ABSTRACT
We found that shochu slop, the residue generated during the production of distilled shochu liquor, which must be treated as industrial waste, can be used as an excellent medium for Escherichia coli culture. LB medium is generally used in laboratories for culturing E. coli. However, it is not the optimal medium for E. coli culture because the bacterial cells cannot grow to very high densities in LB medium. On the other hand, E. coli can grow to higher densities in Terrific broth and this medium is used when researchers want to grow E. coli to high density or to obtain a protein with high yield. In this study, we removed solid matter from shochu slop, adjusted the pH of the mixture to 7 and subsequently used the slop for E. coli culture. The ability of shochu slop to support E. coli growth was compared with those of LB Miller medium and Terrific broth. The results indicate that sweet potato shochu slop as culture medium for E. coli is comparable to Terrific broth and much better than LB Miller medium in terms of supporting cell proliferation, and plasmid and enzyme production. SIGNIFICANCE AND IMPACT OF THE STUDY: Shochu manufacturers incur a cost to dispose shochu slop, which is recognized as food manufactural residues. Escherichia coli has been used in laboratories and in industry. However, culture media used in the laboratories are expensive and those used in industry are expensive because of their large scale. We found that sweet potato shochu slop is an excellent culture medium for E. coli. This finding is not only useful for laboratories and industry, but also beneficial to the effective utilization of this renewable resource to create a sustainable society.
Subject(s)
Alcoholic Beverages/microbiology , Culture Media/chemistry , Escherichia coli K12/growth & development , Escherichia coli K12/metabolism , Industrial Waste/analysis , Escherichia coli K12/genetics , Plasmids/geneticsABSTRACT
OBJECTIVES: The aim was to determine whether daily muscle electrical stimulation (ES) and streptomycin treatment would have positive or negative effects on trabecular bone mass in disuse rats. METHODS: Seven-week-old male F344 rats were randomly divided into five groups of eight animals each: an age-matched control group (CON); a sciatic denervation group (DN); a DN + direct electrical stimulation group (DN+ES); a DN + streptomycin treatment group (DN+SM); and a DN+ES+SM group. The tibialis anterior (TA) muscles in all ES groups were stimulated with 16mA at 10Hz for 30 min/day, six days/week, for one week. Bone volume and structure were evaluated using micro-CT, and histological examinations of the tibiae were performed. RESULTS: Direct ES significantly reduced the disuse-induced trabecular bone loss. Osteoid thickness were also significantly greater in the ES groups than in the DN group. Micro CT and histomorphological parameters were significantly lower in the DN+ES+SM group than in the DN+ES group, while there were no significant differences between the DN and DN+SM groups. CONCLUSIONS: These results suggest that ES-induced muscle force reduced trabecular bone loss, and streptomycin treatment did not induce bone loss, but attenuated the effects of ES-induced muscle force on reducing the loss of disused bone.
Subject(s)
Bone and Bones/drug effects , Electric Stimulation/methods , Muscular Disorders, Atrophic/pathology , Protein Synthesis Inhibitors/pharmacology , Streptomycin/pharmacology , Animals , Bone and Bones/diagnostic imaging , Denervation , Disease Models, Animal , Electromyography , Male , Muscular Disorders, Atrophic/diagnostic imaging , Rats , Rats, Inbred F344 , X-Ray MicrotomographyABSTRACT
OBJECTIVES: We aimed to determine the intensity of muscle stimulation required to prevent structural failure as well as bone and skeletal muscle loss after denervation-induced disuse. METHODS: Seven-week-old rats (weight, 198-225 g) were randomly assigned to age-matched groups comprising control (CON), sciatic nerve denervation (DN) or direct electrical stimulation (ES) one day later [after denervation] with 4, 8 and 16 mA at 10 Hz for 30 min/day, six days/week, for one or three weeks. Bone architecture and mean osteoid thickness in histologically stained tibial sections and tension in tibialis anterior muscles were assessed at one and three weeks after denervation. RESULTS: Direct ES with 16 mA generated 23-30% maximal contraction force. Denervation significantly decreased trabecular bone volume fraction, thickness and number, connectivity density and increased trabecular separation in the DN group at weeks one and three. Osteoid thickness was significantly greater in the ES16 group at week one than in the DN and other ES groups. Trabecular bone volume significantly correlated with muscle weight. CONCLUSIONS: Relatively low-level muscle contraction induced by low-frequency, high-intensity electrical muscle stimulation delayed trabecular bone loss during the early stages (one week after DN) of musculoskeletal atrophy due to disuse.
