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Biomedical subjects

S Kuwabara

Publications and source records attributed to S Kuwabara.

At least 91 records · Page 5Linked to original sources

Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma.

In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for inter- or intra-patient heterogeneity but only a few studies have investigated intratumoral heterogeneity. We investigated this question within individual esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing the p53 gene sequence by direct sequencing of polymerase chain reaction products, we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal cancers. In all areas sampled in the invasive portion of each cancer, the p53 mutational status was identical in a given tumor. In heterogeneous tumors, the invasive area showed one of the p53 mutations found in the pre-invasive area. In nodal metastases, the p53 mutation was identical to that in the invasive area of each primary tumor. These data suggest that the timing of p53 alteration is not as early as might have been expected, indicating that, in regard to p53 gene alteration, some esophageal cancers are composed of various subclones in the pre-invasive stage with invasiveness developing in one of them, which becomes predominant through clonal selection.

Aged↗

Micturitional disturbance in patients with chronic inflammatory demyelinating polyneuropathy.

Eight of 32 patients (25%) with chronic inflammatory demyelinating polyneuropathy (CIDP) had micturitional disturbance, which consisted of voiding difficulty (n = 4), urgency (n = 4), or urgency incontinence (n = 1). Urodynamic studies on four symptomatic patients showed disturbed bladder sensation in two, bladder areflexia in one, and neurogenic changes of the external sphincter in one, indicative of peripheral parasympathetic and somatic nerve dysfunctions. Cystometry also showed detrusor overactivity in two patients but no evidence of CNS involvement, evidence that bladder overactivity occurs by probable pelvic nerve irritation.

Adolescent↗

D-penicillamine treatment for chronic sensory ataxic neuropathy associated with Sjögren's syndrome.

Beneficial treatment has not been established for chronic sensory ataxic neuropathy associated with Sjögren's syndrome (CSAN-SS). We describe two patients with CSAN-SS who clinically improved in response to D-penicillamine treatment. Their neuropathic symptoms were lessened after D-penicillamine, and the results of electrophysiologic studies support the clinical improvement. D-Penicillamine can be considered a potentially beneficial agent in the treatment of CSAN-SS.

Adult↗

Two patterns of clinical recovery in Guillain-Barré syndrome with IgG anti-GM1 antibody.

OBJECTIVE: To investigate the prognostic value of anti-GM1 antibody. BACKGROUND: Whether anti-GM1 antibody is a marker of poor prognosis due to axonal degeneration in Guillain-Barré syndrome (GBS) is a matter of controversy. METHODS: The clinical recovery of 41 consecutive GBS patients was analyzed. RESULTS: The Hughes functional grading scores were similar at the peak, and 1, 3, and 6 months after onset for the groups of patients with (n=19) and without (n=22) immunoglobulin (Ig) G anti-GM1 antibodies. However, the anti-GM1-positive group included significantly higher proportions of patients with poor recovery (inability to walk independently at 6 months, 5 of 19 versus 0 of 22; p=0.01) and those with a markedly rapid recovery (improvement by two or more Hughes grades within a month, 9 of 19 versus 4 of 22; p=0.05). The positivity of IgG anti-GM1 antibody correlated well with the electrodiagnosis of the acute motor axonal neuropathy pattern but was not always associated with poor prognosis. Anti-GM1-positive patients showed two different patterns of clinical recovery-their conditions improved slower or faster than those of the anti-GM1-negative patients, most of whom had acute inflammatory demyelinating polyneuropathy. CONCLUSIONS: Anti-GM1 antibody is not always a marker of poor prognosis and, besides axonal degeneration, early reversible effects other than demyelination could be part of the pathophysiology of Guillain-Barré syndrome with IgG anti-GM1 antibody.

Adult↗

Novel S100 proteins in human esophageal epithelial cells: CAAF1 expression is associated with cell growth arrest.

