Biomedical subjects

L Fang

Publications and source records attributed to L Fang.

At least 73 records · Page 4Linked to original sources

PubMed1999

Regulation of calcitonin gene-related peptide receptors in the rat uterus during pregnancy and labor and by progesterone.

Calcitonin gene-related peptide (CGRP) is a potent smooth muscle relaxant in a variety of tissues. We recently demonstrated that CGRP relaxes uterine tissue during pregnancy but not during labor. In the present study we examined whether uterine (125)I-CGRP binding and immunoreactive CGRP receptors are regulated by pregnancy and labor and by sex steroid hormones. We found that (125)I-CGRP binding to membrane preparations from uteri was elevated during pregnancy and decreased during labor and postpartum. Changes in immunoreactive CGRP receptors were similar to the changes in (125)I-CGRP binding in these tissues, suggesting pregnancy-dependent regulation of CGRP receptor protein. CGRP receptors were elevated by Day 7 of gestation, and a precipitous decrease in these receptors occurred on Day 22 of gestation prior to the onset of labor. Both (125)I-CGRP-binding and immunofluorescence studies indicated that CGRP receptors were localized to myometrial cells. Hormonal control of uterine CGRP receptors was assessed by the use of antiprogesterone RU-486, progesterone, and estradiol-17beta. RU-486 induced a decrease in uterine CGRP receptors during pregnancy (Day 19). On the other hand, progesterone prevented the fall in uterine CGRP receptors at term (Day 22). In addition, progesterone also increased uterine CGRP receptors in nonpregnant, ovariectomized rats, while estradiol had no effects. These hormone-induced changes in uterine CGRP receptors were demonstrated by (125)I-CGRP-binding, Western immunoblotting, and immunolocalization methods. These results indicate that CGRP receptors and CGRP binding in the rat uterus are increased with pregnancy and decreased at term. These receptors are localized to the myometrial cells, and progesterone is required for maintaining CGRP receptors in the rat uterus. Thus, the inhibitory effects of CGRP on uterine contractility are mediated through the changes in CGRP receptors and may play a role in uterine quiescence during pregnancy.

Animals↗

PubMed1999

Passive protective effect of egg-yolk antibodies against enterotoxigenic Escherichia coli K88+ infection in neonatal and early-weaned piglets.

The protective effects of egg-yolk antibodies obtained from hens immunized with fimbrial antigens from a local strain (Escherichia coli K88+ MB, Manitoba, Canada) of K88+ piliated enterotoxigenic E. coli (ETEC) were evaluated in 3- and 21-day-old piglets in which ETEC diarrhea was induced and also in early-weaned piglets in a commercial farm. The results demonstrated that the E. coli K88+ MB-induced diarrhea in 3-day-old piglets was cured 24 h after treating with egg-yolk antibodies while those treated with egg-yolk powder from conventional hens continued to have diarrhea and 62.5% of them died of severe diarrhea. For 21-day-old weaned piglets, those fed egg-yolk antibodies had transient diarrhea, positive body weight gains and 100% survival during the period of the experiment, whereas control piglets that were treated with placebo had severe diarrhea and dehydration and some died within 48 h after infection. In the field trial, the incidence and severity of diarrhea of 14-18-day-old weaned piglets fed egg-yolk antibodies were much lower than in those fed a commercial diet containing an antibiotic. These results indicate that the neonatal and early-weaned piglets that received the egg-yolk antibodies were protected against ETEC infection.

Animals↗

PubMed1999

Impact of temperature and humidity on chemical and sensory emissions from building materials.

The chemical and sensory emissions from five building materials (carpet, polyvinyl chloride (PVC) flooring, sealant, floor varnish and wall paint) were tested under different combinations of temperature and relative humidity in the ranges 18-28 degrees C and 30-70% relative humidity (RH). The experiment was performed in a climate chamber where a specially designed test system was built to study emissions from the five materials. The test system could provide different temperatures and humidities of air around the materials, while the air, after being polluted by the emissions from the materials, could be reconditioned to 23 degrees C and 50% RH for sensory assessments. The experiment was designed to separate the direct impact of temperature and humidity on perception from the impact on sensory emission. The study found little influence of temperature on the emissions from the five materials whether expressed in chemical or sensory terms. The effect of humidity was found to be significant only for the waterborne materials--floor varnish and wall paint. Compared with the direct impact of temperature and humidity on the perception of air quality, the impact of temperature and humidity on sensory emissions from the building materials has a secondary influence on perceived air quality.

