Biomedical subjects

M Kojima

Publications and source records attributed to M Kojima.

At least 91 records · Page 5Linked to original sources

PubMed2001

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle. 2. Rats with pituitary transplants showed increased serum prolactin concentrations and decreased serum concentrations of gonadotropins and increased pituitary concentrations of gonadotropins. Moreover, these rats showed persistent dioestrous and anovulation from 3 to 6 days after transplantation. 3. A single oral administration of cabergoline (at doses between 0.001 and 0.1 mg/kg) dose-dependently inhibited the elevated serum prolactin concentrations in hyperprolactinaemic rats. At 0.1 mg/kg, cabergoline induced a continuous reduction in serum prolactin concentrations for 5 days after administration. Terguride (0.1 mg/kg) and bromocriptine (10 mg/kg) also reduced serum prolactin concentrations at 1 and 3 days after administration. All three dopamine D2 receptor agonists increased serum gonadotropin concentrations and ovarian weight at 3 days after administration. 4. In rats exhibiting anovulation, a single oral administration of any one of the three dopamine D2 receptor agonists dose-dependently restored ovulation and a normal oestrous cycle appeared. Oral administration of cabergoline (0.03 mg/kg) or terguride (0.1 mg/kg) restored ovarian function and abolished the anovulation following a reduction in serum prolactin concentrations. However, bromocriptine (10 mg/kg) did not completely abolish anovulation. Following administration of terguride (0.3 mg/kg) or bromocriptine (30 mg/kg), only one normal oestrous cycle appeared; however, following cabergoline (0.1 mg/kg), two normal oestrous cycles appeared. 5. These results suggest that cabergoline has a potent and long-lasting action as a dopamine D2 receptor agonist and, thus, should be a useful drug for the treatment of galactorrhoea and hyperprolactinaemic amenorrhoea and/or anovulation in humans.

Animals↗

PubMed2001

The Japanese version of the Barratt Impulsiveness Scale, 11th version (BIS-11): its reliability and validity.

No instrument for assessing impulsiveness has been developed in Japan. After translating the Barratt Impulsiveness Scale 11th version (BIS-11) into Japanese, we investigated reliability and validity in student (n = 34) and worker (n = 416) samples. To assess test-retest reliability, the intraclass coefficient between test and retest was calculated in the student sample. Internal consistency was examined by calculating Cronbach's alpha in the worker sample. To see factor validity, we examined by confirmatory factor analysis whether the three-factor model, proposed by a previous report, fit the data. The results showed that the Japanese version of the BIS-11 had excellent test-retest reliability and acceptable internal consistency reliability. In addition, the Japanese version was judged to have similar factor structure to the original one. The Japanese version of the BIS-11 is a reliable and valid measure and has possible utility for assessing impulsiveness.

Adult↗

PubMed2001

Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases.

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.

Adult↗

PubMed2001

Transperineal 12-core systematic biopsy in the detection of prostate cancer.

BACKGROUND: The present study was designed to determine the clinical value of transperineal 12-core systematic prostate biopsy guided by transrectal ultrasonography (TRUS) in the detection of prostate cancer. METHODS: A total of 679 consecutive patients underwent systematic prostate biopsies because of abnormal results on digital rectal examination and/or TRUS and/or an elevated serum prostate-specific antigen level. Systematic six- and 12-core biopsies were taken in 138 patients between April 1994 and February 1995 and in the remaining 541 between March 1995 and February 2000, respectively. Twelve-core biopsy included two samples from the lateral portion of the peripheral zone and four from the anterior portion of the transition zone in addition to the conventional six-core biopsy. RESULTS: In the series overall, systematic biopsy revealed 156 cases of prostate cancer (23.0%). The detection rate increased by 5.2%, although this was statistically not significant, from 18.8% (26/138) by six-core biopsy to 24.0% (130/541) by 12-core biopsy. Out of 130 patients in whom prostate cancer was detected by 12-core biopsy, it was supposed that conventional six-core biopsy would have missed 18 cases (13.8%). CONCLUSIONS: Systematic 12-core biopsy might improve the detection rate for prostate cancer. However, further studies are needed to determine its clinical value in the diagnosis of the disease.

