Evolution of glucose-6-phosphate dehydrogenase variants A+ and A-.
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Biomedical subjects
Publications and source records attributed to A Yoshida.
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Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained. 1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2 mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4). 2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025 micrograms/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05 micrograms/ml and those against 2 strains were 0.10 micrograms/ml and against the other 2 were 0.20 micrograms/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100 micrograms/ml, respectively. 3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No. 8) and moderate elevation of S-GOT and S-GPT in another (case No. 18) (Table 4). In case No. 18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
A female patient what M3 was seen to incur marked hemorrhagic diathesis during therapy. Heparin infusion was performed to inhibit disseminated intravascular coagulation (DIC). However, oozing from the puncture site of the r-subclavian vein was observed. Her data on coagulation were as follows: AT-3 greater than 100%, fibrinogen 69.0 mg, XIII less than 40%, FPA 2.9 ng/ml and FDP-D dimer 256 ng/ml. The alpha-2-plasmin inhibitor (alpha 2-PI) was 44% and FDP 160 microgram/ml. These results suggested DIC with activated fibrinolysis. Thus, epsilon aminocaproic acid in conjunction with heparin, fibrinogen, and concentrated XIII was administered. The abnormal bleeding improved with an increase of alpha 2-PI and XIII. This clinical response indicated that an activated fibrinolysis and a decreased XIII might have been responsible for provoking the bleeding of the patient.
Using a 31P-NMR spectroscopy, we monitored the metabolic kinetics of energy organophosphate compound in rat lens during the process of generating galactose cataract. The most remarkable metabolic change in the earlier phase of galactose cataract formation was found in alpha-glycerophosphate. This increased significantly, as compared to controls, since the day 3 of giving feed containing 25% galactose. The high level lasted for up to three weeks, decrease followed by a gradual decrease and subsequently a significant decrease at five weeks. Adenosine triphosphate (ATP) showed a significant decrease in the galactose group compared to the controls from two weeks after beginning of the experiment and the decrease continued. Inorganic orthophosphate increased gradually in the galactose group as compared to the controls, the increase being of significance at one week reading a maximum at two weeks followed by a subsegment decrease. Our basic study suggests that 31P-NMR spectroscopy is a useful technique in lens of the metabolic kinetics, to noninvasively determine the pathophysiology of galactose cataract, which has been studied biochemically and histologically.
The physiology and morphology of masticatory motoneurons of adult cats were examined by the methods of intracellular recording and intracellular injection of horseradish peroxidase. Masseter and jaw-opening motoneurons were identified by intracellular recordings of the antidromic response following stimulation of the masseter and mylohyoid nerves, respectively. An excitatory postsynaptic potential (EPSP) was recorded from masseter neurons by stimulation of the masseter nerve with stimulus intensity below threshold for antidromic response. In contrast, the EPSP was not recorded from jaw-opening motoneurons by stimulation of the mylohyoid nerve with stimulus intensity below threshold for antidromic response. Patterns of postsynaptic potentials (PSPs) in the masseter motoneurons following stimulation of the tooth pulp or periodontal afferents were classified into 4 types: hyperpolarization (n = 40), depolarization-hyperpolarization (n = 9), hyperpolarization-depolarization (n = 5), and depolarization with spike potentials (n = 10). On the other hand, patterns of the PSPs in the jaw-opening motoneurons following stimulation of the same afferents were classified into two types: depolarization with spike potentials (n = 19), and hyperpolarization (n = 5). Twenty-five masseter and 7 jaw-opening motoneurons and an intranuclear neuron were reconstructed from serial sections in the transverse plane. On the basis of dendritic morphology, the masseter motoneurons could be classified into two major groups, type I (n = 15) and type II (n = 9), whereas two neurons were found to constitute a separate category of the masseter motoneuron. The dendritic distributions of all the jaw-opening motoneurons examined were generally similar and there was no indication of the existence of subtypes, whereas there were 2 or 3 subgroups in type I and type II masseter motoneurons. Type I masseter neurons had primary dendrites which extended radially in all directions, and the whole profile of their dendritic trees presented a spherical and an egg-shaped appearance. In type II masseter neurons, the origin of primary dendrites was bipolar or tripolar, and the whole profile of their dendritic trees presented a hemispherical and mirror-imaged, funnel-shaped appearance. The other two masseter motoneurons had a particular dendritic tree which was much simpler in configuration, with less tapering or branching than those of other neurons examined. In contrast, the dendritic profiles of all the jaw-opening motoneurons were similarly organized and showed vertically oriented dendritic trees which were more developed in the dorsomedial than in the ventrolateral direction.