Adult↗

PubMed1999

Inverse relationship between severity of experimental pyelonephritis and nitric oxide production in C3H/HeJ mice.

The contribution of nitric oxide to host resistance to experimental pyelonephritis is not well understood. We examined whether the inhibition of nitric oxide synthesis alters the sensitivity of lipopolysaccharide (LPS) responder (C3H/HeN) and nonresponder (C3H/HeJ) mice to experimental Escherichia coli pyelonephritis. C3H/HeJ and C3H/HeN mice were implanted subcutaneously with minipumps containing an inhibitor of nitric oxide, NG-nitro-L-arginine methyl ester (L-NAME), or a corresponding vehicle. Ascending urinary tract infection by bladder catheterization with two strains of E. coli, an O75 strain bearing Dr fimbriae and an O75 strain bearing P fimbriae, was developed in tested animals. Twenty-four hours following bladder infection, the kidneys of C3H/HeN and C3H/HeJ mice were colonized at a similar rate. However, 5 weeks postinoculation, C3H/HeN mice cleared infection while C3H/HeJ mice showed persistent colonization. Twenty-four hours following infection, C3H/HeN mice treated with L-NAME showed no significant increase of renal tissue infection compared to the saline-treated control group. However, L-NAME-treated C3H/HeJ mice showed an approximately 100-fold increase in E. coli infection rate compared to the saline-treated controls in the Dr+ group but showed no change compared to those in the P+ group. Dissemination of Dr+ E. coli but not P+ E. coli to the liver and uterus was significantly enhanced with L-NAME treatment in C3H/HeJ mice only. Nitric oxide had no direct killing effect on E. coli in vitro. Nitrite production by various organs was found to be significantly lower in C3H/HeJ mice than in C3H/HeN mice. Alteration of nitric oxide and LPS responsiveness was significantly associated with the increased sensitivity of C3H/HeJ mice to experimental Dr+ but not to P+ E. coli pyelonephritis. These findings are consistent with the hypothesis that nitric oxide synthase activity in concert with LPS responsiveness may participate in the antibacterial defense mechanisms of the C3H mouse urinary tract. This phenomenon is strain dependent and possibly related to the invasive properties of E. coli.

Animals↗

PubMed1999

Involvement of calcitonin gene-related peptide in the modulation of human myometrial contractility during pregnancy.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and relaxes smooth muscle of a variety of tissues, but the effects of CGRP on human myometrial contractions and the changes in CGRP receptors (CGRP-Rs) in human myometrium have not been described. We report that CGRP induced dose-dependent relaxation in spontaneously contracting myometrium from pregnant women. This relaxation effect is diminished in myometrium obtained from patients during labor and in the nonpregnant state. CGRP-induced relaxations are inhibited by a CGRP-R antagonist (CGRP(8-37)), a soluble guanylate cyclase inhibitor (LY(83583)), and a nitric oxide synthase inhibitor (L-NAME). Both Western blotting and mRNA analysis showed that CGRP-Rs are present in human myometrium, and that the expression of these receptors is increased during pregnancy and decreased during term labor. Immunofluorescent staining revealed that CGRP-Rs are abundant in the myometrial cells of pregnant women who are not in labor, and are minimal in uterine specimens from women in labor and in the nonpregnant state. We conclude that increased CGRP-Rs in myometrium, and resulting enhanced myometrial sensitivity to CGRP, may play a role in maintaining human myometrium in a quiescent state during pregnancy, and that a decline in the CGRP-Rs at term could contribute to the initiation of labor.

Adult↗

PubMed1999

[A study on immunogenicity and safety of bivalent inactivated vaccine against hemorrhagic fever with renal syndrome].

