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We encountered a patient with neuroblastoma showing remarkably high total LD activity (12,585 IU/l). His liver and heart function was normal. In the serum LD isoenzyme pattern, LD1 was increased, and LD2 extra band (LD2 ex) was observed on the negative pole side of LD2. However, LD2 ex was absent in erythrocytes of the patient, which demonstrates the exclusion of genetic factors. Neither the enzyme counter current method or immunofixation showed immune complexes, excluding anomalies. The LD isoenzyme in a metastatic lymphnode lesion before treatment showed increased LD1. The LD isoenzymes in the tissue, removed after 5 courses of chemotherapy, showed predominance of LD3 and absence of LD2 ex. Rapid decreases in the serum total LD activity and LD1 fraction and the disappearance of LD2 ex after chemotherapy suggest that these changes in the two LD fractions are associated with production of abnormal LD (LD2 ex) by the tumor.

We measured serum 1,5 anhydroglucitol (1,5AG) levels by HPLC in 32 patients with liver cirrhosis, 32 with diabetes mellitus and 61 normal subjects. Serum 1,5AG was significantly lower in patients with diabetes mellitus and liver cirrhosis compared with that in normal subjects. Serum levels of type IV collagen were higher in patients with liver cirrhosis than in those without liver cirrhosis. A negative correlation was observed between serum 1,5AG and type IV collagen in patients with liver cirrhosis (r = -0.37, p0.05), but not in patients with diabetes mellitus. These data suggest that serum 1,5AG levels reflect the degree of liver cirrhosis.

To evaluate the contribution of the vagal nerve activity in the cardiovascular postural adaptation, effects of decremental head-up tilting (90 degrees, 64 degrees, 53 degrees, 44 degrees, 37 degrees, 30 degrees, 24 degrees, 17 degrees, 12 degrees, 6 degrees and 0 degree) on time- and frequency-domain heart rate variability variables were analyzed in healthy young female.During head-up tilting, a hydrostatic venous pooling in the extremities occurs owing to gravity. To pump up the blood toward the upper body, the sympathetic nerve activity has been shown to play an important role. So, to date, few studies evaluated the effects of vagal nerve activity to stabilize the cerebral blood flow during head-up tilting.Eight young female volunteers (age, 23.3 +/- 0.8 years; mean +/- SD) were evaluated. The electrocardiogram (ECG) by bipolar chest leads was recorded continuously during procedures, and the bed was tilted at 0.1 interval of sine function of tilting angle from upright position (90 degrees) to supine position (0 degree). The time domain measurements of cycle length variability (co-efficient of variance in percent for R-R intervals [CVRR], number of differences between adjacent R-R intervals that are50ms [RR50]) and the frequency domain measurements of low (0.08 to 0.15Hz, LF), high (0.15 to 0.40Hz, HF) and total (0.08 to 0.40, TF) power were performed to assess the cardiac sympathetic and vagal nerve activity.The CVRR showed no significant change during decremental head-up tilting, whereas the RR50 and the square root of HF power, more specific indices of cardiac parasympathetic tone, showed significant negative linear correlations to the sine of the tilting angle. In markers of cardiac sympathetic tone, there were significant positive correlations between the sine of the tilting angle and the normalized LF power or the LF-to-HF power ratio (LF/HF).These findings suggest that, in healthy young female, not only cardiac sympathetic nervous system but also cardiac vagal nervous system respond linearly to the change in body axis component of gravity, and they may contribute reciprocally and coordinately to cardiovascular postural adaptation.

Topographic analysis of the resting EEG was performed in nine patients with presenile Alzheimer's disease(AD) and nine sex- and age-matched normal subjects. We also analyzed EEG activity recorded during photic stimulation(5, 10 and 15 Hz) to evaluate photic driving responses. The square root of absolute power was determined for each frequency band using a Fast Fourier Transform. Compared with the controls, the AD patients had increased delta and theta in the resting EEG mainly over the frontal regions. The patients also had reduced alpha and beta, and did not show posterior predominance of alpha activity. EEG analysis during photic stimulation showed that the patients had a reduction in photic driving responses, and significant topographic differences were found over the parieto-occipital regions. These findings provide further evidence that AD patients have background EEG slowing with a reduction in alpha and fast activity. They also suggest an impairment of visual functioning in AD.

