Paediatric cutaneous lymphoma in Korea: a retrospective study at a single institution.

BACKGROUND: The clinical features and incidences of cutaneous lymphoma (CL) differ by ethnicity and age. However, there is to our knowledge no study to show characteristics and distribution of paediatric CL in Asian population. OBJECTIVE: The aim of this study was to investigate distinctive clinicopathological features of CL in paediatric population, particularly in Korea. METHODS: We conducted a clinicopathological review of 41 paediatric cases with CL, diagnosed at Asan Medical Center from January 1990 to December 2012. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from paediatric patients with CL were analyzed. In addition, the results in this present paediatric group were compared with previously reported studies in the Korean all-ages group and Western paediatric group. RESULTS: Lymphomatoid papulosis was more common in the present paediatric group than in the all-ages group (34.5% vs. 9.4%) and Western paediatric group (34.5% vs. 17.7%). Mycosis fungoides, the most common cutaneous lymphoma in the all-ages group and Western paediatric group, is the second most common subtype in this study. Three of nine paediatric mycosis fungoides patients (33%) have the follicular variant. Compared with all-ages group, B-lmphoblastic lymphoma was relatively higher incidence (10.3% vs. 1%) and NK-/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma was relatively in lower proportions in the paediatric group. CONCLUSION: The clinical features and distribution of paediatric CL in our study suggest that CL of Asian childhood is quite different from that of adulthood and Western childhood.

Structure-activity relationships of apio nucleosides as potential antiviral agents.

Several types of novel apio nucleosides were synthesized starting from 1,3-dihydroxyacetone and evaluated for antiviral activity. Among compounds tested, amino substituted apio dideoxynucleosides exhibited anti-HBV activity, while thioapio dideoxynucleosides were found to be active against HIV-1. Apio dideoxydidehydro nucleosides showed moderate to potent anti-HCMV activity, but their bioisosteric thioapio dideoxydidehydro nucleosides did not exhibit any significant antiviral activity.

Synthesis and antiviral activity of fluoro-substituted apio dideoxynucleosides.

Novel fluoro-substituted apio dideoxynucleosides ((+/-)-3a and (+/-)-3b) were efficiently synthesized starting from 1,3-dihydroxyacetone via Horner-Emmons olefination as a key step. Cyclization of fluoro ester (+/-)-6 under acidic conditions to the fluorolactone was smoothly proceeded in favor of trans-fluorolactone due to the favorable transition state with equatorial hydroxymethyl substituent. Unfortunately, the final nucleosides (+/-)-3a and (+/-)-3b were found to be inactive against several viruses such as HIV-1, HSV-1, HSV-2 and HCMV.

Syntheses and structure--activity relationships of novel apio and thioapio dideoxydidehydronucleosides as anti-HCMV agents.

On the basis of the fact that apio dideoxynucleosides, in which the furanose oxygen and the C2 of the 2,3-dideoxyribose are transposed, exhibited potent anti-HIV activity and 2',3'-dideoxy-2',3'-didehydronucleosides also showed potent anti-HIV activity, we synthesized apio dideoxydidehydronucleosides in which the oxygen atom and the double bond of the 2,3-dideoxy-2,3-didehydroribose are exchanged. The thioapio dideoxydidehydronucleosides were also synthesized since sulfur serves as a bioisostere of oxygen. Apio dideoxydidehydronucleosides 13a--f were synthesized starting from 1,3-dihydroxyacetone, utilizing phenylselenenyl chemistry as a key step. The ratio of the anomeric mixture was variable from 1:1 to 5:1 during the condensation of nucleosidic bases with the phenylselenyl acetate 11 in the presence of a Lewis acid. This is in contrast with other glycosyl donors such as 5-O-(tert-butyldiphenylsilyl)-2-phenylselenenyl-2,3-dideoxyribosyl acetate which shows excellent neighboring group effect (alpha:beta = 1:99). Thioapio dideoxydidehydronucleosides 22a,b were synthesized from the lactone 9 via thiolactone 17 as a key intermediate which was synthesized from dicyclohexylcarbodiimide coupling of the mercapto acid produced from the basic hydrolysis of thioacetate 16. The majority of apio analogues synthesized in this study exhibited moderate to potent anti-HCMV activity, among which the 5-fluorouracil derivative 13c was found to be the most potent against HCMV, while thioapio analogues showed no activity against HCMV. However, all synthesized compounds did not exhibit any significant activities against HIV-1, HSV-1, and HSV-2. The fact that apio dideoxydidehydronucleosides were active against HCMV suggests that the apio dideoxydidehydro sugar moiety can serve as a novel template for the development of new antiviral agents.

A remarkably simple chemicoenzymatic approach to structurally complex bicyclo[3.1.0]hexane carbocyclic nucleosides.

