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.

New flexible endoscopic full-thickness suturing device: a triple-arm-bar suturing system.

BACKGROUND AND STUDY AIM: A reliable full-thickness suturing device is necessary for pure natural orifice transluminal endoscopic surgery (NOTES). The present study focused on assessing the reliability of a new suturing device. METHODS: A total of 60 single sutures were tested to close 5-cm incisions in 8-cm square pieces of resected swine stomach. Each incision was sutured by an over-the-scope clip (OTSC; n = 20), a single hand-sewn stitch (n = 20), or a single triple-arm-bar suturing system (TBSS) stitch. The maximum pulling force durability (MPD) of each suture was tested. To assess the reliability of the TBSS for endoscopic full-thickness resection (EFTR), 60 EFTRs of 50 mm diameter were performed on excised swine stomachs. After EFTR, full-thickness sutures were made using 3-stitch OTSCs (n = 20), 10-stitch hand-sewn sutures (n = 20), or 10-stitch TBSS sutures (n = 20). Outcomes were the MPD test for both single stitch and multiple stitch applications and the suturing time for single-stitch sutures. RESULTS: In the single-stitch MPD tests, there were significant differences between OTSCs and hand-sewn sutures (P = 0.0002) and between OTSCs and TBSS sutures (P = 0.0001), but no significant difference between hand-sewn and TBSS sutures. The multiple-stitch sutures revealed significant differences between OTSCs and hand-sewn sutures (P = 0.0039), and between OTSCs and TBSS sutures (P = 0.013). There was no significant difference between hand-sewn and TBSS sutures. There were significant differences in suture times between OTSC, hand-sewn sutures, and TBSS sutures (P < 0.05). CONCLUSIONS: Both single-stitch and multiple-stitch sutures using TBSS have similar strength to hand-sewn sutures. TBSS is a reliable suturing device.

Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. PATIENTS AND METHODS: A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. RESULTS: Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. CONCLUSIONS: Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity.

Biomechanical and biochemical characteristics of the mandibular condylar cartilage.

The human masticatory system consists of a mandible which is able to move with respect to the skull at its bilateral temporomandibular joint (TMJ) through contractions of the masticatory muscles. Like other synovial joints, the TMJ is loaded mechanically during function. The articular surface of the mandibular condyle is covered with cartilage that is composed mainly of collagen fibers and proteoglycans. This construction results in a viscoelastic response to loading and enables the cartilage to play an important role as a stress absorber during function. To understand its mechanical functions properly, and to assess its limitations, detailed information about the viscoelastic behavior of the mandibular condylar cartilage is required. The purpose of this paper is to review the fundamental concepts of the biomechanical behavior of the mandibular condylar cartilage. This review consists of four parts. Part 1 is a brief introduction of the structure and function of the mandibular condylar cartilage. In Part 2, the biochemical composition of the mandibular condylar cartilage is summarized. Part 3 explores the biomechanical properties of the mandibular condylar cartilage. Finally, Part 4 relates this behavior to the breakdown mechanism of the mandibular condylar cartilage which is associated with the progression of osteoarthritis in the TMJ.

Multiplex real-time PCR for exhaustive detection of diarrhoeagenic Escherichia coli.

AIMS: The source and routes of diarrhoeagenic Escherichia coli (DEC) have not been clarified because it is difficult to detect these organisms in samples with numerous coliform bacteria. We have developed multiplex real-time PCR assays for exhaustive detection of DEC. METHODS AND RESULTS: Primers and TaqMan probes were designed to amplify and quantify one gene (eae, stx1, stx2, elt, est, virB, aggR, astA, and afaB) from each of seven pathotypes of DEC, in duplex or triplex reactions under the same PCR cycling conditions. Specificity was confirmed using 860 strains including 88 DEC strains. The fluorescence threshold cycle and DNA concentrations correlated with decision coefficients of more than 0.99. Subsequently, meat samples and enrichment broths were spiked with DEC and the assays used to detect the genes. The detection limits varied from 7.1 x 10(2) to 1.1 x 10(4) CFU ml(-1), depending on the target genes. All meat samples spiked with a variety of DEC (more than 10 CFU 10 g(-1)) were found to be positive by the method. CONCLUSIONS: The present system allows for the efficient and simultaneous determination of various DEC pathotypes. SIGNIFICANCE AND IMPACT OF THE STUDY: This system makes epidemiological investigations for DEC sensitive and quick, and is a useful tool to clarify the source and routes of DEC.

