Biomedical subjects

J Noh

Publications and source records attributed to J Noh.

At least 19 recordsLinked to original sources

PubMed2000

Is there a place for the late cardioversion of atrial fibrillation? A long-term follow-up study of patients with post-thyrotoxic atrial fibrillation.

AIMS: As atrial fibrillation is associated with significant mortality and morbidity, restoration of sinus rhythm is desirable. However, previous data suggest that cardioversion should be restricted to patients in whom the fibrillation is of limited duration (<1-2 years) because of high relapse rates. It may be the frequent association with cardiac disease, rather than the duration of fibrillation itself, which determined the high relapse of earlier studies. The aim of this study was to investigate rates of cardioversion, maintenance of sinus rhythm and predictors of subsequent relapse in a homogeneous group of patients without evidence of any co-existent cardiac disease. METHODS AND RESULTS: We report on a retrospective series of 106 patients with thyrotoxicosis-induced fibrillation but no other heart disease: 87% had been in atrial fibrillation for >12 months (median duration 28.5, interquartile range 15-47 months). Cardioversion was attempted using disopyramide and then electric shock. Ninety-eight patients were successfully cardioverted: at late follow-up, 80.6+/-37 months (mean+/-SD), 67% were in sinus rhythm. CONCLUSION: Although a relationship between the duration of fibrillation and maintenance of sinus rhythm was found, the high proportion remaining in sinus rhythm, compared with other series, suggests this influence may be less important than the presence or absence of structural heart disease.

Adult↗

PubMed1999

Age-specific decrease in seroprevalence of schistosomiasis in Puerto Rico.

In our previous work, we reported the first systematic, island-wide, serologic survey for schistosomiasis in Puerto Rico in 40 years. In that study, approximately 3,000 serum samples from the 76 municipalities comprising the island of Puerto Rico were tested for the detection of antibodies to S. mansoni microsomal antigens by the Falcon assay screening test-enzyme-linked immunosorbent assay (FAST-ELISA) and those positive were confirmed by an enzyme-linked immunoelectrotransfer blot (EITB). The highest EITB positivity was found in 17 municipalities, which comprised 48% of all seropositive samples. An additional finding was that 10% of the 215 EITB-positive samples were from individuals 25 years or younger and were for the most part of residents from the high seroprevalence areas. Thus, for this study we focused on 766 individuals 25 years of age or younger (45.5% males and 54.4% females), two-thirds of which were from 10 municipalities with the highest EITB seropositivity, and one-third from the 10 municipalities with the lowest EITB seropositivity found in our previous study. Of all samples, the results showed an overall FAST-ELISA positivity of 11.6%, with males similar to females (12.6 versus 10.7%, respectively). Confirmation by EITB was only 1.8%, with a males three-fold higher than females (3% versus 0.7%). When seropositivity was measured by age in five-year increments, a clear age-specific decrease in seropositivity was observed. Thus, by FAST-ELISA, 16.7% of the 21-25-year-old age group was positive, decreasing to 14.6%, 9.9%, 7.9%, and 9.3% in the 16-20-, 11-15-, 6-10-, and 1-5-year-old age groups, respectively. Confirmatory EITB showed even more impressive results: 4.7%, 2.6%, 1.2%, 0.7%, and 0% in the same age brackets. With regard to the high prevalence municipalities, only four of 10 (11 of 228 = 4.8%) had confirmatory EITB-positive samples and most were from municipalities of the Rio Grande de Loiza River basin and tributaries. The male to female positivity ratio was 4:1. Of the low prevalence municipalities, only single positive cases (by EITB) were found in three disperse municipalities. These results support the concept that there has been little transmission of S. mansoni in Puerto Rico during the first half of the 1990s and confirms anecdotal comments of local physicians who have seen virtually no new infections during the past three years. This makes the documentation of eradication of schistosomiasis from Puerto Rico feasible, a goal that should be set as being before the 100th anniversary of its discovery on the island by Isaac Gonzalez-Martinez in 1904.

Adolescent↗

PubMed1998

Neurocysticercosis in persons with epilepsy in Medellín, Colombia. The Neuroepidemiological Research Group of Antioquia.