Adult↗

PubMed2001

[Characteristics and frequency of cortical cataracts at an early stage (Reykjavik Eye Study in Iceland)].

BACKGROUND: The frequency and characteristics of cortical cataract localization within a dilated pupillary area were investigated in a population-based cataract epidemiological survey performed in the city of Reykjavik in Iceland. MATERIALS AND METHODS: Among 1045 randomly selected individuals, the right eyes of 277 persons with mild cortical lens opacification (Grade I) were selected for our study. The localization of cortical cataracts was examined using retroillumination images, which were divided into 56 circular and radial sections, and calculations were made of the percentages for each opacified area. A questionnaire was used to record the number of hours spent outdoors during week days, the time of the day and whether the subjects wore spectacles, sunglasses or hats when outside. RESULTS: The percentage of cortical opacification was significantly higher in the lower nasal quadrant than in all other quadrants (p < 0.05). Furthermore, the percentage of opacification localized in the lower nasal quadrant was higher in individuals with a longer history of outdoor activity than those without (p < 0.05). The percentage of opacification in individuals, who have had the habit of wearing sunglasses for outdoor activities lasting longer than half an hour during weekdays in their 20's and 30's was lower in all quadrants and statistically significantly lower in the upper temporal quadrant (p < 0.05) compared to those not wearing sunglasses. CONCLUSION: This suggests that wearing sunglasses is effective in preventing the development and/or progression of cortical cataracts.

Aged↗

PubMed2001

Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles. A clinicopathological analysis of nine cases.

Autoimmune disease-associated lymphadenopathy shows marked histopathological and clinical diversity. We describe the clinicopathological and immunohistochemical findings of nine cases of autoimmune disease-associated lymphadenopathy, which posed a serious differential diagnostic problem regarding T-zone dysplasia with hyperplastic follicles. There were two males and seven females aged 25 to 65 years (median 37 years). The patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of an "autoimmune disease". Four patients were diagnosed to have systemic lupus erythematosus (SLE), and the remaining five patients had antiphospholipid antibody syndrome and Sjogren's syndrome (SS), rheumatoid arthritis (RA), chronic thyroiditis, RA and SS, and SLE and SS, respectively. None of the nine patients developed malignant lymphomas during the follow-up periods from 44 to 225 months (median 103 months). The lesions were characterized by paracortical hyperplasia with prominent vascular proliferation and many lymphoid follicles with germinal centers. The paracortical area usually contained numerous small T-lymphocytes without cytological atypia, accompanied by a variable number of plasma cells, B-immunoblasts, and histiocytes. Polymerase chain reaction analysis demonstrated no clonal rearrangement of the T-cell receptor chain gene in four cases examined, although immunoglobulin heavy chain rearrangement was detected in only one case. These findings suggest that autoimmune disease-associated lymphadenopathy, especially SLE, shares the histological features with T-zone dysplasia with hyperplastic follicles. The nine cases presented here should be differentiated from T-zone lymphoma with follicles and angioimmunoblastic lymphoma with hyperplastic germinal centers. To avoid overdiagnosis and overtreatment, we emphasize the need to turn attention to these clinical and laboratory findings as well as to the morphological features.

Adult↗

PubMed2001

Marginal zone B cell lymphomas of Waldeyer's ring--a report of two tonsillectomy cases resembling histomorphological features of inflammatory lesions.