It is important to measure anti-HCV antibody(HCV.Ab) in blood to diagnose and treat viral hepatitis C patients. We evaluated one of the third generation reagents, Entymun-Test anti-HCV(Boehringer mannheim), which was developed to minimize false-positive reactions, and compared these results to findings obtained with three second generation tests for HCV.Ab. Coefficients of variation in the Entymum-Test assay were good(within-run, 1.1 approximately 1.8%; between-run, 2.5 approximately 7.5%). Four interfering substances(bilirubin C, bilirubin F, lipid and hemoglobin) hardly affected the HCV.Ab measurement. The HCV.Ab indices of healthy donors(n = 61) were distributed below the cut-off index(C.O.I). Sensitivity of the third generation test was the same as that of second generation tests, calculated from the results of dilution tests. Index of the dilution test in the third generation test formed a plateau until four-fold dilution, but there was no prozone phenomenon. Among the third generation test and three second generation tests, the former had the lowest positive percentage in serum HCV.Ab. Moreover, findings of HCV-RNA agreed more with the results of the third generation test among the four tests. As a result, the third generation test appeared to minimize false-positive results and improve specificity.

To establish a simple identification procedure for Escherichia coli, we developed a disk containing indoxyl-beta-D-glucuronide, the chromogenic substrate of beta-D-glucuronidase. Of 188 isolates of Enterobacteriaceae, 101 (97%) of 104 strains of E. coli and two (67%) of three strains of Shigella species were positive for beta-glucuronidase. We also tested 495 strains (466 strains of E. coli and 29 of Citrobacter freundii) that might be considered lactose-fermenting E. coli under routine conditions, and 458 strains of E. coli showed beta-glucuronidase activity: the sensitivity of the disk method was 92%, specificity was 100%, and the negative predictive value was 44%. Our results suggest that for routine identification of E. coli on primary isolation plates, the disk method is sufficiently rapid (within 3h), simpler, and far less costly than identification methods using commercially available kits.

In a patient with liver cirrhosis, an elevation of serum anti-dsDNA antibody titer (100-193.3 IU/ml) measured by Farr method was found. This anti-dsDNA antibody was not identified by Crithidia Luciliae method, and the analysis using ELISA method showed that the DNA-antibody is an anti-ssDNA antibody (IgG) and that it is reactive only with ssDNA by the suppression test using purified DNA with lambda phage. Based on this finding, the high titer of anti-dsDNA antibody found in this patient using Farr method was considered to be non-specific cross-reaction with ssDNA.

Somatosensory evoked potentials (SEP) to median nerve stimulation were studied in a group of 61 healthy volunteers (36 men, 25 women) between 15 and 79 years of age. The absolute peak latencies of peripheral N9, Erb, cervical N11 and N13, cortical N20, N32 and N60 were analyzed as a function of height and age. Three interpeak latencies, Erb-N13, Erb-N20 and N13-N20, were equally studied. There was no gender difference in the latencies and interpeak latencies of SEP in multiple correlation analysis involving height and age. Multiple regression analysis showed that except for N60 peak latency, the subject's height and age provided better prediction of other SEP latencies, and Erb-N13 and Erb-N20 interpeak latencies than simple and polynomial [correction of polynominal] linear regression. Multiple regression analysis was found to provide better optimal clinical upper limits for individual SEP latencies and interpeak latencies, and may increase the diagnostic sensitivity. The t-value of the multiple regression coefficient for standardized height and standardized age showed that the effects of age on N32 and N60 peak latencies, and on Erb-N13 and Erb-N20 interpeak latencies were a more important factor than those of height. A negative correlation was found between height and age in our subjects. Although this may be a characteristic of modern Japanese, it suggests the necessity of renewing regression models at intervals of 5 or 10 years.

We examined the usefulness of allergen housedust-6 measurement in 44 patients (22 males and 22 females) with atopic dermatitis. The positivity for each of housedust HD-2 and HD-6 and that for each of D-1 and D-2 was well correlated in more than 90% of the patients (correlation coefficient0.85). The positivity for HD-2 and for HD-6 was also correlated in 93.2% of the patients. However, there was a discrepancy between D-1 or D-2 and HD-2 or HD-6 in only a few patients. The positivity for antibody against specific IgE was higher in atopic dermatitis-patients with allergic rhinitis, allergic conjunctivitis or bronchial asthma as compared with patients with only atopic dermatitis. Only one patient with severe atopic dermatitis had a negative result for specific IgE, suggesting the contribution of other circumferencial factors in the development of the disease. In conclusion, our study suggested that housedust-6 is useful in clinical evaluation of patients with atopic dermatitis.

