluded that there was no accumulation of the drug after continuous administration of 5'-DFUR, and that low dose 5'-DFUR is a useful therapy for advanced or recurrent breast cancer.

Synthesis of trimethylhydroquinone derivatives as anti-allergic agents with anti-oxidative actions.

A novel series of trimethylhydroquinone derivatives was synthesized and evaluated for their anti-lipid peroxidation activity in rat liver microsomes, inhibition of rat basophilic leukemia-1 (RBL-1) cell 5-lipoxygenase and 48 h homologous passive cutaneous anaphylaxis (PCA) activity in rats. 4-[4-[4-(Diphenylmethyl)-1-piperazinyl]-butoxy]-2,3,6-trimethyl phenol (9c) exhibited the ability to inhibit Fe(3+)-ADP induced NADPH dependent lipid peroxidation (IC50 = 5.3 x 10(-7) M), 5-lipoxygenase ((IC50 = 3.5 x 10(-7) M) and PCA reaction (57% inhibition at 100 mg/kg p.o.).

Evaluation of propolis (II): effects of Brazilian and Chinese propolis on histamine release from rat peritoneal mast cells induced by compound 48/80 and concanavalin A.

To establish a biological method for evaluating propolis and to reveal their anti-allergic action, the effects of the ethanol and water extracts (EA-ET and WA-WT, respectively) from Brazilian, Chinese and Japanese propolis on the histamine release induced by compound 48/80 and concanavalin A (Con A) were investigated. The relation between the inhibitory activities of these extracts on the histamine release and their E(1 cm)1% values were also examined. As a result, the following was found: 1) 0.003-0.01% ethanol and 0.03-0.1% water extracts inhibited the histamine release induced by compound 48/80 and Con A, and the inhibitory potencies of the former extracts were more than 10 times stronger than those of the latter extracts, making it clear that both the ethanol and water extracts possess an anti-allergic action; 2) most of the ethanol and water extracts responded to the histamine release induced by both the histamine releasers in a concentration-dependent manner; 3) the inhibitory activities of 0.003% EM from Hebei Province, EP from Sichuan Province, EQ from Zhejiang Province and ER from Anhui Province in China were weaker than those of 0.01% corresponding extracts, whereas 0.001% ED-EH from Brazilian propolis, EM, EN from Henan Province in China and EP-ER promoted the Con A-induced histamine release of more than 10%, suggesting that such extracts must be carefully given to humans; 4) the inhibitory potencies of only 0.03-0.1% water extracts from Chinese propolis on the Con A-induced histamine release related excellently with their E(1 cm)1% values; 5) from the results of the relation between the inhibitory potencies of the propolis extracts and their E(1 cm)1% values, it was suggested that an unknown compound, being a poorly water-soluble compound which is a non-flavonoid, with an anti-allergic action is contained in propolis; 6) to precisely evaluate the anti-allergic action of the propolis, the biological method, which measures the inhibitory activities of the propolis extracts on histamine release, was markedly superior to the physicochemical method.

Early Breast Cancer Following Treatment of Myelodysplastic Syndrome: Report of a Case.

A 45-year-old woman was admitted to our hospital complaining of a mass in herleft breast. She had previously been diagnosed with myelodysplastic syndrome(MDS), a type of refractory anemia, based on bone marrow findings and chromosome analysis. She received a preoperative transfusion of fresh packed platelets and a recombinant human granulocyte colony-stimulating factor(rhG-CSF)injection. Left partial mastectomy and axillary lymph nodes dissection were performed to treat early breast cancer. Postoperatively, prophylactic radiotherapy of the residual breast and administration of medroxyprogesterone acetate(MPA)were performed because the tumor tissue was positive for progesterone receptors. She has remained clinically stable, with no evidence of recurrence, for more than three years to date. We report a rare case of breast cancer with MDS, treated with breast-conserving therapy. The strategy of pre- or postoperative platelet transfusion, rhG-CSFinjections, and hormonal therapy (MPA) appears to be suitable treatment for progesterone receptor(PgR)-positive breast cancer patients with MDS.

A case of autoimmune hypophysitis associated with asymptomatic primary biliary cirrhosis.

We report a 61-year old male patient with panhypopituitarism complicated with asymptomatic primary biliary cirrhosis (PBC). T1-weighted magnetic resonance imaging demonstrated high intensity of the anterior pituitary gland. There was no mass lesion or enlargement of the pituitary gland or the stalk. Immunoblot analysis of the patient's sera with rat pituitary antigens revealed a band with a molecular size of 22 kD. Anti-M2 mitochondrial antibody has been consistently positive for five years. Liver biopsy revealed portal hepatitis with periportal infiltration of the inflammatory cells. This is the first case report of autoimmune hypophysitis complicated with asymptomatic PBC.

Effects of rat galanin and galanin message associated peptide (GMAP) on rat growth hormone secretion and stimulating effect of gamma-aminobutyric acid on galanin release from rat hypothalamus.

Immunoreactive galanin and galanin message associated peptide (GMAP) were detectable in rat hypothalamus in the concentration of 563 +/- 23 and 14.3 +/- 3.1 fmol/hypothalamus, respectively. gamma-Aminobutyric acid (GABA) elicited a dose-related increase in galanin release from rat hypothalamic fragments, which was inhibited by picrotoxin, a GABA antagonist. Growth hormone (GH) secretion from rat anterior pituitary cells were stimulated by rat galanin, but not by GMAP. These findings suggest that hypothalamic galanin, but not GMAP, may play roles in GH secretion induced by GABAergic mechanisms in the rat.