Missense Variants in COL4A1/2 Are Associated with Cerebral Aneurysms: A Case Report and Literature Review.

BACKGROUND: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. METHODS: We described a family presenting with a novel variant of the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). RESULTS: This study included 53 COL4A1/2 variants from 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs. 58.1%, p = 0.0035) was identified in the CA-positive group. CONCLUSIONS: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small-vessel disease or other large-vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

Functional recoveries of patients with branch atheromatous disease after rehabilitation: Comparison with other types of cerebral infarction and importance of stratification by clinical categories.

BACKGROUND: Functional recoveries after rehabilitation of patients with branch atheromatous disease (BAD) have not been well investigated, however, clinical category of cerebral infarction including BAD itself could be a potential predictive factor for functional outcome. OBJECTIVE: To describe characteristics of functional recoveries of patients with BAD through comparison with other types of cerebral infarction. METHODS: We retrospectively compared outcomes of patients with BAD (N = 222), cardioembolic cerebral infarction (CE: N = 177) and atherothrombotic cerebral infarction (AT: N = 219) by using functional independence measure (FIM) and FIM effectiveness (the proportion of potential for improvement achieved). RESULTS: Univariate analysis showed that FIM on discharge was comparable among three types of cerebral infarction, but that FIM effectiveness in patients with BAD was significantly higher than those with CE or AT. Stratified analysis revealed higher FIM effectiveness in patients with BAD compared to patients with CE or AT, if they were male, younger (≤72 years) or had supratentorial brain lesions. Multiple regression analysis demonstrated that location of the brain lesion (supratentorial vs infratentorial) and gender (male vs female) were significantly associated with FIM on discharge, and that cognitive function on admission as well as gender were significantly associated with FIM effectiveness in patients with BAD, but not in patients with CE or AT. CONCLUSIONS: Outcomes after rehabilitation of patients with BAD may be characterized by better functional improvement, especially if patients are male, relatively younger or with supratentorial lesions. The impact and the type of factors related to functional recoveries of patients with BAD may be different from other types of stroke. The present study suggested that clinical category of stroke should be taken into consideration in prediction of outcomes and planning of rehabilitation management.

Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus.

Spontaneous hhy mice show hydrocephalus and subcortical heterotopia, and a mutation in the Ccdc85c gene has been identified. To contribute to the comparison of the role of Ccdc85c in different species, we established a Ccdc85c KO rat and investigated its pathological phenotypes. Ccdc85c KO rats were produced by genomic engineering using transcription activator-like effector nuclease (TALEN). The KO rats had an approximately 350-bp deletion in Ccdc85c and lacked CCDC85C protein expression. The KO rats showed non-obstructive hydrocephalus, subcortical heterotopia, and intracranial hemorrhage. The KO rats had many pathological characteristics similar to those in hhy mice. These results indicate that CCDC85C plays an important role in cerebral development in rats, and the function of CCDC85C in the cerebrum are similar in rats and mice.

Multiple cerebral syphilitic gummas mimicking brain tumor in a non-HIV-infected patient: A case report.

We present a unique case of symptomatic early neurosyphilis in a non-HIV-infected patient. A 47-year-old man with a history of diabetes mellitus presented with generalized seizures. He did not manifest any neurological deficits. At first, multiple brain tumors were suspected based on findings from magnetic resonance imaging of the brain. However, serological and cerebrospinal fluid tests for syphilis yielded positive results, and the masses were reduced using amoxicillin. Multiple cerebral syphilitic gummas were therefore diagnosed. High-dose penicillin therapy was initiated and syphilitic gummas disappeared after five months. Treponema pallidum could invade the central nervous system at an early phase, and sometimes may be difficult to distinguish from malignant brain tumor. If intracranial lesions are identified in a syphilis-infected patient, cerebral syphilitic gumma should be considered as a differential diagnosis.

Lambert-Eaton Myasthenic Syndrome Caused by Nivolumab in a Patient with Squamous Cell Lung Cancer.

Lambert-Eaton myasthenic syndrome (LEMS) is a representative paraneoplastic neurological syndrome. Recently, nivolumab, an anti-programmed cell death 1 inhibitor, has been approved for advanced non-small-cell lung cancer. Careful attention should be paid to immune-related adverse events (irAEs), including neurotoxicity. We herein report a 73-year-old woman with LEMS that occurred during nivolumab treatment for pulmonary squamous cell carcinoma. After the 20th week of nivolumab, she experienced various neurological symptoms such as ptosis, lower limb weakness, and photophobia. Findings from a nerve conduction study and a positive anti-P/Q-type voltage-gated calcium channel antibody made a diagnosis of LEMS. Pyridostigmine and 3,4-diaminopyridine temporarily improved her symptoms. This was the first case of LEMS as a neurological irAE. LEMS should be considered as a possible neurological irAE.