We presented two cases with transient hyperphosphatasemia (TH) of infancy, whose serum alkaline phosphatase (EC 3.1.3.1, ALP) activity showed markedly increased and the atypical isoenzyme fractions were seen by electrophoresis. These isoenzymes migrated into normal bone ALP region (alpha 2-beta globulin fraction) and fast liver ALP region (fast alpha 2 globulin fraction). From various investigation such as, heat stability, inhibition test by amino acid, neuraminidase treatment and Triton X-100 treatment, former fraction seemed to derive from bone ALP and later fraction from liver ALP. From our study, increment of the activity of alpha 2-beta gl fraction was in advance one month before maximum ALP activity stage, and fast alpha 2 gl fraction followed increasing 3 weeks after that. On the other hand, decreasing of fast alpha 2 gl fraction showed a shorter delay than alpha 2-beta gl fraction. These results suggest that a differential exchange of sugar chain or an impaired clearance of the enzyme from circulation was possibly occurred. It seemed to be important to increase a study of such a predictive and prognostic change of ALP activity and isoenzyme fraction in TH cases.

We compared and evaluated titers of AMC (anti-microsome antibody), and ATG (anti-thyroglobulin antibody) by passive gelatin-agglutination and by radioimmunoassay in 170 sera from 129 patients with various thyroid diseases and 41 normal subjects. The results of conventional ATG and TgAb by RIA correlated (r = 0.731) and those of conventional AMC and TPOAb correlated well (r = 0.907), with discrepancies mostly limited to sera with low antibody titers. Five patients with Hashimoto's thyroiditis showed positive results in AMC, whilst negative in TPOAb. These sera had positive ATG autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of AMC tests, suggesting ATG producing false positive results in AMC assay. The prevalences of positive TgAb rates were higher than (p0.001) ATG in patients with Hashimoto's disease (96.6% vs 50.0%) and Graves' disease (76.9% vs 46.1%). However, the prevalences of positive TPOAb were not different from AMC (Hashimoto's disease 75.9% vs 81.0%: Graves' disease 80.8% vs 76.9%). In patients with Hashimoto's thyroiditis, our study demonstrates the results of TgAb by RIA reflects the pathological findings and the diagnostic sensitivity increases by using in combination with TPOAb.

It is important to measure certain hormones to make a diagnosis as quickly as possible. We inquired the needs of quick return services (QRS) in the field of endocrinology. First, we sent questionnaires to 86 endocrinologists in Japan (recovery 83%). About 20.2% of the endocrinologists wanted to receive QRS for the diagnosis of thyroid disorders. However, less than 10% of the specialists wanted to receive QRS on pituitary hormones, sex hormones and many other hormones. These responses were as expected. It is clear from our experience reported previously that the appropriate choice of a commercially available kit is essential if serious errors are to be avoided. Accurate and precise results are much more important than receiving QRS.

EEG coherence is a noninvasive technique for studying functional relationships between brain regions. Although EEG coherence would be a useful method to explore the differences in cerebral functional organization between the sexes, sex differences in coherence have not been well documented. The present study was conducted therefore to examine sex differences in interhemispheric EEG coherence during rest and photic stimulation (PS) in 15 male and 15 female healthy young adults. Interhemispheric coherence of the resting EEG revealed no significant sex differences for any frequency band. In contrast, coherence during PS revealed significant sex differences, and the females had a significantly higher coherence than the males in the frequency band (4.5-5.5Hz) corresponding to 5Hz PS. In addition, the changes in interhemispheric coherence from rest to the stimulus condition (i.e., coherence reactivity) showed sex differences at the brain region primarily involved in visual functioning; the females had significantly greater coherence reactivity for O1-O2 in EEG during PS at 5 and 15Hz. These findings indicate sex differences in interhemispheric EEG coherence during PS, and provide further evidence that sex-related differences exist in the degree of lateralization of hemispheric function.

The present study performed quantitative EEG analysis in normal 20 males and 20 females, aged 18-26 years, in order to examine the sex differences in EEG activity at rest. The females had more absolute EEG power than the males, with significant differences observed for delta, theta and beta bands. In contrast, no significant difference was found in peak alpha frequency or relative EEG power for any frequency band. The present findings provide further evidence that females have more absolute power in resting EEG, and emphasize the importance of matching patients and control populations for sex in future investigations dealing with the relationship between resting EEG and various pathological conditions.