OBJECTIVE: To study side effects and effectiveness of bivalent inactivated vaccine against hemorrhagic fever with renal syndrome in population of a randomized controlled field trial. METHODS: Serum indirect immunofluorescent antibody in 167 persons and neutralization antibody (types I and II) in 69 persons, who received three-dose vaccine, were determined two weeks after immunization, and side effects in 657 vaccinees were observed within 72 houses after immunization. RESULTS: Serum positive conversion rate of indirect immunofluorescent antibody was 99.04% (166/167) with GMT of 24.51 +/- 2.06. Serum positive conversion rate of neutralization antibody was 100% (69/69), 91.30% (63/69) for types I and 88.41% (61/69) for type II, respectively. GMTs for type I and II neutralization antibody were 18.27 +/- 2.21 and 12.47 +/- 2.16, respectively. Side effects at local site vaccinated of the body and temperature rising could be seen in 1.48% and 0.36% of the vaccinees, respectively. No severe side effect and abnormal reaction was found in vaccinees on the field. CONCLUSION: Immune response to bivalent inactivated vaccine against hemorrhagic fever with renal syndrome was satisfactory with slight side effect.

Adolescent↗

PubMed1998

Uterine relaxation responses to calcitonin gene-related peptide and calcitonin gene-related peptide receptors decreased during labor in rats.

OBJECTIVES: Our purpose was to investigate (1) whether uterine relaxation responses to calcitonin gene-related peptide are differentially regulated during pregnancy and labor, (2) the involvement of nitric oxide in smooth muscle relaxant action of calcitonin gene-related peptide in the rat uterus, (3) whether receptors for calcitonin gene-related peptide are expressed in rat uterus, and if so (4) whether the concentrations of these receptors are differently regulated during pregnancy and labor. STUDY DESIGN: Rats were killed on day 18 of gestation, at the time of spontaneous labor, or postpartum day 2. The uteri were removed for in vitro contractility measurements, nitric oxide production, and calcitonin gene-related peptide receptor binding assay. RESULTS: (1) Calcitonin gene-related peptide induced a dose-dependent relaxation in spontaneously contracting uterine strips from pregnant rats on day 18 of gestation; (2) the relaxation effects of calcitonin gene-related peptide on the uterus were decreased during spontaneous delivery at term and post partum compared with that during pregnancy; (3) calcitonin gene-related peptide-induced relaxation was inhibited by pretreatment of the uterine tissue with a calcitonin gene-related peptide receptor antagonist, calcitonin gene-related peptide(8-37); (4) nitric oxide synthesis inhibitor (N(G)-nitro-L-arginine methyl ester) and soluble guanylate cyclase inhibitor (LY83583) significantly decreased calcitonin gene-related peptide-induced relaxation of the rat uterus during pregnancy; (5) calcitonin gene-related peptide increased the uterine nitric oxide production in pregnant rats, and this increase was obliterated in the presence of calcitonin gene-related peptide(8-37); and (6) calcitonin gene-related peptide receptors are present in rat uterus, and the concentration of these receptors dramatically increases during pregnancy and decreases during labor at term. CONCLUSIONS: Calcitonin gene-related peptide inhibits uterine spontaneous contractions in rats during pregnancy but not during labor and post partum. The inhibitory effects of calcitonin gene-related peptide on uterine contractility appear to be modulated, at least in part, by the activation of nitric oxide generation in the rat uterus. Changes in calcitonin gene-related peptide receptors could contribute to the changes in calcitonin gene-related peptide-mediated uterine relaxation during pregnancy and labor.

Aminoquinolines↗

PubMed1998

Immunohistochemical localization of constitutive and inducible cyclo-oxygenases in rat uterus during the oestrous cycle and pregnancy.

The uterus is a rich source of eicosanoids synthesized from arachidonic acid metabolism through the cyclo-oxygenase pathway. Two isoforms of cyclo-oxygenase, constitutive (COX-I) and inducible (COX-II) enzyme, have been reported. In the present study, we have immunohistochemically mapped the distribution of both COX-I and COX-II during various physiological states of the rat uterus. Uterine tissue was collected from female rats (a) during different stages of the oestrous cycle, (b) on days 1, 4, 8 and 18 of gestation, (c) after spontaneous delivery and (d) post partum, and fixed in Bouin's fixative. After paraffin wax embedding, 5-microm-thick sections were immunohistochemically stained by the ABC technique. Observation of the stained sections under the light microscope revealed that, in non-pregnant rat uterus, both COX-I and COX-II were abundantly expressed in the endometrium, with minimal staining observed in the myometrium. Staining was more prominent in epithelial cells than in stromal cells. The intensity of staining in epithelial cells was highest at pro-oestrus and oestrus and lowest at dioestrus. In pregnant rats, although the expression of both COX-I and COX-II was localized primarily to the endometrium with very little staining in the myometrium on day 1 of gestation, both of these enzymes were also apparent in myometrial cells by day 4 of gestation. The staining intensity of endometrial and myometrial cells increased further with the progression of gestation, being maximal at the time of spontaneous delivery. During the post-partum period, however, the staining intensity for both of the enzymes in endometrium and myometrium was decreased. Thus, our studies show that the expression of cyclo-oxygenases in various uterine cells vary with the oestrous cycle and with pregnancy. Furthermore, prominent increases in the expression of cyclo-oxygenases in the myometrium during pregnancy and parturition imply that the cyclo-oxygenase system in the myometrium may play a major role in modulating uterine contractility during pregnancy and labour.