PURPOSE: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellín, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. METHODS: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. RESULTS: Prevalence of neurocysticercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellín. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. CONCLUSIONS: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.

Adolescent↗

PubMed1997

Geographic clustering and seroprevalence of schistosomiasis in Puerto Rico (1995).

A systematic, island-wide survey for schistosomiasis in Puerto Rico has not been conducted for more than 40 years. In 1974, a thorough survey of Boqueron de Las Piedras, a small community, showed a prevalence of 40%. No additional information on prevalence in Puerto Rico has been obtained during the ensuing 21 years. Concern for the public health of residents and visitors prompted the formation of the Bilharzia Commission in 1994 and the systematic serosurvey reported herein. Two thousand nine hundred fifty-five plasma samples from healthy donors were obtained randomly from the Red Cross in March and April 1995. Sex, resident municipalities, and age of the donors were recorded. The donors were from all but three of 79 municipalities in Puerto Rico. No sample was available from the three out island municipalities of Mona, Vieques, and Culebra. Male donors (n = 2,027) outnumbered females (n = 928) by more than 2:1, ages ranged from nine to 76 years with most (85.3%) between 19 and 51 years of age. All samples were tested with the Falcon assay screening test:enzyme-linked immunosorbent assay (FAST:ELISA) with microsomal antigens of Schistosoma mansoni. All FAST:ELISA+ samples were confirmed by enzyme-linked immunoelectrotransfer blot (EITB). Our data showed that 15.4% were FAST:ELISA+, and 10.6% were confirmed by EITB; 13.5% of the males and 4.1% of the females were EITB+. If we exclude those municipalities with fewer than five samples, the prevalence of EITB+ ranged from 0% to 38.5%, with the highest seroprevalence rates (21.1-38.5%) concentrated in 17 municipalities, which accounted for 48% of all seropositive samples. These 17 municipalities, however, contain only 18% of the total population of Puerto Rico. Two areas of high seroprevalence rates center around Jayuya (38.5%) and Naguabo (36.4%). The previously surveyed area of Boqueron is located in Las Piedras (35.3%), adjacent to Naguabo. In addition, we found 10% (21) of our total 215 donors less than 25 years of age to be EITB+ and all but two are residents of the high prevalence districts. These data strongly support the contention that schistosomiasis has been transmitted in a focal fashion during the past approximately 20 years.

Adolescent↗

PubMed1997

A recombinant protein from Schistosoma mansoni useful for the detection of S. mansoni and Schistosoma haematobium antibodies.

A recombinant Schistosoma mansoni protein has been identified as a useful antigen for the detection of S. mansoni and Schistosoma haematobium antibodies. The purified recombinant protein, Sm22.3, was assayed using an enzyme-linked immunosorbent assay format against a battery of 491 well defined sera, including S. mansoni, S. haematobium, and Schistosoma japonicum infection sera, normal human sera, sera from 9 other parasitic infections, and sera from 2 additional infections. The sensitivity for detecting S. mansoni and S. haematobium infections with this single recombinant protein is 80.1%. The specificity is 94.8%. However, 15 of the 16 cross-reactive sera are malaria infection sera, and we have data suggesting that these malaria sera are actually recognizing an epitope on the vector-derived 6Xhistidine tag of recombinant Sm22.3. If this is the case, then, the actual specificity of the assay is 99.6%.

Animals↗

PubMed1996

Schistosomiasis in Lake Malawi.

BACKGROUND: In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS: A volunteer cohort of expatriates and visitors representing a cross-section of Malawi's foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawi's southwestern shore. FINDINGS: The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION: S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.

Adult↗

PubMed1994

Relationship between silent thyroiditis and recurrent Graves' disease in the postpartum period.

