Biomedical subjects

H Kouhara

Publications and source records attributed to H Kouhara.

At least 19 recordsLinked to original sources

PubMed2003

Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications.

Atherosclerotic vascular diseases are frequently associated with diabetes mellitus. There has been increasing evidence showing that the atherosclerotic diseases in diabetic patients are distinct from diabetic microvascular complications as to their pathophysiology and epidemiology. However, we have no information on the prevalence of asymptomatic atherosclerosis in diabetic patients before the onset of microvascular diseases. In the present investigation, we aimed to evaluate risk factors for the atherosclerosis in type 2 diabetic patients without the microvascular diseases. For this purpose, we evaluated atherosclerotic change of carotid arteries in 125 Japanese type 2 diabetic patients who had neither atherosclerotic vascular diseases nor diabetic microvascular complications. When atherosclerotic change was defined as the mean intima-media thickness (IMT) of >/= 1.1 mm and/or the presence of plaque lesion, 50% of patients had atherosclerosis of the carotid arteries. Risk factors for the carotid atherosclerosis were age, low-density lipoprotein (LDL)-cholesterol, hypertension, and diabetes treatment. Age and LDL-cholesterol were associated with mean IMT. Age, diabetes treatment, LDL-cholesterol, and hypertension were positively associated with plaque lesion, while high-density lipoprotein (HDL)-cholesterol was negatively associated with it. Fasting plasma glucose, glycosylated hemoglobin (HbA(1c)), and known diabetes duration remained unassociated with any parameters of asymptomatic atherosclerosis of the carotid arteries. These results indicate that glycemic control is unrelated with asymptomatic atherosclerosis in type 2 diabetic patients without diabetic microvascular complications. Conventional risk factors and diabetes treatment are independently associated with atherosclerosis of the carotid arteries in these patients.

Aged↗

PubMed2001

Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways.

The docking protein FRS2 alpha has been implicated as a mediator of signaling via fibroblast growth factor receptors (FGFRs). We have demonstrated that targeted disruption of FRS2 alpha gene causes severe impairment in mouse development resulting in embryonal lethality at E7.0--E7.5. Experiments with FRS2 alpha-deficient fibroblasts demonstrate that FRS2 alpha plays a critical role in FGF-induced mitogen-activated protein (MAP) kinase stimulation, phosphatidylinositol-3 (PI-3) kinase activation, chemotactic response, and cell proliferation. Following FGF stimulation, tyrosine phosphorylated FRS2 alpha functions as a site for coordinated assembly of a multiprotein complex that includes Gab1 and the effector proteins that are recruited by this docking protein. Furthermore, we demonstrate that different tyrosine phosphorylation sites on FRS2 alpha are responsible for mediating different FGF-induced biological responses. These experiments establish the central role of FRS2 alpha in signaling via FGFRs and demonstrate that FRS2 alpha mediates multiple FGFR-dependent signaling pathways critical for embryonic development.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Cilostazol represses vascular cell adhesion molecule-1 gene transcription via inhibiting NF-kappaB binding to its recognition sequence.

Cilostazol is a specific inhibitor of cAMP phosphodiesterase, which is used for treatment of ischemic symptoms of peripheral vascular disease. Although cilostazol has antiplatelet and vasodilator properties, its effect on the expression of adhesion molecules in vascular endothelium is not known. In the present investigation, we examined the effect of cilostazol on the expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured vascular endothelial cells. Cilostazol strongly inhibited tumor necrosis factor (TNF)-alpha-induced expression of VCAM-1 protein and its mRNA. In addition, cilostazol reduced TNF-alpha-induced U937 cell adhesion to the vascular endothelial cells. In transient transfection studies, cilostazol inhibited TNF-alpha-induced transcriptional activation of VCAM-1 promoter. Electrophoretic mobility shift assays revealed that cilostazol repressed TNF-alpha-induced increase in binding of the transcription nuclear factor-kappaB (NF-kappaB) to its recognition site of VCAM-1 promoter. Cilostazol, however, failed to prevent nuclear translocation of the NF-kappaB p65 protein. These data indicate that cilostazol repressed VCAM-1 gene transcription in cultured vascular endothelial cells, via inhibiting NF-kappaB binding to its recognition sequence. Since the expression of the adhesion molecule is one of the earliest events occurred in atherogenic process, cilostazol might have the potential to prevent atherosclerosis at least via inhibition of the expression of the adhesion molecule.