Animals↗

PubMed1998

The CspA family in Escherichia coli: multiple gene duplication for stress adaptation.

CspA was originally found as the major cold-shock protein in Escherichia coli, consisting of 70-amino-acid residues. It forms a beta-barrel structure with five anti-parallel beta-strands and functions as an RNA chaperone. Its dramatic but transient induction upon cold shock is regulated at the level of transcription, mRNA stability and translation. Surprisingly, E. coli contains a large CspA family, consisting of nine genes from cspA to cspI. Phylogenetic analysis of these gene products and the cold-shock domain of human YB-1 protein reveals that there are two major branches in the evolution of CspA homologues: one branch for CspF and CspH, and another for all the other known CspA homologues from both prokaryotes and eukaryotes. The locations of these genes on the E. coli chromosome suggest that the large CspA family probably resulted from a number of gene duplications and, after subsequent adaptation, resulted in specific groups of genes that respond to different environmental stresses; for example, cspA, cspB and cspG for cold-shock stress and cspD for nutritional deprivation. The E. coli CspA family will be discussed in terms of their structures and functions, and their gene structures and regulation.

Adaptation, Physiological↗

PubMed1998

Regulation of inducible nitric oxide synthase messenger ribonucleic acid expression in pregnant rat uterus.

Nitric oxide synthases catalyze the synthesis of the biomediator, nitric oxide, from L-arginine in a variety of tissues. The expression and regulation of inducible isoform of nitric oxide synthase (NOS II) in the uterus were assessed in this study by reverse transcription-polymerase chain reaction with the use of specific primers. Results showed the following: 1) NOS II mRNA expression in the rat uterus was substantially increased during pregnancy and decreased during labor at term; 2) RU-486 (an antagonist of progesterone) induced preterm labor and was associated with a marked decrease in NOS II mRNA expression to 60.9%, 20.3%, and 2.9% at, respectively, 6, 12, and 24 h after treatment compared with the control value (100%); 3) progesterone administration in pregnant rats significantly increased uterine NOS II gene expression (374.1% vs. 100%); 4) NOS II mRNA in the uterus was significantly reduced by prostaglandin F2alpha (PGF2alpha; 11.6% vs. 100% in control); 5) treatment with progesterone prevented PGF2alpha-induced inhibition in NOS II mRNA expression; 6) ICI 164384, an antiestrogen, significantly increased serum progesterone concentration and stimulated NOS II expression by the uterus in a time-dependent manner; 7) as shown by immunofluorescent studies, cells stained by NOS II antibodies were apparent in the decidual compartment as well as in areas between myometrial cell bundles in the pregnant rat uterus. The density of staining decreased in the specimens at labor and postpartum. We conclude that NOS II gene expression in the rat uterus was enhanced during pregnancy and decreased during labor and postpartum. NOS II in rat uterus is up-regulated by progesterone and down-regulated by estrogens and prostaglandins, consistent with their role in uterine activity regulation during pregnancy and labor.

Animals↗

PubMed1998

Role of the cold-box region in the 5' untranslated region of the cspA mRNA in its transient expression at low temperature in Escherichia coli.