We carried out a close follow-up study of 96 episodes of postpartum hyperthyroidism, which developed in women with a history of Graves' disease. Hyperthyroidism had developed 1-6 months (mean +/- SD, 2.3 +/- 1.4) after delivery. Radioiodine uptake (RAIU) values during the thyrotoxic phase, determined after a 1-week restriction of iodine-rich diet, ranged from very low to very high (1-70%). The group with low RAIU values (group L: < 10%, n = 26) and the normal group (group N: 10-40%, n = 33) showed significantly higher urinary excretion of iodine (UI) than the high group (group H: > 40%, n = 37), and UI in group L was comparable to that in patients with silent thyroiditis. TSH binding inhibiting antibody (TBIAb) values were determined in 87 patients at the RAIU testing, and were above normal in most of them: all in group H, 68% in group N, and 52% in group L. The mean TBIAb value in group H was significantly higher than that in group N or L (P < 0.0001 for both). Fifty-one patients in group L and group N were observed without treatment. Of these, hyperthyroidism resolved spontaneously in 39 patients (76%), in whom transient hypothyroidism developed with substantial frequency. Hyperthyroidism subsequently resumed in 18 (46%) of these 39 between 4 and 9 months (mean +/- SD, 7.1 +/- 2.1) after delivery and did not resume in the other 21. RAIU values, determined again during this later phase of hyperthyroidism, were high enough to indicate Graves' hyperthyroidism in all but one patient. During the postpartum period, TBIAb values increased and then declined in the majority of the patients irrespective of the course of hyperthyroidism. Of the 21 patients who maintained euthyroidism after spontaneous resolution of hyperthyroidism, transient increase in TBIAb was observed in 14. These findings suggest that silent thyroiditis commonly develops concomitantly with the activation of Graves' disease and delays or masks the development of Graves' hyperthyroidism.

Autoantibodies↗

PubMed1993

Investigation of antigenic determinants in thyroid peroxidase by synthesis of possible sequential peptides.

One way to locate antigenic determinants in thyroid peroxidase (TPO) is to evaluate the binding of chemically synthesized peptides to autoantibodies. A major epitope of TPO involved in thyroid autoimmunity has been reported to be at residues 590 to 675. Therefore, we synthesized three peptides (P1, residues 603-610; P2, 615-630; and P3, 654-665) in the most antigenic part of this range, as judged by antigenicity analysis, and measured their antigenicity by enzyme-linked immunosorbent assay (ELISA). Amino groups protected with fluorenyl-methoxycarbonyl were used in the synthesis. Sera from 42 untreated patients with Hashimoto's disease and 30 untreated patients with Graves' disease were tested for binding with each peptide. In addition, 6 sera with antibodies against denatured and reduced microsomal antigen were tested. Sera obtained from 22 normal subjects were used as a control. Binding of sera from the patients with autoimmune thyroid disease to the synthetic peptides was weak, about 1% of binding to thyroid microsomes prepared from Graves' thyroid. However, the ELISA index of a mixture of P1, P2, and P3 was significantly higher in the patients with Hashimoto's disease than in the healthy subjects. For both P2 and P3, the ELISA index of the sera with antibodies against denatured and reduced TPO was higher than that of the sera from normal subjects. These results suggested 1) that the antigenic epitopes of TPO recognized by autoantibodies may be conformational and discontinuous, and 2) that antibodies against these linear portions of TPO may exist in patients with Hashimoto's disease.

Autoantibodies↗

PubMed1992

Effects of iodine on thyroid status of fetus versus mother in treatment of Graves' disease complicated by pregnancy.

