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Biomedical subjects

M Ibe

Publications and source records attributed to M Ibe.

At least 37 records · Page 2Linked to original sources

Binding of 8-mer to 11-mer peptides carrying the anchor residues to slow assembling HLA class I molecules (HLA-B*5101).

The binding of 303 8-mer to 11-mer peptides carrying the anchor residues at P2 and the C-terminus to HLA-B*5101 molecules was examined by a stabilization assay in which peptides were incubated with RMA-S-B*5101 cells at 26 degrees C for 3 h. Analysis of the binding of these peptides to HLA-B*5101 molecules showed that Pro and Ala at P2, and Ile, Val, and Leu at the C-terminus functioned as anchor residues, while Gly at P2 and Met at the C-terminus were weak anchors. Pro was a stronger anchor residue than Ala at P2, while Ile was the strongest anchor at the C-terminus. Among 8-mer to 11-mer peptides, the 9-mer peptides showed the strongest binding to HLA-B*5101 molecules. This is in contrast to our recent findings that 10-mer and 11-mer peptides bind to HLA-B*3501 molecules as effectively as 9-mer peptides. Since both HLA class I molecules have the same B-pocket and the binding peptides carry the same anchor residues, it is assumed that the structure of the F-pocket may restrict the length of binding peptides. The ability of HLA-B*5101 binding peptides to stabilize the HLA-B*5101 molecules was markedly lower than that of HLA-B*3501 binding peptides to stabilize the HLA-B*3501 molecules. It is known that HLA-B*5101 is a slow assembling molecule, while HLA-B*3501 assembles rapidly. The results imply that the slow assembling of HLA-B*5101 molecules results from the low affinity of peptides to HLA-B*5101 molecules.

Cell Line↗

A verrucous lesion on skin grafted after necrotizing fasciitis in a diabetic patient successfully treated with combined topical 5-FU and tacalcitol.

Many complications of diabetes mellitus involve the feet. These include infections, neuropathy, vasculopathy, and poor wound healing. Neuropathy causes chronic pressure or friction on an area of sensory loss and occasionally causes verrucous skin lesions. We describe a diabetic patient, complicated by necrotizing fasciitis, who developed a verrucous skin lesion on a skin graft site. The verrucous skin lesion was treated successfully with combined topical 5-fluorouracil and vitamin D3 application.

Administration, Topical↗

[Analysis of children with tuberculosis in the past 20 years].

To characterize the clinical features of childhood tuberculosis, we analyzed the symptoms, signs, and laboratory findings of the 89 children with tuberculosis admitted to the Yokohama City University Hospital from 1975 to 1994. Compared with the numbers of patients admitted from 1975 to 1979, those of patients of the past 5 years (from 1990 to 1994) were reduced by half. Of the 89 subjects, 56.2% were below 3 years of age and 24.7% were under 1 year of age. 51.7% had primary complex and 20.2% had serious tuberculosis (tuberculous meningitis 14.6%, miliary tuberculosis 3.4%, and bone and joint tuberculosis 2.2%). Tuberculous children below 3 years of age consisted of primary complex (60.0%) and serious tuberculosis (32.0%). The majority (86.0%) of tuberculous children below 3 years of age had not received BCG vaccination. In 55 (61.8%) of 89 subjects, the sources of tuberculosis were clarified. Of these subjects, 83.6% were infected in the family. The rate of BCG inocluation tended to decrease with decreasing age, especially that of children below 3 years of age was 14.0%. Of the 89 subjects, only 16.9% proved to be smear-positive. Taken together, in order to eliminate tuberculous children below 3 years of age, the following is necessary; (1) BCG inoculation in early infancy, (2) early diagnosis of index cases with adult tuberculosis, and (3) prompt and appropriate family contact examination.

Adolescent↗

Coombs-negative severe hemolysis associated with hepatitis A.