We identified two cases of lymphoma of the mucosa-associated lymphoid tissue (MALT) type in 11 tonsillectomy specimens of primary B cell lymphoma of Waldeyer's ring. Both patients were Japanese females presenting with bilateral enlargement of the palatine tonsils. One had a history of chronic otitis media. In that case, the lesion was characterized by an extrafollicular growth pattern with marginal zone-like arrangement. The tumor was mainly composed of medium-sized cells with round or indented nuclei with scant cytoplasm (centrocyte-like cells). In the other patient, most tumor cells were mature plasma cells, plasmacytoid cells, proplasmacytes, and immunoblasts with scattered centrocyte-like cells. Tropism of tumor cells for the epithelium was noted in both lesions. Primary marginal zone B cell lymphoma of the MALT type arising from Waldeyer's ring has rarely been reported in the literature, causing certain diagnostic problems. Various florid reactive lymphoproliferative disorders, including chronic tonsillitis and infectious mononucleosis, should be differentiated from this type of primary Waldeyer's ring lymphoma.

Adult↗

PubMed2001

Light response of the circadian waves of the APRR1/TOC1 quintet: when does the quintet start singing rhythmically in Arabidopsis?

We previously identified a novel class of proteins, named A:rabidopsis pseudo-response regulators (APRRs), each of which (APRR1/TOC1, APRR3, APRR5, APRR7, APRR9) has an intriguing structural design containing an N-terminal pseudo-receiver domain and a C-terminal CONSTANS motif. Expression of these APRR1/TOC1 family members is under the control of a coordinate circadian rhythm at the level of transcription such that the APRR-mRNAs start accumulating sequentially after dawn with 2 to 3 h intervals in the order of APRR9-->APRR7-->APRR5-->APRR3-->APRR1/TOC1 in a given 24 h photo-period. Based on these data, we previously proposed that these sequential and rhythmic events of transcription, termed 'circadian waves of APRR1/TOC1 quintet', may be a basis of a presumed Arabidopsis biological clock (named 'bar code clock') [Matsushika et al. (2000) Plant and Cell Physiol. 41: 1002]. Here we further characterized the event of circadian waves, by demonstrating that certain light stimuli are crucial determinants to induce the robust circadian waves, and accordingly, the first-boosted and light-induced APRR9 appears to be primarily responsible for this light response of the circadian waves. Also, as such a light stimulus, a red light pulse that is presumably perceived by phytochromes appears to be sufficient to induce (or synchronize) the APRR1/TOC1 circadian waves.

Arabidopsis↗

PubMed2001

Antitumor activity, optimum administration method and pharmacokinetics of 13,14-dihydro-15-deoxy-deoxy-Delta7 -prostaglandin A1 methyl ester (TEI-9826) integrated in lipid microspheres (Lipo TEI-9826).

13,14-Dihydro-15-deoxy-Delta7-prostaglandin A1 methyl ester (TEI-9826), an antitumor prostaglandin analog, is a candidate for clinical trial. In the present study, we examined its biological stability in vitro, antitumor activity in vitro and in vivo, and pharmacokinetics. Although TEI-9826 was rapidly hydrolyzed to the carboxylic acid form (TOK-4528), TOK-4528 as well as Delta12-prostaglandin J2 (PGJ2) were found to be stable in rat, mouse and human serum in vitro. TEI-9826 exhibited nearly identical or greater potential antitumor activity compared to Delta12-PGJ2 and Delta7-PGA1 in vitro against Colon26 tumor cells. Further evaluation of TEI-9826 using the 38 human cancer cell lines panel and COMPARE analysis suggested that its mode of action is quite different from other anticancer agents that are currently used. TEI-9826 was integrated into lipid microspheres (Lipo TEI-9826) for dosing. Growth inhibition by Lipo TEI-9826 against Colon26 tumor inoculated s.c. in mice depended on administration route, i.e. at 80 mg/kg, no growth suppressive effect was observed for daily bolus i.v., but significant growth suppressive effect was observed for daily i.p., daily s.c. every other day s.c. and 4 times a day continuous (5 min) i.v. These tumor growth-suppressive effects were cytostatic and the tumor started to regrow at the end or a few days after the end of administration. The pharmacokinetic study suggested that maintaining the blood level of TEI-9826 and/or TOK-4528 was essential for their antitumor effects. These results show that continuous i.v. infusion might be the most suitable administration method of Lipo TEI-9826 for clinical trial.

