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Immunizing potency of broth-propagated Hemophilus gallinarum (HG)bacterin was compared with tylosin and thimerosal treatment as the HG-inactivation agent and preservative. The immunizing potency of a tylosin-treated HG bacterin was as stable as a thimerosal-treated bacterin after 53 months storage at 2 to 5 degrees C.

A phenolic trimethylsilyl (TMS) group was selectively exchanged for a dimethylalkylsilyl (DMAS) group on a gas chromatographic column by use of sandwich injection technique with DMAS-imidazole, and a TMS ether derivative of a phenolic steroid was converted into a DMAS ether or a mixed TMS and DMAS ether derivative with over 95% recovery. The selective exchange reaction seemed to be caused by the difference in lability between the ethereal TMS linkages to phenolic and alcoholic hydroxyl groups. This selectivity was found to be useful for discriminating gas chromatographically between the phenolic and alcoholic hydroxyl groups in steroids.

In order to apply the intensity-matching technique to polyhydroxysteroids in biological fluids, the doublet of [M]+ and [M+3]+ was prepared in the process of derivatization by use of a mixture of trimethylsilylimidazole (TSIM) and TSIM-d3 and was used for mass fragmentography. The molar ratio of TSIM and TSIM-d3 was defined by the reciprocal of the number of hydroxyl groups in steroids. This technique may be useful in identifying low levels of the endogenous polyhydroxysteroids of interest in biological fluids.

The articulatory gestures of the velum in two Wernicke aphasic patients were examined to compare their performances with those of an apraxic patient by means of the fiberoptic technique. In contrast to the marked variability in the apraxic performance in terms of velum height and segmental duration, the two fluent aphasic subjects showed a relatively high degree of consistency in velar movements throughout several repetitions of nonsense syllables and meaningful words. In addition, both patients exhibited a normal pattern of anticipatory coarticulation. Analyses of the velar movement patterns during the speech-sound error processes of both patients suggested that these errors were not due to an impairment at the level of articulatory programming but to an error in the selection of a target phoneme.

Speech sound errors exhibited by three conduction and three Broca's aphasic patients on naming and word-repetition tasks were subjected to phonemic and subphonemic analyses. In the conduction aphasic patients, errors occurred equally often on consonants and vowels in both the naming and word-repetition tasks, while in the Broca's aphasic patients errors occurred selectively on consonants. Transposition errors occurred almost as often as substitution errors in the conduction aphasic patients, while substitution errors constituted the majority of errors in the Broca's aphasic patients. The Broca's aphasic patients, as compared to the conduction aphasic patients, exhibited a markedly higher number of substitution errors occurring between phonemes separated by a single subphonemic feature on the naming task. On the basis of these findings, it was hypothesized that the differences in the error patterns of the two types of aphasia reflected differences in the underlying mechanisms of the impairment in each type.

2',5'-Oligoadenylate and 2',5'-oligoadenylate phosphodiesterase activity were detected in the human plasma and serum by sensitive radioimmuno assays. The phosphodiesterase in the serum degraded 20 nM of added 2',5'-oligoadenylate in less than 1 hr. Addition of EDTA in the blood sample inhibited the phosphodiesterase activity completely and allowed the measurement of low levels of 2',5'-oligoadenylate. The concentration in the plasma from healty people was in the range of 0.03 to 0.3 nM.