Subject(s)
Bone Resorption/prevention & control , Muscle, Skeletal/physiology , Muscular Disorders, Atrophic/physiopathology , Tibia/physiopathology , Animals , Denervation , Disease Models, Animal , Electric Stimulation Therapy , Male , Rats , Rats, Wistar , X-Ray MicrotomographyABSTRACT
OBJECTIVE: The present study aimed to clarify the structural recovery, and to compare the time course of morphological changes in trabeculae and the process of bone mass change in rat tibiae following temporary immobilization of hind limb by sciatic neurectomy or nerve freezing. METHODS: In 11-week-old male Fischer 344 rats, 4-5 mm of the sciatic nerve was removed (neurectomy group) or frozen by 5-second application of a stainless steel rod immersed in liquid nitrogen (nerve-freezing group). Quantitative changes in cancellous bone were assessed by histomorphometry. RESULTS: The results clarified that: trabecular bone volume (BV/TV) decreases until 3 weeks after denervation, and in the nerve-freezing group, it then increases from week 4, recovering to pre-surgery levels by week 10 (no recovery was seen in the neurectomy group); in the initial phase of bone atrophy, the decrease in BV/TV is more gradual in the nerve-freezing group than in the neurectomy group; and changes in trabecular architecture in the bone atrophy-recovery process are strongly associated with changes in trabecular thickness. CONCLUSION: The findings suggested that after transient injury by nerve freezing and subsequent recovery of neuromuscular function, bone tissue undergoes recovery from bone loss, but that trabeculae may not show complete structural recovery.
Subject(s)
Bone Remodeling/physiology , Tibia/pathology , Animals , Atrophy/etiology , Atrophy/pathology , Denervation , Disease Models, Animal , Male , Rats , Rats, Inbred F344 , Sciatic Nerve/surgery , Tibia/innervation , TimeABSTRACT
OBJECTIVE: This study aimed to characterize suicide risk screening results for youth in pediatric ambulatory subspecialty clinics. METHOD: The Ask Suicide-Screening Questions was administered to patients ages 9-24 years in 12 subspecialty clinics to assess suicide risk, determined by suicide ideation/behavior. The SAMSHA-HRSA standard framework for integrated health was used to categorize each clinic's level of behavioral health integration. RESULTS: 6365 patients completed 7440 suicide risk screens; 6.2% of patients screened positive at their initial screen and 4.1% at subsequent annual screens. There was no dose-response pattern between increasing level of integration and decreasing likelihood of a positive suicide screen. Youth identifying as gender expansive were 3.1 times (95% CI [2.0, 4.9]) more likely to screen positive as compared to cisgender youth, adjusted for age, gender, race/ethnicity, screen type, year, and clinic integration level. CONCLUSION: Results surrounding disparities in suicide risk based on gender identity underscore the importance of further investigating how to optimally identify and manage high-risk, often understudied youth at suicide risk.
Subject(s)
Gender Identity , Suicidal Ideation , Adolescent , Adult , Ambulatory Care Facilities , Child , Delivery of Health Care , Female , Humans , Male , Mass Screening/methods , Young AdultABSTRACT
In the present study, we aimed to determine whether response training shortens visuo-motor related time in athletes performing a simple reaction task. 14 healthy male athletes were included in the study. Subjects were randomly divided into 2 groups: a training group, which underwent response training consisting of a mastication task in response to a visual signal, and a non-training (control) group, which did not undergo response training. Pre-motor time and transcranial magnetic stimulation over the primary motor cortex for recording motor evoked potentials were measured in the control group, and before and after the response training session in the training group. Both pre-motor time and visuo-motor related time, but not motor evoked potential latency, were significantly reduced after response training in the training group. Subjects who had a longer visuo-motor related time before training showed a greater reduction in visuo-motor related time after training. These results suggest that visuo-motor related time before training could be useful as a predictor of the reduction in reaction time following response training.