To investigate the effect of maternal iodine therapy for Graves' disease on fetal thyroid, we examined serum free T4 (FT4) and TSH levels in the fetus vs. those in the mother. Patients who were severely thyrotoxic were not included. Cord and maternal sera were tested at delivery in 35 patients with Graves' disease treated with iodine alone during pregnancy (6-40 mg daily). At the initiation of therapy, the mothers were at 11-37 weeks gestation, and FT4 levels ranged from 28.3-65.8 pmol/L. At delivery, maternal FT4 values ranged from 9.3-42.0 pmol/L, slightly above normal in 22 of the 35 mothers and normal in the other 13. Fetal FT4 levels were above the normal range occurred significantly less often than maternal levels (2 in 35; P less than 0.001), and no fetus had FT4 below normal. In the 13 mothers with normal FT4 levels, all fetal FT4 levels were normal; the fetal TSH level was above normal in 1 and normal in the remainder. A significant correlation was found between cord and maternal FT4 levels (P less than 0.05). In 12 of the 35 mothers, FT4 levels rose after a transient fall during iodine administration. The correlation of cord FT4 and maternal FT4 was closer when these 12 cases were excluded (P less than 0.001). Neither the dose of iodine nor the duration of therapy correlated with thyroid function in fetuses or mothers. Fetal TSH binding inhibitory antibody values strongly correlated with maternal TSH binding inhibitory antibody values (P less than 0.001). These findings indicate that 1) in the treatment of hyperthyroidism due to Graves' disease, iodine seldom if ever exposes the fetus to the risk of hypothyroidism; 2) the fetal thyroid is influenced by the same stimulatory and inhibitory factors as the maternal thyroid; and 3) escape from the inhibitory effects of iodine occurs less often in fetuses than in mothers, which may account at least in part for the lower thyroid status in the fetus compared to that in the mother.

Adult↗

PubMed1992

Radioimmunoassay for calcitonin gene-related peptide and its measurement in sera of patients with thyroid disease.

To investigate serum levels of calcitonin gene-related peptide (CGRP), we developed a sensitive radioimmunoassay (RIA). RIA for CGRP in serum can present some problems: the serum may degradate the tracer during incubation and suppress the antigen-antibody reaction. We avoided these problems by using aprotinin and CGRP-free serum instead of a buffer for the standard curve. We detected serum CGRP in all 39 healthy subjects when CGRP-free serum was not used for the standard curve, but 34 of these subjects had serum CGRP levels below the detection limit (less than 80 pmol/l) when CGRP-free serum was used for the standard curve. We defined the normal range for serum CGRP as below 100.8 pmol/l, which was the maximum level found in the healthy subjects. We studied serum levels of this peptide in patients with thyroid diseases, because the thyroid may be one origin of circulating CGRP. Four of 10 patients with medullary thyroid carcinoma had elevated serum levels of CGRP. Seven of 24 patients with subacute thyroiditis had elevated serum levels of CGRP, but at least one year after clinical recovery, CGRP was undetectable in all. Seven of the 37 patients with hypothyroidism had elevated serum levels of CGRP. None of the patients with hyperthyroidism, adenomatous goiter, thyroid adenoma, or thyroid carcinoma had elevated serum CGRP levels. It is necessary to use a standard curve obtained by the addition of aprotinin and CGRP-free serum to the assay standards to measure serum CGRP levels. Some patients with subacute thyroiditis, hypothyroidism, or medullary thyroid carcinoma had elevated serum CGRP levels.

Adult↗

PubMed1991

Efficacy of disopyramide in conversion and prophylaxis of post-thyrotoxic atrial fibrillation.

Rhythm conversion in patients with post-thyrotoxic atrial fibrillation (AF) has been performed with disopyramide in order to evaluate the conversion rate and to test its effect on the maintenance of sinus rhythm after cardioversion. The duration of AF ranged from 9 to 122 months (mean 31.8 months). Of 81 patients, 12 (15%) with relatively short duration AF were converted to sinus rhythm with disopyramide. The remaining 69 patients required DC cardioversion, which restored sinus rhythm in 58 patients. The 58 DC-converted patients were divided into two groups: a disopyramide group (D group) and a non-disopyramide group (non-D group). The D group received disopyramide 300 mg per day for 3 months after DC cardioversion and the non-D group did not receive anti-arrhythmic drugs. During the early observation period, only one patient relapsed in the D group into AF, but 5 successive patients in the non-D group reverted to AF, forcing discontinuation of the non-D protocol. A second DC cardioversion performed on 3 of those 5 patients was followed by maintenance therapy with disopyramide 300 mg per day, and they remained in sinus rhythm. With the inclusion of those three subjects, sinus rhythm was still present in 44 of the total of 58 patients converted by DC (76%) at the time of follow-up (64 months). Thus, disopyramide was effective in rhythm conversion and it was essential for the maintenance of sinus rhythm after cardioversion in patients with post-thyrotoxic AF.