Mild anemia can occasionally be observed during viral hepatitis, but severe hemolysis has previously only been reported in a few patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive acute hemolysis associated with an acute hepatitis A in a 39-year-old woman in the absence of G6PD-deficiency. The patient was also suffering from mild rheumatoid arthritis. All known factors responsible for hemolysis were ruled out. Although tests for autoimmune hemolytic anemia were negative the patient made a dramatic recovery after treatment with corticosteroids, suggesting an immune mediated mechanism nonetheless.

Adult↗

Role of strong anchor residues in the effective binding of 10-mer and 11-mer peptides to HLA-A*2402 molecules.

The binding capacity of one-hundred-and-seventy-two 8-mer to 11-mer peptides carrying HLA-A24 anchor residues to HLA-A*2402 molecules was analyzed by using a HLA class I stabilization assay. Most (76. 2%) of these peptides bound to HLA-A*2402 molecules. These results confirmed previous findings that Tyr and Phe at P2 as well as Phe, Trp, Ile, and Leu at the C-terminus were main anchor residues for HLA-A*2402. Tyr at P2 was a stronger anchor residue than Phe, while bulky aromatic hydrophobic residues Phe and Trp at the C-terminus are stronger anchors than aliphatic hydrophobic residues Ile and Leu. These results were also supported by an analysis using a panel of mutated 9-mer peptides at P2 and P9. Taken together, these results suggest that HLA-A*2402 molecules have deep B- and F-pockets because they favor peptides carrying bulky aromatic hydrophobic residues at P2 and the C-terminus. The affinity of 8-mer peptides was significantly lower than that of 9-mer to 11-mer peptides, while there was no difference in affinity between 9-mer, 10-mer, and 11-mer peptides. The affinity of peptides carrying bulky aromatic hydrophobic residues at the C-terminus was higher than that of peptides carrying aliphatic hydrophobic residues in each of the 8-mer to 11-mer peptides, though the greatest difference in affinity was observed in 11-mer peptides. The strong interaction of side chains of these anchor residues with the corresponding pockets may permit the effective binding of 10-mer and 11-mer peptides to HLA-A*2402 molecules.

Binding Sites↗

Refined peptide HLA-B*3501 binding motif reveals differences in 9-mer to 11-mer peptide binding.

HLA-B*3501 is associated with subacute thyroiditis and fast progression of AIDS. An important prerequisite to investigate the T-cell recognition of HLA-B*3501-restricted antigens is the characterization of peptide-HLA-B*3501 interactions. In this study, peptide-HLA-B*3501 interactions were determined in quantitative peptide binding assays. The results were statistically analyzed to evaluate the influence of both anchor and nonanchor positions and the predictability of peptide binding. The binding data demonstrated that all anchor residues at position 2 and the C-terminus found in 9-mers functioned equally as anchors in 10-mers and 11-mers. These minimum requirements of peptide binding were refined by assessing positive and negative effects of nonanchor residues. Aliphatic hydrophobic residues at positions 3, 5, and 8 of 10-mers and position 3 of 11-mers significantly enhanced HLA-B*3501 binding. Similar effects rendered aromatic, bulky residues, acidic or polar residues of 11-mers at position 1 as well as at positions 4, 8, and 10, respectively. Negative effects were observed for residues carrying positively charged side-chains at position 7 of 11-mers. The refined HLA-B*3501 peptide binding motifs enhanced the identification of potential T-cell epitopes. The disparity between positive effects at the middle and C-terminal part (positions 5 - 8 and 10) of 11-mers and shorter peptides supports the extrusion of 11-mer residues at positions 5, 6, and 7, away from the HLA-B*3501 binding cleft.

Amino Acid Sequence↗

Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.

BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen-presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costimulatory molecules by Northern blotting, polymerase chain reaction, and flow cytometry. RESULTS: Both cell types expressed interleukin 1 messenger RNA and could serve equally well as accessory and antigen-presenting cells. B7-2 messenger RNA and surface expression on sinusoidal endothelial cells and on Kupffer cells was shown. Antibodies to the B7 molecules inhibited antigen presentation. Addition of interleukin 10 as a regulatory cytokine secreted by Kupffer cells was suppressive. CONCLUSIONS: Sinusoidal endothelial cells carry functional B7-2 molecules and can serve as effective antigen-presenting cells. However, antigen presentation by sinusoidal endothelial cells may be locally down-regulated by interleukin 10.

