Neurological manifestations in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis in the Amazon.

STUDY DESIGN: A cross-sectional observational study was conducted. OBJECTIVE: The aim was to analyze the clinical-functional profile of patients diagnosed with HTLV-1 (human T-lymphotropic virus type 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in the Amazon region. SETTING: Reference center for HTLV in the city of Belém, state of Pará, Brazil. METHODS: Muscle strength, muscle tone, balance and the need for gait assistance among patients with HAM/TSP were evaluated. RESULTS: Among the 82 patients infected with HTLV-1, 27 (10 men and 17 women) were diagnosed with HAM/TSP. No statistically significant difference in muscle tone or strength was found between the lower limbs. Muscle weakness and spasticity were predominant in the proximal lower limbs. Patients with HAM/TSP are at a high risk of falls (P=0.03), and predominantly use either a cane or a crutch on one side as a gait-assistance device (P=0.02). CONCLUSION: Patients with HAM/TSP exhibit a similar clinical pattern of muscle weakness and spasticity, with a high risk of falls, requiring gait-assistance devices.

Asef, a link between the tumor suppressor APC and G-protein signaling.

The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.

Relation of dietary preference to bite force and occlusal contact area in Japanese children.

The purpose of this study was to examine the relationship of dietary preference to bite force and occlusal contact area in Japanese elementary school children. A total of 348 children, aged 7-12 years, from two public elementary schools located in Okayama Prefecture, Japan, participated in the study. Clinical examination included decayed, missing and filled teeth (dmft and DMFT), and total numbers of deciduous and permanent teeth. Bite force and occlusal contact area were measured using a pressure-detecting sheet. Dietary preference was assessed using a questionnaire in which the answers were given in like/dislike form. Mann-Whitney U-test and multiple logistic regression analysis were applied to analyse the data. In multiple logistic regression analysis after adjustment for age, gender and total number of teeth present, children who liked cabbage and celery showed significantly higher bite force (P = 0.05 and P < 0.01, respectively) than those who disliked these. Children who liked cabbage and celery also showed higher occlusal contact area (P < 0.05 and P < 0.01, respectively) than those who disliked these. The Japanese elementary school children who liked hard foods such as cabbage and celery showed higher bite force and higher occlusal contact area than those who disliked these foods. A positive attitude towards harder food items might contribute to healthy development of the masticatory apparatus.

Relationship between body mass index and periodontitis in young Japanese adults.

BACKGROUND AND OBJECTIVE: Obesity has been implicated as a risk factor for several chronic health conditions. Recent studies have reported a relationship between obesity and periodontitis, but few studies have investigated this relationship in adolescents. The purpose of the present study was to investigate the relationship between body composition (i.e. body mass index and body fat) and periodontitis in university students in Japan. MATERIAL AND METHODS: Medical and oral health data were collected in a cross-sectional examination conducted by the Health and Environment Center of Okayama University. Students aged 18-24 years (n = 618), who were interested in receiving an oral health examination, were included in the analysis. The community periodontal index was used to assess periodontal status. Subjects with a community periodontal index score of 0-2 were considered as controls and those with a community periodontal index score of > 2 were considered to have periodontitis. Logistic regression analysis was used to estimate the association between body mass index and periodontitis. RESULTS: The body mass index of all subjects was < 30 kg/m2. Age and body mass index were significantly associated with the community periodontal index. Logistic regression analysis revealed a 16% increased risk for periodontitis per 1-kg/m2 increase in body mass index (adjusted odds ratio, 1.16; 95% confidence interval, 1.03-1.31; p < 0.05). CONCLUSION: Body mass index could be a potential risk factor for periodontitis among healthy young individuals (i.e. those with a body mass index of < 30 kg/m2). It may be useful to include an evaluation of body mass index on a regular basis in university general and oral health examinations.

Neonatally born granule cells numerically dominate adult mice dentate gyrus.