Cell Adhesion↗

PubMed2001

Characteristics of type 2 diabetic patients responding to voglibose administration as an adjunct to sulfonylurea.

In this study, we characterized type 2 diabetic patients responding well to the alpha-glucosidase inhibitor voglibose administration as an adjunct to sulfonylurea treatment. Thirty-three type 2 diabetic patients were enrolled in an open prospective study. All the patients had been treated for at least 1 year with a sulfonylurea drug, in whom HbA1c level had been stable for at least 12 weeks. The patients were given voglibose at a dose of 0.2 mg t.i.d. for 12 weeks. Voglibose administration significantly decreased the mean HbA1c level in all the patients at 4, 8, and 12 weeks. Twelve (36%) of the study patients were responders, when the responders were defined as patients whose HbA1c level at 12 weeks fell by at least 1.0% from baseline, or those whose HbA1c level at 12 weeks was < or =7.0%, falling by at least 0.5% from baseline. The baseline fasting plasma glucose (FPG) was significantly lower, and the baseline homeostasis model assessment (HOMA) beta-cell function (HOMA-%beta) was significantly higher in the responders than in the non-responders. There were more patients who had FPG <170 mg/dl and/or HOMA-%beta > or =30% in the responders than in the non-responders (P<0.005). None of the patients with both FPG > or =170 mg/dl and HOMA-%beta >30% responded to the adjunct treatment. These results indicate that baseline FPG and HOMA-%beta are useful clinical markers to predict the effectiveness of the adjunct therapy of voglibose in sulfonylurea-treated type 2 diabetic patients.

Administration, Oral↗

PubMed2001

Characterization of premature atherosclerosis of carotid arteries in acromegalic patients.

OBJECTIVE: Acromegalic patients have increased mortality from vascular diseases. Although atherosclerotic risk factors such as hypertension, diabetes mellitus and dyslipoproteinaemia are highly associated with acromegaly, the prevalence of premature atherosclerosis in acromegalic patients and its relationship to these risk factors have not been reported. DESIGN: We measured mean intima-media thickness (IMT) of the carotid arteries in 21 acromegalic patients without symptomatic atherosclerotic vascular disease, by ultrasound high-resolution B-mode imaging. In analysis 1, it was compared with the predicted mean IMT based on data from existing risk factors (age, male sex, dyslipoproteinaemia, hypertension, diabetes mellitus, smoking status) in 282 non-acromegalic subjects. In analysis 2, the mean IMT in the 21 acromegalic patients was compared with that in 42 non-acromegalic subjects matched for age, sex and the other atherosclerotic risk factors. We also analysed clinical characteristics between the acromegalic patients with and without the atherosclerosis. RESULTS: Mean IMT in 21 acromegalic patients was 0.92 +/- 0.21 (mean +/- SD) mm. It was significantly (P < 0.05) lower than the mean IMT (1.03 +/- 0.12 mm) predicted from their existing risk factors (analysis 1). It was also less than that in 42 non-acromegalic subjects matched for atherosclerotic risk factors (1.07 +/- 0.37 mm; P < 0.05) (analysis 2). Among the acromegalic patients, 10 patients (48%) had increased mean IMT (> or = 1.1 mm) and/or plaque lesions whereas the other 11 had no such atherosclerotic changes. In the patients without the atherosclerotic changes, plasma insulin-like growth factor-I (IGF-I) concentration was significantly (P < 0.01) higher, and the prevalence of hypertension was significantly (P < 0.05) lower than in those with the atherosclerotic changes. CONCLUSIONS: The extent of carotid atherosclerosis in the acromegalic patients was not higher than that in non-acromegalic subjects, considering their atherosclerotic risk factors. Increased concentration of IGF-I might be involved in the lack of susceptibility to atherosclerosis in some acromegalic patients.

Acromegaly↗

PubMed2001

Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells.