(ABSTRACT TRUNCATED AT 400 WORDS)
Horseradish peroxidase (HRP) was injected into the somata located in the rostrodorsomedial part (Vo.r) of the trigeminal nucleus oralis; an axonal projection to the trigeminal motor nucleus (Vmo) was demonstrated in two Vo.r neurons. The two neurons differed in their morphological and functional properties. The first Vo.r neuron responded to stimulation of low-threshold mechanoreceptors and its stem axon gave off massive axon collaterals that issued terminal branches to the dorsolateral subdivision of Vmo, Vo.r, and the medial and lateral parts of the lower brainstem reticular formation. The second Vo.r neuron was activated by stimulation of the tooth pulp or lingual nerve at twice longer latency than that of the first neuron. This stem axon was divided into two main ascending and one descending branches, and one of the main ascending branches was further bifurcated into two branches. The main non-bifurcated ascending branch gave off 4 collaterals, two of which sent terminal branches into the dorsolateral subdivision of Vmo and others into the Vo.r and juxta-trigeminal regions. The somato-dendroarchitectonic differences were also described in the two Vo.r neurons stained.
The morphology of single neurons in the trigeminal mesencephalic nucleus (Vmes) that innervate periodontal ligament was studied in cats by the method of intraaxonal injection of horseradish peroxidase (HRP). Two kinds of Vmes neurons were distinguished on the basis of differences in axon profile and its central projection. The first type of Vmes neurons was unipolar in shape and its axon was divided into united (U), peripheral (P), and central axons (C). The U axon traveled caudally within the Vmes from the soma to the dorsolateral aspect of trigeminal motor nucleus (Vmo), where it split into the P and C axons with a T-shaped appearance. The P axon joined the spinal trigeminal tract across the trigeminal principal nucleus and ran within the tract and sensory root to exit the brainstem. The C axon traveled caudally within Probst's tract. All 3 axons issued axon collaterals. Axon collaterals from the U, P and the proximal C axons sent their terminal branches into the supra (Vsup) and intertrigeminal regions (Vint). Most axon collaterals from the C axon sent their terminal branches into the juxtatrigeminal regions (Vjuxta). The second type of Vmes neurons was bipolar and issued P and C axons. The C axon ran a short distance in the Vmes to leave the Vmes, and then it traveled caudolaterally in the rostrodorsomedial aspect of the Vmo. Finally, it entered in the Vmo and traveled caudally in the dorsolateral subdivision of the nucleus to its rostrocaudal mid-level. The C axon gave off massive axon collaterals.(ABSTRACT TRUNCATED AT 250 WORDS)
The morphology of functionally identified single axons of mesencephalic trigeminal neurons was studied in the cat by the method of intra-axonal injection of horseradish peroxidase (HRP). Each axon can be divided into united (U), peripheral (P) and central branches (C). The united axon (U) descends from its soma within the tract of the trigeminal mesencephalic nucleus to the dorsal aspect of the trigeminal motor nucleus (Vmo), where it splits into peripheral and descending central branches with a Y-shaped bifurcation. The peripheral axon (P) joins the motor root of the trigeminal nerve to exit the brainstem. The central axon (C) travels caudally within the juxtatrigeminal regions (or lateral reticular formation). All 3 branches issue axon collaterals that distribute terminal boutons within the dorsolateral subdivision of Vmo, supra- and intertrigeminal regions. Collaterals emanating from the central axon (C) except for its proximal segment travel ventrolaterally within the juxtatrigeminal regions, and send their terminal branches into the lateral boundaries adjacent to the spinal trigeminal nucleus. The trajectory of terminal branches distinguishes group Ia afferents from the possible group II afferents. The majority of terminal boutons are found to distribute in the supra- and intertrigeminal regions for group II afferent fibers and in the dorsolateral subdivision of Vmo for group Ia afferents.