Spontaneous nephroblastoma with striated muscle differentiation in an F344 rat.

An eleven-month old male F344/DuCrj (F344) rat was found dead and had right kidney mass at necropsy. Histopathologically, the mass was composed of nests of neoplastic stellate cells. At the center of the nests, neoplastic epithelial cells formed a tubular structure. In the fibrous connective tissue surrounding the nests, neoplastic cells with striations demonstrable by phosphotungstic acid hematoxylin were observed. Immunohistochemically, neoplastic stellate cells were partially positive for Wilms Tumor 1 and vimentin, and neoplastic cells with striations were partially positive for desmin. We diagnosed this tumor as a nephroblastoma with striated muscle differentiation. To our knowledge, this is the first case of nephroblastoma with apparent striated muscle differentiation in an F344 rat.

SRPP, a Cell Wall Protein is Involved in Development and Protection of Seeds and Root Hairs in Arabidopsis thaliana.

Enhancement of root hair development in response to phosphate (Pi) deficit has been reported extensively. Root hairs are involved in major root functions such as the absorption of water, acquisition of nutrients and secretion of organic acids and enzymes. Individual root hair cells maintain these functions and appropriate structure under various physiological conditions. We carried out a study to identify protein(s) which maintain the structure and function of root hairs, and identified a protein (SEED AND ROOT HAIR PROTECTIVE PROTEIN, SRPP) that was induced in root hairs under Pi-deficient conditions. Promoter assay and mRNA quantification revealed that SRPP was expressed in root hairs and seeds. A knockout mutant, srpp-1, consistently displayed defects in root hairs and seeds. Root hairs in srpp-1 were short and the phenotypes observed under Pi-deficient conditions were also detected in ethylene-treated srpp-1 plants. Propidium iodide stained most root hairs of srpp-1 grown under Pi-deficient conditions, suggesting cell death. In addition to root hairs, most srpp-1 seeds were withered and their embryos were dead. SRPP tagged with green fluorescent protein was detected in the cell wall. Electron microscopy showed abnormal morphology of the cell wall. Wild-type phenotypes were restored when the SRPP gene was expressed in srpp-1. These data strongly suggest that SRPP contributes to the construction of robust cell walls, whereby it plays a key role in the development of root hairs and seeds.

Expression of Ccdc85C, a causative protein for murine hydrocephalus, in the mammary gland tumors of dogs.

Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for hemorrhagic hydrocephalus mouse which shows hydrocephalus with frequent brain hemorrhage and formation of subcortical band heterotopia. A previous study revealed that Ccdc85C protein is expressed in the systemic simple epithelial cells with proliferative activity in rats and suggested that Ccdc85C expression may be related to the cell proliferation of simple epithelial cells. To reveal the roles of Ccdc85C in the proliferative lesion, we examined the expression patterns of Ccdc85C in the mammary gland tumor of dogs, a common representative tumor derived from simple epithelial cells. In canine mammary gland tumors, Ccdc85C was expressed at the apical junctions of the luminal epithelial cells. Ccdc85C was also distributed throughout the entire cytoplasm of the myoepithelial cells. Ccdc85C expression was observed at the epithelial cells with luminal structures, but was not observed at the epithelial cells forming sheet growth pattern without luminal structure. In carcinomas, Ccdc85C expression in mammary tumor tissue tended to be weaker than that in surrounding normal mammary gland tissue. Ccdc85C is known to cause neurological diseases such as hydrocephalus, and subcortical heterotopia, and the present study is the first to demonstrate Ccdc85C expression in canine mammary tumors and a relationship between Ccdc85C expression and tumor malignancy.

Titanium Dioxide Particle Type and Concentration Influence the Inflammatory Response in Caco-2 Cells.

Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreens, biomedicine, and food products. When used as a food additive, TiO2 nanoparticles are used in significant amounts as white food-coloring agents. However, the effects of TiO2 nanoparticles on the gastrointestinal tract remain unclear. The present study was designed to determine the effects of five TiO2 particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Twenty-four-hour exposure to anatase (primary particle size: 50 and 100 nm) and rutile (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner in THP-1 macrophages, but in not Caco-2 cells. However, 72-h exposure of Caco-2 cells to anatase (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner. The highest dose (50 µg/mL) of anatase (100 nm), rutile (50 nm), and P25 TiO2 particles also reduced cellular viability in Caco-2 cells. The production of reactive oxygen species tended to increase in both types of cells, irrespective of the type of TiO2 particle. Exposure of THP-1 macrophages to 50 µg/mL of anatase (50 nm) TiO2 particles increased interleukin (IL)-1ß expression level, and exposure of Caco-2 cells to 50 µg/mL of anatase (50 nm) TiO2 particles also increased IL-8 expression. The results indicated that anatase TiO2 nanoparticles induced inflammatory responses compared with other TiO2 particles. Further studies are required to determine the in vivo relevance of these findings to avoid the hazards of ingested particles.