-It has been shown that ovarian steroid hormones can reduce the incidence of cardiovascular disease in postmenopausal women. As hormone replacement therapy for postmenopausal women, progestins are added to estrogens to eliminate the increased risk of endometrial cancer. However, the effects of progestins on the atherogenic process have not been well understood. In the present study, we examined the effects of progestins on the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Immunocytochemical analysis revealed the presence of progesterone receptors in HUVECs. Progesterone clearly inhibited tumor necrosis factor-alpha-activated expression of VCAM-1 protein and its mRNA in HUVECs. Synthetic progesterone receptor agonist R5020 also inhibited the tumor necrosis factor-alpha-activated VCAM-1 expression, whereas medroxyprogesterone acetate (MPA) failed to do so. Electrophoretic mobility shift assays demonstrated that progesterone, but not MPA, inhibited DNA binding of the transcription nuclear factor-kappaB, which is critical for the inducible expression of VCAM-1. Because the expression of VCAM-1 is one of the earliest events that occurs in the atherogenic process, this adhesion molecule might be a target molecule for progesterone on vascular walls. The contrasting effects of progesterone and MPA seem clinically important, inasmuch as MPA is a widely used progestin in the regimen of hormone replacement therapy.

Endothelium, Vascular↗

PubMed2001

PPARalpha and GR differentially down-regulate the expression of nuclear factor-kappaB-responsive genes in vascular endothelial cells.

The antiinflammatory action of glucocorticoids is mediated partly by the inhibition of the expression of several cytokines and adhesion molecules. Some activators for nuclear receptors other than the GR have also been shown to inhibit the expression of these inflammatory molecules, although their molecular mechanisms remain unidentified. We therefore examined the effects of the PPARalpha activator fenofibrate and the GR activator dexamethasone on TNFalpha-stimulated expression of IL-6 and vascular cell adhesion molecule-1 in vascular endothelial cells. Both fenofibrate and dexamethasone reduced TNFalpha-induced IL-6 production in human vascular endothelial cells, but only fenofibrate reduced TNFalpha-stimulated vascular cell adhesion molecule-1 expression in these cells. Transient transfection of bovine aortic endothelial cells with an IL-6 promoter construct or a vascular cell adhesion molecule-1 promoter construct revealed that fenofibrate inhibited TNFalpha-induced IL-6 promoter as well as vascular cell adhesion molecule-1 promoter activities, whereas dexamethasone inhibited only the former. EMSA demonstrated that both fenofibrate and dexamethasone reduced nuclear factor-kappaB binding to its recognition site on the IL-6 promoter, but only fenofibrate reduced such binding to the vascular cell adhesion molecule-1 promoter. Thus, down-regulation of nuclear factor-kappaB activity by PPARalpha occurs in both the IL-6 and vascular cell adhesion molecule-1 genes, whereas that by GR occurs only in the IL-6 gene in vascular endothelial cells. These results strongly suggest the existence of a target gene-specific mechanism for the nuclear receptor-mediated down-regulation of nuclear factor-kappaB activity.

Biological Transport↗

PubMed2000

Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients.

OBJECTIVE: Abnormal glucose tolerance is often demonstrated in acromegalic patients. Although insulin resistance is a common feature of acromegaly, it remains unclear whether the extent of insulin resistance per se determines the abnormal glucose tolerance. In order to elucidate this issue, we investigated insulin sensitivity and beta-cell function in acromegalic patients. DESIGN: Twenty-four acromegalic patients were studied in comparison with 24 healthy control subjects. To estimate insulin sensitivity and beta-cell function, we used correct homeostasis model assessment (HOMA) model, a computer-solved model. We also investigated the effects of surgical success on both parameters. RESULTS: HOMA insulin sensitivity (HOMA-%S) in the acromegalic patients was 74 +/- 51 (SD)%, significantly lower than that in 24 healthy controls (144 +/- 49%). HOMA-%S in 12 normal glucose tolerance (NGT) patients was 54 +/- 31%, not significantly different from that in impaired glucose tolerance (IGT; n = 11) or diabetes mellitus (DM; n = 1) patients (93 +/- 60%). By contrast, HOMA beta-cell function (HOMA-%beta) in the NGT acromegalic patients was 163 +/- 67%, significantly higher than the IGT/DM acromegalic patients (89 +/- 34%) and the healthy controls (72 +/- 19%). In 11 patients who achieved complete normalization of GH excess after surgery, HOMA-%S significantly increased to control ranges (from 76 +/- 26 to 159 +/- 61%) within 2 weeks after the surgical success. CONCLUSIONS: We conclude that insulin sensitivity is reduced to a similar extent in acromegalic patients with normal glucose tolerance and those with impaired glucose tolerance or diabetes. Compensatory hyperfunction of beta-cells appears to counterbalance the reduced insulin sensitivity in the acromegalic patients with normal glucose tolerance but not in those with impaired glucose tolerance or diabetes.