Animals↗

[Triphasic spiral CT in the diagnosis of liver diseases: comparison with CT arteriography and CT arterio-portography].

PURPOSE: Assessment of the diagnostic efficacy of triphasic spiral-CT scanning (TPS-CT) for liver disease evaluation. CT arteriography (CTA) and CT arterio-portography (CTAP) were used as reference, methods which together have the highest sensitivity for detecting tumours and the perfusion conditions of the liver. MATERIAL AND METHODS: 50 TPS-CT and CTA/CTPA were performed in 49 patients. After an initial examination without enhancement the first scan was initiated 15-25s after the peripheral bolus injection of contrast medium, the second after an interscan delay of 20-25s. By this means the liver was imaged in different phases of perfusion. In the course of the CTA/CTPA-exam the imaging was carried out after selective, intraarterial application of contrast agent. RESULTS: The differentiation of the perfusion phases succeeded in 90% of the patients. When compared with standard CT, which images only the portal venous phase, the new technique, which additionally shows the arterial perfusion, accomplished an increase in sensitivity for hypervascular lesions (51% vs. 60%). Yet in comparison with CTA/CTPA fewer lesions could be detected (87 vs. 138). Furthermore, by documenting the contrast agent kinetics, characterisation of the lesion was also facilitated. CONCLUSION: DPS-CT is a valuable additional tool for imaging the liver, even if the information yield is less when compared to CTA/CTPA.

Adult↗

Satisfactory remission achieved by PUVA therapy in Langerhans cell hisiocytosis in an elderly patient.

Langerhans cell histiocytosis is currently regarded as a reactive proliferative process of Langerhans cells rather than a malignancy. The disease is characterized by Langerhans cell infiltration of skin, lung, bone and other organs. We report a 74-year-old man with Langerhans cell histiocytosis who had generalized hemorrhagic and crusted papules. He also had diabetes insipidus. Because he did not have any severe constitutional symptoms or failure of vital organs, we applied topical PUVA treatment to his skin lesions, which responded well to the therapy. Diabetes insipidus, however, remained, in spite of X ray radiotherapy for the pituitary lesion.

Aged↗

[HIV and pregnancy: risks of transmission and therapeutic possibilities].

In Europe, transmission of HIV-1 during pregnancy occurs in 14% of children born to HIV-infected women. Risk factors for transmission are (1) virus load measured by p-24 antigenemia and HIV RNA level, (2) low CD4+ lymphocyte counts (below 600/microliter, (3) placental membrane inflammation and (4) time interval between membrane rupture and delivery. Breast feeding and vaginal delivery increase the risk of transmission of HIV infection. Antiretroviral therapy with zidovudine (Retrovir) at a dose of 500 mg/day reduces the transmission of HIV infection by two thirds. No malformation of the newborn due to zidovudine has been reported so far, but the possibility of unknown long-term adverse effects on children exposed to zidovudine must be weighed against the benefit of a considerable decrease in HIV transmission. Pregnancy is not associated with a higher rate of progression to AIDS, and HIV infection has no adverse effect on the pregnancy outcome in asymptomatic women.

Anti-HIV Agents↗

A single nine-amino acid peptide induces virus-specific, CD8+ human cytotoxic T lymphocyte clones of heterogeneous serotype specificities.