Scalp-recorded somatosensory evoked potentials (SEP) to posterior tibial nerve stimulation were studied in healthy volunteers (27 males and 25 females) aged 15-67 years. Age alone was not correlated with SEP latencies, except for P 60 latency, but multiple regression analysis with two independent variables (height and age) showed that not only height but also age is a significant parameter in determining the optimal clinical limits for individual SEP latencies, and may increase the diagnostic sensitivity of absolute SEP latencies. There was no gender difference in the latencies of SEP in multiple correlation analysis involving height and age. A negative correlation tended to be found between height and age in adult subjects, although this is thought to be a characteristic of Japanese, it may show the necessity of renewing regression models at intervals of 5 or 10 years.

We report a patients with squamous cell carcinoma of tongue showing transient M-protein (IgG-kappa type) on electrophoresis using a Separax membrane. The M-protein was detected in the alpha 1 to beta regions as a broad band, and it was detected in the slow gamma region as a monoclonal band on electrophoresis using other types of membranes. The unusual electrophoretic pattern of globulin found in this patient was considered to be caused by alternation of globulin by unusual sugar chains.

The present study deals with electrophysiological findings 3 months after the patient fell into an apallic state during the course of Creutzfeldt-Jacob disease (CJD), when periodic limb myoclonus synchronizing with periodic synchronous discharge (PSD) began to diminish. The findings were as follows: On 2 Hz intermittent photic stimulation (IPS), myoclonus and the diffuse bisynchronous high amplitude sharp wave showed dissociation; the myoclonus was completely suppressed, while the high amplitude sharp wave was elicited. On 3 Hz IPS, myoclonus was incompletely suppressed, corresponding to every other high amplitude sharp waves which were induced synchronous to IPS. On 1 Hz IPS, the high amplitude sharp waves were scarcely induced while neither PSD nor the myoclonus were suppressed. The frequency of the PSD was about 1.2 Hz. Based on these findings, we propose that in addition to the cortical refractory period after PSD or the giant response to photic stimulation, there must be another refractory period in the distal impulse pathway longer than the cortical one. Although the exact electrophysiological mechanism involved in the present findings remains unknown, the possible mechanism responsible for the suppression of myoclonus by IPS and the specificity of IPS frequency in the suppression could be due to competitive suppression of the impulse between periodic myoclonus and the cortical reflex myoclonus through the interaction of the two independent refractory periods in the transmission pathway of the impulse.

Serum level of type IV collagen was measured in 104 patients with various thyroid disease, and the relationship between its level and thyroid hormone level was examined. The type IV collagen was measured by the method of one step sandwich enzyme immunoassay (EIA) using two distinct monoclonal antibodies recognized triple-helical (TH) domain and 7-S domain, respectively. The serum level of type IV collagen was significantly high in the hyperthyroid patients compared with that in normal controls, and a significant positive correlation was found between its value and thyroid hormone levels (T3, T4, FT3, FT4). The elevated level of type IV collagen in hyperthyroid patients was decreased to normal level, when they became to euthyroid after antithyroid drug therapy for hyperthyroidism. The serum level of type IV collagen was in normal range in hypothyroid patients, but the value was increased to high normal range after T4-replacement therapy for hypothyroidism. This evidence indicates that the serum level of type IV collagen is closely related to thyroid hormone level in patient with various thyroid disease. Type IV collagen concentration might be one of the useful variables for evaluating the thyroid function, although its mechanism is not elucidated.

A diagnosis of mycobacterial infection may be suggested by a patient's symptoms, clinical or radiographic findings. However, the definite diagnoses of mycobacterial infections are dependent upon the isolation and identification of etiologic agents. Recently, nontuberculous mycobacteria are being increasingly recognized as the causes of lung diseases. Therefore, it is important to rapidly differentiate nontuberculous mycobacteria from Mycobacterium tuberculosis, since treatments, epidemiologic implications, and prognoses due to these various causative organisms may be considerably different. The isolation of mycobacteria from clinical samples takes several weeks for culture on presently available solid media, and biochemical identifications take additional several weeks after isolation of mycobacteria. Rapid, sensitive, and specific tests for detection of the organism as species in clinical specimens have been a long-standing goal. Recently, new diagnostic procedures based on molecular biology have been developed. The identifications of the species by DNA probes and PCR and a new test by means of luciferase reporter phages were discussed.