Animals↗

PubMed2001

Role of Ca2+-sensitive protein kinase C in phenylephrine enhancement of Ca2+ sensitivity in rat tail artery.

We investigated the role of protein kinase C (PKC) isoforms on changes in sensitivity of contractile mechanisms to intracellular Ca(2+) (force /[Ca(2+)]i) by phenylephrine (0.1-100 microM) in rat tail arterial helical strips using simultaneous measurements of force and [Ca(2+)]i. Force/[Ca(2+)]Ii induced by phenylephrine was greater than that induced by 80 mM K+. Force/[Ca(2+)]i induced by phenylephrine in physiologic saline solution or low Ca(2+) solution was dependent on the agonist concentration. Removal of Ca(2+) completely abolished the phenylephrine-induced contraction. The PKC inhibitors staurosporine and calphostin C inhibited the increase in force/[Ca(2+)]i induced by phenylephrine to a much greater extent than that induced by 80 mM K+. LY379196, a specific PKCbeta inhibitor, did not inhibit the increase of calcium sensitivity due to phenylephrine. The classic PKC isoforms, alpha, betaI, and II not gamma were demonstrated in the artery by immunohistochemistry. These results suggest that in rat tail arterial smooth muscle, PKCalpha, and not beta or gamma, mediates the increase of changes in sensitivity of contractile mechanisms to intracellular Ca(2+) to high dose of alpha1 receptor stimulation (phenylephrine 100 microM) on nonphysiologic conditions.

Animals↗

PubMed2001

Primary structure and expression of a 24-kD vacuolar protein (VP24) precursor in anthocyanin-producing cells of sweet potato in suspension culture.

A 24-kD vacuolar protein (VP24) accumulates abundantly in intravacuolar pigmented globules in anthocyanin-containing sweet potato (Ipomoea batatas) cells in suspension culture. A cDNA clone encoding VP24 was isolated from a cDNA library constructed from light-irradiated suspension-cultured cells. Sequence analysis revealed that a 2.9-kbp VP24 cDNA encodes a protein of 893 amino acid residues with a molecular mass of 96.3 kD. According to the deduced amino acid sequence of VP24 cDNA, VP24 is probably synthesized as a large precursor protein with an N-terminal extension composed of a signal peptide and a propeptide, plus the polypeptide of the mature VP24 and its C-terminal propeptide, which contains the multiple transmembrane domains. A search in the ProDom database revealed the mature VP24 domain belongs to the zinc metalloprotease family. Northern analysis revealed that the single 2.9-kb VP24 mRNA increases rapidly after light irradiation, whereas VP24 mRNA was undetectable in the dark-cultured cells or in the presence of a high concentration of 2,4-dichlorophenoxyacetic acid. Light-induced VP24 gene expression closely correlated with the accumulation of anthocyanin in the vacuoles. These results suggested that proteins derived from the VP24 precursor protein may be involved in vacuolar transport and/or accumulation of anthocyanin synthesized in the cytosol.

Amino Acid Sequence↗

PubMed2001

Hemodynamic and hormonal effects of human ghrelin in healthy volunteers.

To investigate hemodynamic and hormonal effects of ghrelin, a novel growth hormone (GH)-releasing peptide, we gave six healthy men an intravenous bolus of human ghrelin (10 microg/kg) or placebo and vice versa 1-2 wk apart in a randomized fashion. Ghrelin elicited a marked increase in circulating GH (15-fold). The elevation of GH lasted longer than 60 min after the bolus injection. Injection of ghrelin significantly decreased mean arterial pressure (-12 mmHg, P < 0.05) without a significant change in heart rate (-4 beats/min, P = 0.39). Ghrelin significantly increased cardiac index (+16%, P < 0.05) and stroke volume index (+22%, P < 0.05). We also examined ghrelin receptor [GH secretagogues receptor (GHS-R)] gene expression in the aortas, the left ventricles, and the left atria of rats by RT-PCR. GHS-R mRNA was detectable in the rat aortas, left ventricles, and left atria, suggesting that ghrelin may cause cardiovascular effects through GH-independent mechanisms. In summary, human ghrelin elicited a potent, long-lasting GH release and had beneficial hemodynamic effects via reducing cardiac afterload and increasing cardiac output without an increase in heart rate.

