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Biomedical subjects

C Terai

Publications and source records attributed to C Terai.

At least 37 records · Page 2Linked to original sources

Changes of the interleukin-6 levels in skin at different sites after thermal injury.

OBJECTIVE: To delineate the regulation of IL-6 production in unburned skin adjacent to a burn in an animal model. METHODS: In C57BL/6 mice, at 15, 30, and 60 minutes after a 20% full-thickness burn, skin was removed from various sites. Control samples were obtained from unburned mice. Normal skins were incubated with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL-1 beta, and IL-6. Unburned skin specimens were incubated with anti-TNF-alpha and IL-1alpha antibodies. Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: The burn increased the IL-6 levels at 30 minutes (p < 0.05) and the IL-1alpha levels at 15 and 60 minutes in the unburned skin. TNF-alpha, IL-1alpha, and IL-1beta increased IL-6 production in normal skin (p < 0.05). Anti-IL-1alpha antibody decreased IL-6 production in the unburned skin (p < 0.05). CONCLUSIONS: IL-1alpha modulates IL-6 production in unburned skin after injury. IL-6 and IL-1alpha might contribute to the alterations after a burn.

Animals↗

Eosinophilic fasciitis complicated with peripheral polyneuropathy.

Peripheral polyneuropathy and the complication of eosinophilic fasciitis (EF) is rare; only 2 such cases have been described previously. A 40-year-old woman suffered from swelling of the extremities after strenuous exercise and complained of bilateral paresthesia on the soles of her feet. The diagnosis was EF according to clinical symptoms, peripheral eosinophilia, and histological examination of the fascia. Nerve conduction tests also revealed sensory disturbance as mononeuritis multiplex. After administration of prednisolone, the swelling and tenderness of the extremities improved immediately but the neuropathy lasted for 6 months.

Adult↗

[Pneumoperitoneum with systemic sclerosis].

We report a case of systemic sclerosis (SSc) complicated with benign pneumoperitoneum without apparent pneumatosis cystoides intestinalis (PCI). A 43-year-old woman was admitted to our hospital because of prominent abdominal distension in April 1997. Raynaud's phenomenon has been detected since 1991. She was suffering from recurrent diarrhea, constipation, and subileus. The diagnosis of SSc was made in 1996 based on the sclerosis in her face, forearms, and chest, and hypomotility of the esophagus. On admission, she presented no signs of peritoneal irritation. The laboratory data revealed that white blood cell count was 7,400/mm3 and C-reactive protein was 0.1 mg/dl. Chest and abdominal roentgenograms showed massive free air under the diaphragm, dilatation of small and large intestine, and air-fluid level. PCI was not apparent. Pneumoperitoneum was improved after four weeks with intravenous hyperalimentation. But she presented recurrent severe diarrhea and high fever whenever she tried to take food orally. Klebsiella pneumoniae was proved in her jejunal juice by bacteriologic examination. Intravenous prostaglandin F2 alpha and oral fosfomycin calcium intake made her condition better. Benign pneumoperitoneum without PCI is rarely reported in the patients with SSc. In her condition, weakness of intestinal wall, hypomotility of intestine, unusual bacterial overgrowth, and elevated intraluminal pressure made intraluminal gas go through the wall of the fragile intestine of SSc. As operation of intestine of SSc usually cause miserable outcome, pneumoperitoneum accompanied with SSc even if PCI is apparent or not must be treated with conventional manner while there is no signs of peritoneal irritation.

Adult↗

[A patient with acute sarcoidosis associated with fever, polyarthritis, and erythema nodosum: a typical of Löfgren's syndrome].