Upon temperature downshift, a group of proteins called cold shock proteins, such as CspA, CspB, and CsdA, are transiently induced in Escherichia coli. However, when the 5' untranslated region (5' UTR) of cspA mRNA is overproduced at low temperature, the expression of cold shock genes is prolonged or derepressed. It has been proposed that this effect is due to highly conserved 11-base sequences designated the "cold box" existing in the 5' UTRs of cspA, cspB, and csdA. Here, we demonstrate that the overproduction of the 5' UTR of not only cspA but also cspB and csdA mRNAs causes derepression of all three genes at the same time. Conversely, when the cold-box region was deleted from the cspA 5' UTR its derepression function was abolished. The amount of mRNA from the chromosomal cspA gene was much higher in cells overproducing the wild-type 5' UTR by means of a plasmid than it was in cells overproducing the cold-box-deleted 5' UTR. The stability of the chromosomal cspA mRNA in cells overproducing the wild-type 5' UTR was almost identical to that in cells overproducing the cold-box-deleted 5' UTR. Therefore, the derepression of cspA caused by overproduction of 5' UTR at the end of the acclimation phase occurs at the level of transcription but not by mRNA stabilization, indicating that the cold-box region plays a negative role in cspA transcription in cold shock-adapted cells. The role of the cold-box region was further confirmed with a cspA mutant strain containing a cold-box-deleted cspA gene integrated into the chromosome, which showed a high level of constitutive production of CspA but not CspB during exponential growth at low temperature.

Bacterial Proteins↗

PubMed1998

[The relationship between HBV infection and injury of tubuli and interstitium in IgA nephropathy].

OBJECTIVE: To clarify the correlation between HBV infection and the injury of tubuli and interstitium of IgA nephropathy. METHODS: Renal biopsy specimens from 91 patients with primary IgA nephropathy were investigated by use of in situ hybridization (HBV DNA), immunohistochemistry (HBsAg, HBcAg, CD3, CD8) and HBV DNA, HBAg-CD43 double staining techniques. RESULTS: The positive rate of HBAg in renal tissue as detected by immunohistochemistry was 69.2% and that of HBV DNA detected by in situ hybridization was 42.9%. Double staining showed that HBV DNA positive tubular epithelial cells might coexpress HBsAg and/or HBcAg. The numbers of the infiltrated CD3+ cells and CD8+ cells in cases with positive HBV infections markers were significantly higher than those of cases without infection (P < 0.01). In addition, CD43+ T lymphocytes infiltrated around or invaded into the tubuli walls which had positive HBcAg or HBsAg expression. CONCLUSION: After HBV infection, the renal cells could express HBAg and induce infiltration of CD3+ cells and CD8+ cells, resulting in aggravation of the injury of tubuli and interstitium. Therefore, it is considered that HBV infection might play an important role in the occurrence and progress of IgA nephropathy.

Adult↗

PubMed1997

Molecular cloning of a cDNA encoding the neuropeptides APGWamide and cerebral peptide 1: localization of APGWamide-like immunoreactivity in the central nervous system and male reproductive organs of Aplysia.

While much is known about the neural and endocrine mechanisms that control egg laying in the gastropod mollusk Aplysia, relatively little is known about the regulation of male reproductive activity in this simultaneous hermaphrodite. In the present study, we have cloned and sequenced a cDNA that encodes a precursor protein, the predicted posttranslational processing of which presumably generates nine copies of the neuropeptide Ala-Pro-Gly-Trp-NH2 (APGWamide), five connecting peptide sequences, and a C-terminal peptide. The sequence of one connecting peptide is identical to the previously characterized cerebral peptide 1. Northern blot analysis identified two major APGWamide mRNA transcripts (approximately 1.3 kb, approximately 2.4 kb), which were present in central nervous system ganglia, but were most abundant in the right cerebral and right pedal ganglia. Immunohistochemical studies using sexually mature Aplysia demonstrated that the vast majority of APGWamide-like immunoreactivity was localized in 30-40 neurons along the anterior and medial margins of the right cerebral ganglion and in a cluster of 15-20 neurons in the right pedal ganglion. A total of only about ten immunoreactive neurons were located in other ganglia. Immunohistochemistry also demonstrated that APGWamide was present in the reproductive organs that participate in the storage or transport of sperm, including the small hermaphroditic duct (site of sperm storage before mating), the white hemiduct (also known as the copulatory duct), and penial complex. As a group, these data suggest that APGWamide may play a role in regulating male reproductive function in Aplysia, as it does in other gastropods.

Amino Acid Sequence↗

PubMed1997

The HumD21S11 system of short tandem repeat DNA polymorphisms in Japanese and Chinese.

