Biomedical subjects
Publications and source records attributed to Y Kikawa.
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A 7 years 3 months old Japanese boy with familial thyroxine binding globulin (TBG) excess associated with growth hormone (GH) deficiency is reported. The patients height was 106.4 cm (-2.86 s.d.) and his bone age was 5 years and 3 months. He had no goiter and his developmental milestones were normal. The serum thyroid stimulating hormone (TSH) was 2.8 microU/mL, triiodothyronine (T3) 3.1 ng/mL, thyroxine (T4) 23.4 micrograms/dL and free T4 1.8 ng/dL. The serum TBG level was beyond 80.0 micrograms/mL, with normal TSH response to the thyrotropin-releasing hormone (TRH) test. Familial study revealed that his grandmother, mother, uncle, younger sister and younger brother had high TBG and T3 levels, thus an X-linked co-dominant transmission was suggested. The peak GH responses to insulin and clonidine hydrochloride were 5.8 and 8.2 ng/mL, respectively. The mean nocturnal GH concentration was 2.5 ng/mL. His growth velocity increased from 4.8 to 8.4 cm/year and his serum TBG levels decreased gradually after human growth hormone (hGH) treatment.
The relative proportions (% of total fatty acids) of odd-chain (15:0-29:0) and long-chain (22:0-30:0) saturated fatty acids in phospholipids of biotin-deficient rat lymphocytes were significantly increased as compared with biotin-supplemented rats, and the ratio of unsaturated fatty acids to saturated fatty acids in the former was significantly decreased mainly due to the reduced composition of polyunsaturated fatty acids in the omega-3, omega-6, and omega-9 pathway. The ratio of cis-vaccenic acid to palmitoleic acid in biotin-deficient rats was significantly lower than that in control rats, and was thought to be another important, but previously unreported indicator of biotin deficiency. These changes imply that the elongation and desaturation of unsaturated fatty acids are depressed in lymphocytes of biotin-deficient rats, and may contribute to the associated immunological dysfunction in biotin deficiency through abnormal prostaglandin metabolism and/or cell membrane functions.
The increase of fructose-1,6-diphosphatase activity during culture with calcitriol, which was reported in monocytes, was found not to occur in lymphocytes. Monocytes cultured with calcitriol were accordingly used as more reliable diagnosis of heterozygotes for fructose-1,6-diphosphatase deficiency, instead of mononuclear cells (lymphocyte-fraction-containing monocytes) cultured without calcitriol by a conventional method. Variation of fructose-1,6-diphosphatase values in leukocytes from nine healthy adults was smallest in monocytes cultured with calcitriol, among four different experimental conditions: monocytes cultured with or without calcitriol and mononuclear cells cultured with or without calcitriol. Both parents of two sisters with fructose-1,6-diphosphatase deficiency were successfully confirmed as carriers of fructose-1,6-diphosphatase deficiency by this method. However, confirmation by the conventional method using mononuclear cells cultured without calcitriol was possible only in the father, not in the mother. Thus, the new method using monocytes cultured with calcitriol seems more reliable for detecting heterozygotes for fructose-1,6-diphosphatase deficiency.
Two sisters with fructose-1,6-diphosphatase deficiency are reported. They presented with ketonuria, elevated plasma transaminase activity and severe metabolic acidosis during hypoglycaemic crises, which resembled Reye syndrome. Intravenous fructose tolerance tests provoked severe hypoglycaemia and metabolic acidosis. Fructose-1,6-diphosphatase activities in both peripheral leukocytes and cultured lymphocytes were below the limit of detection. Urinary organic acid analysis during crises revealed markedly increased excretion of lactate, ketone bodies, glycerol and glycerol-3-phosphate. We newly identified other glycolytic intermediates, glyceraldehyde, 3-phosphoglycerate and fructose-1,6-diphosphate, in the urine during hypoglycaemic attacks or after fructose tolerance tests. Identification of such compounds may be useful in the early diagnosis of this disease.