Effects of the spermine analogue canavalmine on proliferation of murine erythroleukemia cells in culture.

The effects of canavalmine, a structural analogue of spermine, were studied in cultured murine erythroleukemia cells 745A. Canavalmine exerted an inhibition on murine erythroleukemia cell growth at concentrations over 50 microM. The cell proliferation was, however, restored when canavalmine was removed from the culture medium after 24 h. Treatment of the cells with 500 microM canavalmine blocked the accumulation of intracellular polyamines. Especially, both spermine and spermidine levels were reduced below 50% of those in control cells after 48 h and below 30% after 96 h. The decreased contents of spermine and spermidine were compensated for by the increased content of canavalmine incorporated within the cells. In these cells, RNA and protein contents also decreased. The degree of growth inhibition by canavalmine during the cell cycle was examined using synchronized cells. Serum-induced growth stimulation was inhibited by canavalmine most effectively in the cells at G1 phase prior to DNA synthesis. The antiproliferative effect decreased when canavalmine was added to the cells after commencement of DNA synthesis. The results suggest that the growth-inhibitory action of canavalmine on murine erythroleukemia cells is most likely due to an inhibition of early events of the cell cycle, possibly due to the interference of a structure-specific function of spermidine and/or spermine on DNA replication.

Erythroid differentiation of cultured murine erythroleukemia cells by the spermine analogue canavalmine.

Canavalmine, an analogue of spermine, induced erythroid differentiation of murine erythroleukemia cells 745A, as evidenced by benzidine staining and heme content of cultured cells. Benzidine-positive cells synthesizing hemoglobin appeared on day 4 after addition of 250 microM canavalmine. The canavalmine-induced cell differentiation was inhibited by the addition of agents which alter the structure of the cell membrane, such as local anesthetics (procainamide and lidocaine) or Ca2+ antagonists (nifedipine and verapamil) at dosages not toxic for the cell growth. Canavalmine did not significantly affect the levels of conjugated polyamines in the acid-insoluble fraction of the cells. In contrast, the level of free spermidine in the acid-soluble fraction greatly decreased during the 18 h after canavalmine treatment. Putrescine and spermidine, when added externally to the growth medium, showed dose-dependent inhibition of canavalmine-induced cell differentiation. Neither cadaverine nor spermine had any significant effect. These results suggest that not only structural change of cell membrane but alteration of the polyamine metabolism, especially a regulation of the cellular level of free spermidine, might have a key importance in erythroid differentiation of murine erythroleukemia cells induced by canavalmine.

Modulation of nuclear protein import: a novel means of regulating gene expression.

Eukaryotic cells depend upon the regulated exchange of proteins and RNA between the cytoplasm and the nucleus for survival. Various cytoplasmic and nuclear proteins play a fundamental role in this specific transport process. Over the last few years the components and stages of nuclear protein transport have been characterized in significant detail. Because many of the proteins that are transported into the nucleus are transcription factors, the import process is an interesting target for the manipulation of gene expression. Over time the eukaryotic cell has assembled a number of methods by which to regulate the nuclear localization of transcription factors. Within the last few years, there have been several reports of the pharmacologic manipulation of the localization of nuclear proteins as well. In addition, a recent study suggests that viruses are able to modulate host cell nuclear protein transport in vivo. This report will present an overview of nuclear protein import, describe the various in vivo mechanisms by which the cell regulates this process, and discuss recent attempts to manipulate the process with small molecule compounds. As nuclear import is a fundamental cellular process, potential opportunities for the future may arise from direct and specific ways to modulate this process and thereby treat diseases characterized by dysregulation of transcription factor activity.

Formation of two major nicotine metabolites in livers of guinea pigs.

Using antibody against NADPH-cytochrome P-450 reductase and several effectors of cytochrome P-450 and FAD-containing monooxygenase, we investigated nicotine metabolites formed by these two enzymes. When [3H]nicotine was metabolized by the combination of liver microsomes of guinea pigs and partially purified aldehyde oxidase, three distinct spots corresponding to nicotine, cotinine and nicotine-1'-oxide were observed on fluorograms of thin-layer chromatography. Antibody against NADPH-cytochrome P-450 reductase inhibited the formation of cotinine but not nicotine-1'-oxide. Metyrapone and n-octylamine inhibited the cotinine formation, while methimazole prevented the formation of nicotine-1'-oxide. These results show that microsomal electron transport systems participate in the formation of nicotine-1'-oxide and strongly suggest the involvement of FAD-containing monooxygenase in the formation of nicotine-1'-oxide.