Endogenous peroxidase activity in the upper tracheal epithelium and submucosal gland of specific pathogen-free rats was examined cytochemically using the DAB method in animals bred in a conventional room without special equipment for air filtration (conventional system), and those bred under a semibarriered system in which fresh air was filtered and controlled to flow in one way (semibarriered system). Peroxidase activity was consistently positive in the serous cells of the gland of all the rats in both groups. In 22 (71.0%) of the 31 rats in the conventional system, peroxidase activity was demonstrated also in ciliated cells, mucous cells, and goblet cells of the tracheal epithelium, and in mucous cells and duct cells of the tracheal submucosal gland. However, the activity was detected in these cells only in 2 (6.7%) of the 30 rats in the semibarriered system. Goblet cells were not observed in the latter group of rats. The fine localization of peroxidase activity was similar among the peroxidase positive cells, and was demonstrated in the cisternae of the nuclear envelope and rough-surfaced endoplasmic reticulum, some parts of Golgi apparatus, secretory granules, and in some cases in the intraductal spaces of the gland. The present study indicated that environmental conditions markedly influence peroxidase activity in the upper tracheal epithelium and gland of rats.

This study examines identification of the synthetic speech stimuli [ga] and [ka] of varying voice onset times (VOTs) in 17 Japanese aphasic subjects. Approximately two-thirds of the aphasic subjects showed deterioration in performance of VOT identification of the stimuli. A quantitative analysis of the results indicates that the problems of the majority of these subjects may be attributable not only to difficulty in labeling the stimuli but also to difficulty in processing the acoustic and/or phonetic information of the stimuli.

A sandwich enzyme immunoassay for epidermal growth factor (EGF) has been developed which measures EGF concentrations in serum, urine, saliva, gastric and pancreatic juices without pretreatment. Sensitivity for human EGF is 500 fg/tube. Serum EGF concentration in normal males and females is 780 and 604 pg/ml, respectively. Urinary human EGF is 51.3 ng/mg creatinine for males, and 68.3 ng/mg creatinine for females. The difference is not significant, and no correlation between serum and urinary concentrations exists, but serum concentration changes with age. The highest concentration is seen up to 9 years of age, suggesting that EGF promotes cell proliferation during growth.

Various 9-O-acyl derivatives of N-acetyl- and N-glycoloyl-neuraminic acid, and O-(5-acetamido-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-2-nonulopyranosylonic acid)-(2----6)-O-beta-D-galactopyranosyl-(1----4)-D-glucopyranose were regioselectively synthesized by use of ortho esters. In addition, 5-acetamido-4-O-acetyl-D-glycero-D-galacto-2-nonulopyranosonic acid was prepared starting from the benzyl and methyl esters of N-acetylneuraminic acid.

A new two-site enzyme immunoassay for pepsinogen II(PGII) has been developed. The detection limit of PGII was 0.15 ng/ml (15 pg/tube) and the optimal assay range was 1.5 to 150 ng/ml (150 pg to 15 ng/tube). Mean serum PGII concentrations in normal males and females were 17.2 and 14.6 ng/ml, respectively. The chronological analysis among 5 age groups from 20 to 69 yr, males and females together, revealed that the serum level was low (11.9 ng/ml) between 20-39 yr, gradually increased from 40 yr of age and attained the maximum (22.5 ng/ml) in the 50-yr group. Total gastrectomy markedly lowered the serum level to 1.9 ng/ml, suggesting that the majority of PGII in serum was derived from the gastric mucosa. This assay makes it possible to measure trace amounts of PGII derived from extragastric as well as gastroduodenal tissues.

The interactions of T-cell receptor with self-Ia antigen on non-T cells induced IL-2 production and IL-2 receptors on the cell surface and thus responsiveness to IL-2 of T cells in autologous mixed-lymphocyte reaction (AMLR). Four-day-cultured autologous non-T cells lost their ability to stimulate T cells to produce and respond to IL-2 with concurrent decrease of HLA-DR and HLA-DQ antigen expressed on the cell surface. Culturing of non-T cells with 500 U/ml of recombinant interferon gamma (IFN-gamma) maintained their stimulating ability which was otherwise lost. Treatment of non-T cells with monoclonal anti-HLA-DR or anti-HLA-DQ antibody before mixture with T cells abrogated their ability to induce IL-2 production and IL-2 responsiveness of T cells. The combined data suggested that Ia antigen expressed on non-T cells is modulated by IFN-gamma, which increases the ability of non-T cells to stimulate autologous T cells to produce and respond to IL-2.