HumD21S11 is a short tandem repeat DNA polymorphic system with a complex basic structure of (TCTA)4-6 (TCTG)5-6 (TCTA)3 TA (TCTA)3 TCA (TCTA)2 TCCA TA (TCTA)n. Using the allelic ladder prepared by us, the distribution of alleles among Japanese and Chinese was investigated, and four new alleles 28.2, 34, 35.2, and 36.2, were discovered. DNA sequencing was performed on the newly found alleles as well as on family samples and led to the discovery of different gene structures within alleles 28 and 32. Forensic materials, including hairs and seminal stains, were tested in parallel with blood samples from the same individual and were successfully typed for D21S11.

Alleles↗

PubMed1997

Promoter-independent cold-shock induction of cspA and its derepression at 37 degrees C by mRNA stabilization.

The gene for CspA, the major cold-shock protein of Escherichia coli is known to be dramatically induced upon temperature downshift. Here, we report that three-base substitutions around the Shine-Dalgarno sequence in the 159-base 5'-untranslated region of the cspA mRNA stabilizes the mRNA 150-fold, resulting in constitutive expression of cspA at 37 degrees C. This stabilization was found to be at least partially due to resistance against RNase E degradation. The cold-shock induction of cspA was also achieved by exchanging its promoter with the non-cold-shock Ipp promoter. The results presented indicate that the cspA gene is efficiently transcribed even at 37 degrees C. However, the translation of the cspA mRNA is blocked because of its extreme instability at 37 degrees C. The presented results also demonstrate that the cspA gene is constitutively transcribed at all temperatures; however, its expression at 37 degrees C is prevented by destabilizing its mRNA.

Bacterial Proteins↗

PubMed1997

Deletion analysis of cspA of Escherichia coli: requirement of the AT-rich UP element for cspA transcription and the downstream box in the coding region for its cold shock induction.

In order to analyse the mechanism of cold shock induction of CspA, a major cold shock protein of Escherichia coli, deletion analysis of the cspA gene was carried out. It was found that (i) the AT-rich sequence (-47 to -38) upstream of the cspA -35 region may act as the UP element playing a crucial role in cspA transcription at both 37 degrees C and 15 degrees C; (ii) the unusually long 5'-UTR of the cspA mRNA has negative effects on cspA expression at 37 degrees C; and (iii) in contrast, the 5'-UTR exerts a positive effect on mRNA stabilization at low temperature. Furthermore, it was demonstrated that the 14 base downstream box (DB) locating 12 bases downstream of the initiation codon of the cspA mRNA and complementary to a region near the decoding region of 16S rRNA was essential for the mRNA translation during the growth lag acclimation phase immediately after cold shock. During this phase, translation of non-cold shock gene mRNAs is blocked, since they require cold shock-specific ribosomal factors for the formation of the translation initiation complex. It is proposed that DB in cold shock mRNAs allows the formation of a stable initiation complex at low temperature in the absence of the cold shock ribosomal factors.

Bacterial Proteins↗

PubMed1997

Lethal outcome of uterine infection in pregnant but not in nonpregnant rats and increased death rate with inhibition of nitric oxide.

PROBLEM: Limited information is available on potential differences in sensitivity to urogenital infections between pregnant and nonpregnant hosts. METHOD OF STUDY: In this study, we evaluated Escherichia coli infectious complications in pregnant and nonpregnant rats and the effect of nitric oxide (NO) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the outcome of an experimental uterine infection. RESULTS: Of the infected pregnant animals, 31% were found dead in 24-48 hr. The death rate was increased 2-fold (66%) with L-NAME treatment. No deaths occurred in nonpregnant animals with or without L-NAME treatment. The rate of uterine infection in pregnant animals was about 10-fold higher than in nonpregnant animals. CONCLUSION: We propose that infectious complications of pregnancy may be related to gestation-dependent sensitivity to the pathogenic microorganism and the host NO status.

Animals↗

PubMed1997

Novel mutations and a mutational hotspot in the MODY3 gene.

Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q. We have identified four novel HNF-1alpha missense mutations in MODY3 families. In four additional and unrelated families, we observed an identical insertion mutation that had occurred in a polycytidine tract in exon 4. Among those families, one exhibited a de novo mutation at this location. We propose that instability of this sequence represents a general mutational mechanism in MODY3. We observed no HNF-1alpha mutations among 86 unrelated late-onset diabetic patients with relative insulin deficiency. Hence mutations in this gene appear to be most strongly associated with early-onset diabetes.

Chromosomes, Human, Pair 12↗