A novel-type phosphatidylinositol phosphate-interactive, Ca-binding protein PCaP1 in Arabidopsis thaliana: stable association with plasma membrane and partial involvement in stomata closure.

The Ca(2+)-binding protein-1 (PCaP1) of Arabidopsis thaliana is a new type protein that binds to phosphatidylinositol phosphates and Ca(2+)-calmodulin complex as well as free Ca(2+). Although biochemical properties, such as binding to ligands and N-myristoylation, have been revealed, the intracellular localization, tissue and cell specificity, integrity of membrane association and physiological roles of PCaP1 are unknown. We investigated the tissue and intracellular distribution of PCaP1 by using transgenic lines expressing PCaP1 linked with a green fluorescence protein (GFP) at the carboxyl terminus of PCaP1. GFP fluorescence was obviously detected in most tissues including root, stem, leaf and flower. In these tissues, PCaP1-GFP signal was observed predominantly in the plasma membrane even under physiological stress conditions but not in other organelles. The fluorescence was detected in the cytosol when the 25-residue N-terminal sequence was deleted from PCaP1 indicating essential contribution of N-myristoylation to the plasma membrane anchoring. Fluorescence intensity of PCaP1-GFP in roots was slightly decreased in seedlings grown in medium supplemented with high concentrations of iron for 1 week and increased in those grown with copper. In stomatal guard cells, PCaP1-GFP was strictly, specifically localized to the plasma membrane at the epidermal-cell side but not at the pore side. A T-DNA insertion mutant line of PCaP1 did not show marked phenotype in a life cycle except for well growth under high CO2 conditions. However, stomata of the mutant line did not close entirely even in high osmolarity, which usually induces stomata closure. These results suggest that PCaP1 is involved in the stomatal movement, especially closure process, in leaves and response to excessive copper in root and leaf as a mineral nutrient as a physiological role.

Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients.

A phase I study of a new cancer vaccine (KRM-10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose-limiting toxicity (DLT), or safety and immune responses, respectively. Peptide-specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty-one patients were vaccinated with KRM-10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment-related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM-10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.

Detection of Multiple Budding Yeast Cells and a Partial Sequence of 43-kDa Glycoprotein Coding Gene of Paracoccidioides brasiliensis from a Case of Lacaziosis in a Female Pacific White-Sided Dolphin (Lagenorhynchus obliquidens).

Lacaziosis, formerly called as lobomycosis, is a zoonotic mycosis, caused by Lacazia loboi, found in humans and dolphins, and is endemic in the countries on the Atlantic Ocean, Indian Ocean and Pacific Ocean of Japanese coast. Susceptible Cetacean species include the bottlenose dolphin (Tursiops truncatus), the Indian Ocean bottlenose dolphin (T. aduncus), and the estuarine dolphin (Sotalia guianensis); however, no cases have been recorded in other Cetacean species. We diagnosed a case of Lacaziosis in a Pacific white-sided dolphin (Lagenorhynchus obliquidens) nursing in an aquarium in Japan. The dolphin was a female estimated to be more than 14 years old at the end of June 2015 and was captured in a coast of Japan Sea in 2001. Multiple, lobose, and solid granulomatous lesions with or without ulcers appeared on her jaw, back, flipper and fluke skin, in July 2014. The granulomatous skin lesions from the present case were similar to those of our previous cases. Multiple budding and chains of round yeast cells were detected in the biopsied samples. The partial sequence of 43-kDa glycoprotein coding gene confirmed by a nested PCR and sequencing, which revealed a different genotype from both Amazonian and Japanese lacaziosis in bottlenose dolphins, and was 99 % identical to those derived from Paracoccidioides brasiliensis; a sister fungal species to L. loboi. This is the first case of lacaziosis in Pacific white-sided dolphin.

Rat malignant fibrous histiocytoma (MFH)-derived cloned cell lines (MT-8 and MT-9) show different differentiation in mesenchymal stem cell lineage.