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Retrograde and anterograde transport of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) conjugate was used to study the organization of primary afferent neurons innervating the masticatory muscles. HRP applied to the nerves of jaw-closing muscles--the deep temporal (DT), masseter (Ma), and medial pterygoid (MP)--labeled cells in the trigeminal ganglion and the mesencephalic trigeminal nucleus (Vmes), whereas HRP applied to nerves of the jaw-opening muscles--anterior digastric (AD) and mylohyoid (My)--labeled cells only in the trigeminal ganglion. Cell bodies innervating the jaw-closing muscles were found with greater frequency in the intermediate region of the mandibular subdivision, while somata supplying the jaw-opening muscles were predominant posterolaterally. The distribution of their somatic sizes was unimodal and limited to a subpopulation of smaller cells. Projections of the muscle afferents of ganglionic origin to the trigeminal sensory nuclear complex (TSNC) were confined primarily to the caudal half of pars interpolaris (Vi), and the medullary and upper cervical dorsal horns. In the Vi, Ma, MP, AD, and My nerves terminated in the lateral-most part of the nucleus with an extensive overlap in projections, save for the DT nerve, which projected to the interstitial nucleus or paratrigeminal nucleus. In the medullary and upper cervical dorsal horns, the main terminal fields of individual branches were confined to laminae I/V, but the density of the terminals in lamina V was very sparse. The rostrocaudal extent of the terminal field in lamina I differed among the muscle afferents of origin, whereas in the mediolateral or dorsoventral axis, a remarkable overlap in projections was noted between or among muscle afferents. The terminals of DT afferents were most broadly extended from the rostral level of the pars caudalis to the C3 segment, whereas the MP nerve showed limited projection to the middle one-third of the pars caudalis. Terminal fields of the Ma, AD, and My nerves appeared in the caudal two-thirds of the pars caudalis including the first two cervical segments, the caudal half of the pars caudalis and the C1 segment, and in the caudal part of the pars caudalis including the rostral C1 segment, respectively. This rostrocaudal arrangement in the projections of muscle nerves, which corresponds to the anteroposterior length of the muscles and their positions, indicates that representation of the masticatory muscles in lamina I reflects an onion-skin organization. These results suggest that primary muscle afferent neurons of ganglionic origin primarily mediate muscle pain.(ABSTRACT TRUNCATED AT 400 WORDS)
The protective effect of heat-killed Lactobacillus casei (LC) against murine cytomegalovirus (MCMV) infection was examined. ICR mice treated once with LC 1 day or 2 days before challenge survived lethal infection, but untreated or Lactobacillus fermentum (LF)-treated mice did not. The protective effect was evidenced by an increase in plaque-forming units (PFU) per 50% lethal dose (LD50) and a decrease in titers of infectious viruses replicated in the target organs. This was further confirmed by severity of histopathological damage to the target organs, especially the liver. LC neither inactivated MCMV nor inhibited its replication in mouse embryonic fibroblasts (MEF). The spleen cells from LC-treated mice inhibited its replication in MEF on co-cultivation. Augmentation by LC of splenic natural killer (NK) cell activity correlated with survival of mice from otherwise lethal MCMV infection. Cytotoxic activity of peritoneal cells and level of serum interferon (IFN) were elevated after MCMV infection, but they were not associated with survival of mice nor with treatment of LC. The protective effect of LC was not clear in NK-deficient beige mutant (bgJ/bgJ) mice, when compared with that in their littermate (bgJ/+) mice. Poor protection of bgJ/bgJ mice by LC treatment correlated with failure to induce NK cell activity by LC treatment in the mutant mice. Thus, it is likely that LC protects mice from MCMV infection by augmentation of NK cell activity.
