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Biomedical subjects

I A Kourides

Publications and source records attributed to I A Kourides.

At least 19 recordsLinked to original sources
PubMed2001

Inhaled human insulin treatment in patients with type 2 diabetes mellitus.

BACKGROUND: Despite demonstrated benefits, intensive insulin therapy has not gained widespread clinical acceptance for several reasons: Multiple daily injections are inconvenient, adherence is a concern, and the time-activity profile may not mimic normal insulin secretion. As such, alternate means of administering insulin are being evaluated. OBJECTIVE: To assess the efficacy and safety of pulmonary delivery of insulin in type 2 diabetic patients who require insulin. DESIGN: Randomized, open-label, 3-month study consisting of a screening visit, a 4-week baseline lead-in phase, and a 12-week treatment phase. SETTING: General clinical research center and outpatient research clinics. PATIENTS: 26 patients (16 men, 10 women) with type 2 diabetes (average age, 51.1 years; average duration of diabetes, 11.2 years). INTERVENTION: Patients received inhaled insulin before each meal plus a bedtime injection of ultralente insulin, performed home glucose monitoring, and had weekly adjustment of insulin dose; target level for preprandial plasma glucose was 5.55 to 8.88 mmol/L (100 to 160 mg/dL). MEASUREMENTS: Glycemic control (hemoglobin A(1c) level) obtained at baseline and monthly for 3 months. Pulmonary function tests were done at baseline and at the end of the study. RESULTS: Inhaled insulin treatment for 3 months significantly improved glycemic control compared with baseline: Mean hemoglobin A(1c) levels decreased by 0.0071 +/- 0.0072 (0.71% +/- 0.72%). Patients experienced an average of 0.83 mild to moderate hypoglycemic event per month; no severe events were recorded. Patients showed no significant weight gain or change in pulmonary function compared with baseline. CONCLUSIONS: Pulmonary delivery of insulin in type 2 diabetic patients who require insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects. Larger-scale studies are ongoing to provide long-term efficacy and safety data.

Administration, Inhalation↗
PubMed2001

Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study.

BACKGROUND: Effective glycaemic control in type 1 diabetes mellitus usually requires two or more insulin injections daily. Inhaled intrapulmonary delivery of insulin offers a potential new way to deliver meal-related insulin, eliminating the need for preprandial injections. METHODS: 73 patients with type 1 diabetes mellitus were studied in an open-label, proof-of-concept, parallel-group randomised trial. Patients in the experimental group received preprandial inhaled insulin plus a bedtime subcutaneous ultralente insulin injection. Patients in the control group received their usual insulin regimen of two to three injections per day. Participants monitored their blood glucose four times daily, and adjusted insulin doses weekly to achieve preprandial glucose targets of 5.6-8.9 mmol/L. The primary outcome measure was change in glycosylated haemoglobin (HbA1c) after 12 weeks. Secondary outcomes were fasting and postprandial glucose response to a mixed meal; hypoglycaemia frequency and severity; pulmonary function; and patients' satisfaction. FINDINGS: Changes in HbA1c were indistinguishable between groups (difference 0.2% [95% CI -0.2 to 0.5]). Changes in fasting and postprandial glucose concentrations, and occurrence and severity of hypoglycaemia were also similar between groups. Inhaled insulin was well tolerated and had no effect on pulmonary function (ie, spirometry, lung volumes, diffusion capacity, and oxygen saturation). INTERPRETATION: This proof-of-concept study shows that preprandial insulin can be given by inhalation in individuals with insulin-deficient type 1 diabetes as a less invasive alternative to conventional preprandial insulin injections.

Administration, Inhalation↗
PubMed2001

Treatment satisfaction with inhaled insulin in patients with type 1 diabetes: a randomized controlled trial.

OBJECTIVE: In patients with type 1 diabetes, glycemic control can be achieved as effectively with an inhaled insulin regimen, comprising preprandial inhaled intrapulmonary insulin plus a bedtime ultralente injection, as with a conventional subcutaneous insulin regimen involving two to three injections per day. Our objective was to compare patient satisfaction between inhaled insulin and subcutaneous insulin. RESEARCH DESIGN AND METHODS: Subjects with type 1 diabetes participated in a 12-week open-label trial and were randomized to either an inhaled insulin regimen or a subcutaneous insulin regimen. Subjects (n = 69) were asked to complete a 15-item self-administered satisfaction questionnaire, the Patient Satisfaction with Insulin Therapy (PSIT) Questionnaire, at baseline and week 12. Outcomes included mean percentage changes in global (overall) satisfaction and two subscales: convenience/ease of use and social comfort. RESULTS: The mean percentage improvement in overall satisfaction with inhaled insulin (35.1%, 95% CI 18.0-52.2) was greater than with subcutaneous insulin (10.6%, 4.7-16.5) (P < 0.01), as was the improvement in convenience/ease of use: inhaled insulin 41.3% (22.9-59.6) versus subcutaneous insulin 11.2% (4.1-18.3; P < 0.01). Improvement in social comfort was greater with inhaled insulin but was not statistically significant. The 12-week change in HbA(1c) was associated with improved overall satisfaction (r = -0.27, P = 0.04). CONCLUSIONS: Inhaled insulin may offer the first practical, noninvasive alternative to insulin injections. For patients with type 1 diabetes, inhaled insulin maintains glycemic control and provides greater overall satisfaction and convenience/ease of use than subcutaneous insulin.