This research examined the structure of internal representation and the conceptual operation of color in two pure alexic cases (Case I and Case II) with color naming defects. Experiment I investigated the structure of the internal representation of different kinds of colors using a similarity judgment task. Experiment II examined categorical judgments of perceived colors using a two-alternative-forced choice task. Experiment III tested the classification of perceived colors using a color sorting task. The performance of Case I essentially fell within the normal range while the results of Case II showed some impairment in the conceptual operation of color. Analysis of the responses obtained from these experiments indicated that the color naming defects in Case I can be explained in terms of visual-verbal disconnection. However, the naming defects in Case II reflect disfunction in some other higher cortical processes coupled with visual-verbal disconnection.

The concentration of free N-acetylneuraminic acid in various rat organs was estimated by gas chromatography/mass spectrometry. Its concentration was in the range of 3.95 to 104.72 micrograms/g wet tissues, being particularly high in the endocrine glands. The ratio of free N-acetylneuraminic acid to total N-acetylneuraminic acid varied from 0.031 to 0.183, being especially high in the adrenal gland (0.181) and heart (0.183).

A two-site enzyme immunoassay for slow moving protease (SMP) of human gastric mucosa has been developed. The detection limit of SMP was 50 pg/tube and the optimal assay range was 0.5 to 50 ng/tube. This assay system made it possible to measure a trace amount of gastric mucosal SMP in endoscopic biopsy-specimens. Mean gastric mucosal SMP contents of the antrum, the angles, and the distal and proximal corpuses were 4.5, 3.7, 2.6, and 2.5 micrograms/mg protein, respectively. The antral mucosa contained a larger amount of SMP than the gastric mucosa of other area. The present enzyme immunoassay system is sufficiently sensitive for the clinical study of SMP in gastrointestinal tract.

To examine the role of monoamines in regulating beta-endorphin levels in discrete brain nuclei, the levels of beta-endorphin-like immunoreactivity (beta-ENDi) were determined in the hypothalamic nuclei of rats 2 h after they were treated with monoaminergic drugs. Sulpiride decreased the levels of beta-ENDi in the nucleus paraventricularis, nucleus arcuatus and median eminence. Domperidone decreased the levels of beta-ENDi in the nucleus aracuatus and median eminence. L-DOPA increased the levels of beta-ENDi in the nucleus anterior hypothalami and median eminence. Phenylephrine or prazosine did not alter the levels of beta-ENDi. Yohimine decreased the levels of beta-ENDI in the nucleus anterior hypothalami. Isoproterenol increased the levels of beta-ENDi in the nucleus arcuatus, and propranolol reversed this effect. These results suggest that dopamine and noradrenaline (via beta-adrenoceptors) may regulate beta-endorphinergic neurons in the rat hypothalamus.