A 26-year-old female was admitted to Aoyama Hospital in February 1996, for evaluation of abnormal chest shadows and polyarthritis. She visited our clinic in December 1995 with complaints of fever, fatigue, and polyarthralgia which lasted for 3 weeks. Two weeks later she developed erythema nodosum on her lower legs with the exacerbation of polyarthritis. Erythrocyte sedimentation rate was 108 mm/hr and CRP 4.9 mg/dl. A chest radiograph showed hilar lymphadenopathy and multiple nodular shadows in both lung fields. On admission, she had arthritis of the shoulders and knees, erythema nodosum on her lower extremities, and keloid-like skin lesion on her left knee. Thoracoscopic lung biopsy of nodular lesion and skin biopsy of keloid-like lesion revealed noncaseating granuloma of epithelioid cells with lymphocytes, macrophages, and giant cells, confirming the diagnosis of sarcoidosis. She was cured in three months, and was well and free of the symptoms thereafter. Löfgren's syndrome is acute sarcoidosis, characterized by arthritis, erythema nodosum, and bilateral hilar lymphadenopathy. This syndrome is common in Europe and is closely related to HLA-B8 and DR-3. The frequency of HLA-B8 and DR-3 in Japanese is almost 0%, explaining the rare onset of this syndrome in Japan. Our case is the second report of typical Löfgren's syndrome in Japan, although the patient did not have these HLA loci.

Acute Disease↗

Acute sympathetic hyperfunction in overlapping syndromes of systemic lupus erythematosus and polymyositis.

A 20-year-old woman with arthralgia, serositis, thrombocytopenia, proteinuria, muscle weakness, elevated creatinine kinase, and positive anti-Sm antibody was diagnosed as having polymyositis and systemic lupus erythematosus (SLE). She had persistent high temperature, sinus tachycardia, hyperhidrosis, mydriasis, visual disturbance, hallucination, and loss of consciousness. Levels of plasma adrenaline, noradrenaline, and dopamine and cerebrospinal fluid interleukin (IL)-6 and IL-8 were all high. A diagnosis of sympathetic hyperfunction accompanied by central nervous system (CNS) involvement in SLE was made parenteral. Pulse administration of high dose corticosteroid therapy was effective. This is the first reported case of a connective tissue disease with CNS involvement manifesting as sympathetic hyperfunction with high plasma catecholamine levels.

Acute-Phase Reaction↗

MR imaging of the central nervous system in divers.

BACKGROUND: Magnetic resonanse imaging (MRI) frequently reveals asymptomatic cerebral infarctions in the general population. HYPOTHESIS: The central nervous system (CNS) of divers is affected by a hyperbaric environment even if they are asymptomatic. METHODS: We examined 25 uniformed service divers by MRI and compared them with normal controls. RESULTS: Of 25 divers, 9 had CNS lesions vs. 2 of 25 controls (p = 0.02). There was a significant relationship between the CNS lesions, age, and smoking. CONCLUSION: The divers had a risk of accumulating CNS lesions. These results suggested that divers should undergo periodic medical evaluations and MRI brain scanning.

Adult↗

Intervention of somatic mutational events in vivo by a germline defect at the adenine phosphoribosyltransferase locus.

Both germline and somatic mutations are known to affect phenotypes of human cells in vivo. In previous studies, we cloned mutant peripheral blood T cells from germline heterozygous humans for adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7) deficiency and found that approximately 1.3 x 10-4 peripheral T cells had undergone in vivo somatic mutations. Loss of heterozygosity (LOH) was the major cause of the mutations at the APRT locus since approximately 80% of the mutant T cell clones exhibited loss of normal alleles. In the present study, we identified three heterozygous individuals for APRT deficiency (representing two separate families), in whom none of the somatic mutant cells exhibited LOH at the APRT locus. The germline mutant APRT alleles of these heterozygotes from two unrelated families had the same gross DNA abnormalities detectable by Southern blotting. None of the germline mutant APRT alleles so far reported had such gross DNA abnormalities. The data suggest that the germline mutation unique to these heterozygous individuals is associated with the abrogation of LOH in somatic cells. The absence of LOH at a different locus has already been reported in vitro in an established cell line but the present study describes the first such event in vivo in human individuals.