Subject(s)
Athletes , Psychomotor Performance/physiology , Reaction Time , Adolescent , Evoked Potentials, Motor , Humans , Male , Mastication , Time Factors , Transcranial Magnetic Stimulation , Young AdultABSTRACT
BACKGROUND: Suicide risk screening is recommended in pediatric care. To date, no previous studies illustrate the implementation of suicide risk screening in pediatric subspecialty care, even though chronic medical conditions are associated with a higher risk of suicide. METHODS: A large multidivision pediatric ambulatory clinic implemented annual suicide risk screening. Patients ages 9-21 years participated in suicide risk screening using the Ask Suicide-Screening Questions during the project. A multidisciplinary team employed quality improvement methods and survey-research design methods to evaluate the feasibility and acceptability of the screening process for patients, families, and medical providers. RESULTS: During the quality improvement project period, 1,934 patients were offered screening; 1,301 (67.3%) patients completed screening; 82 patients (6.3% of 1,301 patients) screened positive. The monthly compliance rate held steady at 86% following several Plan-Do-Study-Act cycles of improvement. The survey results demonstrate that providers rated the suicide risk screening process positively; however, a subset of providers indicated that the screening process was out of their scope of practice or impeded their workflow. CONCLUSIONS: Suicide risk screening is feasible in pediatric specialty care and can identify at-risk patients. Continued efforts are needed to standardize suicide risk screening practices. Future directions include identifying factors associated with suicide risk in patients in pediatric subspecialty care settings.
ABSTRACT
AIM: There is convergent evidence that exercise increases psychological well-being; however, the mechanism of this psychological effect of exercise is not yet completely understood. The purpose of this study was to examine the effects of aerobic exercise training on brain structure and psychological well-being in young adults. METHODS: University students who had not regularly exercised were divided into training group (N.=15) and control group (N.=15). The training group performed a total 30 periods of aerobic exercise training, while the control group never performed. Whole-brain magnetic resonance imaging scans and mental health questionnaire examinations were performed before and after the exercise training period for all of the participants. A voxel-based morphometry (VBM) analysis was used to compare the changes in gray-matter volumes in the two groups. VBM is an objective whole-brain technique for characterization of regional cerebral volume and tissue concentration differences in structural magnetic resonance images. RESULTS: The results of VBM analysis revealed no change in gray-matter volume in the training group, although the gray-matter volume of the left insula was significantly decreased in the control group after the exercise training period. The training group exhibited significant improvement in some scores on the mental health questionnaire after the exercise training period, compared with the control group. CONCLUSIONS: These findings suggest that aerobic exercise training may inhibit gray-matter volume loss in the insula, and that a relationship may exist between preservation of insula gray-matter and improvement of psychological well-being by aerobic exercise training.
Subject(s)
Cerebral Cortex/anatomy & histology , Exercise/psychology , Mental Health , Female , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Male , Organ Size , Surveys and Questionnaires , Young AdultABSTRACT
The WT1 gene is overexpressed in human primary leukemia and a wide variety of solid cancers. The WT1 gene is alternatively spliced at two sites, yielding four isoforms: 17AA(+)KTS(+), 17AA(+)KTS(-), 17AA(-)KTS(+), and 17AA(-)KTS(-). Here, we showed that 17AA(+)WT1-specific siRNA induced apoptosis in three WT1-expressing leukemia cell lines (K562, HL-60, and Kasumi-1), but not in WT1-non-expressing lymphoma cell line (Daudi). 17AA(+)WT1-specific siRNA activated caspase-3 and -9 in the intrinsic apoptosis pathway but not caspase-8 in the extrinsic one. On the other hand, 17AA(-)WT1-specific siRNA did not induce apoptosis in the three WT1-expressing cell lines. The apoptosis was associated with activation of proapoptotic Bax, which was activated upstream of the mitochondria. Constitutive expression of 17AA(+)WT1 isoforms inhibited apoptosis of K562 leukemia cells induced by apoptosis-inducing agents, etoposide and doxorubicin, through the protection of mitochondrial membrane damages, and DNA-binding zinc-finger region of 17AA(+)WT1 isoform was essential for the antiapoptotic functions. We further studied the gene(s) whose expression was altered by the expression of 17AA(+)WT1 isoforms and showed that the expression of proapoptotic Bak was decreased by the expression of 17AA(+)KTS(-)WT1 isoform. Taken together, these results indicated that 17AA(+)WT1 isoforms played antiapoptotic roles at some points upstream of the mitochondria in the intrinsic apoptosis pathway.