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Volatile organic acid levels in plasma and tissues and nonvolatile organic acid levels in urine of biotin-deficient (BD) rats were measured and compared with other factors of biotin deficiency. Biotin levels and the activities of propionyl coenzyme A (CoA) carboxylase (PCC) in the livers of these rats were decreased, respectively, to 22% +/- 3% and 3.6% +/- 0.3% of the average values of pair-fed controls. Plasma concentrations of propionate were higher (15 to 223 micrograms/mL) than those of controls (5 to 7 micrograms/mL), whereas plasma levels of 3-methylcrotonate were only minimally increased as compared with those of controls. Concentrations of these volatile acids in the tissues were similarly increased, although those in brain showed less remarkable increases as compared with levels in other tissues. In the urine of BD rats, large amounts of organic acids derived from propionyl CoA, as well as those from 3-methylcrotonyl CoA, were excreted. Plasma propionate levels were not apparently related to the severity of clinical symptoms, biotin levels, or carboxylase activities, but were related to the amounts of urinary ketone bodies, lactate, and some of the organic acids derived from branched-chain amino acids, including those from propionyl CoA.
An 8 year old girl with adult type Philadelphia (Ph1)-positive chronic myelogenous leukemia received natural alpha-interferon therapy in the chronic phase. Complete suppression of the Ph1 clone of bone marrow cells was achieved after 1 month of therapy, which was determined by disappearance of rearranged breakpoint cluster region (BCR) gene in Southern blot analysis. Complete hematological remission was also attained following 2 months of therapy. Both the suppression and the hematological remission have been sustained for 24 months with alpha-interferon, in spite of the detection of the chimeric BCR/ABL mRNA in her bone marrow by polymerase chain reaction assay 12 months after therapy.
To assess the role of sulfidopeptide leukotrienes in the pathogenesis of exercise-induced asthma (EIA), the urinary levels of leukotriene E4 (LTE4), a metabolite of LTC4 and LTD4, were measured by RIA before and after exercise in 13 children with EIA and 10 healthy children. Mass spectrometry was used to confirm the presence of LTE4 in urine and the specificity of the RIA. There was no significant difference in the urinary LTE4 levels before exercise between the children with asthma and healthy children (109 [21 to 265] versus 122 [45 to 156] pg/mg of creatinine; median and range). Urinary LTE4 levels increased significantly after exercise in the children with EIA (from 109 [21 to 265] to 196 [40 to 655] pg/mg of creatinine; median and range; p less than 0.05) but not in the healthy children. The children with asthma demonstrated no significant correlation between the LTE4 level after exercise and the degree of bronchoconstriction, as revealed by the maximal percent fall in the peak expiratory flow rate. Taken together with a recent study that pretreatment with a potent and selective LTD4 antagonist markedly attenuated EIA, our findings suggest that sulfidopeptide leukotrienes may play some role in the pathogenesis of this type of asthma with other factors also being involved in determining the overall airway response.
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A Japanese boy aged 13 months was referred to us because thickened ribs had been observed on a chest X-ray taken during a respiratory infection. mucopolysaccharidosis type VI (MPS VI) was diagnosed based on urinary glycosaminoglycan analysis and low activity of arylsulfatase B in peripheral leukocytes. He had mild pupillary membrane remnants, but no corneal opacities. The auditory brainstem response revealed moderate hearing impairment, which may have caused his subnormal DQ score of 85 at the age of 19 months. Although MPS VI is characterized by normal intellectual development with normal hearing in early infancy, it is important to examine for hearing loss, especially when an infant with this disease shows developmental delay.
Urinary levels of leukotriene (LT) E4, a stable end-product of LTC4 and LTD4, were measured before and after exercise in 10 children with severe asthma and seven children with moderate asthma using HPLC and RIA to clarify the relationship of LT to the severity of asthma and to the degree of bronchospasm in exercise-induced asthma. The urinary LTE4 level significantly increased after exercise in the severe asthma group, but not in the moderate asthma group (14.3 +/- 14.5 to 24.3 +/- 20.6 versus 19.6 +/- 12.3 to 17.6 +/- 10.8 ng/mmol creatinine, p less than 0.05). The urinary LTE4 level increased in 10 patients (eight with severe asthma), and it decreased in seven patients (five with moderate asthma). A significant difference in the degree of bronchospasm after exercise (as shown by the maximal % fall in the peak expiratory flow rate), was seen when patients with increased urinary LTE4 excretion were compared with those with decreased excretion (60.4 +/- 17.3 versus 24.1 +/- 14.3%, p less than 0.01). Our findings suggest that exercise-induced asthma, or at least a subtype of exercise-induced asthma, may partly develop through the release of LTC4.