[reaction: see text] Intramolecular cyclopropanation of a carbene engendered from the corresponding diazo beta-ketoester produced the desired bicyclo[3.1. 0]hexane pseudosugar. Purine nucleosides obtained via Mitsunobu coupling were resolved with adenosine deaminase. The requisite beta-ketoester was assembled in one step from ethyl acetoacetate and acrolein.

Construction of the bicyclo[3.1.0]hexane template of a conformationally locked carbocyclic adenosine via an olefin keto-carbene cycloaddition.

An intramolecular olefin keto-carbene cycloaddition reaction created the bicyclo[3.1.0]hexane template 10 that was necessary for the synthesis of carbocyclic amine 15. This amine is a direct precursor to a family of rigid nucleosides that are conformationally locked in the Southern hemisphere of the pseudorotational cycle. The synthesis of the conformationally locked adenosine analogue is reported herein as an illustrative example of the methodology. The racemic (South)-methanocarba adenosine analogue (+/-)-4 is the first example of a conformationally locked ribonucleoside version in the Southern hemisphere.

Chromosome abnormalities in a referred population for suspected chromosomal aberrations: a report of 4117 cases.

A cytogenetic study was performed on 4,117 Korean patients referred for suspected chromosomal abnormalities. Chromosome aberrations were identified in 17.5% of the referred cases. The most common autosomal abnormality was Down syndrome and Turner syndrome in abnormalities of sex chromosome. The proportions of different karyotypes in Down syndrome (trisomy 21 92.5%, translocation 5.1%, mosaic 2.4%) were similar to those reported in other countries. However, it was different in Turner syndrome (45, X 28.1%, mosaic 50.8%, 46, X, del (Xq) 4.4%, 46, X, i (Xq) 16.7%), in which proportions of mosaics and isochromosome, 46, X, i(Xq), were higher than those reported in other countries. In structural chromosome aberrations of autosome, translocation was the most common (43.6%), and duplication (21.3%), deletion (14.4%), marker chromosome (7.9%) and ring chromosome (4.0%) followed in order of frequency. Rates of several normal variant karyotypes were also described. Inversion of chromosome 9 was observed in 1.7% of total referred cases.

Synthesis and hybridization property of sugar and phosphate linkage modified oligonucleotides.

1-[3-Deoxy-5-O-(4,4'-dimethoxytriphenylmethyl)-3-C-hydroxymethyl-2 -O-(2-methoxyethoxymethyl)-beta-D-erythro-pentofuranosyl]thymine (13) was synthesized from 1,2-isopropylidene-D-xylose (1) as a building block of modified oligonucleotides. Three types of novel oligonucleotides were synthesized from 13 and their T(m)s were compared with those of the corresponding natural oligonucleotides. It was found that our synthesized oligomers had lower affinity to DNA and RNA than the natural oligomers.

Synthesis and antiviral activity of L-2'-deoxy-2'-up-fluoro-4'-thionucleosides.

L-2'-Deoxy-2'-up-fluoro-4'-thionucleosides were efficiently synthesized from D-xylose via L-4-thioarabitol derivative as a key intermediate and evaluated for antiviral activities against HIV-1, HSV-1,2 and HBV.

Synthesis and antiviral activities of 1,3-oxathiolanyl nucleosides with 5-hydroxymethyl substituent.

Novel 1,3-oxathiolanyl pyrimidine nucleosides with 5-hydroxymethyl substituent were synthesized starting from D-mannose and evaluated for antiviral activities against HIV-1, HSV type 1,2 and HCMV.

Synthesis and antiviral activity of D- and L-isodideoxy nucleosides with exocyclic-methylene.

Novel D- and L-isodideoxynucleosides were synthesized starting from D- and L-xylose and evaluated for antiviral activities against HIV-1, HSV-1, HSV-2, HBV and HCMV, respectively.

Base specific complex formation of norfloxacin with DNA.

We examined the base specificity of the norfloxacin-DNA interaction by measuring the binding constant of norfloxacin to various synthetic polynucleotides, using the Stern-Volmer and the Benesi-Hildebrand methods. The equilibrium constants were largest for poly[d(G-C)2] and poly(dG).poly(dC), suggesting that norfloxacin binds preferentially to the G-C bases of calf thymus DNA. We also found that norfloxacin has a greater affinity for purine than for pyrimidine. The binding mode of norfloxacin to double-stranded polynucleotide was studied using circular and linear dichroism (CD and LD). When the norfloxacin was complexed to poly[d(G-C)2], poly(dG).poly(dC) and DNA, all of the complexes exhibited a similar weak, positive CD band and negative LD in the 300-350-nm region. A closer examination of the LD spectra suggests that the molecular plane of norfloxacin is near perpendicular relative to DNA helix axis that excludes the groove binding mode or surface binding of norfloxacin.

Synthesis and antiviral activity of apio dideoxy nucleosides with azido or amino substituent.