Acromegaly↗

PubMed1998

Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.

FRS2 is a lipid-anchored docking protein that plays an important role in linking fibroblast growth factor (FGF) and nerve growth factor receptors with the Ras/mitogen-activated protein (MAP) kinase signaling pathway. In this report, we demonstrate that FRS2 forms a complex with the N-terminal SH2 domain of the protein tyrosine phosphatase Shp2 in response to FGF stimulation. FGF stimulation induces tyrosine phosphorylation of Shp2, leading to the formation of a complex containing Grb2 and Sos1 molecules. In addition, a mutant FRS2 deficient in both Grb2 and Shp2 binding induces a weak and transient MAP kinase response and fails to induce PC12 cell differentiation in response to FGF stimulation. Furthermore, FGF is unable to induce differentiation of PC12 cells expressing an FRS2 point mutant deficient in Shp2 binding. Finally, we demonstrate that the catalytic activity of Shp2 is essential for sustained activation of MAP kinase and for potentiation of FGF-induced PC12 cell differentiation. These experiments demonstrate that FRS2 recruits Grb2 molecules both directly and indirectly via complex formation with Shp2 and that Shp2 plays an important role in FGF-induced PC12 cell differentiation.

3T3 Cells↗

PubMed1997

A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway.

Activation of the Ras/MAPK signaling cascade is essential for growth factor-induced cell proliferation and differentiation. In this report, we describe the purification, cloning, and characterization of a novel protein, designated FRS2, that is tyrosine phosphorylated and binds to Grb2/Sos in response to FGF or NGF stimulation. We find that FRS2 is myristylated and that this modification is essential for membrane localization, tyrosine phosphorylation, Grb2/Sos recruitment, and MAPK activation. FRS2 functions as a lipid-anchored docking protein that targets signaling molecules to the plasma membrane in response to FGF stimulation to link receptor activation with the MAPK and other signaling pathways essential for cell growth and differentiation. Finally, we demonstrate that FRS2 is closely related and probably indentical to SNT, the long-sought target of FGF and NGF receptors.

3T3 Cells↗

PubMed1995

Ligand-independent activation of tyrosine kinase in fibroblast growth factor receptor 1 by fusion with beta-galactosidase.

To examine the biological role of fibroblast growth factor receptor 1 (FGFR1) oligomerization for its signal transduction, we construct an expression vector encoding a FGFR1-beta-galactosidase fusion protein. This vector is designed to fuse the 3'-portion of FGFR1 to beta-galactosidase. Transfection of this vector into FGFR-negative rat L6 myoblast cells results in ligand-independent inhibition of differentiation into myocytes, suggesting that FGFR1 within this fusion protein is constitutively activated. This can be confirmed by demonstrating that this fusion protein exhibits the tyrosine kinase activity and phospholipase C gamma 1 is tyrosine-phosphorylated even in the absence of ligand stimuli. Since the transfected cells also exhibit the enzyme activity of beta-galactosidase which is known to be active only in a tetramer form, this constitutive activation can be elicited by tetramerization of FGFR1. Furthermore, deletion of a region corresponding to C terminal 10 amino acids important for tetramerization of beta-galactosidase from this expression vector abolishes the constitutively active nature of FGFR1 with simultaneous loss of beta-galactosidase activity. Transfection of non-deleted expression vector into NIH3T3 cells results in acquisition of focus-forming activity while a deleted form of expression vector fails to show this activity even in the presence of basic FGF. These results would suggest that tetramerization of FGFR1 can produce a constitutively active form responsible for transformation of NIH3T3 cells.