Administration, Inhalation↗
PubMed2000

Development and factor analysis of a questionnaire to measure patient satisfaction with injected and inhaled insulin for type 1 diabetes.

OBJECTIVE: To develop a self-administered questionnaire to address alternative delivery routes of insulin and to investigate aspects of patient satisfaction that may be useful for subsequent assessment and comparison of an inhaled insulin regimen and a subcutaneous insulin regimen. RESEARCH DESIGN AND METHODS: Attributes of patient treatment satisfaction with both inhaled and injected insulin therapy were derived from five qualitative research studies to arrive at a 15-item questionnaire. Each item was analyzed on a five-point Likert scale so that higher item scores indicated a more favorable attitude. There were 69 subjects with type 1 diabetes previously taking injected insulin therapy who were enrolled in a phase II clinical trial. Their baseline responses on the questionnaire were evaluated and subjected to an exploratory factor analysis. Meaningful factors were retained and interpreted based on their psychometric properties. RESULTS: Exploratory factor analysis suggested a two-factor solution accounting for 66 and 20% of the variance, respectively. The first factor contained 10 reliable items (Cronbach's alpha = 0.89) relating to convenience and ease of use, and the second contained 5 reliable items (Cronbach's alpha = 0.82) relating to social comfort. CONCLUSIONS: Among patients with type 1 diabetes, this analysis highlighted and quantified two key factors contributing to patient satisfaction: convenience/ease of use and social comfort. The questionnaire underwent rigorous development, had reliable properties, and an interpretable and rich factor structure. This report is intended to help advance, in subsequent investigations, the understanding and measurement of treatment satisfaction with novel and existing forms of insulin delivery.

Administration, Inhalation↗
PubMed1997

Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group.

OBJECTIVE: To investigate the efficacy, safety, and dose-response characteristics of an extended-release preparation of glipizide using the gastrointestinal therapeutic system (GITS) on plasma glucose, glycosylated hemoglobin (HbA1c), and insulin secretion to a liquid-mixed meal in NIDDM patients. RESEARCH DESIGN AND METHODS: Two prospective, randomized, double-blind, placebo-controlled, multicenter clinical trials were performed in 22 sites and 347 patients with NIDDM (aged 59 +/- 0.6 years; BMI, 29 +/- 0.3 kg/m2; known diabetes duration, 8 +/- 0.4 years) were studied. Each clinical trial had a duration of 16 weeks with a 1-week washout, 3-week single-blind placebo phase, 4-week titration to a fixed dose, and 8-week maintenance phase at the assigned dose. In the first trial, once-daily doses of 5, 20, 40, or 60 mg glipizide GITS were compared with placebo in 143 patients. In the second trial, doses of 5, 10, 15, or 20 mg of glipizide GITS were compared with placebo in 204 patients. HbA1c, fasting plasma glucose (FPG), insulin, C-peptide, and glipizide levels were determined at regular intervals throughout the study. Postprandial plasma glucose (PPG), insulin, and C-peptide also were determined at 1 and 2 h after a mixed meal (Sustacal). RESULTS: All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82%). Pharmacodynamic analysis indicated a significant relationship between plasma glipizide concentration and reduction in FPG and HbA1c over a dose range of 5-60 mg, with maximal efficacy achieved at a dose of 20 mg for FPG and at 5 mg for HbA1c. PPG levels were significantly lower, and both postprandial insulin and C-peptide levels significantly higher in patients treated with glipizide GITS compared with placebo. The percent reduction in FPG was comparable across patients with diverse demographic and clinical characteristics, including those with entry FPG > or = 250 mg/dl, resulting in greater absolute decreases in FPG and HbA1c in patients with the most severe hyperglycemia. Despite the forced titration to a randomly assigned dose, only 11 patients in both studies discontinued therapy because of hypoglycemia. Glipizide GITS did not alter lipids levels or produce weight gain. CONCLUSIONS: The once-daily glipizide GITS 1) lowered HbA1c, FPG, and PPG over a dose range of 5-60 mg, 2) was maximally effective at 5 mg (using HbA1c) or 20 mg (using FPG) based on pharmacokinetic and pharmacodynamic relationships, 3) maintained its effectiveness in poorly controlled patients (those with entry FPG > or = 250 mg/dl), 4) was safe and well tolerated in a wide variety of patients with NIDDM, and 5) did not produce weight gain or adversely affect lipids.

