Morphology of the cockerel's comb after androgen administration.

1. Androgen receptor (AR) expression and morphological changes in blood capillaries were investigated in the comb of cockerels, both untreated controls and after the administration of testosterone (T) or the androgen antagonist flutamide (F) for 7 weeks. 2. Twenty-six male Single Comb White Leghorn roosters were divided into T-treated, F-treated and untreated groups. Tissue sections were examined histologically, immunohistochemically, and comb blood vessel castings were analysed by scanning electron microscopy. 3. Histologically, the capillaries of the peripheral dermis layer in the T-treated group were dilated compared with controls. Many red blood cells were seen in the lumen. Although the capillary diameter in the F-treated group did not show a significant difference as compared with control, blood capillaries with small diameters were often observed, and there were few red blood cells in the capillaries. Some capillary castings were extended markedly in the T treated group, and small blood vessels were observed arborising from the extended blood capillaries. In contrast, all capillaries were slender in the F-treated group, and the casting surface was rough. 4. Immunoreactivity for AR was found in capillary endothelial cells in the peripheral dermis layer of the comb. The intensity of staining in these cells was increased in the T-treated group but was reduced in the F-treated group. 5. It is concluded that immunoreactivity for AR was found in capillary endothelial cells in the peripheral dermis layer of the rooster's comb. The intensity of staining in these cells was increased in the T-treated group but reduced in the F-treated group. Thus, the capillary endothelial cells in the peripheral dermis layer of the comb are androgen targets.

Treatment of a citrin-deficient patient at the early stage of adult-onset type II citrullinaemia with arginine and sodium pyruvate.

Citrin deficiency is a common congenital metabolic defect not only in East Asian populations but also in other populations around the world. It has been shown that although liver transplantation is ultimately required in many patients to prevent neurological decompensation associated with hyperammonaemia, arginine is effective in lowering ammonia in hyperammonaemic patients, and a high-protein low-carbohydrate diet may provide some benefit to infants in improving failure to thrive. In the present study, the clinical symptoms and laboratory findings are reported for a 13-year-old citrin-deficient girl in the early stage of adult-onset type II citrullinaemia (CTLN2), and the therapeutic effect of orally administered arginine and sodium pyruvate was investigated. The patient complained of anorexia, lethargy, fatigue and poor growth, and showed laboratory findings typical of CTLN2; elevated levels of plasma citrulline, threonine-to-serine ratio, and serum pancreatic secretory trypsin inhibitor. Oral administration of arginine and sodium pyruvate for over 3 years improved her clinical symptoms and has almost completely normalized her laboratory findings. It is suggested that the administration of arginine and sodium pyruvate with low-carbohydrate meals may be an effective therapy in patients with citrin deficiency in order either to prolong metabolic normalcy or to provide a safer and more affordable alternative to liver transplantation.

Skin morphology of thyroidectomized rats.

We induced hypothyroidism in rats by conducting a thyroidectomy (TD) and investigated subsequent changes in the morphology of the skin, especially that of the epidermis and hair follicles. The 6 rats in the TD group seemed less active than the 3 rats in the control group and had cold, dry paws. All of the rats in the TD group exhibited retarded hair growth 12 weeks after surgery. Histologically, all of the rats in the TD group exhibited epidermal thinning from 12 weeks after surgery. Many hair follicles were in the telogen phase: the bulbs and papillae were involuted and had migrated towards the epidermis. Hair follicle atrophy involving thinning of the outer root sheath and the inner root sheath was often observed. The immunoreactivities of antithyroid hormone receptors alpha and beta in the outer root sheaths of 5 of the TD rats were weaker than those of control rats. Cell proliferation in hair follicles of TD rats was weaker than in follicles of control rats 4 weeks after surgery. It is suggested that decreased expression of TRs and decreased cell proliferation activity in the hair follicles of rats is associated with a lack of thyroid hormone and results in retardation of hair growth.

High prevalence of bipolar disorder comorbidity in adolescents and young adults with high-functioning autism spectrum disorder: a preliminary study of 44 outpatients.

BACKGROUND: Psychiatric comorbidity of autism spectrum disorder (ASD) has not been well examined. METHODS: Mood disorders in 44 consecutive outpatients with high-functioning ASD were examined at a university hospital according to DSM-IV. Inclusion criteria were an IQ of 70 or higher on the Wechsler Intelligence Scale and age of 12 years or over. RESULTS: Sixteen patients (36.4%) were diagnosed with mood disorder. Of these 16 patients, four were diagnosed as having major depressive disorder, two patients as bipolar I disorder, six patients as bipolar II disorder, and four patients as bipolar disorder not otherwise specified. Bipolar disorder accounted for 75% of cases. Twelve patients had Asperger disorder and four patients had pervasive developmental disorder not otherwise specified. None of the patients had autistic disorder. LIMITATIONS: The sample size was small. We could not use Autism Diagnostic Interview - Revised. Referral bias could not be avoided in this study. CONCLUSIONS: The major comorbid mood disorder in patients with high-functioning ASD is bipolar disorder and not major depressive disorder. The autistic spectrum may share common vulnerability genes with the bipolar spectrum.