Hippocampal granule cells (GCs) are continuously generated in the subgranular zone of the dentate gyrus (DG) and functionally incorporated to dentate neural circuits even in adulthood. This raises a question about the fate of neonatally born GCs in adult DG. Do they exist until adulthood or are they largely superseded by adult-born GCs? To investigate this question, we examined the contributions of postnatally born GCs to the adult mouse DG. C57BL/6 mice were grouped in three different postnatal (P) ages (group 1: P0, group 2: P7, and group 3: P35) and received a daily bromodeoxyuridine (BrdU) injection for three consecutive days (P0/1/2, P7/8/9, and P35/36/37, respectively) to label dividing cells. At 6 months old, hippocampal sections were prepared from the animals and immunostained with anti-BrdU antibody and an antibody against the homeobox prospero-like protein Prox1, a marker of GCs. We defined BrdU- and Prox1-double positive cells as newborn GCs and analyzed their density and distribution in the granule cell layer (gcl), revealing that newborn GCs of each group still existed 6 months after BrdU injections and that the density of GCs born during P0-2 (group 1) was significantly higher compared with the other groups. Although the density of newborn GCs in the each group did not differ between male and female, the radial distribution of them in gcl showed some differences, that is, male newborn GCs localized toward the molecular layer compared with female ones in group 1, while to the hilus in group 2. These results suggest that GCs born in early postnatal days numerically dominate adult DG and that there exist sex differences in GC localizations which depend on the time when they were born.

Experimental febrile seizures induce age-dependent structural plasticity and improve memory in mice.

Population-based studies have demonstrated that children with a history of febrile seizure (FS) perform better than age-matched controls at hippocampus-dependent memory tasks. Here, we report that FSs induce two distinct structural reorganizations in the hippocampus and bidirectionally modify future learning abilities in an age-dependent manner. Compared with age-matched controls, adult mice that had experienced experimental FSs induced by hyperthermia (HT) on postnatal day 14 (P14-HT) performed better in a cognitive task that requires dentate granule cells (DGCs). The enhanced memory performance correlated with an FS-induced persistent increase in the density of large mossy fiber terminals (LMTs) of the DGCs. The memory enhancement was not observed in mice that had experienced HT-induced seizures at P11 which exhibited abnormally located DGCs in addition to the increased LMT density. The ectopic DGCs of the P11-HT mice were abolished by the diuretic bumetanide, and this pharmacological treatment unveiled the masked memory enhancement. Thus, this work provides a novel basis for age-dependent structural plasticity in which FSs influence future brain function.

GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice.

Autologous transplantation of bone marrow cells (BMCs) transduced with the multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has already been applied in clinical chemoprotection trials. However, anticancer drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, are not relevant to MDR1 or DHFR gene products. In this context, we have previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced human CD34(+) cells showed resistance in vitro against 4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the present study, a subsequent attempt was made in a murine model to evaluate the effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow against high-dose CY. The gene transfection was carried out retrovirally, employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM was 30%. After the transplantation, recipient mice (GST-pi mice) received three sequential courses of high-dose CY. As the chemotherapy courses advanced, both shortening of recovery period from WBC nadir and shallowing of WBC nadir were observed. In contrast to the fact that three of seven control mice died, possibly due to chemotoxicity, all seven GST-pi mice were alive after the third course, at which point the vector GST-pi gene was detected in 50% of CFU-GM derived from their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from BMCs showed positive signals for vector GST-pi DNA after 6 months. These data indicate that the GST-pi gene can confer resistance to bone marrow against CY by being transduced into long-term repopulating cells.

A case of diffuse large B-cell lymphoma transformed from immunoglobulin A-producing marginal zone B-cell lymphoma.

We present a rare case of diffuse large B-cell lymphoma transformed from immunoglobulin (Ig) A-secreting marginal zone B-cell lymphoma. A 62-year-old woman was admitted to our hospital for examination of a disseminated pulmonary shadow. Gradual swelling of bilateral axilla and right inguinal lymph nodes were noted after admission. Histological examination of the lymph node biopsy specimen revealed the appearance of marginal zone B-cell lymphoma. The surface Ig of lymphoma cells was IgA-kappa, which coincided with the class of monoclonal Ig found in the patient's serum. The lymph node swelling and pulmonary shadow subsided, and the serum IgA level was normalized by 3 courses of systemic chemotherapy. However, after 4 courses of treatment, new tumor lesions at the right chest wall and left arm progressively became apparent. The biopsy specimen of the tumor showed a feature of diffuse large B-cell lymphoma. Despite intensive chemotherapy, the patient died of spreading tumor burden into the central nervous system.