It is generally accepted that virus-specific CD8+ cytotoxic T lymphocytes (CTLs) recognize nine-amino acid peptides in conjunction with HLA class I molecules. We recently reported that dengue virus-specific CD8+ CTLs of two different serotype specificities, which were established by stimulation with dengue virus, recognize a single nine-amino acid peptide of the nonstructural protein NS3 of dengue virus type 4 (D4V) in an HLA-B35-restricted fashion. To further analyze the relationships between the serotype specificities of T cells and the amino acid sequence of the recognized peptides, we examined the ability of this viral peptide D4.NS3.500-508 (TPEGIIPTL) to stimulate T lymphocytes of an HLA-B35-positive, dengue virus type 4-immune donor. Peptide stimulation of the PBMC generated dengue virus-specific, HLA-B-35-restricted CD8+ CTL clones. These clones lysed dengue virus-infected autologous cells, as well as autologous target cells pulsed with this peptide. Four patterns of dengue virus serotype specificities were demonstrated on target cells infected with dengue-vaccinia recombinant viruses or pulsed with synthetic peptides corresponding to amino acid sequences of four dengue virus serotypes. Two serotype-specific clones recognized only D4V. Three dengue virus subcomplex-specific clones recognized D1V, D3V, and D4V, and one subcomplex-specific clone recognized D2V and D4V. Three dengue virus serotype-cross-reactive clones recognized D1V-D4V. Thus, a single nine-amino acid peptide induces proliferation of a heterogeneous panel of dengue virus-specific CD8+ CTL clones that are all restricted by HLA-B35 but have a variety of serotype specificities. Peptides that contain a single amino acid substitution at each position of D4.NS3.500-508 were recognized differently by the T cell clones. These results indicate that a single epitope can be recognized by multiple CD8+ CTLs that have a variety of serotype specificities, but the manner of recognition by these multiple CTLs is heterogeneous.

Amino Acid Sequence↗

Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues.

The prerequisites of peptide HLA-B*3501 interactions have been revisited by quantitative peptide binding assays with 190 chemically synthesized peptide possessing two anchor residues corresponding to the HLA-B*3501 peptide motif and a statistical residue-position analysis of binding and nonbinding peptides. According to the peptide motif of HLA-B*3501, aliphatic hydrophobic (Leu, Ile, and Met) or aromatic residues (Tyr and Phe) specify the main anchor at the C terminus, and position 2 renders an auxiliary anchor for proline. The importance of these residues was confirmed as a minimum requirement for peptide binding. Moreover, we demonstrated that high affinity peptide binding requires more than one favorable position of positions 3, 4, and 7. Aliphatic hydrophobic residues and residues that contain -OH or -SH side chains in position 3, 7, and 4 significantly enhance binding. Positions 1 and 5, or 7 may deteriorate peptide binding if these positions are held by proline and small residues (Ala and Gly) or basic residues carrying positively charged side chains (Arg and Lys), respectively. Positions 6 and 8 were statistically free of constrains. Yet, bulky aromatic residues and basic residues with a positively charged side chain at position 8 decreased the binding affinity. These findings were used to assess the predictability of binding and nonbinding peptides. Our binding predictions of 28 nonamers were verified by experimental data. Taking into account the importance of anchor and nonanchor positions in peptide binding and their practical value in peptide binding prediction, the search for peptide epitopes becomes more efficient.

Amino Acid Sequence↗

[Analysis of children with tuberculosis in recent 10 years].

To make an early diagnosis and decision for prompt treatment of the children with tuberculosis, we analyzed 61 cases in both inpatients and outpatients for the clinical and laboratory characteristics. One fourth of the 61 cases were below 1-year-old, and 43 cases (70.5%) had a positive family history. The tuberculin test revealed that all of the 61 cases were positive, and 18 of them had a strongly positive reaction (> or = 30 mm). Although the serum levels of inflammatory markers including white blood cells counts, erythrocyte sedimentation rate and CRP value increased only slightly in most cases, serum IgM levels in 59.0% of the children with tuberculosis were twice to three times higher than those in normal average levels. Especially in 96.2% of the children hospitalized for the need of isolation the IgM levels were demonstrated high. Thus, in children with tuberculosis the detection of serum IgM levels as well as family history, tuberculin reaction, and chest X-ray findings may be helpful for the early diagnosis and prompt decision of hospitalization.