Adenine Phosphoribosyltransferase↗

Measurement of interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in tissues and plasma after thermal injury in mice.

BACKGROUND: Cytokines are important modulators of physiologic alterations after thermal injury. Indeed, an increase in the level of circulating cytokines has been documented after thermal injury. However, the mechanism of the increase has not been clarified. We determined cytokine levels in local tissue after thermal injury to identify the tissues responsible for the increase. METHODS: Female C57BL/6 mice each received a 20% full-thickness burn injury. Blood, burned skin, unburned skin, muscle underlying the burn, and muscle of the thigh, liver, spleen, and mesenteric lymph node were sampled at 1, 2, 4, 8, and 24 hours after injury. Uninjured control mice were treated similarly. The samples were cultured, and concentrations of tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-10 in the culture media were measured by using an enzyme-linked immunosorbent assay. RESULTS: IL-6 levels in unburned skin were significantly increased at 1 hour and decreased at 24 hours, compared with the control. IL-6 levels in muscle underlying the burn were significantly decreased at 8 hours. No elevation of plasma IL-6 levels was observed after injury. Neither tumor necrosis factor-alpha IL-10 was detected in any tissue. CONCLUSIONS: Results indicate that unburned skin may be a major source of IL-6 production after thermal injury and may contribute to the physiologic alterations occurring after such injury.

Animals↗

Generation and molecular characterisation of monoclonal IgG4 rheumatoid factor from a patient with rheumatoid arthritis.

OBJECTIVE: To characterise IgG4 rheumatoid factor (RF) at the molecular level from a patient with rheumatoid arthritis. METHODS: B cells were cloned from the peripheral blood of a patient with rheumatoid arthritis, using EB virus transformation. The supernatants of the clones were screened for IgG RF activity by ELISA. Nucleotide sequences of the expressed immunoglobulin heavy and light chain genes of one IgG RF producing clone were determined by direct sequencing of the products of a polymerase chain reaction. RESULTS: One clone producing monospecific IgG4 RF was obtained. Sequence analysis of the heavy and light chain genes suggested the accumulation of somatic mutations resulting in amino acid replacement in complementarity determining regions. CONCLUSIONS: The results may suggest an antigen driven response in the generation of IgG4 RF in rheumatoid arthritis disease processes.

Amino Acid Sequence↗

Sclerosing cholangitis associated with hypereosinophilic syndrome.

A 15-year-old male with hypereosinophilic syndrome was admitted to our hospital because of general malaise and abnormal liver function tests. Endoscopic retrograde cholangiopancreatography demonstrated bile duct changes consistent with primary sclerosing cholangitis. The patient's liver profile tests returned to normal after treatment with prednisolone and ursodeoxycholic acid. In this case, eosinophils might have played an important role in the pathogenesis of the bile duct lesion.

Adolescent↗

[A case of traumatic hematoma in the basal ganglia: successful drainage with ultrasound-guided aspiration surgery via burr hole].

A case was reported of massive traumatic hematoma of the basal ganglia which was treated successfully by ultrasound-guided aspiration surgery. A 8-year-old girl was transferred to our hospital 20 minutes after a traffic accident. She was in stupor and had right hemiplegia. A skull x-rays showed right temporal linear fracture and a head CT disclosed left massive putaminal hematoma. Ultrasound-guided aspiration surgery via a burr hole was performed under general anesthesia and 30 ml of hematoma was successfully evacuated. Her symptoms and signs improved gradually and she was discharged on foot 3 weeks after the accident. The clinical feature and mechanism of development of the hematoma in this lesion, and usefulness of ultrasound-guided aspiration surgery were also discussed.

Basal Ganglia↗

Similarity of in vivo somatic mutations at an autosomal adenine phosphoribosyltransferase locus between T- and B-cells in human peripheral blood.