CAAF1 and CAAF2, newly identified calcium-binding proteins from bovine amniotic fluid, have been revealed to be members of the S100 protein family preferentially produced by fetal squamous epithelial cells, including epidermal keratinocytes. Having previously cloned the cDNA of human CAAF1 protein from the esophageal epithelium, we report here on the characteristic expression pattern of CAAF1 and related S100 proteins in human esophageal epithelial cells. Normal cells of the human esophageal epithelium expressed CAAF1, and also expressed the homologous novel S100 proteins including CAAF2, MRP8, and MRP14, but not S100alpha. An immunohistochemical study with specific monoclonal antibodies against CAAF1 proteins demonstrated that CAAF1 proteins were produced by the esophageal epithelial cells in the process of cell differentiation. The immature proliferating cells in the epithelium did not produce CAAF1 proteins, but the differentiated cells expressed CAAF1, which overlay the immature cells and were stratifying in the epithelium. These CAA 1-producing cells did not show any proliferating activities. Esophageal carcinoma cells did not express CAAF1, except for the keratinized cells with no proliferating activity. In addition, the forced expression of CAAF1 proteins in the carcinoma cells resulted in a marked decrease in DNA synthesis. These findings indicate that human esophageal epithelial cells express the multiple genes of S100 proteins including CAAF proteins, and that CAAF1 is closely associated with the terminal differentiation of these cells. CAAF1 expression also might play some role in cell growth.

Amino Acid Sequence↗

Tumor recurrence in patients with early gastric cancer: a clinicopathologic evaluation.

We conducted a retrospective study on 711 patients with early gastric cancer. Twenty-two patients (4.0%) developed recurrent disease and 21 died of recurrence during this study. One hundred and sixty-three patients died of unrelated or unknown causes. The recurrence patterns of 22 patients were as follows: hematogeneous metastasis to the liver in 11 patients, peritoneal dissemination in 3, recurrence in the remnant stomach in 3, and in the distant lymphonodes in 1. The mean survival period of patients with recurrent disease was 50.4 months, and 7 of these patients (31.8%) died more than 5 years after surgery. A retrospective clinicopathologic evaluation of the 22 patients and 526 patients without recurrence revealed significant differences between the two groups with respect to mean age at the time of surgery (62.5 years in the recurrent group vs 57.3 years in the nonrecurrent group), tumor size (41.2 vs 30.6 mm), depth of invasion (submucosal cancer: 19 vs 256), lymphnode metastasis (11 vs 48), lymphatic (11 vs 89) and venous (7 vs 18) invasion, and operative curability (curability B: 8 vs 48). Three patients with intramucosal cancer who died of hematogenous and/or peritoneal recurrence within 7 years after surgery had neither lymphnode metastasis nor lymphatic or venous invasion, suggesting that new techniques are needed for prediction of recurrent disease in patient with early gastric cancer.

Adult↗

Slowly conducting, low-threshold components of sensory nerve potentials in peripheral neuropathy: a microneurographic study.

By recording the averaged potential from a microelectrode inserted into the nerve, small late components of the sensory nerve action potential can be analyzed. We studied the thresholds of the late components in median nerves of 15 normal subjects and 37 patients with peripheral neuropathies. Under normal conditions, the late components reflected the activities of small myelinated fibers which had high thresholds. In the patients with peripheral neuropathies, a part of the late components often had abnormally low thresholds, occasionally the lowest. The presence of low-threshold, late components was related to the pathologies of the different types of neuropathy and correlated with the numbers of regenerating clusters in sural nerve biopsies. These slowly conducting, low-threshold components may originate from regenerating or remyelinating fibers, and therefore should have prognostic value.

Action Potentials↗

Mitochondrial damage by a new antitumour agent furanonaphthoquinone derivative in human cervical cancer HeLa cells.