Adolescent↗

PubMed1991

Thyroid microsomal antigen in Graves' thyroid is not different from that in normal thyroid.

Differences from normal in microsomal antigen (M-Ag) may be involved in the development of autoimmune thyroid disease. We compared the M-Ag in Graves' thyroid immunologically and biochemically to that in normal thyroid. The concentration of M-Ag, measured with an enzyme-linked immunosorbent assay, was significantly greater in the Graves' microsomes than in normal microsomes. Binding of a patient's microsomal antibody to Graves' microsomes was completely inhibited when the serum was first incubated with normal thyroid microsomes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting were done with a monoclonal antibody to denatured M-Ag. In both Graves' and normal thyroids, M-Ag existed as 107-, 101-, and 95-kDa peptides. After incubation with V8 protease, the residual antigenic peptide had a molecular weight of less than 60,000 and after incubation with trypsin, 95- and 87-kDa peptides and several smaller antigenic peptides were found. There were no significant differences in the pattern of normal and Graves' microsomes after digestion. Two-dimensional gel electrophoresis of Graves' microsomes showed that the isoelectric point for the 107-kDa peptide was at pH 7.2; that for the 101-kDa peptide was at pH 6.2, and that for the 95-kDa peptide was at 6.5. These values were not different from those observed for normal microsomes. These results indicate that M-Ag in Graves' thyroid does not differ from that in normal thyroid, and that microsomal antibodies in autoimmune thyroid disease probably do no arise from differences in the antigen.

Autoantigens↗

PubMed1991

Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function in autoimmune thyroid disease?

We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.

Antigens↗

PubMed1990

Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis.

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.

Adult↗

PubMed1989

Recovery from foetal hypothyroidism: evidence for the safety of breast-feeding while taking propylthiouracil.

We assessed the post-natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast-fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants' thyroid function. These results assure the safety of breast-feeding for the infants of mothers with Graves' disease taking propylthiouracil.

Adult↗

PubMed1989

Evidence against the importance in the disease process of antibodies to bovine thyroid-stimulating hormone found in some patients with Graves' disease.

The antibody to TSH (TSH-Ab) found in some patients with Graves' disease may be either an antiidiotype (anti-id-Ab) to the TSH receptor antibody (TRAb) or the antigen (idiotype) for which the anti-id-Ab is in fact TRAb. Four groups have found antibodies to bovine TSH (bTSH-Ab) in Graves' disease patients in a TSH binding-inhibiting immunoglobulin (TBII) RRA that uses [125I]bTSH. In this assay serum samples containing bTSH-Ab give highly negative TBII values. The purpose of this study was to look for any clinical significance of potential idiotypic-antiidiotypic network regulation related to bTSH-Ab. Twenty-one (0.49%) of 4285 Graves' disease patients had TBII values less than the mean -4 SD of normal subjects. In all 21, bTSH-Ab was found by incubation of [125I]bTSH with the patient's serum, and significant inhibition of binding of bTSH-Ab to bTSH by human TSH was found in only 3 of these serum samples. We investigated next whether the binding site of the anti-TSH-Ab mimicked the TSH receptor-binding site. Binding of [125I]bTSH to bTSH-Ab-positive serum was not inhibited by bTSH-Ab-negative, thyroid-stimulating immunoglobulin-positive [(+)], and/or TBII(+) immunoglobulin G. In one patient with human TSH-Ab, TSH-Ab appeared and disappeared, and when TSH-Ab was negative, TBII was positive. Inhibition of [125I]bTSH binding to TSH-Ab by the same patient's serum when that patient was serum thyroid-stimulating immunoglobulin(+), TBII(+), and TSH-Ab-negative was sought but not found. Changes in serum TSH-Ab activity and disease activity were not correlated in this patient. In six untreated patients with Graves' hyperthyroidism with bTSH-Ab, the serum T3 and T4 concentrations and the time required to become euthyroid during antithyroid drug treatment were not significantly different from those in 52 such patients without bTSH-Ab. These data suggest that bTSH-Ab is not an anti-id-Ab to TRAb and that TSH-Ab does not directly modulate the activity of Graves' disease.