Methylmalonate or propionate was i.v. infused into B12-deprived and control rats. In the B12-deprived rats, the plasma and liver concentrations of B12 decreased to 8 and 13%, respectively, of those of the control rats. The propionate loading produced a disproportionate increase in liver propionate levels; the mean ratio of methylmalonate to propionate in the liver was approximately 1.0 after methylmalonate loading, whereas it was 0.1 to 0.2 after propionate loading. The liver propionate and methylmalonate levels in the B12-deprived rats were twice as high as those in the control rats. The mean ratio of beta-ATP to inorganic phosphate in the liver, measured with 31P-magnetic resonance spectroscopy, decreased from 0.60 to 0.48 in the B12-deprived rats and from 0.78 to 0.63 in the control rats after methylmalonate loading; the ratio decreased from 0.57 to 0.37 in the B12-deprived rats and from 0.76 to 0.56 in the controls after propionate loading. Statistical analysis showed that propionate loading caused a more marked decrease in ATP than did methylmalonate loading (F = 26.33, degree of freedom 1 and 15; p less than 0.001), while B12-deprivation caused a more marked decrease in ATP than did the control diet (F = 92.26, df 1 and 15; p less than 0.001). The concentrations of tricarboxylic acid cycle intermediates and related organic acids in the livers of the rats suggested that propionate inhibited NAD(+)-dependent enzymes in the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
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Leukotriene B4 (LTB4) production in polymorphonuclear leucocytes (PMN) was examined in ten children with steroid-responsive nephrotic syndrome (SRNS) before, during, and after steroid administration. Comparison of LTB4 production was made in 14 children with non-inflammatory disease who were not receiving steroid therapy. No significant change was noted in PMN LTB4 biosynthesis in children with SRNS throughout any phase of the disease. Furthermore, there was no significant difference in LTB4 biosynthesis in PMN between SRNS patients before steroid therapy and patients with non-inflammatory disease. These findings suggest that inhibition of LTB4 production is not involved in the mechanism underlying steroid action in SRNS.
A 10-month-old girl with mild developmental delay became hemiplegic after seizures. Cranial CT scan and magnetic resonance imaging (MRI) revealed no lesions related to vascular diseases, but brain atrophy on the right side was remarkable. Digital subtraction angiography showed slightly decreased visualization of peripheral branches of the right medial cerebral artery. Propionic acidaemia was diagnosed on the basis of high plasma levels of propionic acid and its metabolites and the elevated urinary excretion of these acids. With therapy, the levels of these acids fell, and her left hemiplegia disappeared 3 months later.
A patient with iliopsoas muscle pyomyositis was successfully treated with intravenous antibiotics alone. The diagnosis was made by ultrasonography and X-ray computed tomography after five days of spiking fevers. Ultrasonography and X-ray computed tomography revealed swelling of the muscle body but no abscess formation. We emphasize the usefulness of early diagnostic imaging to allow conservative treatment of iliopsoas muscle pyomyositis.
We recorded the auditory brainstem responses of rats fed a thiamin-deficient diet. The interpeak latencies between waves I and III, as well as those between waves I and IV, were significantly prolonged from day 24, while the latency of wave I was prolonged on day 26 of the thiamin-deficient diet. These delayed responses were corrected in 2 to 4 days after the initiation of daily intraperitoneal thiamin injections from day 32. The rats that were fed the thiamin-deficient diet, and then sacrificed on day 32, showed a decrease of total thiamin levels in the brain (26% of the level in control rat brains). Based on these results, we emphasize the value of the auditory brainstem response to detect thiamin deficiency.