The present study demonstrates the relationship between urinary albumin excretion rate (AER) and renal structural changes in patients with non-insulin-dependent diabetes mellitus (NIDDM) without clinical proteinuria. Resting AER in 30 control subjects and 67 NIDDM patients were 10.4 +/- 4.8 (mean +/- SD) micrograms/min (range 4.3-21.1 micrograms/min) and 26.4 +/- 32.3 micrograms/min (range 0.4-155 micrograms/min), respectively. Persistent normoalbuminuria (less than 20 micrograms/min) and microalbuminuria (20-200 micrograms/min) were found in 43 (Group A) and 24 (Group B) diabetics. There were significant differences in age, diabetes duration, and frequency of retinopathy (background and proliferative) as well as that of proliferative retinopathy between Groups A and B, but not in the other clinical parameters such as body mass index, HbA1, Ccr, or systolic and diastolic blood pressure (SBP, DBP). When compared with 11 normoalbuminuric patients of similar age and equal diabetes duration to those in Group B, the sole difference in clinical parameters was the existence of proliferative retinopathy in Group B. Renal structural changes were investigated by light microscopy in 14 people in Group A and 13 people in Group B, and additionally in 5 NIDDM patients with both macroalbuminuria (greater than or equal to 200 micrograms/min) and normal or nearly normal renal function (Group C). The diffuse glomerular lesion (Gellman's classification) was grade I or II in A, II or III in B, and III in C.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a 2-year-4-month-old boy with retrobulbar optic neuritis. He had a sudden onset of impaired vision, which progressed to total blindness within a day. The visual evoked potential (VEP) showed no activity, but the electroretinogram was normal. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no abnormal findings in the visual tract. The cerebrospinal fluid (CSF) myelin basic protein (MBP) level was elevated and serum anti-myelin antibody was positive. These findings suggested that optic neuritis in our patient was induced by retrobulbar demyelination, perhaps as a result of an autoimmune process. His visual impairment recovered gradually, but not completely, following oral prednisolone therapy. We have followed him for one year since discharge and have found neither recurrence of optic neuritis nor any other neurological disorders. Optic neuritis in children is rare and, to our knowledge, this patient is one of the youngest to be reported. This case suggests that autoimmune mechanisms may induce optic neuritis even in early childhood. In addition to VEP and MRI studies, the CSF MBP and serum anti-myelin antibody can be useful in the diagnosis and follow-up the patients with optic neuritis.

The effect of activin A on meiotic maturation was analyzed in oocytes from immature rats treated with PMSG. Activin A, which was purified as the erythroid differentiation factor, accelerated the maturation of not only follicle-enclosed oocytes and oocyte-cumulus complexes, but also denuded oocytes, as measured by an increase in the percentage of oocytes with germinal vesicle breakdown (GVBD). Oocyte maturation was not accelerated by activin A in the presence of the inhibitor of GVBD such as cyclic-AMP. These results showed activin A is a potent in vitro stimulator of oocyte maturation.

We report 4 cases of delayed thoracic closure after cardiac surgery in infants: 3 cases with transposition of the great arteries and one with hypoplastic left heart syndrome. Sternal and skin closure in the primary operation sometimes causes haemodynamic cardiac compression. Postoperative correction of haemodynamic and haemostatic functions are allowed by delayed sternal and skin closure. No complications were encountered.

We report a case of asymptomatic cor triatriatum in a 75-year-old man in whom the anomaly was incidentally revealed by computed tomography (CT). To our knowledge, this patient is the oldest case reported and the only such case in which the anomaly was demonstrated by CT.

We measured the anti-skeletal muscle (SM) antibody titers in sera from 46 patients with thymoma but without Myasthenia gravis (MG) in order to determine whether the presence of anti-SM antibody is linked to the combination of thymoma-MG, or to thymoma alone. We detected anti-SM antibodies in 18 of these sera, of which 15 had concomitantly elevated titers of anti-AChR antibodies. Moreover, 9 of whom had experienced the onset of MG after surgery. In contrast, no patient without elevations in both antibodies developed MG during the followup. We conclude that the presence of anti-SM antibodies is linked strongly with thymoma associated with MG, but not with thymoma alone.

We describe 3 children (from two families) with a multisystemic disorder characterized by mental retardation, nonprogressive ataxia, polyneuropathy, hepatopathy during infancy and growth retardation. Due to the clinical similarities to a recently recognized disorder associated with carbohydrate-deficient transferrin, we examined serum transferrin by means of isoelectric focusing, and found increases in disialo transferrin and asialotransferrin. Removal of sialic acid with neuraminidase revealed the same transferrin phenotypes as in their parents. Similarly, carbohydrate-deficient fractions of serum alpha 1-antitrypsin were also detected. Therefore, the diagnosis was made of the recently identified carbohydrate-deficient glycoprotein syndrome. This is a genetic disorder with distinctive clinical features and multiple carbohydrate-deficient glycoproteins. These seem to be the first reported Japanese patients with this syndrome.