Adult↗
PubMed1994

Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM.

OBJECTIVE: To compare the efficacy and safety of controlled-release glipizide (glipizide-GITS [gastrointestinal therapeutic system]) and immediate-release glipizide in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation. Plasma glucose, serum insulin, C-peptide, and plasma glipizide levels were measured at fasting and post-Sustacal challenge at the end of 1 and 8 weeks of each treatment phase. HbA1c was measured at the end of weeks 7 and 8 of each treatment phase. RESULTS: Both formulations of glipizide yielded similar mean HbA1c values. However, mean fasting plasma glucose (FPG) levels were significantly lower with glipizide-GITS treatment than with immediate-release glipizide at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fasting insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate-release glipizide. Glucose responses to Sustacal were similar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-GITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stable by the end of week 1, and the concentrations increased proportionately with dose. Once-daily Glipizide-GITS provided effective mean glipizide concentrations (> 50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated. CONCLUSIONS: Glipizide-GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial plasma glucose levels equally; however, glipizide-GITS exerted its control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C-peptide levels. This suggests that glipizide-GITS improves insulin sensitivity.

Administration, Oral↗
PubMed1992

Reduction in size of a thyrotropin- and gonadotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog).

TSH as well as alpha-subunit, secretion has been shown to decrease after the administration of the somatostatin analog octreotide acetate (SMS 201-995). We have studied a 59-yr-old, male patient with a TSH- and gonadotropin-secreting tumor who, because of severe cardiomyopathy, was treated with long-term somatostatin analog rather than surgical resection of the pituitary tumor. Thirteen weeks of treatment with thrice daily sc injection of 100 micrograms octreotide acetate resulted in decreased TSH and alpha-subunit secretion, normal serum thyroid hormone levels, reduction in LH and testosterone level, and significant tumor size reduction. Long-term treatment for 51 weeks has not been associated with any significant side effects. We have shown that octreotide acetate may be a therapeutically valuable modality for certain patients with neoplastic inappropriate secretion of TSH (NIST). A probable effect of octreotide acetate on neoplastic gonadotropes, as evidenced by the reduction of the LH level with a concomitant decrease in testosterone level, is, likewise, suggested.

Adenoma↗
PubMed1990

Thyroid hormone regulates expression of the thyrotropin beta-subunit gene from both transcription start sites in the mouse and rat.

Thyroid hormones suppress transcription of the gene for the beta-subunit of thyrotropin (TSH beta). Since the TSH beta gene in both the mouse and the rat contains two start sites of transcription in exon 1, we have investigated whether expression of the gene from each start site is differentially regulated by thyroid hormones in each species. RNase protection analysis was used to assay the levels of mRNA specifically transcribed from the upstream (TSS 1) and downstream (TSS 2) transcription start sites in the mouse and rat pituitary. In euthyroid and hypothyroid pituitaries there was an approximately 5-fold and 2-fold greater abundance of mRNA derived from TSS 2 than TSS 1, respectively. Hypothyroidism induced an 18- and a 9-fold increase in TSH beta gene expression from TSS 1 and TSS 2, respectively. Treatment of hypothyroid animals for 1 day with triiodothyronine (T3) reduced expression from both start sites by about 50%; after 4 days of T3 treatment, TSH beta mRNAs derived from both start sites were below detectable levels. These results were confirmed in the rat by primer extension analysis. Expression from TSS 1 in the mouse was also shown to be dependent on thyroid status using the polymerase chain reaction (PCR) technique. In contrast to previous results from primer extension studies, PCR analysis demonstrated that alternative splicing of the TSH beta RNA primary transcript can occur when transcription is initiated at the upstream start site. We conclude that, in both the mouse and the rat pituitary, expression of the TSH beta gene from both transcription start sites is regulated by thyroid hormones.

Animals↗
PubMed1990

Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene.

