Tetsuo Mori

Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.

Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities

CD27/CD70 interaction directly induces natural killer cell killing activity.

The CD27 molecule is expressed on a portion of natural killer (NK) cells as well as T and B cells. To provide the functional capacity of CD27 molecule on NK cells, we here highly purified CD3− CD56+ NK cells by flow cytometry (purity >98%), and investigated their NK cell activity via CD27/CD70 interaction using a CD70‐transfectant by a 4h 51Cr‐release assay. The enhancement of NK activity by purified NK cells in the presence of interleukin‐2 (IL‐2) or interleukin‐12 (IL‐12) against CD70/Nalm‐6 was not recognized as compared to against mock/Nalm‐6. However, after a coculture with the fixed CD70/300‐19, the purified NK cells increased the NK cell activity against K562, the value being 10 to 20% higher than coculture with the mock/300‐19 in the presence of IL‐2 or IL‐12. The enhancement of NK activity was blocked by the addition of anti‐CD70 monoclonal antibody (mAb). In addition, conjugation of NK cells to the target was increased by coculture with the CD70/300‐19 without increased expression of adhesion molecules. In the parallel experiment, there was no increase in the killing capacity of NK cells. These results strongly show that CD27/CD70 interaction directly enhances NK activity in the presence of IL‐2 or IL‐12 by increasing the effector and target conjugate formation, indicating that CD27/CD70 interaction plays an important role in the cytotoxic function of NK cells.

A direct evidence for defect in glucose-6-phosphate transport system in hepatic microsomal membrane of glycogen storage disease type Ib

Uptake of glucose-6-phosphate by microsomes of hepatocyte in rats, human controls and patients with glycogen storage disease type Ia and Ib was studied. In rat the uptake of glucose-6-phosphate increased rapidly and reached to a plateau, but mannose-6-phosphate was not accumulated. These findings indicate that a glucose-6-phosphate specific transport system exists in the microsomal membrane. In human controls and patients with glycogen storage disease type Ia the uptake of glucose-6-phosphate was clearly observed. On the other hand, no accumulation of it was detected in a patient with glycogen storage disease type Ib. These data provide a direct evidence of the defect in the glucose-6-phosphate transport system of hepatic microsomal membrane in glycogen storage disease type Ib.

TWO TYPES OF THYROID FUNCTION‐BLOCKING ANTIBODIES IN AUTOIMMUNE ATROPHIC THYROIDITIS AND TRANSIENT NEONATAL HYPOTHYROIDISM DUE TO MATERNAL IgG

We examined the effects of IgG from four patients with autoimmune atrophic thyroiditis on cAMP responses and iodine metabolism (post‐receptor processes), using cultured thyroid cells. We found two types of thyroid function‐blocking antibodies: (1) one blocks TSH binding to its receptors and inhibits TSH‐stimulated cAMP responses but does not block cAMP‐stimulated iodine uptake and organification; (2) the other blocks TSH binding to its receptors, inhibits TSH‐stimulated cAMP responses and does block cAMP‐stimulated iodine uptake and organification (post‐receptor processes). Among the four patients with autoimmune atrophic thyroiditis, three had TSH binding blocking antibodies only and one had antibodies which block post‐receptor processes. These antibodies might be responsible for thyroid dysfunction in autoimmune atrophic thyroiditis. The daughter of one of the women with autoimmune atrophic thyroiditis had transient neonatal hypothyroidism and recovered spontaneously from the hypothyroid state with the disappearance of the maternal blocking antibodies.

Preperitoneal fat thickness in childhood obesity: association with serum insulin concentration.

Abstract Background : The clinical significance of visceral fat accumulation in childhood obesity has remained controversial.

Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis

Abstract  Background : The involvement of neutrophil‐mediated inflammation may play an important role in the pathogenesis of acute respitory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil‐mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre‐α‐/inter‐α‐trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated.

Genetic and long-term data on a patient with permanent isolated proximal renal tubular acidosis.

Abstract A 12-year-old girl presented with permanent isolated proximal renal tubular acidosis (pRTA), glaucoma, band keratopathy, mild cataract and short stature. Severe metabolic acidosis was caused by the impairment of bicarbonate reabsorption in the proximal tubules and alkali therapy improved her acidaemia. A homozygous G to A transition at nucleotide 1,678 in the basolateral kidney type Na+/HCO3− (kNBC) co-transporter gene SLC4A4, which is critical in HCO3− resorption in renal proximal tubules, was identified. Her height and height velocity (HV) were very low (−4.0 SD and −4.4 SD, respectively) before alkali treatment, but both improved after initiating alkali therapy at the age of 2 years and 3 months. The patients body height and HV were 131.5 cm (−2.7 SD) and 4.0 cm (−2.0 SD), respectively at the age of 12 years. Conclusion This case demonstrates that early administration of alkali therapy and sustained correction of acidosis, even if inadequate to correct the metabolic acidosis, can markedly improves growth in permanent isolated proximal renal tubular acidosis.

A case report of infantile striatal necrosis with an acute onset

We report here an autopsy case, an 8-year-old boy diagnosed as having infantile striatal necrosis, characterized by a preceding febrile illness followed by acute encephalopathy with abrupt obtundation, seizures and dystonia, with remarkable improvement of the disturbed consciousness and intelligence after TRH-T therapy. These clinical symptoms were linked with bilateral necrosis of the striata on CT scanning. The presented case belonged to a newly described subgroup of the heredogenous disorders that produce necrosis of the putamina in children.

Hypercalcemia associated with all-trans-retinoic acid in the treatment of acute promyelocytic leukemia

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.

Genital abnormalities in Pallister–Hall syndrome: Report of two patients and review of the literature†

We describe two patients with Pallister–Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.