An autopsy case, a 6-month-old girl, with an interstitial deletion of the long arm of chromosome 15;del(15)(q11.1q12) was reported. Muscle hypotonia, poor sucking and intermittent ocular deviation were noticed soon after birth. She also exhibited external features peculiar to the Prader-Willi syndrome (PWS). The muscle hypotonia persisted and head control was not achieved. She died at the age of 6 months due to bronchopneumonia. G-banding analysis of prometaphase chromosomes revealed a deletion of chromosome 15. Bronchopneumonia of the lungs and fatty metamorphosis of the liver were found. Neuropathological anomalies recognized were; disturbed undulating structures, resembling cortical micropolygyria and pachygyria, in the dentate nucleus and the inferior olivary nucleus, grumose degeneration of the nerve cells in the dentate nucleus, and heterotopia of middle-sized neurons in the cerebellar white matter. No abnormalities were observed in the hypothalamus-pituitary system. In some autopsy cases of PWS, cerebellar lesions have been reported. These might be related to the muscle hypotonia in PWS.

OSF-1 (also known as pleiotrophin, HB-GAM, HBGF-8 or HBNF) is a heparin-binding, neurotrophic protein. Its tissue-specific expression in rats is developmentally regulated and the protein is highly conserved between species. The protein is believed to be involved in neuronal development. Previous experiments in our laboratory showed that OSF-1 is primarily expressed in brain and bone. The biological function of OSF-1 in bone is unknown. In order to overcome the limited availability of the native protein, we now report on the high-level expression of human OSF-1 in Escherichia coli. The protein is present in the form of inclusion bodies, which were isolated and solubilized. The partially purified protein was refolded and further purified employing heparin sepharose chromatography. N-terminal sequence determination revealed the same amino acid sequence as the natural mature protein. The isolated backfolded recombinant human OSF-1 did promote neurites outgrowth in primary cultures of cortical neurons.

6-Hydroxymellein synthase, an induced polyketide biosynthetic enzyme in carrot cell extracts, was purified about 240-fold and its properties were compared with those of fatty acid synthetases. Synthetic activity of 6-hydroxymellein was inhibited in the presence of sulfhydryl reagents; however, cerulenin, a well-known inhibitor of fatty acid synthetases, showed no inhibitory activity to the enzyme. Biosynthesis of 6-hydroxymellein includes an NADPH-dependent ketoreduction, and, in this reaction, the 4-pro-S-hydrogen of NADPH was specifically transferred to the compound. On the basis of stereochemical analyses of the biosynthetic process, it was concluded that the product of the ketoreduction is an optically active alcohol of R configuration. These stereo-specificities of the reduction process are identical to those of beta-ketoacyl reductase in fatty acid biosynthesis which are considered to be conserved in all organisms. The synthetic rate of 6-hydroxymellein was markedly reduced when the assay was carried out with deuterium-labeled NADPH. The observed isotope effect on the catalytic rate (kH/kD) was 5.20, suggesting that this ketoreduction is one of the rate-limiting processes in 6-hydroxymellein synthesis. More than 85% of the synthetic activity was found in the soluble fraction of carrot cells, and, unlike in fatty acid synthetases in higher plants, organelle-localizing activity was not observed.

To assess the clinical manifestations and therapy of secondary spontaneous pneumothorax (SSP), 123 episodes of SSP in 67 patients were retrospectively reviewed and were compared with 254 episodes of primary spontaneous pneumothorax in 130 patients. The major underlying lung diseases associated with SSP were emphysema (22 patients) and tuberculosis (21 patients). The average age of patients with SSP was 66.8 years, and the most common symptom was dyspnea. The average arterial oxygen tension at onset of SSP was 61.1 +/- 12.1 mm Hg (mean +/- standard deviation), which was lower than that of patients with primary spontaneous pneumothorax (p < 0.01). The recurrence rate of open thoracotomy with pleural abrasion was 12.5% (3 of 24 episodes), which was not lower than that of thoracostomy tube drainage with chemical pleurodesis using tetracycline (recurrence rate, 18.8%) (p > 0.5). We concluded that considering the high age of the patients, the presence of underlying lung diseases, and the increased operative risk, thoracostomy tube drainage rather than open thoracotomy was preferred as the first choice of therapy for SSP.