Subject(s)
Apoptosis Regulatory Proteins/physiology , Apoptosis/genetics , Signal Transduction/genetics , WT1 Proteins/physiology , Apoptosis Regulatory Proteins/genetics , Cell Line, Tumor , HL-60 Cells , Humans , K562 Cells , Mitochondria/genetics , Mitochondria/metabolism , Protein Isoforms/genetics , Protein Isoforms/physiology , RNA, Small Interfering/physiology , WT1 Proteins/geneticsABSTRACT
We investigated the expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR/Flk-1) during muscle regeneration by immunohistochemistry and real-time RT-PCR. On days 5 and 7 after the induction of injury, VEGF and Flt-1 were detected in the cytoplasm and KDR/Flk-1 in the cytoplasm and on cell membranes of the same regenerating muscle fibers. The levels of these proteins in the regenerating muscle fibers gradually decreased until day 20. In contrast, these proteins were not detected in the fibers of normal muscle. This suggests that regenerating muscle fibers express VEGF and its receptors in response to injury. In addition, we found that the VEGF mRNA transcript transiently increased after 12 h of muscle injury and then returned to the basal levels observed in normal muscles on day 1. The expression of Flt-1 and KDR/Flk-1 mRNA transcripts also peaked on day 3 and then returned to the basal levels observed in normal muscles on day 10. These findings suggest that regenerating muscle fibers are an important source of VEGF and that VEGF signaling through Flt-1 and KDR/Flk-1 may be involved in the process of muscle regeneration in vivo.
Subject(s)
Muscle, Skeletal/metabolism , Regeneration , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Body Weight , Cell Membrane/metabolism , Cytoplasm/metabolism , Freezing , Immunohistochemistry , Male , Mice , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/surgery , Organ Size , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Time FactorsABSTRACT
The nucleotide sequence (658 bp) of the cDNA coding for glutathione S-transferase Y-2 of yeast Issatchenkia orientalis was obtained. The cDNA clone contains an open reading frame of 570 nucleotides encoding a polypeptide comprising 190 amino acids with a molecular weight of 21,520. The primary amino acid sequence of the enzyme exhibits only 25.0% and 21.1% identity with 177 and 151 amino acid residues of maize glutathione S-transferase I and rat glutathione S-transferase Yb2, respectively.
Subject(s)
DNA/genetics , Glutathione Transferase/genetics , Yeasts/enzymology , Amino Acid Sequence , Base Sequence , Molecular Sequence Data , Open Reading Frames , Restriction Mapping , Sequence Alignment , Sequence Homology, Nucleic Acid , Yeasts/geneticsABSTRACT
We examined the effect of recombinant human interleukin (IL)-11 alone or in combination with various colony-stimulating factors (CSFs), including IL-3, granulocyte/macrophage (GM)-CSF, granulocyte (G)-CSF, stem cell factor (SCF), flt3 ligand (FL), and thrombopoietin (TPO), on colony formation by leukemic progenitor cells (L-CFU) obtained from 33 patients with acute myelogenous leukemia (AML). Leukemic colony formation was found in approximately 70 to 80% of the patients in the presence of at least one of the above CSFs. Although IL-11 alone did not support L-CFU, the growth of these progenitors in the presence of other cytokines was enhanced by IL-11 in 16 out of 33 patients and it showed a synergistic action with G-CSF in 12 of them. This synergistic action occurred in seven out of nine M5 patients (French-American-British (FAB) classification). A single cell clone-sorting experiment clearly demonstrated that this synergistic effect was operative at the single progenitor cell level. The number of leukemic cells proliferating in the presence of G-CSF+IL-11 was significantly higher than in the presence of G-CSF alone, suggesting that IL-11 recruited dormant leukemic progenitors into the cell cycle. Flow cytometric analysis revealed that all types of AML blast cells (M0 approximately M6) ubiquitously expressed gp130, although the level of expression was significantly higher in M5 cells. In contrast, expression of the IL-11 receptor alpha chain (IL-11Ralpha) varied between FAB types. Blast cells obtained from M1, M3 and M5 patients showed higher levels of expression, with M5 cells showing the strongest expression. Interestingly, the leukemic progenitor cells for which proliferation was synergistically enhanced by IL-11 had significantly higher expression of both IL-11Ralpha and gp130. These results suggest that administration of IL-11 in vivo may stimulate the proliferation of leukemic progenitor cells, particularly M5 cells, in the presence of G-CSF, and that the responsiveness of L-CFU to IL-11 may be predicted by a simple receptor assay.