Reduced carbohydrate intake in citrin-deficient subjects.

Citrin is the liver-type aspartate-glutamate carrier that resides within the inner mitochondrial membrane. Citrin deficiency (due to homozygous or compound heterozygous mutations in the gene SLC25A13) causes both adult-onset type II citrullinaemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). Clinically, CTLN2 is characterized by hyperammonaemia and citrullinaemia, whereas NICCD has a much more varied and transient presentation that can include multiple aminoacidaemias, hypoproteinaemia, galactosaemia, hypoglycaemia, and jaundice. Personal histories from CTLN2 patients have repeatedly described an aversion to carbohydrate-rich foods, and clinical observations of dietary and therapeutic outcomes have suggested that their unusual food preferences may be directly related to their pathophysiology. In the present study, we monitored the food intake of 18 Japanese citrin-deficient subjects whose ages ranged from 1 to 33 years, comparing them against published values for the general Japanese population. Our survey confirmed a marked decrease in carbohydrate intake, which accounts for a smaller proportion of carbohydrates contributing to the total energy intake (PFC ratio) as well as a shift towards a lower centile distribution for carbohydrate intake relative to age- and sex-matched controls. These results strongly support an avoidance of carbohydrate-rich foods by citrin-deficient patients that may lead to worsening of symptoms.

Morphology of thyroid follicular cells of methimazole-treated rats.

Thyroids of rats treated with methimazole (MMI) were analysed histologically, immunohistochemically and electron microscopically. Thyroids of MMI-treated rats displayed greater hypertrophy and were heavier than those of control rats. Thyroids of MMI-treated rats were composed of variant or small follicles and contained more columnar cells than those of control rats. Strong staining of thyroid granules by azocarmine G was evident in the apical regions of follicular cells from MMI-treated rats. Anti-thyroglobulin positivity was detected in the apical regions of follicular epithelial cells, especially those of MMI-treated rats. After application of a post-embedding method to detect thyroglobulin, colloidal gold particles were often observed in apical vesicles of MMI-treated rats. Our study suggests that apical vesicles may serve as markers of hyperthyroidism. When the functional state of the thyroid gland is known from histological analysis, use of the Azan stain could provide useful additional information.

Ghrelin stimulates phagocytosis and superoxide production in fish leukocytes.

To clarify the role of ghrelin in the fish immune system, the in vitro effect of ghrelin was examined in phagocytic leukocytes of rainbow trout (Oncorhynchus mykiss). Administration of trout ghrelin and des-VRQ-trout ghrelin, in which three amino acids are deleted from trout ghrelin, increased superoxide production in zymosan-stimulated phagocytic leukocytes from the head kidney. Gene expression of growth hormone (GH) secretagogue-receptor (GHS-R) was detected by RT-PCR in leukocytes. Pretreatment of phagocytic leukocytes with a GHS-R antagonist, [D-Lys3]-GHRP-6, abolished the stimulatory effects of trout ghrelin and des-VRQ-trout ghrelin on superoxide production. Ghrelin increased mRNA levels of superoxide dismutase and GH expressed in trout phagocytic leukocytes. Immunoneutralization of GH by addition of anti-salmon GH serum to the medium blocked the stimulatory effect of ghrelin on superoxide production. These results suggest that ghrelin stimulates phagocytosis in fish leukocytes through a GHS-R-dependent pathway, and also that the effect of ghrelin is mediated, at least in part, by GH secreted by leukocytes.

Cell proliferation activity of proliferating bile duct after bile duct ligation in rats.

The cell proliferation activity of proliferating bile ducts produced by bile duct ligation (BDL) in rats was examined histologically, immunohistochemically, and ultrastructurally. Proliferating bile ducts, which were similar to normal bile ducts, increased with time after BDL. The cell proliferation activity of proliferating bile ducts, measured using proliferating-cell nuclear antigen and 5-bromo-2'-deoxyuridine antibodies, tended to be high at 1 and 3 days after BDL and decreased progressively at 2 to 4 weeks after BDL. On the other hand, alpha-smooth muscle actin-positive myofibroblast-like cells increased continuously after BDL. These findings indicate that there is a negative correlation between the cell proliferation activity of proliferating bile ducts and that of myofibroblast-like cells.