Malignant fibrous histiocytomas (MFHs) show a storiform growth pattern consisting of fibroblastic, histiocytic and undifferentiated mesenchymal cells with possible multipotency. Because MFH-like tumors are induced experimentally by some chemicals and materials, it is important to know the histogenesis of MFHs. We analyzed in vitro and in vivo characteristics of two cloned cell lines (MT-8 and MT-9) established from a spontaneous MFH found in an aged F344 rat. MT-8 and MT-9 cultured cells and their tumors induced in syngeneic rats by injection were investigated morphologically, and their tumors were evaluated by immunohistochemistry. Gene expression profiles of their cultures and induced tumors were analyzed by the comprehensive gene analysis. MT-8 cells had less developed organelles and the induced tumors represented histological characteristics of undifferentiated sarcoma (sarcoma not otherwise specified (NOS)), whereas MT-9 cells had relatively well-developed intracytoplasmic organelles such as endoplasmic reticulum, mitochondria and lysosomes and the tumors showed a storiform growth pattern typical of MFHs. MT-8 and MT-9 tumors were immuno-positive for vimentin, and the reactivity for stem cell markers (nestin, CD90, CD34, and A3) appeared to be greater in MT-9 tumor cells, and their tumor cells did not react to markers for well-differentiated cells of epithelial, myogenic and neurogenic tissues except for faint reaction for S-100 protein in MT-9 tumors. The gene analyses revealed that genes relating to "cell differentiation" were more activated in MT-9 than MT-8 tumors, whereas those involved in "cell cycle" were greater in MT-8 than MT-9 tumors. In MT-8 and MT-9, additionally, genes involved in "cell differentiation" were much greater in their tumors than in their cultures. These findings indicate that MT-8 cells are poorly differentiated mesenchymal stem cells which induce sarcomas NOS, whereas MT-9 cells, which can develop typical MFHs, have more differentiated stem cell nature with greater multipotential differentiation. In MFHs, collectively, MT-8 and MT-9 cells are regarded as "tumor stem cells" and "tumor precursors" in the stem cell lineage, respectively, according to the concept of "cancer stem cell theory".

Ccdc85C, a causative protein for hydrocephalus and subcortical heterotopia, is expressed in the systemic epithelia with proliferative activity in rats.

Coiled-coil domain containing 85c (Ccdc85c) is a causative gene for spontaneous mutant mouse with non-obstructive hydrocephalus and subcortical heterotopia. Detailed functions of Ccdc85C protein have not been clarified. To reveal roles of Ccdc85C, we examined the distribution and expression pattern of Ccdc85C in the systemic developing organs in rats. Ccdc85C was expressed in various simple epithelia but not stratified epithelia. In the various epithelia, Ccdc85C was localized at cell-cell junctions and its expression was strong at apical junctions. Furthermore, intense expression was seen at developing period and gradually decreased with advancing development. Distribution of Ccdc85C coincides with that of proliferating epithelial cells. These results suggest that Ccdc85C plays an important role in the proliferative property of simple epithelia.

Fecoflowmetric analysis of anorectal motor function in postoperative anal-preserving surgery patients with low rectal cancer comparison with the wexner score and anorectal manometry.

The aim of this study was to elucidate whether fecoflowmetry (FFM) could evaluate more detailed evacuative function than anorectal manometry by comparing between FFM or anorectal manometric findings and the clinical questionnaires and the types of surgical procedure in the patients who received anal-preserving surgery. Fifty-three patients who underwent anal-preserving surgery for low rectal cancer were enrolled. The relationships between FFM or the manometric findings and the clinical questionnaires and the types of procedure of anal-preserving surgery were evaluated. There were significant differences between FFM markers and the clinical questionnaire and the types of the surgical procedure, whereas no significant relationship was observed between the manometric findings and the clinical questionnaire and the types of the surgical procedure. FFM might be feasible and useful for the objective assessment of evacuative function and may be superior to manometry for patients undergoing anal-preserving surgery.

Characterization of the histidine-rich loop of Arabidopsis vacuolar membrane zinc transporter AtMTP1 as a sensor of zinc level in the cytosol.

The vacuolar Zn(2+)/H(+) antiporter of Arabidopsis thaliana, AtMTP1, has a long cytosolic histidine-rich loop. A mutated AtMTP1 in which the first half of the loop (His-half) was deleted exhibited a 11-fold higher transport velocity in yeast cells. Transgenic lines overexpressing the His-half-deleted AtMTP1 in the loss-of-function mutant were evaluated for growth and metal content in the presence of various zinc concentrations. These overexpressing lines (35S-AtMTP1 and 35S-His-half lines) showed high tolerance to excess concentrations of zinc at 150 µM, as did the wild type, compared with the loss-of-function line. The His-half AtMTP1 transported cobalt in a heterologous expression assay in yeast, but the cumulative amount of cobalt in 35S-His-half plants was not increased. Moreover, the accumulation of calcium and iron was not changed in plants. Under zinc-deficient conditions, growth of 35S-His-half lines was markedly suppressed. Under the same conditions, the 35S-His-half lines accumulated larger amounts of zinc in roots and smaller amounts of zinc in shoots compared with the other lines, suggesting an abnormal accumulation of zinc in the roots of 35S-His-half lines. As a result, the shoots may exhibit zinc deficiency. Taken together, these results suggest that the His-loop acts as a sensor of cytosolic zinc to maintain an essential level in the cytosol and that the dysfunction of the loop results in an uncontrolled accumulation of zinc in the vacuoles of root cells.

Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer.

The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days, with 1- and 2-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of prevaccination factors showed that plasma IL6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR), 1.508, P = 0.043; HR, 1.579, P = 0.024; HR, 0.509, P = 0.002, respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR, 0.231; P = 0.021), suggesting a causal relationship between biologic and clinical efficacy of PPV. On the basis of the safety profile and potential clinical efficacy, we believe that clinical trials of PPV would be warranted for previously treated patients with aCRC.

Minichromosome maintenance protein 7 is a risk factor for recurrence in patients with Dukes C colorectal cancer.

BACKGROUND: It has been hypothesized that minichromosome maintenance (MCM) proteins, which are replicative control factors, can be used to detect tumor proliferation. The aim of the present study was to investigate the expression of MCM in colorectal cancer tissues and correlate it to clinical outcomes. PATIENTS AND METHODS: The study included 145 patients with colorectal cancer who underwent curative surgery, from January 2002 until December 2004, at the Kurume University Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The expression of MCM7 in tissues was studied by immuno-histochemical staining. The labeling index (LI) of MCM7 was calculated by dividing the number of positively-stained cells by the total number of cells counted. We divided samples into two groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%). RESULTS: In patients with Dukes A and B, there were no significant differences in either overall survival (OS) or recurrence-free survival (RFS) between patents with MCM7-positive and those with MCM7-negative disease. On the other hand, in patients with Dukes C, there was significantly worse OS and RFS for patients with MCM7-positive compared to those with MCM7-negative disease. CONCLUSION: We found that the expression of MCM7 is an independent risk factor for RFS in patients with Dukes C colorectal cancer. Further studies are required to investigate the validity of MCM7 protein expression for its potential clinical use in colorectal cancer therapy and prognosis.

Characteristics of a root hair-less line of Arabidopsis thaliana under physiological stresses.

The plasma membrane-associated Ca(2+)-binding protein-2 of Arabidopsis thaliana is involved in the growth of root hair tips. Several transgenic lines that overexpress the 23 residue N-terminal domain of this protein under the control of the root hair-specific EXPANSIN A7 promoter lack root hairs completely. The role of root hairs under normal and stress conditions was examined in one of these root hair-less lines (NR23). Compared with the wild type, NR23 showed a 47% reduction in water absorption, decreased drought tolerance, and a lower ability to adapt to heat. Growth of NR23 was suppressed in media deficient in phosphorus, iron, calcium, zinc, copper, or potassium. Also, the content of an individual mineral in NR23 grown in normal medium, or in medium lacking a specific mineral, was relatively low. In wild-type plants, the primary and lateral roots produce numerous root hairs that become elongated under phosphate-deficient conditions; NR23 did not produce root hairs. Although several isoforms of the plasma membrane phosphate transporters including PHT1;1-PHT1;6 were markedly induced after growth in phosphate-deficient medium, the levels induced in NR23 were less than half those observed in the wild type. In phosphate-deficient medium, the amounts of acid phosphatase, malate, and citrate secreted from NR23 roots were 38, 9, and 16% of the levels secreted from wild-type roots. The present results suggest that root hairs play significant roles in the absorption of water and several minerals, secretion of acid phosphatase(s) and organic acids, and in penetration of the primary roots into gels.

Primary cerebral T-cell lymphoma in a sea otter (enhydra lutris).

A 10-year-old female sea otter exhibited convulsions, arrhythmia, hyperthermia, forced breathing and anorexia and died after a week. Histopathological examination revealed neoplastic proliferation of small round cells with scant cytoplasm and round or oval nuclei distributed mainly in the thalamus. The proliferation of neoplastic cells was observed in the cerebral parenchyma and perivascular areas. The neoplastic cells were immunopositive for CD3, but not CD20. No neoplastic proliferation of T-cells was found in other organs. Taken together, we diagnosed this case as a primary cerebral T-cell lymphoma. To our knowledge, this is the first case of primary cerebral T-cell lymphoma in a sea otter.