Leukoencephalopathy with cerebral amyloid angiopathy: a semiquantitative and morphometric study.

To investigate changes in caliber of vessels in leukoencephalopathy with cerebral amyloid angiopathy (CAA) we performed a histological and morphometric study of cerebral arteries in this disease. We histologically examined changes in cortico-leptomeningeal arteries in five cases of leukoencephalopathy with CAA and compared their morphometrically determined wall-to-lumen ratio [(external diameter-internal diameter) x 0.5/internal diameter] with those of amyloid-negative arteries to estimate stenotic changes. Additionally, we compared wall-to-lumen ratios of medullary arteries in brains with CAA and white matter lesions (WML) (CAA(+)/WML(+), n = 5), subcortical arteriosclerotic encephalopathy without CAA (CAA(-)/WML(+), n = 7), and neither CAA nor white matter lesions (CAA(-)/WML(-), n = 5). Amyloid-positive arteries had thinned walls and dilated lumens. The external diameter and the wall-to-lumen ratio for amyloid-positive arteries was smaller than for amyloid-negative arteries in CAA(+)/WML(+) brains. There was no significant difference in the external diameters among the three groups. The wall-to-lumen ratio for medullary arteries in CAA(-)/WML(+) brains was significantly greater than for CAA(+)/WML(+) and CAA(-)/WML(-), but there was no significant difference between CAA(+)/WML(+) and CAA(-)/WML(-). Amyloid deposition causes degeneration of the tunica media, resulting in thinning of the wall and dilation of the lumen. The tunica media of small arteries is important in regulation of cerebral blood flow with degeneration causing impairment of cerebrovascular autoregulation in response to blood pressure. This impairment may lead to white matter lesions.

Lack of evidence for protein AA reactivity in amyloid deposits of lattice corneal dystrophy and amyloid corneal degeneration.

Amyloid fibrils occurring in primary and myeloma-associated (AL), secondary (AA), and certain neuropathic hereditary forms of systemic amyloidosis can be distinguished biochemically or immunohistologically as being composed of immunoglobulin light chain, protein AA, or prealbumin respectively. All types of systemic and several localized forms of amyloidosis contain amyloid P component (protein AP). We studied formalin-fixed tissue from eight cases of lattice corneal dystrophy by the immunoperoxidase method using antisera to proteins AA and AP, to normal serum prealbumin and prealbumin isolated from a case of hereditary amyloidosis, and to light-chain determinants; additional cases were examined by indirect immunofluorescence of fresh-frozen material. We found weak (1:10 dilution) staining with anti-AP, but no reactivity with other antisera. Congo red staining was resistant to pretreatment of sections with potassium permanganate, a characteristic of non-AA amyloid. Two-dimensional gels of solubilized proteins from frozen tissue from two cases of lattice corneal dystrophy resembled those obtained from normal human cornea. Western blots of two cases of polymorphous amyloid degeneration and solubilized protein from normal cornea did not react with radioactive iodine-labeled anti-AA or anti-AP with purified protein AP and unfixed protein AA amyloid tissue as controls. We were unable to corroborate the presence of protein AA in the amyloid deposits of lattice corneal dystrophy. Although staining with antiserum to protein AP was demonstrable, the molecular configuration of this protein in stromal deposits remains to be defined.

Panic attacks and panic disorder in Japanese non-patient population: epidemiology and psychosocial correlates.

To investigate the prevalence rates of panic disorder and panic attacks in the general population of Japan, a set of questionnaires were administered to 207 people aged 18 or over, who were then interviewed. Seven (3.4%) had experienced one or more unexpected panic attacks in their lifetime. Two subjects (1.0%) had had panic disorder (DSM-III-R), and five (2.4%) had had panic attacks not meeting the criteria for panic disorder. Seventy percent of the persons with panic disorder or panic attacks had sought medical care. There was comorbidity with agoraphobia in two cases, and with major depression in five. Harsh discipline, frequent quarrel, between parents, and serious illness before the age of 16 were more frequent in individuals suffering from panic attacks, compared to those without.

Early parental separation experiences among patients with bipolar disorder and major depression: a case-control study.