Two types of alleles exist in the human alcohol dehydrogenase-2 (ADH2) locus. The usual ADH12 allele is common in Caucasians, while the atypical ADH22 allele is predominant in Orientals. The ADH22 produces the beta 2 subunit, which is catalytically far more active than the beta 1 subunit produced by the ADH12 gene. The racial difference in alcohol-related problems could be related to the genetic differences in ADH and other ethanol-metabolizing enzymes. In order to examine the possibility, a method for determining ADH2 genotypes was developed. Two 21-base synthetic oligonucleotides, one complementary to the usual ADH12 allele and the other complementary to the atypical ADH22 allele, were used as specific probes for in-gel hybridization analysis of human genomic DNA from peripheral blood. Under appropriate hybridization conditions, these two probes can hybridize to their specific complementary alleles and, thus, allow the genotyping of the ADH2 locus. Genotypes of the ADH2 locus of 49 unrelated Japanese individuals were determined. The frequency of the atypical ADH22 gene was found to be 0.71 in the Japanese population examined.
Impairment of thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been documented in patients with uncontrolled diabetes mellitus (DM). In acromegalic patients, however, there have been no data regarding TSH secretion studied taking the existence of DM into consideration. Therefore, we investigated the TSH response to TRH [expressed as TSH increment (delta TSH)] in 14 untreated acromegalic patients, who did not show the suprasellar extension of adenoma, divided into two groups on the basis of either presence or absence of uncontrolled DM, and in 28 normal subjects. The mean max delta TSH was significantly reduced (p less than 0.02) in acromegalic patients despite similar mean serum T4 and free T4 index (FT4l) levels. Furthermore, the mean basal and max delta TSH in 7 patients with DM (FBS, 120-300 mg/dl; HbA1, 8.8-15.2%) were significantly lower than those in 7 patients without DM (p less than 0.05 and p less than 0.02, respectively) despite similar the mean serum T3, T4, FT4l, growth hormone (GH) and prolactin (PRL) levels and sellar volume. In 4 patients with DM the TSH response to TRH 6-8 weeks after insulin therapy, when their HbA1 levels were normal, increased compared to that before insulin therapy. The mean max delta TSH after selective adenomectomy in 8 patients (3 in DM group and 5 in non-DM group), whose fasting basal GH fell to less than 5 ng/ml, was almost identical to that in normal subjects. In conclusion, the present study suggests that the abnormality in TSH secretion in acromegalic patients may be increased by the existence of uncontrolled DM.