3T3 Cells↗

PubMed1995

Identification of alternatively spliced messenger ribonucleic acid encoding truncated growth hormone-releasing hormone receptor in human pituitary adenomas.

The expression of GHRH receptor (GHRH-R) messenger ribonucleic acid (mRNA) was studied in 22 pituitary adenomas and 2 normal anterior pituitaries. Northern blot analysis revealed that GHRH-R mRNA were expressed in all 14 GH-producing adenomas, 1 of 3 ACTH-producing adenomas, the 1 PRL-producing adenoma, 2 of 4 nonfunctioning adenomas, and the 2 normal anterior pituitaries. Their expression levels varied among GH-producing adenomas and were relatively low in GH-nonproducing adenomas. In addition to the major transcript with a molecular mass of 2.0 kilobases (kb), the transcripts were identified at 2.8 and 4.5 kb in some GH-producing adenomas. To examine the structural variations in GHRH-R mRNA in pituitary adenomas, we amplified the complementary DNA fragment encompassing the region from the third cytoplasmic loop to the sixth transmembrane domain of GHRH-R. This region was selected because this region of the G protein-coupled receptor has been known to interact with G protein. Two amplified fragments with the molecular masses of 250 and 810 base pairs were identified by the reverse transcriptase-polymerase chain reaction method. The nucleotide sequence of a smaller fragment, which was the expected size, revealed that no mutations were found in this region in 10 GH-producing adenomas examined. However, a larger fragment contained the currently unidentified insertion. Compared with the genomic DNA sequence, this insertion was found to be generated through alternative splicing. In addition, this variant form contained the premature stop codon in-frame, indicating that it encodes the truncated GHRH-R. This insertion-specific probe could hybridize with 2.8- and 4.5-kb species of GHRH-R mRNA on Northern blot analysis, and these transcripts were expressed mainly in GH-producing adenomas. Finally, study of cell transfection and cAMP measurement revealed that this truncated GHRH-R was unable to transmit GHRH signals. These results suggest that some GH-producing adenomas preferentially express the truncated GHRH-R as a nonfunctioning receptor through alternative splicing.

Adenoma↗

PubMed1994

Murine fibroblast growth factor receptor 1 gene generates multiple messenger RNAs containing two open reading frames via alternative splicing.

The arrangement of exons and introns encoding 5'-side of murine fibroblast growth factor (FGF) receptor 1 (FGFR-1) gene was mapped. A large intron with a size of 14 kb was identified between exon 1 and exon 2. In addition, all FGFR-1 subtypes including a unique variant form with 12 amino acids insertion and two amino acids deletion were observed to be able to be generated through alternative splicing. Furthermore, complete sequencing of the 5'-region of FGFR-1 mRNA revealed that a relatively large open reading frame precedes the major open reading frame encoding FGFR-1. These results indicate that FGFR-1 mRNAs are uniquely translated from an internal translation start site.

3T3 Cells↗

PubMed1994

Unsaturated fatty acids are required for continuous proliferation of transformed androgen-dependent cells by fibroblast growth factor family proteins.

Increase in dietary fat intake has been reported to be associated with progression of hormone-dependent cancers. To explore its mechanism, we examined the effects of fatty acids on the growth of androgen-dependent SC-3 cells cloned from mouse mammary cancer (Shionogi carcinoma 115). Their androgen-dependent growth was potentiated by linoleic acid in the defined medium. The effect of linoleic acid on fibroblast growth factor (FGF)-dependent growth was also addressed because androgen had been demonstrated to exert its mitogenic activity on SC-3 cells through an induction of the unique FGF family protein termed as androgen-induced growth factor. Exposure of SC-3 cells to basic FGF or androgen-induced growth factor exhibited only transient growth response. However, simultaneous addition of linoleic acid to the medium sustained the proliferation of FGF-stimulated, but not FGF-unstimulated, cells, although linoleic acid did not exert the significant effect on the process of S-phase entry of basic FGF-stimulated cells. Palmitoleic acid and oleic acid appeared to exert the actions similar to linoleic acid, while stearic acid was without any effect. Neither cyclooxygenase inhibitor nor 5-lipoxygenase inhibitor could block the growth-promoting ability of linoleic acid. Linoleic acid also enhanced their anchorage-independent growth in the presence of basic FGF. These results indicate that these unsaturated fatty acids play a role in sustaining the proliferation of FGF-stimulated SC-3 cells.