Adult↗

PubMed2001

Purification and distribution of ghrelin: the natural endogenous ligand for the growth hormone secretagogue receptor.

Growth hormone secretagogues (GHS) are small synthetic molecules that act through a specific G-protein coupled receptor (GPCR) termed GHS-R, which is a distinct receptor from that of growth hormone releasing hormone (GHRH). This receptor was one of the orphan GPCR, i.e. a GPCR with no known natural ligand, until we purified its endogenous ligand from rat stomach and named it "ghrelin". Ghrelin is a 28-amino-acid peptide, in which the serine 3 is modified by an n-octanoic acid and this modification is essential for ghrelin's activity. The discovery of ghrelin indicates that the release of GH from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelin from the stomach and hypothalamus.

Amino Acid Sequence↗

PubMed2001

Effect of the central nervous system on mucosal growth and apoptosis in the small intestine.

Recently our studies have demonstrated that the central nervous system regulates in part mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase (ODC) activity is a key enzyme for polyamine synthesis which plays an important role for the intestinal mucosal growth. We have demonstrated that the increase of ODC activity in the duodenum just before the dark period is abolished by truncal vagotomy and that the infusion of 2-deoxy-D-glucose into the third cerebroventricle activates ODC activity in the small intestine. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. Our preliminary data showed that intestinal mucosal apoptosis decreased in the ventromedial-hypothalamus-lesioned rat. These results indicate that the central nervous system, in addition to local factors, is related to regulation of mucosal homeostasis in the intestinal mucosa.

Animals↗

PubMed2001

Inflammatory pseudotumor of lymph nodes: clinicopathologic and immunohistological study of 11 Japanese cases.

We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node. There were 7 males and 4 females with ages ranging from 5 to 68 years (median; 48). Only 2 patients had systemic lymphadenopathy, and all others had involvement of only 1 lymph node group. Constitutional symptoms such as fever were present in 8 patients and laboratory abnormalities were detected in 5. All patients recovered and were alive and well after 2 to 180 months (median; 32 months). Histologically, the process mainly involved the connective tissue framework of the lymph node, secondarily spreading into the lymph node parenchyma and the perinodal tissue. It was characterized by a storiform growth pattern of myofibroblasts, marked vascularity with associated vascular lesions, and a polymorphous reactive cellular infiltrate in a collagen-rich stroma. An immunohistochemical study revealed numerous myofibroblasts, histiocytes, and vascular endothelial cells expressing vascular endothelial growth factor (VEGF) in 6 cases. It was suggested that VEGF may be involved, in part, in the induction of the angiogenesis of IPT. Moreover, the present study indicates that follicular dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic large cell lymphoma should be added to the differential diagnosis from IPT of the lymph node. Int J Surg Pathol 9(3):207-214, 2001

Adolescent↗

PubMed2001

Follicular lymphoma of the salivary gland: a clinicopathological and molecular study of six cases.