Subject(s)
Antigens, CD/analysis , Interleukin-11/therapeutic use , Leukemia, Myeloid/drug therapy , Membrane Glycoproteins/analysis , Peptide Fragments/analysis , Receptors, Interleukin/chemistry , Signal Transduction/drug effects , Acute Disease , Adolescent , Adult , Aged , Cell Division/drug effects , Cytokine Receptor gp130 , Female , Flow Cytometry , Humans , Interleukin-11 Receptor alpha Subunit , Leukemia, Myeloid/pathology , Male , Middle Aged , Receptors, Interleukin-11 , Tumor Cells, Cultured , Tumor Stem Cell AssayABSTRACT
The Wilms' tumor gene, WT1, is a tumor marker for leukemic blast cells. The WT1 expression levels were examined for 57 patients with myelodysplastic syndromes (MDS) (refractory anemia (RA), 35; RA with excess of blasts (RAEB) 14; RAEB in transformation (RAEB-t), six; and MDS with fibrosis, two) and 12 patients with acute myeloid leukemia (AML) evolved from MDS. These levels significantly increased in proportion to the disease progression of MDS from RA to overt AML via RAEB and RAEB-t in both bone marrow (BM) and peripheral blood (PB). WT1 expression levels in PB significantly correlated with the evolution of RAEB or RAEB-t to overt AML within 6 months. Therefore, WT1 expression levels in PB were superior to those in BM for early prediction of the evolution to AML by means of quantitation of the WT1 expression levels. Furthermore, WT1 expression in PB of patients with overt AML evolved from MDS was significantly decreased by effective chemotherapy or allogeneic stem cell transplantation and became undetectable in long-term survivors. These results clearly showed that WT1 expression levels are a tumor marker for preleukemic or leukemic blast cells of MDS and thus reflect the disease progression of MDS. Therefore, monitoring of WT1 expression levels has made continuous assessment of the disease progression of MDS possible, as well as the prediction of the evolution of RAEB or RAEB-t to overt AML within 6 months. The results also showed that quantitation of WT1 expression levels is useful for diagnosis of minimal residual disease of MDS with high sensitivity, thus making it possible to evaluate the efficacy of treatment for MDS.
Subject(s)
Biomarkers, Tumor , Genes, Wilms Tumor , Myelodysplastic Syndromes/pathology , Adult , Aged , Aged, 80 and over , Base Sequence , DNA Primers , Disease Progression , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Sections of formalin-fixed, paraffin-embedded tissues from 210 human breast cancers were immunohistochemically examined using the mAb against human tenascin (TN) RCB1. Immunoreactive TN was detected in the breast cancer stroma in 77 (36.7%) cases, whereas the remaining 133 (63.3%) were negative. Of the 77, 12 (5.7%) cases also showed positive staining in the carcinoma cell cytoplasm. The positive cells were often observed in the margin of the cancer nests at the site adjacent to the stroma. According to the staining pattern of TN, the breast cancer cases were classified into the three groups of cancer cell TN(+)/stromal TN(+), cancer cell(-)/stromal TN(+), and cancer cell(-)/stromal TN(-). Analysis of the relationship of these TN patterns with various clinicopathological characteristics of the tumors and the patient outcome revealed that, in comparison to the cancer cell(-)/stromal TN(-) group, the cancer cell TN(+)/stromal TN(+) group exhibited increased frequency of lymph node metastasis and exceptionally poor outcome, and the cancer cell(-)/stromal TN(+) group also showed more frequent metastasis and poorer outcome. Most of the cancer cell TN(+)/stromal TN(+) cases were c-erbB-2 positive and estrogen receptor negative. Furthermore, in situ hybridization of freshly obtained breast cancer tissues demonstrated that both cancer cells and stromal cells express TN mRNA. These results indicate that the TN in breast cancer is produced by cancer epithelial cells as well as by stromal mesenchymal cells, and that cancer cell TN might be involved in cancer spreading, resulting in unfavorable patient prognosis.