Effect of caffeine on ibuprofen-induced gastric mucosal damage in rats.

During investigations on the effect of caffeine on ibuprofen-induced gastric mucosal lesions in rats, we have found that caffeine (p.o.) inhibits the development of ibuprofen-induced gastric lesions in a dose-dependent manner (ED50 18.4 mg kg(-1)). To investigate this protective effect of caffeine, we have studied the effect of caffeine on HCl-ethanol-induced gastric mucosal lesions with or without indomethacin pretreatment. Caffeine inhibited the development of HCl-ethanol-induced gastric lesions with and without indomethacin pretreatment. These results indicate that caffeine did not act as a mild irritant but, on the contrary, had protective effects. We measured the gastric mucosal prostaglandin E2 (PGE2) concentrations and gastric mucosal blood flow, as representative protective factors for gastric mucosa. Caffeine did not affect the gastric mucosal PGE2 concentrations 4h after administration of ibuprofen. However, topical administration of caffeine resulted in an increase in gastric mucosal blood flow, as measured by laser Doppler flowmetry. We investigated the gastric acid secretion and gastric mucosal myeloperoxidase activity as representative aggressive factors for gastric mucosa. When caffeine was administered intraduodenally in pylorus-ligated rats, gastric acid secretion decreased in a dose-dependent manner, with an ED50 of 44.9 mg kg(-1). Caffeine decreased ibuprofen-induced gastric myeloperoxidase activity in a dose-dependent manner, with an ED50 of 9.1 mg kg(-1). These findings indicate that caffeine, at least in rats, may inhibit the development of acute gastric mucosal injury. The mechanisms underlying the protective actions of caffeine are unclear, but may be related in part to an increase in gastric mucosal blood flow and suppression of neutrophil activation.

Novel variable-temperature chuck for use in the detection of deep levels in processed semiconductor wafers.

This paper describes the design, construction, and characterization of a variable-temperature wafer apparatus for use in the detection of electrically active defects which produce deep levels in the band gap of silicon. In its present form, the wafer chuck can heat and cool wafers as large as 51 mm in diameter over the temperature range from -196 degrees to 350 degrees C. Heating rates as high as 7 degrees C/s have been achieved. Sensitivity for electrical measurements is sufficient to allow current measurements as low as 0.2 pA or capacitance changes (1 MHz) as small as 5 fF. The use of this apparatus is illustrated by wafer mapping the gold defect density in diodes fabricated across a silicon wafer.

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

[A case of pulmonary tuberculosis with HIV infection--review of 5 cases in Japan].

Recently we encountered a case of pulmonary tuberculosis with HIV infection. The patient was 54-years old male. His chief complaints were anemia, emaciation and severe diarrhea. He was admitted to our hospital on September 18, 1992. He had been diagnosed in another clinic as having pulmonary tuberculosis before the admission to our hospital. His chest films taken on admission revealed homogeneous infiltrates with cavitation in right upper lobe. Serial chest X-rays consisted with the findings of post-primary tuberculosis. Sputum smear for acid fast bacilli was positive. From his clinical manifestations and life-history, we had a suspicion that he had infected with HIV. Laboratory findings were as follows: serum albumin level was 1.9 g/dl, CRP was 10.2 mg/dl, serological tests for HIV were positive by EIA, IFA and western blott method, total lymphocyte count was 819/microliters, CD4+ T lymphocyte count was 120/microliter CD4+/CD8+ ratio was 0.2. He was treated with AZT, isoniazid, streptomycin and rifampicin. The disease progressed rapidly and interstitial pneumonia, jaundice and clouding of consciousness appeared at the terminal stage. He expired on October 14, 1992. In this paper, the authors reported a case of pulmonary tuberculosis with HIV infection and also reviewed 5 cases of pulmonary tuberculosis associated with HIV in Japan.