Hereditary hypothyroidism caused by thyroid-stimulating hormone (TSH) deficiency is a rare autosomal recessive disease. Affected individuals show symptoms of severe mental and growth retardation that can be prevented by early administration of exogenous thyroid hormone. In this paper, we describe two related Greek families with three children affected by congenital TSH-deficient hypothyroidism. Sequence analysis of the TSH beta-subunit gene (TSHB) showed that the mutation responsible for the hypothyroidism in these families is a nonsense mutation in exon 2. This mutation is a G-to-T transversion at nucleotide 94 that destroys the only TaqI site in the TSHB-coding region and gives rise to a novel 8.5-kb TaqI fragment. Restriction analysis showed that the three affected children are homozygous for the 8.5-kb allele and that the four parents and two unaffected children are heterozygous. This mutation gives rise to a truncated peptide which includes only the first 11 of 118 amino acids of the mature TSHB peptide.

Alleles↗
PubMed1989

Regulation of the transfected human glycoprotein hormone alpha-subunit gene by dexamethasone and thyroid hormone.

A chimeric plasmid, (-1,500)h alpha CAT, containing approximately 1,500 bp of 5'-flanking DNA of the human glycoprotein hormone alpha-subunit gene directing the expression of the bacterial chloramphenicol acetyl transferase (CAT) gene, was transfected transiently into rat pituitary-derived GH3 cells. (-1,500)h alpha CAT expression was stimulated 5- to 20-fold by dexamethasone and 3- to 5-fold by 8-bromo-cAMP (8-Br-cAMP), and was inhibited by 50% by L-triiodothyronine (T3). Thus, suppression by T3 in this system was similar to that seen in pituitary thyrotropes. Induction of (-1,500)h alpha CAT expression by dexamethasone was antagonized by T3 but was unaffected by 8-Br-cAMP. However, T3 augmented the stimulation of (-1,500)h alpha CAT activity by 8-Br-cAMP. Deletants containing less than 346 bp of 5'-flanking alpha DNA showed a stepwise decrease in induction by dexamethasone, suggesting that multiple sequence elements located in this region are required for full induction of h alpha CAT activity. Deletion analysis also indicated that a thyroid hormone response element is located between 207 and 172 bp of the alpha gene transcriptional start site. Our finding of induction of alpha expression by dexamethasone in pituitary cells contrasts with the inhibition of alpha gene activity by glucocorticoids which has previously been shown in placental cells. Therefore, these data indicate that cell-type-specific factors play an important role in the modulation of alpha gene transcription.

Animals↗
PubMed1988

Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), are located less than 310 kb apart in both human and mouse genomes.

Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), have been assigned to mouse chromosome 3 and human chromosome 1p22. We have used the techniques of linkage analysis and pulsed field gel electrophoresis to determine the proximity of these two antithetically regulated genes in this conserved linkage group. Four novel restriction fragment length polymorphisms were identified at the human TSHB gene. Two-point linkage analysis between TSHB and NGFB in 46 families, including the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel, demonstrated no recombination (theta = 0.00, Z = 42.8). Analysis of this region by pulsed field gel electrophoresis showed that the genes for TSHB and NGFB are located less than 310 kb apart in man and 220 kb in the mouse.

Animals↗
PubMed1988

The human thyrotropin beta-subunit gene differs in 5' structure from murine TSH-beta genes.

The gene encoding the beta-subunit of human thyrotropin (hTSH-beta) was isolated, and its nucleotide sequence was determined. The gene is 4.3 kb in length, consists of three exons and two introns, and is present as a single copy as determined by Southern blot analysis of total genomic DNA. The protein coding portion of the gene, which includes exons 2 and 3, was isolated from a human genomic phage library, while exon 1, which encodes only 5' untranslated mRNA sequence, was isolated from a plasmid library of size-selected genomic DNA fragments. Here we describe the isolation of the 5' untranslated exon of the hTSH-beta subunit and 5'-flanking region. The structure of the hTSH-beta gene is very similar to the previously characterized TSH-beta genes from mouse and rat. The genes from all three species have two distinct promoter regions, but while both promoters are utilized by the murine TSH-beta genes, the human TSH-beta gene apparently utilizes only the proximal promoter for transcription initiation. A striking difference in hTSH-beta gene structure compared to the murine genes is that exon 1 of the human gene is 36 nucleotides. An analysis of the mouse, rat, and human exon 1 and 5'-flanking region shows a high percentage of sequence homology, with the exception of a 9-nucleotide insertion 13 bases 3' from the proximal TATA box found in the human gene but not found in the other two species. We propose that this insertion results in the additional length of human exon 1 compared to the mouse and rat genes. By isolating the promoter region of the hTSH-beta gene, we can begin to identify specific sequences involved in the regulation of hTSH gene expression.

Animals↗
PubMed1988

Central serotoninergic stimulation by fenfluramine challenge does not affect plasma thyrotropin-stimulating hormone levels in man.

Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

Administration, Oral↗
PubMed1988

Gonadotropin-producing pituitary adenoma in a man with long-standing primary hypogonadism.

Pituitary adenomas that secrete gonadotropins are generally believed to arise spontaneously rather than as a response to chronic primary gonadal failure. However, two women who were found to have gonadotroph adenomas several years after ovarian ablation have been reported. We describe a middle-aged man who developed bitemporal hemianopia and was found to have a large pituitary tumor 35 yr after castration. He had never received any replacement therapy. The tumor was considered to be a primary gonadotroph adenoma, rather than secondary gonadotroph hyperplasia, on the basis of its secretory capabilities, its reticulin patterns, and its specific immunostaining for human FSH beta, human LH beta, and alpha-subunit. Furthermore, the tumor did not decrease appreciably in size after 12 months of testosterone treatment, although plasma gonadotropin levels decreased. Unless the association of primary gonadal failure with a gonadotroph adenoma was coincidental, it suggests that some human gonadotroph adenomas may be secondary to failure of the gonads.

Adenoma↗
PubMed1988

The glycoprotein alpha-subunit is critical for secretion and stability of the human thyrotropin beta-subunit.

TSH is a member of a family of heterodimeric glycoprotein hormones which have a common alpha-subunit but differ in their hormone-specific beta-subunit. To study the posttranslational processing and assembly of human TSH, eukaryotic expression vectors were constructed that contained either the human TSH beta gene only or both the TSH beta and alpha-genes. These vectors were transfected into Chinese hamster ovary cells and stable cell lines synthesizing TSH beta or TSH dimer were isolated. The kinetics of secretion of TSH beta and the rate of assembly of TSH dimer were compared to the known secretion and assembly of human LH and human CG. In the absence of the alpha-subunit, CG beta is secreted efficiently, but TSH and LH beta-subunits are slowly degraded intracellularly (t1/2 approximately equal to 6 h) and less than 10% is secreted into the medium. In the presence of the alpha-subunit CG beta was also secreted efficiently as dimer but only 50% of the LH beta appeared in the medium as LH dimer. However, unlike LH beta, the alpha-subunit efficiently combines with TSH beta since greater than 95% was secreted as TSH dimer. Thus, the determinants for human TSH beta secretion and assembly are unique from the other human glycoprotein hormone beta-subunits.

Animals↗
PubMed1987

Expression of the gene for the beta subunit of mouse thyrotropin results in multiple mRNAs differing in their 5'-untranslated regions.

The gene encoding the beta subunit of mouse thyrotropin (TSH beta) has been isolated from a mouse genomic library, and its nucleotide sequence has been determined. Blot hybridization analysis of restriction enzyme digests of mouse DNA indicates that there is a single mouse TSH beta gene. The gene is 4.8 kilobases in length and contains five exons, which are 27, 47, 41, 163, and 328 base pairs long. Exons 1, 2, and 3 encode only 5'-untranslated mRNA sequences and are separated by introns that are 150 and 380 base pairs long. The protein-coding mRNA sequences are found in exons 4 and 5 and are interrupted by a 460-base pair intron. The position of this intron, between the codons for amino acids 34 and 35, has been conserved in all the known glycoprotein hormone beta subunit genes. Exons 3 and 4 are separated by a large 3.2-kilobase intron. When primer extension analysis, using an oligonucleotide primer complementary to exon 4 sequences, was employed to locate the transcription start site, four products were obtained. Nucleotide sequencing of these products showed that they were derived from separate TSH beta mRNAs that differed in the lengths of their 5'-untranslated regions. These 5'-untranslated mRNA sequences are derived from different combinations of exons 1, 2, and 3, each spliced to exons 4 and 5. The longest 5'-untranslated sequence, 116 nucleotides long, includes exons 1, 2, and 3 and the first base of exon 4; the shorter 5'-untranslated regions, 75, 69, and 28 nucleotides long, arise by splicing out the second and/or the third exon sequences. In contrast to the mouse TSH beta gene, transcription of the rat TSH beta gene from the analogous start site has been reported to give only a single mRNA, with a 5'-untranslated region of 28 nucleotides. Divergence of the mouse and rat TSH beta gene sequences at RNA splice sites can account for the absence of exon 2, but not exon 3, sequences in rat TSH beta mRNA. Primer extension and RNase protection analyses also showed that the mouse TSH beta gene contains a second transcription start site, located 43 base pairs upstream of the first start site, in a position corresponding to that in the rat TSH beta gene. Each start site in the mouse gene is flanked by characteristic TATAA box and CAAT box sequences.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