Morphological changes in the rat endocrine pancreas within 12 h of intravenous streptozotocin administration.

We examined early morphological changes in pancreatic endocrine cells within 12 h of intravenous streptozotocin (STZ) administration (60 mg/kg). Thirty rats were allocated either to a control group (vehicle alone) or to one of four experimental groups tested after 3, 6, 9 and 12 h. Karyopyknosis and cytoplasmic vacuoles were first observed in beta-cell cytoplasm 3 h after STZ administration (STZ-3 h), and the most severe damage was found in beta cells at STZ-12 h. Insulin-positive non-islet cells were observed near the intercalated duct (ICD) and/or centroacinar (CA) cells at STZ-6 h and their numbers peaked at STZ-6 h. The distribution patterns of the insulin-positive cells and those of nestin and insulin-like growth factor-1 were similar and their nuclei were positive for proliferating cell nuclear antigen. Thus, ICD cells and/or CA cells reacted immediately to transform into insulin-secreting cells to replace injured beta cells (or to compensate for the lack of beta cells) within 12 h of STZ administration.

Morphological characterization of ductular reactions in canine liver disease.

Intrahepatic bile duct proliferation (ductular reaction) was examined histologically, immunohistochemically and ultrastructurally in four cases of canine liver disease, diagnosed as chronic hepatitis, liver fibrosis, cirrhosis and cholangiocellular carcinoma. Ductular reaction was a common finding in all cases. Most of the proliferated bile ducts were similar to normal bile ducts. In addition, duct-like structures occurred, consisting of hepatocytes and of intermediate cells that had phenotypic characteristics of both cholangiocytes and hepatocytes. The proliferated bile ducts were immunohistochemically negative for proliferating cell nuclear antigen (PCNA) and stem cell factor (SCF). The proliferated bile ducts in these four cases of canine liver disease thus showed both typical ductular reactions, such as elongation and tortuosity of the existing bile ducts, and atypical ductular reactions resulting from metaplasia of hepatocytes.

Expression of nestin and IGF-1 in rat pancreas after streptozotocin administration.

The present study examines whether centroacinar (CA) and intercalated duct (ICD) cells can serve as stem cells, after administration of the diabetogenic agent streptozotocin (STZ). Thirty rats were divided into five experimental groups: (1) control, (2) 1 day after STZ (STZ-1), (3) 3 days after STZ (STZ-3), (4) 7 days after STZ (STZ-7) and (5) 14 days after STZ (STZ-14). Many small pancreatic islets were observed in the STZ-7 group than in the other experimental groups, and many of these small islets were in close contact with ICD and CA cells. A higher number of nestin, insulin-like growth factor-1 (IGF-1) and IGF-1-receptor positive ICD and CA cells were observed at STZ-3 and STZ-7 than at the others. These expression patterns coincided well with the proliferating cell nuclear antigen pattern. The results suggest that rat pancreatic endocrine cells after damage by STZ administration might be recovered from newly generated cells derived from ICD and CA cells.

Testicular atrophy after bile duct ligation in chickens.

Testicular atrophy associated with biliary obstruction in chickens, produced by the ligation of both extrahepatic bile ducts, was examined grossly, histologically, immunohistochemically, and ultrastructurally. Grossly, reduction in testicular size and volume was evident in chickens that underwent bile duct ligation (BDL). Histologically, there was marked reduction in tubular diameter, peritubular fibrosis, loss of spermatogenic cells, and tubules lined only by Sertoli cells. In addition, Leydig cells, which accumulated in the interstitium of the testes, contained numerous large lipid vacuoles, as determined by electron microscopy. These features suggest that BDL in chickens causes hypogonadism and low serum testosterone.

Morphological relationship between intercalated duct and pancreatic islet in streptozotocin and/or camostat mesilate administrations in the chicken.

Present electron microscopical and immunocytochemistrical studies elucidated some morphological relationship between intercalated duct (ICD) and pancreatic islet cells in the chicken in streptozotocin (STZ) and/or camostat mesilate (CM) administrations. Twenty-one chickens were set into four experimental groups: (1) control group, (2) STZ administration group, (3) CM administration group, and (4) STZ + CM administration group. Cytoplasms of ICD cells stained more strongly with eosin in STZ administration group than other groups, and electron-dense materials and intercalated processes between ICD and islet cells were also increasing in time dependence in STZ administration. Number of pancreatic islet in STZ + CM co-administration was about 3.1 times larger than other groups. Many small sized cells were detected at surrounding area of ICD and they incorporated 5-bromo-2'-deoxyuridine better than other experimental groups. Present morphological data suggested that ICD cells might support some tolerances of pancreatic endocrine cells against toxic substances and also involve in regeneration of new pancreatic islet cells in STZ + CM co-administration.