Adolescent↗

[A case of juvenile dermatomyositis with calcinosis universalis--remarkable improvement with aluminum hydroxide therapy].

Juvenile dermatomyositis (JDM) is a multisystem disease characterized by acute and chronic nonsuppurative inflammation of striated muscle and skin. JDM is classified into an independent entity in the classification of dermatomyositis, and it is marked by the development of calcinosis late in the course of the disease. Since an appropriate steroid therapy for the disease was established, the prognosis of the JDM has been improved except for a fulminant case. Frequency of calcinosis in JDM also has been decreasing because of the adequate steroid therapy. However, once calcinosis universalis occurs, this is the most troublesome and debilitating complication in JDM. Treatment of calcinosis universalis in JDM, so far, remains unsatisfactory. We report here a case of JDM, who suffered from at the age of 3 years, with calcinosis universalis that showed remarkable improvement to orally administrated aluminum hydroxide.

Adolescent↗

[Thermographic assessment of Raynaud's phenomenon in childhood mixed connective tissue disease].

To assess Raynaud's phenomenon objectively, thermographic estimation of hands and fingers was performed before and after the disease- and Raynaud's phenomenon-directed therapy in 3 children with mixed connective tissue disease. All the cases were positive in Raynaud's phenomenon, and the surface temperature of their hands and fingers were decreased even before cold challenge. After the cold provocation test at 4 degrees C for 10 sec., the temperature of all or some of the fingers were rapidly decreased, and the recovery of surface temperature of these fingers were markedly delayed. Even after methylprednisolone pulse therapy the pattern of the finger temperature were essentially unchanged, suggesting that steroids are not effective in the treatment of Raynaud's phenomenon. The long-term administration of vitamin-E, oral prostaglandin E1, and/or serotonin-receptor inhibitor were also proved to be not beneficial in improving Raynaud's phenomenon. Thus, thermography is useful in diagnosing Raynaud's phenomenon objectively, in determining the efficacy of anti-Raynaud drugs, and in estimating long-term course of the phenomenon.

Adolescent↗

[Evaluation of serum C3 and CH50 levels as markers of disease-activity and indicators of efficacy of treatment of lupus nephritis in childhood].

Serum levels of complement components (C3 and C4) and its activity (CH50) were analysed in 20 children with lupus nephritis from view points of disease-activity and efficacy of therapy. After the initiation of prednisolone or methylprednisolone pulse therapy for children in active phases the depressed C3 and CH50 levels were rapidly recovered to normal ranges within 4 months and 2 months, respectively. On the contrary serum C4 levels were normalized later in 11 months. Increased levels of antinuclear antibody and anti-DNA antibody titers have reciprocally dropped in response to those therapy. However, in 9 of 20 children the titers of antinuclear antibody and anti-DNA antibody remained high. Proteinuria observed in active phases of lupus nephritis has disappeared by therapy in all but two exceptions: these two children were complicated with nephrotic syndrome. Histological improvement after therapy was not observed (WHO classification). These findings suggested that it is useful to monitor serum C3 and CH50 levels but not C4 levels to judge disease-activity, and to evaluate efficacy of therapy of lupus nephritis in childhood.

Adolescent↗

[Behçet's disease in childhood--case reports and review of literature].

Two childhood with Behcet's disease were reported. To evaluate the clinical features of Behcet's disease in childhood, fifty eight case studies (domestic; 19 cases, world-wide; 39 cases) were examined from the literature including two cases in our clinics. Oral ulcers (100%), genital ulcers (82.8%), skin manifestations (77.6%), and articular involvement (51.7%) were frequently found as seen in adult cases. Gastrointestinal manifestations were more common in childhood than in adults (50.0% vs. 29.3%). However, ocular inflammatory disease was less frequently seen in pediatric patients as opposed to adults. Three fourth of children with Behçet's disease was effectively treated with oral or intravenous prednisolone. These findings suggested that the criteria for childhood Behçet's disease will be necessary for early and proper diagnosis.

Behcet Syndrome↗