Animals↗

PubMed1994

Mapping of a transcription element critical for expression of the fibroblast growth factor receptor 1 gene.

The fibroblast growth factor receptor 1 (FGFR1) gene has no TATA or CCAAT-elements. To examine its mechanism of expression, we characterized the transcription element of this gene. The basal promoter element was mapped to the 5'-flanking region from -89 to -43. The DNase I protection assay and gel shift analysis revealed that a nuclear protein extracted from FGFR1-expressing cells (NIH3T3 and SC-3), but not from FGFR1-nonexpressing cells (P3U1), could bind to the nucleotide sequence from -62 to -42. The molecular weight of this protein was approximately 100 kDa by Southwestern analysis. In addition, both the promoter activity and the nuclear protein binding activity were markedly impaired by the substitution of two bases within this footprint site. Interestingly, this footprint site appeared to lack the consensus sequence of the currently reported transcription factors. These results indicate that the 5'-flanking region from -62 to -42 plays a pivotal role in FGFR1 gene expression.

3T3 Cells↗

PubMed1994

Facilitation of autonomous phenotype acquisition in androgen-dependent Shionogi carcinoma 115 cells by transfection of androgen-induced growth factor expression vector.

Androgen-induced growth factor (AIGF) is an autocrine growth factor for androgen-dependent SC-3 cells, which is induced by androgen stimuli. To elucidate the mechanism of the progression from hormone-dependent to -independent tumor, we transfected an expression vector of cDNA encoding AIGF into SC-3 cells and established a stable transfectant (A1) expressing AIGF. A1 cells showed enhanced DNA synthesis. This enhanced DNA synthesis was blocked by exposing the cells to AIGF antisense oligonucleotides, heparin, or suramin, indicating that enforced AIGF expression is responsible for the increase in DNA synthesis. However, A1 cells did not grow in serum-free medium unless stimulated with androgen. Recloning from A1 cells in semi-solid agar supplemented with fetal calf serum but without androgen quickly generated an autonomous subline that was able to grow rapidly in the serum-free medium irrespective of androgen stimulus. Mock-transfected SC-3 cells failed to form any colony under identical conditions. These results suggest that stable expression of AIGF alone is not sufficient for, but facilitates the conversion of SC-3 cells from androgen-dependent to -independent phenotype.

Androgens↗

PubMed1994

Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas.

OBJECTIVE: Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized in human pituitaries. In addition, altered or insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non-tumorous and tumorous human pituitaries should be examined. DESIGN: Total RNAs were extracted from non-tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression. SAMPLES: Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non-functioning adenomas were obtained at surgery. Two non-tumorous pituitaries were also included in this study. MEASUREMENTS: The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products. RESULTS: PC2 and PC3 mRNAs in non-tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT-PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas. CONCLUSION: The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.

Adenoma↗

PubMed1994

Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor.

Intracranial germ cell tumors are known to be frequently associated with anterior pituitary hypofunction and diabetes insipidus. In general, these manifestations are not ameliorated even after successful radiotherapy. Since platinum based chemotherapy is introduced as a therapeutic approach to these tumors, its effectiveness is compared with the outcome obtained by radiotherapy in terms of tumor regression and endocrine functions. In this study, six patients received conventional radiotherapy and one received chemotherapy as an initial treatment. In all patients, complete remission was achieved irrespective of the therapeutic method. Their diabetes insipidus was not improved. Many patients treated with radiotherapy did not show the complete improvement of pre-existing hypofunction of the anterior pituitaries. In contrast, chemotherapy achieved almost complete hormonal remission. These clinical observations suggest that chemotherapy is quite effective in oncological as well as endocrinological aspects in treating intracranial germ cell tumors.

Adolescent↗