Animals↗

PubMed1989

Thyroid peroxidase activity-inhibiting immunoglobulins in patients with autoimmune thyroid disease.

The thyroid microsomal antibody (M-Ab) has been found to be an antibody against thyroid peroxidase (TPO), and such antibodies have been reported not only to bind TPO but also to directly inhibit TPO activity. In this study we investigated the relationship between TPO activity-inhibiting immunoglobulin (TPII) and thyroid function in 55 untreated patients with hyperthyroidism due to Graves' disease and 35 untreated patients with Hashimoto's disease. TPO partially purified from the microsomal fraction of Graves' thyroid tissue by Sephacryl S-300 gel filtration was incubated with immunoglobulin (Ig) fractions of serum prepared by precipitation with 15% polyethylene glycol. At the end of incubation, TPO activity was measured by a guaiacol assay. The TPII level was expressed as the TPII index, defined as the inhibition of TPO activity by patient Ig divided by inhibition produced by a known positive Ig. We also measured serum free T4, free T3, and TSH concentrations and anti-M-Ab titers, the latter by a microenzyme-linked immunosorbent assay. When a positive TPII index was defined as more than the mean + 2 SD of the TPII index (0.38) for 15 normal subjects, 13 patients with Graves' disease and 14 patients with Hashimoto's disease had positive TPII index values. There was a positive correlation between the TPII index values and the M-Ab titers in patients with either Graves' disease (r = 0.38; P less than 0.01) or Hashimoto's disease (r = 0.52; P less than 0.01). The mean TPII index in patients with Hashimoto's disease was significantly higher than that in patients with Graves' disease [0.38 +/- 0.42 (+/- SD) vs. 0.19 +/- 0.41; P less than 0.05]. The slope of the regression line between the TPII index values and the M-Ab titers for patients with Hashimoto's disease was steeper than that for patients with Graves' disease. The mean serum free T4 concentration was significantly lower in those patients with Hashimoto's disease who had positive TPII index values than in those with negative TPII index values (14.0 +/- 5.0 vs. 9.6 +/- 3.7 pmol/L; P less than 0.01). There was no significant difference in thyroid function between the patients with Graves' disease with positive and negative TPII index values. TPII appears to inhibit thyroid function in some patients, but no simple relationship between TPII and thyroid function in autoimmune thyroid disease was demonstrated. Understanding the factors that control access of anti-TPO antibody to its antigen may help to elucidate the significance of circulating anti-TPO antibody.

Adolescent↗

PubMed1989

Serum parathyroid hormone concentration measured by highly sensitive assay in post-thyroidectomy hypocalcemia of patients with Graves' disease.

To investigate the role of parathyroid function in transient hypocalcemia after subtotal thyroidectomy for Graves' disease, the serum parathyroid hormone (PTH) concentration and nephrogenous (N) cAMP were measured in 16 patients before and after surgery. Serum PTH was measured with two commercially available kits (PTH-M, PTH-C), PTH-M is a recently developed highly sensitive assay using an antibody recognizing the mid-portion of human PTH and a synthetic 125I-tyr45-human PTH (43-68) as a radioligand. One of the 16 patients had severe clinical tetany and had a markedly lower PTH-M concentration and NcAMP after thyroidectomy. However, no significant change in serum PTH-M, PTH-C and NcAMP were observed in the other patients, although their serum calcium (Ca) concentrations decreased significantly. The Data were analyzed by dividing the patients according to the change in serum Ca or PTH. Serum PTH-M and PTH-C significantly decreased in 4 patients whose serum Ca clearly decreased after surgery. Serum Ca on the first postoperative day was significantly lower in patients whose serum PTH decreased after thyroidectomy than in patients whose serum PTH did not. Furthermore, the serum Ca concentration was significantly correlated with PTH-M, and with NcAMP on the third postoperative day. These data proved that hypofunction of the parathyroid gland is important in transient hypocalcemia after subtotal thyroidectomy for Graves' disease. The pathogenetic mechanism of transient hypocalcemia was discussed in comparison with the data from a patient who had overt parathyroid injury.

Calcium↗