Novel apio dideoxynucleosides with azido or amino or amino substituent were synthesized starting from 1,3-dihydroxyacetone utilizing an acid-catalyzed 1,4-conjugated addition as a key step and evaluated for antiviral activity. Unfortunately, they were found to be neither active against HIV-1, HSV-1,2 and poliovirus nor toxic.

Immunoblot analysis for serum antibodies to Pneumocystis carinii by age and intensity of infection in rats.

The present study aims to observe changing patterns of serum antibody to Pneumocystis carinii in normal rats of different ages and in immunosuppressed rats. The serum IgG antibody was observed by immunoblotting with crude antigen of P. carinii which were purified from the lungs of infected rats. The crude antigens separated in SDS-PAGE resolved more than 20 protein bands from 20 to 200 kDa. Of them, 40-45, 50-55, 116 and 200 kDa bands were major antigens of P. carinii. Most of the normal rats of up to 4 weeks had the antibodies reacting the 4 bands, but none of 8-week-old rats revealed the specific antibody. After the rats grew for 40 weeks, all were found to have the antibody in their serum. Same pattern of serum antibody level by age was found in ELISA. When immunosuppressed rats became heavily infected, the antibody in their serum decreased distinctively. The present results suggest that antibodies in normal newborn rats are transferred from their mother and lowered up to 8 weeks. Thereafter, the levels of the antibodies begin to increase by natural exposure to P. carinii. It was also confirmed that the intensity of P. carinii infection is inversely related with levels of serum antibodies.

[Comparative susceptibility of different cell lines for culture of Toxoplasma gondii in vitro].

In order to establish a useful cell culture system for T. gondii, we compared the degree of proliferation of T. gondii tachyzoites among 8 different cell lines; 2 kinds of normal animal cells (MDCK-canine kidney cells; Vero-monkey kidney cells) and 6 kinds of human tumor cells (A 549, PC 14-lung cancer cells; SNU 1, SNU 16, MKN 45-stomach cancer cells; HL-60-promyelocytic leukemia cells), through morphological observation and 3H-uracil uptake assay. The degree of susceptibility to infection with T. gondii tachyzoites was highest in A 549 and PC 14 cells, medium in Vero, HL-60, MDCK and SNU 1, and lowest in SNU 16 and MKN 45 cells. The kinetics of T. gondii multiplication during the post-infection 60 hours were highly dependent upon the dose of tachyzoites administered and the duration of cultivation. These results show that A 549 and PC 14 are the most suitable cell lines among the 8 tested for the growth and multiplication of T. gondii in vitro.

Fragile site X chromosomes in mentally retarded boys.

The fragile X syndrome is a common X-linked mental retardation and autism, affecting females as well as males. The fragile site X chromosomes were studied in a series of 153 mentally retarded boys of unknown etiology to determine the frequency of fragile X syndrome, and to assess the feasibility of making a clinical diagnosis of the fragile X syndrome in young boys before cytogenetic results were known. The 10 boys (6.4%) were positive for fra (X) (q27). The phenotype of fra (X) (q27) positive patients were typical except one who also had sex chromosomal mosaicism. There were three pairs of siblings among the fra (X) (q27) positive patients. Frequency of expression of the fragile site was in 10 to 47 per cent of cells. In addition, 19 boys showed a previously unsuspected chromosomal abnormality. The frequency of the fragile X syndrome in the present study is not significantly different from those in Caucasians and Japanese population. The fragile X syndrome can be recognized by noting key aspects of family history as well as the clinical features in mentally retarded boys.

A study on nesidioblastosis in hyperinsulinemic hypoglycemia--diagnosis, treatment, and neurologic sequelae.

The medical records of six cases of nesidioblastosis were examined to determine the diagnostic approach, treatment, and neurologic sequelae. All six patients were male, and their ages at the onset of the disease ranged from one day to six months (mean 3.36 +/- 2.5 mo.). Initial clinical features were seizure, cyanosis, poor feeding, and apnea. Other subsequent symptoms were developmental delay, hyperactivity, and cold sweating. The Birth weight of the neonatal onset group was heavier than the postneonatal onset group (4.4 +/- 0.3 vs 3.26 +/- 0.04 kg). Before the diagnosis of hyperinsulinism, steroids of ACTH proved effective for seizure control. Initially, hyperinsulinemia (serum insulin greater than 10 microU/ml) was detected in four cases, but another two cases also showed hyperinsulinism by insulin/glucose(I/G) ratio greater than 0.3 during the fasting test. The glucagon response performed in 2 cases, showed normal and partial responses. Euglycemia was obtained by near total pancreatectomy (95% pancreatic resection)without malabsorption or persistent diabetes. In one case, nesidioblastoma coexisted with nesidioblastosis. Developmental delay was noted in three cases. In this group, the mean duration between symptom onset and operation was longer than the group without developmental delay (1.25 +/- 0.47 vs 0.38 +/- 0.19 yr).