In vivo somatic mutations have been detected at several human loci by using clonal cultures of peripheral blood T-cells. It has not been fully understood whether or not the somatic mutations in T-cells are similar to those of other cell types. To address this issue, we cloned, from human peripheral blood, T- and B-cells with mutations at an autosomal adenine phosphoribosyltransferase (APRT) locus. For the efficient detection of somatic mutations at the APRT locus, a blood sample from a human individual heterozygous for germline APRT deficiency was used. T- and B-cells deficient in APRT enzyme activity were cloned from peripheral blood mononuclear cells using a selecting agent, 2,6-diaminopurine. The APRT-deficient mutant frequencies were on the order of 10(-4) in both T- and B-cells. The single-strand conformation polymorphism analysis of the APRT DNA of mutant B-cell clones suggested that the molecular mechanisms leading to the APRT deficiency in B-cells were similar to those in T-cells. Our observations suggest that both the frequency and the mode of in vivo somatic mutations occurring spontaneously at general autosomal loci in B-cells are similar to those in T-cells.

Adenine Phosphoribosyltransferase↗

Differential binding avidities of human IgM for staphylococcal protein A derive from specific germ-line VH3 gene usage.

Human IgM that express the variable region genes of the VH3 family bind staphylococcal protein A (SPA). We previously reported that the SPA-binding IgM can be divided into two groups based on the differential binding avidities for solid-phase SPA. To study the molecular basis for these differences, we cloned B cells from human blood by EBV transformation. The nucleotide sequences of the expressed Ig heavy chain genes were determined on 20 B cell clones that produce SPA-binding IgM. The germ-line VH3 gene usage in IgM with high avidities for SPA were distinct from the germ-line VH3 genes used in IgM with low avidities for SPA. There was no correlation in the usage of D or JH genes or in the usage of light chains in IgM according to the SPA binding avidity. These results suggest that the differential binding avidities for SPA are at least partly due to specific germ-line VH3 gene usage. An investigation of direct binding of SPA to the synthetic peptides corresponding to the portions of the variable regions of SPA-binding and non-SPA-binding IgM showed that the peptides corresponding to the VH3 family specific framework region 3 sequences had significant SPA binding capacities, while the peptides corresponding to the other subdomains and those corresponding to framework region 3 of the reported VH3 sequences from non-SPA-binding IgM showed little or no binding. It is of interest that the Ig-framework region 3 subdomain corresponds to the fourth hypervariable region, which in the TCR-beta chain has been implicated as a critical site for T cell superantigen binding.

Adult↗

The origin of the most common mutation of adenine phosphoribosyltransferase among Japanese goes back to a prehistoric era.

The incidence of adenine phosphoribosyltransferase (APRT) deficiency is higher among Japanese nationals than among other ethnic groups, and the most common mutation (APRT*J, ATG to ACG mutation at codon 136) accounts for 68% of the disease-causing genes among Japanese. To investigate the origin of these mutations, we studied the geographical distribution of the mutant genes in Japan. The APRT*J mutation is distributed nearly uniformly in the four main islands of Japan and Okinawa, suggesting a very early origin. The products of PCR amplification between positions 2344 and 2750 of the genomic APRT sequence were examined by SSCP analysis in random blood samples from Japanese, Korean, and Taiwanese nationals. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for the APRT*J mutation, giving a calculated heterozygote frequency of 1.1% among Japanese for the entire APRT deficiency. None of 231 Taiwanese samples contained heterozygotes for the APRT*J mutation, while 2 (0.53%) of 356 Korean samples were heterozygous. In addition to the APRT*J sequence, a total of five variant sequences was found. Sequencing one variant revealed a base substitution in intron 4, suggesting therefore that they are harmless mutations. Since the APRT*J mutation is present in Koreans and Okinawans who share ancestors only before the Yayoi era (third century BC to third century AD), the origin of the APRT*J mutation predates 300 BC.

Adenine Phosphoribosyltransferase↗

Development of a potassium-specific adsorbent for direct hemoperfusion.