The intracellular ultrastructural changes induced by the new antitumour agent 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) were investigated in human cervical cancer HeLa cells in comparison with normal cervix cells. The normal cells were isolated from cervixes surgically resected from myoma patients and were keratin positive. FNQ3 at 3-5 micrograms ml-1 selectively damaged the HeLa cell mitochondria followed by rough-surfaced endoplasmic reticulum resulting in cell death. In contrast, normal cells remained unaffected at that concentration but were damaged by 20 micrograms ml-1 FNQ3. The FNQ3-induced tumour cell toxicity was inhibited 52% and 36% by trolox and a water-soluble fraction of the antioxidative substance AOB, respectively. The results indicated that FNQ3 is selectively toxic to HeLa cells at approximately eight times that of normal cells in terms of mitochondrial alteration and free radical formation.

Antineoplastic Agents, Phytogenic↗

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-alpha.

We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor-alpha (TNF-alpha), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H-7 and H-8, a calmodulin antagonist W-7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC-9. H-7, more potent in inhibiting PKC than H-8, failed to attenuate the increase in permeability induced by TNF-alpha. Neither PMA nor SC-9 increased permeability. However, H-8, which is a potent inhibitor of cyclic nucleotide-dependent protein kinases, prevented the increase in permeability induced by TNF-alpha. These results suggest that protein kinase other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF-alpha. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF-alpha.

Albumins↗

Long term melphalan-prednisolone chemotherapy for POEMS syndrome.

The effects of long term melphalan-prednisolone (MP) therapy was studied on 12 patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. Six were treated with MP every six weeks for 16 to 52 months; three also with cyclophosphamide, and three with localised irradiation for osteoclastic lesions. Five of the six survived during the follow up period and showed various degrees of lessening of their neuropathy and other symptoms. There were no serious side effects. The other six patients received treatments that included corticosteroids, short term chemotherapy, or irradiation, but not long term chemotherapy. Five showed transient lessening of their non-neurological symptoms, and one, obvious neurological improvement. Five of these six patients died from nine to 70 months after POEMS onset. The findings suggest that long term MP therapy may be an effective treatment for the POEMS syndrome.

Adult↗

Micturitional disturbance in patients with Guillain-Barré syndrome.

OBJECTIVES: To examine the frequency and pathophysiology of micturitional disturbance in patients with Guillain-Barré syndrome. METHODS: Micturitional symptoms were noted and neurological examinations made repeatedly during admission to hospital of patients with clinical and neurophysiologically definite Guillain-Barré syndrome. Urodynamic studies consisted of uroflowmetry, measurement of residual urine, urethral pressure profilometry, medium fill water cystometry, and external sphincter EMG. RESULTS: Seven of 28 (25%) patients with Guillain-Barré syndrome showed micturitional disturbance. The symptoms included voiding difficulty in six, urinary retention in three, nocturnal urinary frequency in three, and urge incontinence in two. These micturitional symptoms appeared after weakness occurred, and improved gradually along with the neurological signs. All three patients who showed retention became able to urinate. Urodynamic studies were made on four symptomatic patients two of whom underwent repeated study. Disturbed bladder sensation was noted in one patient, bladder areflexia in one, and absence of the bulbocavernosus reflex in one. Cystometry showed decreased bladder volume in two and bladder overactivity in two, one of whom had urge urinary incontinence and the other urinary retention. CONCLUSIONS: A quarter of the patients with Guillain-Barré syndrome tend to have micturitional disturbance. The patients studied had evacuation and storage disorders, as well as bladder areflexia and disturbed bladder sensation indicative of peripheral types of parasympathetic and somatic nerve dysfunction. Decreased bladder volume with bladder overactivity but no evidence of CNS involvement was also found, evidence that bladder overactivity also occurs in peripheral nerve lesions with probable pelvic nerve irritation.

Adolescent↗

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis.

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.

Adenoviruses, Human↗

Magnetic resonance imaging at the demyelinative foci in chronic inflammatory demyelinating polyneuropathy.