A group of 10 healthy control subjects and 10 patients with hemiparkinsonism (HD) were studied by positron emission tomography (PET) using 6-[18F]fluorodopa (FDOPA). FDOPA metabolism in the caudate nucleus and the putamen was separately estimated by measuring target-to-background ratios (TBRs) using composite images added between 30 and 60 min after FDOPA injection and by TBR-versus-time slopes during PET study. TBRs in the caudate nucleus and the putamen were 1.81 +/- 0.23 (mean +/- SD) and 1.92 +/- 0.28 in the 10 controls, respectively. In HD patients, on the dominantly affected hemisphere related to main clinical symptoms, TBRs were significantly decreased in the caudate nucleus (P < 0.01) and the putamen (P < 0.05) compared with those in the corresponding areas on the contralateral hemisphere, though those TBRs on both hemispheres were significantly decreased compared with the TBRs of normal subjects (P < 0.01). TBRs and TBR slopes in both the caudate nucleus and the putamen were correlated with disease severity according to Hoehn and Yahr. On the dominantly affected hemisphere, TBR and TBR slopes in the putamen were well correlated with individual clinical measures for bradykinesia and rigidity, and those in the caudate nucleus were also correlated with the severity of tremor. Our data suggest that in HD patients, PET study using FDOPA may provide unique and efficient information on the dysfunction of the dominantly affected caudate nucleus and the putamen which are correlated with diseased severity and individual clinical symptoms.

Two clonal fibroblast cell lines with simple chromosome aberrations-one with del(3)(p24) and the other with t(1;16)(q21;q11.2)-were established from a high dose (5.14 Gy) female atomic bomb survivor by serial culture of skin fibroblasts. These two types of clonal cells showed a more extended life span than did the cells with 44 other types of chromosome aberrations and normal cells. In addition to these results, a prominent clonal population was observed in the peripheral blood cells in this subject. It is assumed that these clonal populations arose in vivo as a result of radiation exposure to the atomic bomb.

The effects of serotonin (5-HT) and various serotonin receptor antagonists on the spinal cord thyrotropin releasing hormone (TRH) content were studied in the rolling mouse Nagoya (RMN) and in the unaffected C3H mouse. TRH was extracted from the cervical, thoracic, lumbar, and sacral cord, at 1 h after the intraperitoneal injection of a serotonin precursor, 2 serotonin agonists, and 5 serotonin receptor antagonists. Administration of 5-hydroxytryptophan and 2-methyl-5-hydroxytryptamine resulted in an increase of the spinal cord TRH content in C3H mice, but not in RMN. Parachlorophenylalanine decreased the spinal cord TRH content in C3H mice, while it increased TRH levels in all regions of the RMN spinal cord. The TRH contents were decreased in all regions of the spinal cord after 5,7-dihydroxytryptamine administration in both C3H mice and RMN. In C3H mice, methysergide, mianserin, ketanserin, and spiperone significantly decreased the TRH content in all regions of the spinal cord, while 3 alpha-tropanyl-1H-indole-3-carboxylic acid ester (ICS205-930) did not affect it. These antagonists paradoxically increased TRH levels in the cervical cord in RMN. The degradation of synthetic TRH by cord homogenates and the number and affinity of spinal cord serotonergic receptors (5-HT1 and 5-HT2) showed no significant difference between C3H mice and RMN. These results suggest that TRH turnover is abnormally regulated by serotonergic neurons in the RMN and that the dysfunction of the serotonergic nerves is attributable to the serotonin autoreceptor.