[Follicular lymphoma associated with t(14;18)(q32;q21) chromosome translocation and bcl-2 gene rearrangement: report of a case].

A 31-year-old Japanese male who complained of low-grade fever, fatigue and generalized lymphadenopathy had shown an increase in peripheral white cell count, and 84% of peripheral blood cell and 76% of nuclear bone marrow cells consisted of small cleaved lymphoblastic abnormal cells with or without barely visible nucleoli. Cytogenic study of cervical lymph node biopsy specimens showed a t(14;18)(q32;q21) chromosome translocation. Histologically the lymph node cells were classified according to the International Working Formulation as follicular small cleaved-cell lymphoma. Molecular analysis of DNA fragments of peripheral lymphocytes revealed both J-H gene and bcl-2 oncogene rearrangements. Immunophenotypes of peripheral lymphocytes, bone marrow cells and lymph node cells expressed a clonally distinct B-cell population bearing surface immunoglobulin-G, kappa-chain, CD-10, CD-19, CD-20, CD-21 and OKIa-1 antigens. We diagnosed this case as follicular lymphoma in the leukemic phase,

[Successful high-dose chemotherapy combined with autologous bone marrow transplantation in a case of refractory follicular lymphoma].

A 34-year-old patient with follicular lymphoma who was treated with CHOP followed by COPP for 3 years, became resistant to treatment in December 1993. Histological findings and surface markers of cervical lymph node cells revealed no change from previous findings. Tumor cell involvement of bone marrow was also observed by molecular analysis of DNA fragments with bcl-2 oncogene and J-H gene probes. Following 2 courses of salvage chemotherapy with NOAC-M regimen (novantrone, cytarabine and methylprednisolone), There was an 88% reduction of tumor mass on computed tomographic findings. Through the use of polymerase chain reaction analysis of residual cells with the bcl-2 translocation, we confirmed the in vivo purging of tumor cells from bone marrow and we harvested marrow cells for autologous transplantation. After high-dose chemotherapy (HDC) with ranimustine, cisplatin, etoposide and cyclophosphamide followed by bone marrow transplantation (BMT), complete remission was achieved. The patient has survived for 16 months and remains disease free. The standard chemotherapy regimen for advanced low grade non-Hodgkin's lymphoma has not yet been defined. Although we must follow this patient carefully to determine the effect of HDC with BMT for a long time, this seems to be an effective complementary treatment for patients responding to conventional salvage regimens.

[Sézary syndrome showing a stable clinical course for more than four years after oral administration of etoposide and methotrexate].

A 62-year-old woman was admitted because of leukocytosis, systemic lymph node swelling and erythroderma. Laboratory data disclosed a WBC count of 15,600/microliter (CD4-positive cells: 91%). CD25 and HTLV-1 were negative. A skin biopsy revealed the involvement of T cells. These data and findings were consistent with a diagnosis of Sézary syndrome. Although the patient was treated with 2 courses of CHOP, the leukocyte count did not decrease. We then treated the patient orally with etoposide (25 mg/day) and methotrexate (10 mg/week), and this resulted in reduction of the leukocyte count and lymph node swelling, and amelioration of the erythroderma. As Sézary syndrome is an extremely rare disease, it is worthwhile reporting cases like the present one, where therapy was successful.

[IBL like T cell lymphoma associated with hemolytic anemia and polyploidy chromosomal abnormality--a case report].

