Different patterns of cerebellar abnormality and hypomyelination between POLR3A and POLR3B mutations

Background

Mutations of POLR3A and POLR3B have been reported to cause several allelic hypomyelinating disorders, including hypomyelination with hypogonadotropic hypogonadism and hypodontia (4H syndrome). Patients and methods: To clarify the difference in MRI between the two genotypes, we reviewed MRI in three patients with POLR3B mutations, and three with POLR3A mutations. Results: Though small cerebellar hemispheres and vermis are common MRI findings with both types of mutations, MRI in patients with POLR3B mutations revealed smaller cerebellar structures, especially vermis, than those in POLR3A mutations. MRI also showed milder hypomyelination in patients with POLR3B mutations than those with POLR3A mutations, which might explain milder clinical manifestations. Conclusions: MRI findings are distinct between patients with POLR3A and 3B mutations, and can provide important clues for the diagnosis, as these patients sometimes have no clinical symptoms suggesting 4H syndrome.     

Structure-Guided Design of Novel l-Cysteine Derivatives as Potent KSP Inhibitors

l-cysteine derivatives as selective KSP inhibitors. Here, we report further optimizations using docking modeling in the L5 allosteric binding site, which led to the discovery of several high affinity derivatives with two fused phenyl rings in the trityl group giving low nanomolar range KSP ATPase inhibition. The representative derivatives potently inhibited cell growth of HCT116 cells in correlation with KSP inhibitory activities and significantly suppressed tumor growth in the xenograft model in vivo.     

Changes in the prevalence of intestinal parasites among Japanese expatriates in developing countries]

In order to study the prevalence of intestinal parasites among Japanese expatriates of developing countries, we conducted fecal specimen examinations annually from 1995 to 2000. Fecal specimens were collected from Japanese expatriates of each area: Asia, the Middle East, East Europe, Africa and Latin America. The specimens were fixed with 10% formalin in the local area, and then examined in Japan. We used the formalin-ether sedimentation method to find protozoan cysts or helminth eggs. In 1995, the infection ratio was 3.0% (N = 981), decreasing to 2.4% (N = 1,275) in 1996, 2.3% (N = 1,620) in 1997 and 1.6% (N = 1,574) in 1998. However, the ratio began to increase in 1999 (2.0%, N = 1,713) and 2000 (2.5%, N = 1,806). The ratio in Africa was the highest in each year, followed by Asia and Latin America. Heterophyidae (51 cases), Giardia lamblia (42) and Trichuris trichiura (30) were detected most frequently. In Egypt, the ratio of Heterophyidae rose by 28.8% in 2000. This was the prime reason for the increase in the overall ratio of infections worldwide. Most of the Japanese infected with Heterophyidae in Egypt had ingested dried mullet roe. This may explain the reason for the increase in the infection ratio there. Although the prevalence of intestinal parasites among Japanese expatriates in developing countries is decreasing, those who eat fish in these areas are still at risk. In order to eradicate intestinal parasitosis from this group, we must continue preventive measures such as health education.     

Cryofiltration Apheresis for Major ABO-Incompatible Kidney Transplantation

Abstract: The barrier of ABO-incompatible kidney transplantation is the presence of anti-A and anti-B antibodies in the recipient's circulating blood. Double filtration plasmapheresis (DFPP) is usually used to eliminate those antibodies. We tried cryofiltration apheresis (CRYO) in 2 recipients. Patient 1 was a 45-year-old male with B, Rh(±). The titers of IgM anti-A antibody were only reduced from ×64 to ×32 by the end of 3 sessions of standard CRYO. Renal allografting was not performed. Case 2 was a 29-year-old male with B, Rh(+). CRYO was introduced for 3 sessions. The initial IgM and IgG titers were ×128 and negative, respectively. The standard CRYO system was modified by temperature, treated volume, and filter pore size. The IgM anti-A antibody titer was markedly reduced to ×2 after the final session of CRYO. The donor was a 56-year-old father with A, Rh(+). Tacrolimus, azathio-prine, methylprednisolone, and antilymphocyte globulin were used as the introductory immunosuppression therapy.     

Fibrous dysplasia of the maxilla: a case report together with its conventional imaging and dynamic magnetic resonance imaging findings

We previously reported that dynamic contrast-enhanced MRI parameters and time–signal intensity curves (TICs; also known as contrast index curves) are useful for the differential diagnosis of jawbone lesions. In particular, odontogenic fibroma and ossifying fibroma, which possess similar histopathological features (i.e., a mixture of hard and soft tissue components), display unique TIC patterns, and we consider that the TIC patterns of these lesions reflect their hard and soft tissue components. Therefore, fibrous dysplasia, which contains fibrous tissue and immature isolated trabeculae composed of woven bone, is expected to display an interesting TIC. The purpose of this study was to assess the utility of TICs for differentiating between the abovementioned lesions, which have similar histopathological components.     