Direct hemoperfusion (DHP) over an exchange resin for sodium is capable of rapidly lowering an elevated serum potassium level but has not been used clinically because of subsequent electrolyte abnormalities. After the completion of detailed in vitro studies, we developed a sodium/calcium/magnesium exchange resin mixture specifically to remove potassium from the blood. The mixture, which consisted of exchange resins for sodium (48%), calcium (48%), and magnesium (4%), gave the most satisfactory results in vitro. DHP through these resin-mixture columns for 2 h reduced elevated plasma potassium levels (6.7 +/- 1.1 to 3.5 +/- 0.6 mEq/L, p < 0.001) in anephric dogs without including any significant change in the levels of sodium, calcium, magnesium, albumin, total protein, or cholesterol. The platelet losses and changes in the plasma free hemoglobin levels observed were similar to those found with activated charcoal hemoperfusion. These results suggest that this resin hemoperfusion may be useful in patients with acute hyperkalemia.

Animals↗

Differential cytotoxic effects of mizoribine and its aglycone on human and murine cells and on normal and enzyme-deficient human cells.

The growth inhibitory mechanisms of mizoribine, an immunosuppressive imidazole nucleoside used clinically to inhibit rejection reactions after renal transplantation and in the treatment of systemic lupus erythematosus and rheumatoid arthritis, were studied in human and murine cells. We found that (a) human cells were 20- to 60-fold more resistant than murine cells to both mizoribine and its aglycone, (b) adenine phosphoribosyltransferase (APRT)-deficient human cells were resistant to aglycone but not to mizoribine, (c) hypoxanthine phosphoribosyltransferase (HPRT)-deficient human cells were at least 100-fold more sensitive to both mizoribine and aglycone, and (d) the decrease in intracellular GTP broadly paralleled the cytotoxicity in each case. Therefore, data obtained from studies using non-human tissues should be interpreted carefully before clinical application. Results indicate that the growth inhibitory effect of the aglycone but not of mizoribine is mediated by APRT, and depletion of guanine nucleotides is responsible for the effects of both drugs. Our data also suggest that the drugs may reduce mutant HPRT-deficient somatic cells in vivo, and may cause enhanced adverse reactions in HPRT-deficient individuals. The drug may have altered effects in patients receiving other purine or pyrimidine analogs.

Adenine Phosphoribosyltransferase↗

Selection against blood cells deficient in hypoxanthine phosphoribosyltransferase (HPRT) in Lesch-Nyhan heterozygotes occurs at the level of multipotent stem cells.

Lesch-Nyhan syndrome is caused by a severe genetic deficiency of hypoxanthine phosphoribosyltransferase (HPRT) and is characterized by central nervous system disorders, gout, and in some cases, macrocytic anemia. Women heterozygous for HPRT deficiency are healthy but their somatic cells are mosaic for enzyme deficiency owing to random inactivation of the X chromosome. Frequencies of red blood cells and T cells deficient in HPRT are significantly lower than the expected 50% in heterozygotes, suggesting that HPRT-negative blood cells are selected against in heterozygotes. To determine at which stage of hematopoiesis such selection occurs, we determined the frequencies of HPRT-negative T, B and erythroid precursor cells in three heterozygotes. Since the cloning efficiencies of T and B cells and colony forming efficiency of burst-forming unit erythroid (BFU-E) for sample from Lesch-Nyhan patients were similar to those of normal cells, HPRT deficiency does not seem to render the differentiated cells less efficient for proliferation. However, the frequencies of HPRT-negative T and B cells, and BFU-E were all less than 10% in each of the three heterozygotes. Although the frequencies of HPRT-negative cells showed tenfold variations between the heterozygotes, each heterozygote had similar frequencies of HPRT-negative cells in the three cell types. These results suggest that HPRT is important at early stages of hematopoiesis, but less so after the cells have differentiated into T cells, B cells and erythroid precursor cells.

Adult↗