Possible induction of systemic lupus erythematosus by zonisamide.

An epileptic male to whom zonisamide and ethosuximide had been administered exhibited fever, pericarditis, pleuritis, arthralgia, and elevated titers of antinuclear antibody and anti-DNA-antibody at 5 years, 11 months of age. It was suggested that zonisamide induced the systemic lupus erythematosus symptoms because the antinuclear antibody titers began to rise after zonisamide was administered, and clinical recovery and a decrease in the anti-DNA-antibody levels promptly followed the discontinuation of the drug. The positive lymphocyte transformation test results against zonisamide further supports the etiologic relationship of the male's lupus and the drug. This first case of zonisamide-induced lupus should alert physicians to the possibility of this serious unwanted effect in patients receiving zonisamide.

Immunohistochemical localization of carbonic anhydrase isoenzymes in salivary gland and intestine in adult and suckling pigs.

Localizations of carbonic anhydrase isoenzymes (CA I, CA II and CA III) were investigated immunohistochemically in the salivary glands and intestine of mature and suckling pigs. Carbonic anhydrase isoenzymes were not detected in the salivary glands of sucklings, but were present in the adult. Bicarbonate ion in saliva might be important for the digestion of solid foods in mature pigs, but unnecessary for the digestion of milk in sucklings. Expressions of CA I and CA II were detected strongly in the large intestine of the adult and sucklings, and faintly only at duodenum in the small intestine. CA I and CA II isoenzymes in the large intestine may be involved, at least in part, in ion absorption and water metabolism during digestion and absorption of milk in suckling pigs. In addition, CA I and CA II expression in the duodenal villus enterocyte may support the process of bicarbonate absorption in the duodenum.

Measurement of telescope aberrations through atmospheric turbulence by use of phase diversity.

We conduct computer simulations of the reconstruction of a wave front at a telescope pupil with the phase-diversity method. An instantaneous wave front is reconstructed from focused and defocused specklegrams of a point star. In the wave-front reconstruction we do not fit the wave front to Zernike polynomials but retrieve the phase with a phase-unwrapping procedure. Averaging over many atmospherically perturbed wave fronts leads to the residual phase error, namely, the aberration of the telescope. The scintillation effect, nonuniformity of amplitude on a telescope pupil, is also discussed.

Expression of goose parvovirus VP1 capsid protein by a baculovirus expression system and establishment of fluorescent antibody test to diagnose goose parvovirus infection.

The gene encoding VP1 capsid protein of a goose parvovirus was cloned into a baculovirus transfer vector and a recombinant baculovirus was produced. The recombinant virus expressed a protein of 88 kDa corresponding to the molecular weight of VP1 protein and the protein was detected by immunoblotting. By indirect fluorescent antibody (IFA) test, the expressed protein was detected in the nucleus of the insect cells as big granules and electron microscopy also showed several big granules in the nucleus infected with the recombinant virus. The IFA test was developed for screening antibody in Muscovy ducks.

Intercalated duct cells in the chicken pancreatic islet with special reference to the alloxan administration.

The intercalated duct cells were observed in the A and B islets of the chicken pancreas. These cells adhered with each other by intercellular junctional complexes at the apical side. They had many microvilli projecting into the lumen. Abluminally, they displayed extended slender cytoplasmic processes between islet endocrine cells. Administration of alloxan resulted to denser cytoplasm and a more prominent thickening of cytoplasmic processes of the intercalated duct cells, although the blood glucose levels did not show appreciable changes by the treatment. The intercalated duct epithelial cells appeared clearly as stellate cells. The lysosomes increased in size and number with passage of time after alloxan administration. The present findings may suggest that intercalated ducts are not only anatomically important as a structure passing through the islet but also play physiologically by protecting the islet endocrine cells.

Intercalated duct cells in the moorhen (Gallinula chloropus) pancreatic islet.

Intercalated duct cells are present in the alpha and beta islets of the moorhen pancreas. The intercalated duct cells adhere to each other via intercellular junctional complexes on the apical side, projecting many microvilli into the lumen. They also extend slender cytoplasmic processes between islet endocrine cells. These intercalated duct cells appear to have a stellate shape, and to wrap their cytoplasm around the endocrine cells. These observations suggest that intercalated ducts not only pass through the islets, but also play a role in support to islet cells.