Recombinant human interferon α-2b (rh IFNα-2b) therapy for steroid resistant idiopathic thrombocytopenic purpura (ITP)

The efficacy of recombinant human interferon α-2b (rh IFNα-2b) in the treatment of steroid resistant idiopathic thrombocytopenic purpura (ITP) was studied in 50 cases. Forty-one patients treated with rh IFNα-2b three times a week, six of 18 (33.3%) in the low dose group (150 × 10⁴IU: 3 MIU) and four of 20 (20.0%) in the high dose group (300 × 10¹⁰IU: 3 MIU) responded with platelet counts increasing to above 50 × 10⁹/L. Because of the exacerbation of thrombocytopenia and nasal bleeding, treatment was discontinued within 2 weeks in three patients out of 41 cases. On the other hand, six of nine patients (66.7%) treated with 3 MIU of IFNα-2b once a week for 8 weeks showed satisfactory response. Treatment with either administration schedule did not result in sustaining platelet counts above 50 × 10⁹/L for a long time after treatment. The results indicate that once a week administration schedule of rh IFNα-2b is more efficacious for platelet counts increasing for short period in patients who failed to respond to steroid and other medications than other schedules. The maintenance of this treatment schedule will allow sustained increased platelet levels, resulting in relief of bleeding tendency, while also being cost effective in comparison with other IFN treatment schedules and achieving better patient compliance without flu-like symptoms. © 1996 Wiley-Liss, Inc.     

Comparative allelotype of early and advanced stage non-small cell lung carcinomas

To identify chromosomal loci of tumor suppressor genes involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), comparative allelotype analysis was performed in 23 stage I primary lung tumors and in 22 metastatic lung tumors to the brain. In total, 84 loci on all 22 autosomal chromosomes were examined for loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) analysis with 40 polymorphic DNA probes and polymerase chain reaction (PCR)-LOH analysis of 44 polymorphic loci. LOH on chromosome arms 3p, 13q, and 17p was detected frequently (>60%) in both stage I primary lung tumors and brain metastases, whereas the incidence of LOH on chromosome arms 2q, 5q, 9p, 12q, 18q, and 22q was more than 60% only in brain metastases. In particular, the incidence of LOH on chromosome arms 2q, 9p, 18q, and 22q in brain metastases was significantly higher than that in stage I primary lung tumors (P < 0.05). These results indicate that tumor suppressor genes on chromosome arms 3p, 13q, and 17p are involved in the genesis of NSCLC, whereas those on several chromosome arms, especially on 2q, 9p, 18q and 22q, play an important role in the progression of NSCLC. Genes Chromosom Cancer 17:71–77 (1996). © 1996 Wiley-Liss, Inc.     

Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants

ObjectivePatients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments.MethodsWe recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis. We retrospectively reviewed clinical, electroencephalogram, neuroimaging, and genetic information.ResultsWe identified 29 patients (21 females, eight males). All patients showed severe developmental delay, especially in males. Involuntary movements were observed in 15 patients. No antiepileptic drugs (AEDs) achieved seizure freedom by monotherapy. AEDs achieving ≥ 50% reduction in seizure frequency were sodium valproate in two patients, vigabatrin in one, and lamotrigine in one. Seizure aggravation was observed during the use of lamotrigine, potassium bromide, and levetiracetam. Adrenocorticotrophic hormone (ACTH) was the most effective treatment. The ketogenic diet (KD), corpus callosotomy and vagus nerve stimulation did not improve seizure frequency in most patients, but KD was remarkably effective in one. The degree of brain atrophy on magnetic resonance imaging (MRI) reflected disease severity. Compared with females, males had lower levels of attained motor development and more severe cerebral atrophy on MRI.ConclusionOur patients showed more severe global developmental delay than those in previous studies and had intractable epilepsy, likely because previous studies had lower numbers of males. Further studies are needed to investigate appropriate therapy for CDD, such as AED polytherapy or combination treatment involving ACTH, KD, and AEDs.     

Surface phenotypic changes of spleen cells on acquisition of encephalitogenicity

The relationship between surface marker expression and encephalitogenicity of spleen cells was studied in Lewis rats. Donors were sensitized with either BP/CFA or BP/IFA, or given BP-cultured naive spleen cells. The adoptive transfer of EAE was successfully achieved in every case after culture with BP, although only spleen cells from BP/CFA-sensitized rats proliferated significantly in response to BP. The observed encephalitogenicities were BP/CFA-sensitized cells greater than BP/IFA-sensitized cells much greater than cells from recipients of BP-cultured naive cells in descending order. In BP/CFA-sensitized cells, the expression of both W3/25 and OX-3 antigens on T cells increased markedly after culture with BP, but the expression of neither OX-19 nor OX-8 antigen increased significantly. Cells from neither BP/IFA-sensitized rats nor recipients of BP-cultured naive cells showed a significant change in the surface marker expression after culture with BP. Therefore, the generation of T cells coexpressing large amounts of both W3/25 and OX-3 antigens after culture with BP seems to correspond to the acquisition of the strong encephalitogenicity in vivo.