Methacholine provocation test, bronchial reversibility test, aspirin inhalation test, and cough provocation test have been performed at our institute to examine pathophysiology and to diagnose bronchial diseases. Bronchial responsiveness to methacholine correlated to baseline pulmonary functions, especially to % predicted value of forced expiratory volume in 1 second (%FEV1) in asthma and sinobronchial syndrome. Bronchial reversibility was greater with beta 2-agonists than with muscarinic antagonists in asthma while it was less with beta 2-agonists than with muscarinic antagonists in sinobronchial syndrome. Our protocol for aspirin inhalation test consists of a screening test and threshold measurement test and is useful for diagnosis of analgesics-induced asthma. Capsaicin provocation test to measure airway cough receptor sensitivity is used to diagnose chronic cough.

In this article, we describe the usefulness of thyroid needle biopsy in the differential diagnosis of thyroid disorders revealing unusual thyroid function. Firstly, we describe the relationship between thyroid function and its histology in 601 cases of chronic thyroiditis. In the histologic group A, the majority of the cases showed a latent or overt hypothyroidism and in histologic group B, hyperthyroid, euthyroid and latent hypothyroid cases were found in nearly equal frequency, respectively. In histologic group C, most cases were in euthyroid and in histologic group D, most cases showed a hyperthyroidism. In the silent thyroiditis and postpartum thyroiditis, known to show a characteristic clinical and laboratory finding, the histologic features of thyroid gland were as follows: the observed characteristic histologic changes in both diseases were an extensive follicular destruction associated with chronic diffuse thyroiditis. These destructive changes disappeared in association with the clinical and laboratory recovery. In the patients with iodine-excess hypothyroidism, the thyroid glands also revealed characteristic histologic changes. A marked hyperplastic change of follicular cells and a lack of colloid material in the follicular lumen was the predominant histologic feature. Based on our personal experiences, thyroid needle biopsy should be recommended as a useful tool for differentiation of causes of hyper- or hypothyroidism.

We evaluated five commercially available immunoassay kits for pituitary-thyroid function tests. The possible interference in analysis by immunoglobulin G (IgG) has also been examined. The BeriLux TSH assay kit (Hoechst co. FRG) was compared with two other non-RI methods (AIA-1200 and IMx) and two other immunoradiometric assays (RIA-gnost TSH IRMA and EIKEN IRMA kits) in 32 normal subjects and 92 patients with Graves' disease. The new ICMA BeriLux kit had a marked improved analytical and clinical sensitivity. The minimal detectable level of TSH in the assay was 0.006 mU/l. The precision was 2.8% and 6.1% at 0.093 +/- 0.003 mU/l and 0.028 +/- 0.002 mU/l, respectively, whereas the levels for the other methods were above 17.2% and 59.4% respectively. The TSH pattern was always less than 0.006 mU/l with the BeriLux kit, before and after TRH administration whereas the other methods showed random fluctuations which indicated their low accuracy at this concentration. This new ICMA BeriLux kit appears far more reliable than the ordinary immunometric assay kits.

We found M-proteins with two peaks by agarose electrophoresis in the serum of a myeloma patient. The M-proteins were identified as both IgG 1-kappa type, and classified as IgG-F (fast mobility) and IgG-S (slow mobility). 1) The possibility that the two M-proteins were derived from the post translational differences of sugar moieties of the same IgG molecule was unlikely, because no migration changes were observed in IgG-F and IgG-S after the treatment with 4 different sugar enzymes. 2) Fab fractions of IgG-F and IgG-S were analyzed. After papain or pepsin digestion, western blotting with anti-Fab antiserum revealed that the Fab fraction of IgG-F and IgG-S had identical mobility by agarose electrophoresis. However the Fc fractions of IgG-F and IgG-S analyzed by the same procedures with anti-Fe antiserum, were different. 3) Anti-idiotype antiserum prepared in rabbits against IgG-S, or -F, and absorbed by normal IgG and normal human serum showed a fused precipitin line with IgG-F and IgG-S. These findings suggest that two M-proteins with both IgG 1 and kappa type, have the same VH and VL regions but have different constant regions of heavy chain. Since one copy of IgG 1 constant gene is found in each human haploid gene. It is speculated that the switching of the rearranged VDJ gene to constant region gene occurred not only between cis chromosome but also between trans chromosome.