Using MRI, we investigated the morphology and blood-nerve barrier function of the peripheral nerve trunk in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Eight patients had a focal demyelinative segment in the median or ulnar nerve trunk that was defined by conduction block or abnormal temporal dispersion over a short distance. These demyelinative foci showed nerve enlargement with high signal intensity on proton or T2-weighted images. In four patients with progressive illness or relapse, the enlarged segment showed gadolinium enhancement that disappeared during remission induced by immune therapies. The other four were in the steady phase and showed no gadolinium enhancement of the enlarged nerves. The two patients who showed conduction slowing, but no focal demyelinative focus, had neither nerve enlargement nor gadolinium enhancement. In CIDP, focal conduction abnormalities correlate well with anatomic changes that suggest intermittent, repeated inflammation associated with the breakdown of the blood-nerve barrier.

Adolescent↗

Guillain-Barré and virus-associated hemophagocytic syndromes contracted simultaneously following Epstein-Barr viral infection.

The virus-associated hemophagocytic syndrome (VAHS) is a lymphoproliferative disorder induced by viral infection. The peripheral nervous system is rarely involved in this syndrome and, when reported, the involvement has been axonal in nature. This paper presents a case of Guillain-Barré syndrome accompanied by VAHS subsequent to Epstein-Barr virus infection. The patient's condition improved following treatment with intravenous immunoglobulin infusion and high-dose corticosteroids.

Adrenal Cortex Hormones↗

[Destructive spondyloarthropathy of the cervical spine in hemodialyzed patients].

To assess the prevalences and neurological symptoms of destructive spondyloarthropathy (DSA) and other cervical spinal diseases in long-term hemodialysis, a questionnaire survey of the medical histories and subjective sensory-motor symptoms was taken on 191 patients undergoing dialysis for 0.2-23 years (mean 8.6 +/- 6.3) with a mean age of 56.6 +/- 11.8 years (range 23-86). Furthermore, plain radiographic examinations of the cervical spine were carried out in 90% of the patients, and neurologic examinations were also performed on 29 patients. DSA was diagnosed in 18 cases (10%): moderate narrowing of the intervertebral space (NIS-I) in 8, severe narrowing (NIS-II) in 18, ossification of posterior longitudinal ligaments (OPLL) in 6, cervical spondylosis (CS) in 12 and other abnormalities in 6; 104 cases were normal. NIS-I was considered to reflect an early stage of DSA. The age of patients with DSA (mean 61.5 +/- 10.2 years), as well as with CS, was significantly higher than the normal group (52.2 +/- 10.6; p < 0.001), but younger than CS (68.5 +/- 10.0). The duration of dialysis in DSA patients (mean 12.1 +/- 6.0 years) was the longest and significantly longer than normal (7.7 +/- 6.5; p < 0.01) and (:S patients (3.8 +/- 3.0; p < 0.001). Through comparative evaluations of prior histories of the diseases, such as diabetes mellitus, carpal tunnel syndrome, amyloid osteoarthropathy (AOA) and parathyroidectomy, along with large calcification of the nuchal soft tissues on plain films, it was found that DSA, in conjunction with NIS-I, correlated with only AOA (p < 0.05). Subjective sensory symptoms, which consisted chiefly of arthralgic type followed by polyneuritic type, were noted in 60% of all patients and 56% of DSA patients. No significant differences were evident between any two particular groups. The score of subjective motor symptoms of the lower extremities in 5 patients with myelopathy was significantly higher than that in 5 other patients without neurological disorders (p < 0.05). Thirty-eight percent of DSA patients showed myelopathy; the frequency was higher than those of previous similar studies (0 = 5%). In conclusion, this study demonstrated that 1) DSA occurred in 10% of dialysis patients, which was also evident in previous reports (9 = 10%); this prevalence was higher than those of CS or OPLL, 2) DSA correlated with the duration of dialysis and AOA, 3) subjective motor symptoms of the lower extremities could indicate presence of myelopathy whereas subjective sensory symptoms contributed little to differential diagnosis, and 4) a careful neurologic examination can more frequently disclose myelopathy in patients with DSA than so far believed.

Adult↗