BACKGROUND: Although the association between childhood parental loss and later development of mood disorder has received much research interest in the past, the results obtained and conclusions drawn have been various, and inconsistent with each other. The present study aims to examine this old, yet unresolved, question among the Japanese. METHODS: Patients with bipolar disorder (n = 73) and unipolar depression (n = 570) and community healthy controls (n = 122) were examined as to their psychopathology and childhood parental loss experiences with semi-structured interviews. RESULTS: Stratified for sex and age, no statistically significant difference was observed in the incidence of paternal or maternal death or separation before age 16 between bipolar patients and healthy controls. Female patients with unipolar depression under the age of 54 experienced significantly more maternal loss than the corresponding controls. This excess in loss appeared to be largely due to the patients experiencing separation from their mothers. CONCLUSION: Our findings concerning bipolar disorder have replicated the previous two studies reported in the literature. Those concerning unipolar depression appear to be in line with several recent studies on the subject but, as stated, many discrepant findings can also be found in the literature.

Childhood parental loss and schizophrenia: evidence against pathogenic but for some pathoplastic effects.

Childhood parental loss has been associated with a number of psychiatric disorders in adulthood. The present article aims to examine, firstly, the etiologic relationship between early parental loss and later development of schizophrenia and, secondly, the pathoplastic effect of the former on the symptomatology of the latter. We have administered semi-structured interviews inquiring into psychopathology and early separation experiences to a representative sample of first-visit patients to the 31 hospitals and clinics all over Japan (n=1963) and also to a community sample in a small city in Japan (n=218). When 225 patients diagnosed with schizophrenia according to DSM-III-R criteria were compared with 122 healthy control subjects without any lifetime psychiatric disorder, controlled for sex and age, there was no statistically significant difference in the rates of childhood parental loss (death or separation). As regards the pathoplastic effects, it was found that schizophrenic men were less likely to present with negative symptoms if they had experienced separation from the father, and were more likely to show panic attacks if they had experienced separation from the mother. Schizophrenic women were more likely to present with hallucinations if they had suffered any loss of the father. Childhood parental loss is not pathogenic of schizophrenia but appears to exert some pathoplastic influences on its presenting symptoms.

Prevalence of mood and anxiety disorders in a working population in Japan.

To learn the prevalence of mood and anxiety disorders (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised) in a working population in Japan, we analyzed data from a population-based survey. Among 140 respondents who had a job, 8% experienced any of seven mood and anxiety disorders in the past 6 months and 19% had in their lifetime. The 6-month and lifetime prevalence rates of major depressive episodes were 4% and 14%, respectively. The 6-month and lifetime prevalence rates of phobic disorders were both 4%. The lifetime prevalence rates for other anxiety disorders were 1% or less. The 6-month rate of any disorder, as well as 6-month and lifetime rates of phobic disorders, was higher in white-collar employees than in self-employed workers (P < 0.05). The multiple logistic regression confirmed the tendency after controlling for sex and age, although the result was not significant (P > 0.05).

Cytology of Langerhans cell histiocytosis in effusions: a case report.

BACKGROUND: Langerhans cell histiocytosis is a relatively rare disorder of children, characterized by abnormal proliferation of Langerhans cells. There has been no report on the cytologic appearance of Langerhans cells in effusions. CASE: A 20-year-old had a 12-year history of the disease, since he was 8 years old. He had multiple mass lesions in the bones, lung and liver, and Langerhans cells appeared in the pleural fluid and ascites. They had indented, twisted or grooved nuclei, with a finely or coarsely granular chromatin pattern. Some of the nuclei were eccentrically located, and prominent nucleoli were occasionally seen. Immunohistochemically the cells showed positivity for S-100 protein. Electron microscopic examination revealed abortive Birbeck granules. CONCLUSION: The cytologic appearance was somewhat accentuated and different from that reported for other sites. Immunohistochemical staining for S-100 protein and/or electron microscopic examination should be employed.

Congophilic angiopathy in the pathogenesis of Alzheimer's degeneration.

The pathologic manifestations in 45 valid cases of Alzheimer's degeneration were evaluated with specific focus on the presence of Congophilic angiopathy. The latter lesion was found in 89% of the cases and had a definite temporal relationship to the presence of neuritic plaques and neurofibrillary tangles. Two types of plaques were defined, the neuritic and perivascular. The latter was associated spatially with vessels, but not neurofibrillary tangles, while the converse was true of the neuritic plaques. Based on the pattern of mural involvement of vessels, distinctions could be made to differentiate morphologically between cerebral and peripheral amyloid angiopathy. Alzheimer's degeneration appears to be a disease complex with a variety of etiologies. Little or no differences in morphologic characteristics between the presenium and senium process could be discerned. Congophilic angiopathy appears to be a major feature in the pathogenesis of Alzheimer's degeneration.