To clarify the clinicopathologic, immunohistologic, and genotypic features of follicular lymphoma arising from the salivary glands, we examined 20 cases of operatively resected primary salivary gland lymphoma and identified 6 such cases. There were 4 women and 2 men with ages ranging from 38 to 64 years (median 50 years). The tumor arose from the parotid gland in 4 cases and the submandibular gland in the remaining 2. Four patients were stage IE and 2 were stage IIE-1. The median follow-up period was 49 months and all patients were alive and well at the time of going to press. Histologically, 5 patients were follicular lymphoma grade 2, and 1 was grade 3. In all specimens in noninfiltrating salivary gland tissue, there was periductal lymphocytic infiltration near the lymphoma. Moreover, myoepithelial sialoadenitis was noted in 2 lesions. An immunohistochemical study revealed all 6 cases were CD10+, CD79a+, bcl-6+, CD3-, CD5-, CD21-, CD23-, and CyclinD1-. The tumor cells expressed bcl-2 in 3 cases and p53 oncoprotein in 4 cases. Two cases revealed clonal bands with polymerase chain reaction (PCR) assay for the immunoglobulin heavy (IgH) gene. The bcl-2/IgH translocation at the major breakpoint region was detected in 1 case (16%). We found a relatively high incidence of follicular lymphomas (30%) in salivary gland lymphomas. Among the mucosa-associated lymphoid tissue (MALT) system, follicular lymphomas appeared to occur frequently in the salivary glands as well as the duodenum and skin. Moreover, follicular lymphoma arising from the salivary glands appeared to have some of the characteristics of MALT-type lymphoma including indolent prognosis, presence of myoepithelial sialoadenitis, and rarity of the BCL-2 gene rearrangement.

Adult↗

PubMed2001

Ghrelin, a novel placental-derived hormone.

Ghrelin, a GH-releasing acylated peptide, has been recently identified from the rat stomach. The purified peptide consists of 28 amino acids in which the serine 3 residue is n-octanoylated. Here we show that ghrelin messenger RNA and ghrelin peptide are present in the human as well as in rat placentae. In human placenta, ghrelin was detected by PCR at both first trimester and after delivery. While ghrelin was not detected by immunohistochemistry in human placenta at term, it was easily identified by immunohistochemistry at first trimester being mainly expressed in cytotrophoblast cells and scarcely in syncytiotrophoblast ones. Ghrelin was also identified in a human choriocarcinoma cell line, the BeWo cells. Ghrelin was found, by immunohistochemistry, in the cytoplasm of labyrinth trophoblast of rat placenta, whereas other placental cell types seems to be negative for ghrelin immunostaining. Moreover, placental ghrelin messenger RNA, in pregnant rats, showed a characteristic profile of expression being practically undetectable during early pregnancy, with a sharp peak of expression at day 16 and decreasing in the latest stages of gestation. In conclusion, ghrelin has been detected in human and rat placenta showing a pregnancy-related time course of expression. Whether placenta-derived ghrelin is involved in the modulation of GH release, or placental cell growth and differentiation remains to be established.

Animals↗

PubMed2001

Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans.

Ghrelin, an endogenous ligand for the GH secretagogue receptor, was isolated from rat stomach and is involved in a novel system for regulating GH release. Although previous studies in rodents suggest that ghrelin is also involved in energy homeostasis and that ghrelin secretion is influenced by feeding, little is known about plasma ghrelin in humans. To address this issue, we studied plasma ghrelin-like immunoreactivity levels and elucidated the source of circulating ghrelin and the effects of feeding state on plasma ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like immunoreactivity concentration in normal humans measured by a specific RIA was 166.0 +/- 10.1 fmol/ml. Northern blot analysis of various human tissues identified ghrelin mRNA found most abundantly in the stomach and plasma ghrelin-like immunoreactivity levels in totally gastrectomized patients were reduced to 35% of those in normal controls. Plasma ghrelin-like immunoreactivity levels were increased by 31% after 12-h fasting and reduced by 22% immediately after habitual feeding. In patients with anorexia nervosa, plasma ghrelin-like immunoreactivity levels were markedly elevated compared with those in normal controls (401.2 +/- 58.4 vs. 192.8 +/- 19.4 fmol/ml) and were negatively correlated with body mass indexes. We conclude that the stomach is a major source of circulating ghrelin and that plasma ghrelin-like immunoreactivity levels reflect acute and chronic feeding states in humans.

Adult↗