Subject(s)
Breast Neoplasms/metabolism , Neoplasm Proteins/metabolism , Tenascin/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , In Situ Hybridization , Middle Aged , RNA, Messenger/metabolism , Stromal Cells/metabolismABSTRACT
The roles of alpha- and beta-subunits of human TSH (hTSH) were studied by investigating the inhibitory effects of monoclonal antibodies on the biological activity of hTSH. Four monoclonal antibodies directed toward different epitopes on the beta-subunit (hTSH beta) inhibited completely the receptor binding of hTSH to FRTL-5 rat thyroid cells. In contrast, five monoclonal antibodies directed toward different epitopes on the alpha-subunit had little or no effect on the receptor binding. Furthermore, four of five alpha-subunit-specific antibodies and three of four hTSH-specific antibodies inhibited both hTSH-induced cAMP accumulation and thymidine uptake in FRTL-5 cells, in a dose-response manner. One hTSH (alpha-beta heterodimer)-specific antibody which did not recognize the free subunits also had the inhibitory effect on both the receptor binding and hTSH-induced cAMP accumulation. These results strongly suggest that hTSH beta is indispensable for recognizing the receptors on FRTL-5 cells and that the alpha-subunit is required for signal transduction in postreceptor step(s). In addition, it is also suggested that the highly conformational structure of hTSH is absolutely essential for the biological activity.
Subject(s)
Glycoprotein Hormones, alpha Subunit/metabolism , Receptors, Thyrotropin/metabolism , Thyroid Gland/metabolism , Thyrotropin/metabolism , Animals , Antibodies, Monoclonal/pharmacology , Cell Line , Cyclic AMP/biosynthesis , DNA/biosynthesis , Epitopes/immunology , Glycoprotein Hormones, alpha Subunit/immunology , Glycoprotein Hormones, alpha Subunit/pharmacology , Rats , Signal Transduction , Structure-Activity Relationship , Thyroid Gland/drug effects , Thyrotropin/immunology , Thyrotropin/pharmacologyABSTRACT
The prevalence of TSH receptor antibody (TRAb), measured by RRA assay (TSH-binding inhibitor immunoglobulin, TBII) and biological stimulation-blocking assay (thyroid-stimulation blocking antibody, TSBAb), was examined in 134 consecutive patients with primary hypothyroidism due to autoimmune thyroiditis [83 patients with goitrous Hashimoto's disease (group A) and 51 with primary atrophic hypothyroidism (group B)]. In group A, TBII was detected in 6 patients (7%), TSBAb in 7 (8%), and both in 4 (5%). Similarly, in group B, TBII was detected in 7 patients (14%), TSBAb in 7 (14%), and both in 5 (10%). TBII with TSBAb activity was low or moderate in group A, but strongly positive in group B. No relationship was apparent in either group between TBII or TSBAb activity and any clinical or laboratory parameter examined. Moreover, no clinical or laboratory findings distinguished patients with TRAb from those without. The low prevalence of TRAb in primary hypothyroidism suggests that intrathyroidal cell-mediated destructive mechanisms may be more important in the pathogenesis of hypothyroidism in autoimmune thyroiditis.