A 56-year-old man was admitted to Sapporo Kitano Hospital on May 30, 1987 because of fever, retention of ascites and pleural effusion, generalized lymphnode swelling and hepatosplenomegaly. Laboratory findings showed Coombs' positive hemolytic anemia, leukocytosis and polyclonal hypergammaglobulinemia. Serological test included positive RA factor, anti-DNA 16 U/ml, thyroglobulin Ab 1600 x and microsome Ab 3200 x. A cervical lymphnode specimen exhibited typical histologic picture of IBL like T cell lymphoma. The surface markers of lymphoma cells were CD2(+), CD8(+) and CD4(-). Chromosomal analysis of these cells revealed polyploidy abnormality for all chromosomes except for No. 14's which are disomy. All lymphoma cells have XXY sex chromosome and mar1, mar2, mar3. Gene rearrangement for beta-chain of T cell receptor was proved in these lymphoma cells. He was treated with prednisolone, vincristine, cyclophosphamide, adriamycin etc, but died of respiratory failure 171 days after admission. We reported a rare case of IBL like T cell lymphoma with polyploidy chromosomal abnormality accompanied with hemolytic anemia.

[A case of pure red cell aplasia accompanied with granular lymphocytic leukemia the tumor cells of which suppressed colony formation of BFU-E, and which was successfully treated by cyclophosphamide and cyclosporin A].

A 69-year-old woman with pure red cell aplasia and granular lymphocytic leukemia was reported. Because her granular lymphocyte count was in the normal range at the time of admission, we diagnosed the patient as primary pure red cell aplasia (PRCA). The granular lymphocyte count increased slowly, and we find monoclonal T cell receptor rearrangement, the case was diagnosed as granular lymphocytic leukemia accompanied with PRCA. Although single administration of cyclosporin or cyclophosphamide induced severe side effects obtained combined administration of low doses of these agents obtained good Hb increase. This case was granular lymphocytic leukemia with normal granular lymphocytic count at the time of diagnosis, the tumor cell suppressed BFU-E colony formation, and combined administration of low dose CPM and CyA yielded good effects.

[Clinical phase II study of 5'-DFUR for cancer of the digestive organs by a cooperative study group].

Phase II study of a new 5-fluorouracil derivative, 5'-deoxy-5-fluorouridine (5'-DFUR), was performed with oral administration. Forty-nine patients with advanced cancer of the digestive organs, lung and breast were entered, and 8 institutions in Hokkaido were involved. 5'-DFUR was administered three or four times a day at a daily dosage of 600 to 1200 mg. Partial response was observed in three gastric cancer cases and two breast cancer cases out of 39 evaluable cases, and minor response was observed in one colorectal cancer case. Overall response rate was 12.8%, 15.8% in gastric cancer and 66.7% in breast cancer. Side effects were observed in 15 cases out of 45 (33.3%), which mainly consisted of gastro-intestinal disturbances such as diarrhea.

[Gamma-enolase (gamma-eno)].

Enolase catalyzes the interconversion of 2-phosphoglycelate and phosphoenolpyruvate in the glycolytic pathway. Enolase isozymes are dimers formed from three subunits (alpha, beta, and gamma). The gamma subunit, containing enolase (gamma-enolase) in serum, is important in the diagnosis of tumors originating from APUD (amine precursor uptake and decarboxylation) cells, like neuroblastoma, small cell carcinoma for the lung and certain carcinomas of the thyroid, the pancreas and the gut. Therefore, the determination of serum gamma-enolase levels is useful as a tumor marker of these neoplasms. On the other hand, raised gamma-enolase levels in cerebrospinal fluid have been demonstrated in patients suffering from various neurological disorders. In this paper, the author reviews the results of some of many studies related to gamma-enolase, up to now.

Pure red cell aplasia associated with systemic lupus erythematosus.

Pure red cell aplasia is a rare condition described in patients with autoimmune diseases such as systemic lupus erythematosus. Bone marrow examination of a 52-year-old female showed selective severe hypoplasia, scarce hematopoietic reserves, and no abnormality in other cell lineages, which are findings compatible with red cell aplasia. This condition has not responded to corticosteroids, cytotoxic drugs or intravenous immunoglobulin. After therapy with high doses of glucocorticoids, cyclophosphamide, and immunoglobulin failed, she was treated with human recombinant erythropoietin, monthly pulses of methylprednisolone, and cyclophosphamide, simultaneously. Data on treatment with erythropoietin for pure red cell aplasia associated with systemic lupus erythematosus is limited, but it appears to be reasonable to try in refractory cases.