The sequential changes in serum thyroglobulin (Tg), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3) and thyrotropin (TSH) were evaluated in ten patients on whom partial thyroidectomy for nontoxic nodular goiter had been performed. These changes were compared with those in ten patients who underwent upper abdominal surgery (cholecystectomy) under similar anesthesia, and whose calorie and fluid intake was similar until at least 48 hours after surgery. In agreement with previous reports, marked elevations in serum Tg that reached peak concentration (660 to 1350 ng/mL) at one or two hours after the thyroid incision (mean +/- SD; 787 +/- 304.0 ng/mL and 839 +/- 345.7 ng/mL, respectively) were observed. On the other hand, the significant but minimal increases in serum T4 and FT4 were observed at 24 hours (P less than .001 and P less than .001, respectively), 48 hours (P less than .01 and P less than .001, respectively), and 72 hours (P less than .01 and P less than .01, respectively) after the thyroid incision compared with the level just prior to the thyroid incision. Similarly, serum T3 also increased significantly at 6 to 168 hours after the thyroid incision (P less than .01, P less than .05, P less than .05, P less than .05, and P less than .05, respectively). These increases in serum T4, FT4 and T3 were not observed in the cholecystectomy patients. The mean serum TSH levels at 24 to 72 hours after thyroid incision and those at 6 to 48 hours after the abdominal incision were significantly decreased compared with those before thyroid and abdominal incision, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was proposed to clarify the impairment of first-phase insulin response to glucose in subjects with glucose intolerance by analysis of C-peptide secretion rate after glucose or glucagon injection. The rate was calculated from kinetic analysis of peripheral C-peptide behavior. The rate reached the peak two minutes after glucose injection and then rapidly declined (first-phase secretion) in control subjects. In nonobese subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM), the rate promptly increased in response to glucose and was followed by a second phase increase. The time course of the rate in the subjects was slightly different from that in control subjects. There was a progressively greater deficit in the first-phase increase with increasing severity of glucose intolerance. The time course of the rate in the obese subjects with NIDDM was different from that in control subjects. The first-phase increase was reduced in the obese subjects with NIDDM. The glucose disappearance rate was correlated with the first-phase increase. Since the time course of the rate after glucagon injection in all subjects did correspond well with that in the control subjects, variation of metabolic clearance rate of endogenous C-peptide among the subjects may be negligible for this study. This study provides the precise time course of first- and second-phase insulin response to glucose injection in nonobese and obese subjects with IGT or NIDDM as well as convincing evidence of the progressive reduction of first-phase insulin response with increasing severity of glucose intolerance. First-phase insulin response to glucose might be slightly delayed in some obese subjects with NIDDM.
We have used the cDNA probes for human aldehyde dehydrogenase-1 (ALDH1) and aldehyde dehydrogenase-2 (ALDH2) to determine regional chromosomal locations of these two genes by in situ hybridization. Results presented here allow localization of ALDH1 to band q21 on chromosome 9 and ALDH2 to band q24 on chromosome 12.
We have isolated and characterized four overlapping clones from two cosmid human genomic libraries, which span about 90 kilobase pairs (kbp) and contain the entire human mitochondrial aldehyde dehydrogenase (ALDH2) gene. Restriction maps of the genomic clones were elucidated utilizing cDNA probes and specific oligonucleotide probes. The organization of exons and introns was established by DNA sequencing of each exon and splicing junctions. The ALDH2 gene is about 44 kbp in length and contains at least 13 exons which encode 517 amino acid residues. Except for the signal NH2-terminal peptide, which is absent in the mature enzyme, the amino acid sequence deduced from the exons coincided with the reported primary structure of human liver ALDH2 (J. Hempel, R. Kaiser, and H. Jörnvall, 1985, Eur. J. Biochem. 153: 13-28). Several introns contain Alu repetitive sequences. A TATA-like sequence (TTATAAAA) and a CAAT-like sequence (GTCATCAT) are located 473 and 515 bp, respectively, upstream from the translation initiation codon. Primer extension and S1 nuclease mapping were performed to characterize the 5'-region of the gene.
The pharmaceutical usefulness of natural, crystalline cyclodextrins can be improved by chemical conversions into water-soluble, amorphous mixtures of their derivatives. Reaction of beta-cyclodextrin with 2-chloroethanol, 3-chloropropanol, isobutylene oxide, or iodoacetamide yielded the title compounds. Distributions of the substitution degree were close to symmetrical and relatively narrow. The average substitution degrees increased with the amount of alkylating reagent used in the preparation. The number of components (half-width of distribution) increased with increasing average substitution degree. Further, distributions of the substitution degree were measured in glucose derivatives after hydrolysis of 2-hydroxyethyl, 2-hydroxypropyl, and 2-hydroxyisobutyl-beta-cyclodextrin. The results show an uneven distribution of substituents around the cyclodextrins, suggesting that growth of oligoglycol side chains and/or clustering of substituents on one glucose residue occurs.