Subject(s)
Autoantibodies/analysis , Hypothyroidism/immunology , Receptors, Thyrotropin/immunology , Adult , Female , Humans , Hypothyroidism/diagnosis , Hypothyroidism/epidemiology , Hypothyroidism/etiology , Immunoglobulins, Thyroid-Stimulating , Japan , Male , Radioimmunoassay , Thyroid Hormones/analysis , Thyroiditis, Autoimmune/complications , Thyroiditis, Autoimmune/diagnosis , Thyrotropin/analysisABSTRACT
We reported that gestational thyrotoxicosis is induced by thyroid-stimulating activity (TSA) of circulating hCG. However, the serum immunological hCG concentration did not correlate to TSA. To elucidate this, we examined the relation of carbohydrate moieties of hCG to bioactivity in 79 early pregnant women, divided into 4 groups: no emesis, mild emesis, hyperemesis, and gestational thyrotoxicosis with hyperemesis. Serum free T4 (FT4) and free T3 (FT3) levels were significantly higher and TSH was lower in the hyperemesis (FT4, 23.42 +/- 5.02 pmol/L; FT3, 6.26 +/- 1.80 pmol/L; TSH, 0.30 +/- 0.44 mU/L) and in gestational thyrotoxicosis (FT4, 48.65 +/- 14.80 pmol/L; FT3, 14.71 +/- 3.47 pmol/L; TSH, < 0.04 mU/L) groups than in the no emesis group (FT4, 16.99 +/- 2.48 pmol/L; FT3, 5.51 +/- 0.75 pmol/L; TSH, 1.37 +/- 1.23 mU/L; P < 0.0005). TSA was also significantly higher in the hyperemesis (566 +/- 187%) and gestational thyrotoxicosis (832 +/- 168%) groups than in the no emesis group (321 +/- 135%). We found no significant difference among serum hCG concentrations measured by immunoassay in the four groups. To characterize the carbohydrate chains, serum hCG was fractionated by Concanavalin-A and ricin lectin affinity chromatography. The fraction firmly bound to Con-canavalin-A, which contains hCG with high mannose and hybrid-type carbohydrate chains, was significantly higher in the hyperemesis group (91.07 +/- 2.06%; n = 15) than in the no emesis group (89.61 +/- 2.38%; n = 24; P < 0.04). The fraction firmly bound to ricin column, which contains hCG with asialo-carbohydrate chains, was significantly increased in the gestational thyrotoxicosis group (3.44 +/- 1.70%; n = 5) compared with that in the no emesis group (1.77 +/- 0.49%; n = 24; P < 0.03). Serum FT4 positively correlated to the hCG fraction firmly bound to ricin column (r = 0.61; P < 0.001). We conclude that thyrotoxicosis with hyperemesis may be caused by circulating asialo-hCG with higher thyrotropic bioactivity.
Subject(s)
Asialoglycoproteins/physiology , Chorionic Gonadotropin/physiology , Pregnancy Complications , Thyrotoxicosis/etiology , Adult , Chorionic Gonadotropin/blood , Female , Humans , Hyperemesis Gravidarum/blood , Hyperemesis Gravidarum/etiology , Pregnancy , Thyrotoxicosis/blood , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood , Vomiting/bloodABSTRACT
Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.
Subject(s)
Antibodies, Antinuclear/analysis , DNA/immunology , Puerperal Disorders/immunology , Thyroiditis, Autoimmune/immunology , Adult , Female , Graves Disease/immunology , Humans , Pregnancy , Thyrotoxicosis/immunologyABSTRACT
The long term clinical outcome of postpartum hypothyroidism was investigated by follow-up studies of 44 patients (59 postpartum episodes; mean age of mothers at delivery, 28.2 yr) 5 or more yr later (mean interval after delivery, 8.7 yr; range, 5-16 yr). Forty-nine episodes (83%) in 34 women were followed by recovery within 1 yr postpartum, and those women remained euthyroid thereafter (group A); 10 women [10 episodes (17%)] developed permanent hypothyroidism during the follow-up period (group B). Five women in group B recovered during the first year, but became hypothyroid again later, the other 5 women in Group B remained persistently hypothyroid. HLA typing revealed significantly higher frequencies of HLA-DR3, -DRW8, -DRW9, -A26, -BW46, and -BW67, and significantly lower frequencies of HLA-DR2, -BW52, -BW62, and -CW7 in women with postpartum hypothyroidism than in normal women. Of 9 women with postpartum hypothyroidism who had HLA-DRW9 and/or -B51 associated with antithyroglobulin-antibody titers of 2(3) X 10 or higher, 6 developed permanent hypothyroidism. We conclude that long term follow-up is essential for women of postpartum hypothyroidism because of the risk of permanent hypothyroidism. The results suggest that some immunogenetic factors may be related to the etiology of postpartum hypothyroidism and that women with HLA-DRW9 and/or -B51 and higher titers of antithyroglobulin antibody are likely to develop permanent hypothyroidism.