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Biomedical subjects

N Kuwabara

Publications and source records attributed to N Kuwabara.

At least 37 records · Page 2Linked to original sources

Long-term prognosis of chronic hepatitis C after treatment with interferon alpha 2b and characterization of incomplete responders.

OBJECTIVES: During the long-term follow-up of chronic hepatitis C patients treated with interferon alpha-2b, we have identified some patients who had continuous normalization, or transient elevation of the serum alanine aminotransferase levels within the first 6 months of follow-up and subsequent normalization, but HCV RNA was still found to be positive during the follow-up period (incomplete responder; ICR). We wished to clarify the characteristics of these patients, and to investigate the factors predictive of the response to interferon. METHODS: Seventy patients were treated with 6 MU of rIFN alpha-2b, three times weekly for 24 wk. Sixty-six patients (94%) completed the entire therapy and 2-yr follow-up protocol. RESULTS: Twenty-four months after cessation of IFN treatment, 24 patients (36%) were defined as complete responders (CR; continuously normal alanine aminotransferase levels, and HCV RNA negative). Nine patients (14%) were defined as ICR. Thirty-three patients (50%) were defined as nonresponders (NR). Compared with the CR or NR groups, the patients in the ICR group tended to have the mildest histological severity and lowest histological activity index scores, but there were no significant differences in any of the other histological features. The complete response rate was significantly higher in patients with low concentration of HCV RNA, and genotypes other than type II. CONCLUSIONS: After long-term follow-up of the 66 patients, 24 patients (36%) were CR, nine (14%) were ICR, and 33 (50%) were NR. The histological stage and indices of chronic hepatitis may help to predict a patient's response to IFN therapy.

Adult↗

Adenocarcinoma arising from gastric immature teratoma. Report of a case in an adult and a review of the literature.

BACKGROUND: Gastric teratoma is an uncommon tumor and usually occurs in infancy or childhood. To the authors' knowledge, malignant transformation in gastric teratoma has not been reported previously. METHODS: An 83-year-old Japanese man presented with a large polypoid gastric tumor composed of teratomatous components and invasive adenocarcinoma. Numerous blocks of this tumor were analyzed histologically and immunohistochemically. RESULTS: Histologically, the gastric tumor consisted of teratomatous components with diverse maturation, such as fibroblastic mesenchymal cells, striated muscle cells, cartilaginous islands, neuroepithelial components, glial tissues, squamous cell nests, glandular components, and foci of adenocarcinoma infiltrating the benign gastric tissues adjacent to the tumor stalk. Metastatic foci of teratomatous components in the resected lymph nodes contained adenocarcinomatous glands. An immunohistochemical study helped confirm the differentiation in the immature components and the differential diagnosis between atypical neuroepithelial cells and the adenocarcinoma. CONCLUSION: This study indicates that the adenocarcinoma arose from immature gastric teratoma. A review of the literature suggests that this is the oldest reported patient with gastric teratoma and to the authors' knowledge is the first report describing gastric teratoma with malignant transformation.

Adenocarcinoma↗

Aberrant patterns of immunoglobulin levels in Wiskott-Aldrich syndrome.

We have investigated IgM deficiency in Wiskott-Aldrich syndrome patients. From the assessment of T and B cell functions in pokeweed mitogen-induced immunoglobulin (Ig) production, IgM deficiency was chiefly thought to result from B cell dysfunction. The percentages of surface IgM-bearing cells were decreased in peripheral blood mononuclear cells (PBMCs) and the number of IgM-secreting cells was also decreased. Lymphoblast cell lines (LCLs) from the patients have produced IgG and IgA, but never IgM. Moreover the expression of the C mu transcript from the patients' PBMCs and their LCLs were decreased, whereas the C gamma gene was well expressed. No germ-line polymorphism existed between the patients and the controls in the C mu region, and no mutation was detected in the mu s C-terminal and the M exon by nucleotide sequencing. These suggest that the Ig heavy chain (IGHC) isotype switch may be abnormally accelerated in the patients' B cells. While the methylation patterns of the human Ig enhancer gene region were the same between the patient and the control, the methylation patterns of the I gamma 1 region showed less methylation in the patient than in the control, which may cause low IgM expression and high expression levels of other classes located downstream of the IGHC gene.

Adolescent↗

Paget sarcoma of the cervical vertebrae: an autopsy case report and review of the literature.

A 69 year old Japanese woman was hospitalized for emergency treatment of sudden onset of tetraplegia and somnolence. The patient had a long history of occipital pain without definite diagnosis. After admission, the patient progressively developed generalized palsy including respiratory paralysis, and died of bronchopneumonia. Autopsy revealed osteosarcoma of the cervical vertebrae with the features of Paget's disease involving the skull and the cervical vertebrae. Paget sarcoma is rare in Japan, where Paget's disease of the bone is an uncommon condition. A review of the world literature failed to reveal any reports describing Paget sarcoma of the cervical vertebrae. The present report indicates that the development of Paget sarcoma in the upper cervical vertebrae may cause life-threatening neurologic complications.

Aged↗

Methylation patterns of I epsilon region in B cells stimulated with interleukin 4 and Epstein-Barr virus in patients with a high level of serum IgE.

Human IgE synthesis requires the presence of both interleukin 4 (IL-4) and T-cells. However, it is not clear what role IL-4 and T-cells play in the induction of IgE synthesis at the level of gene regulation. B cells that were obtained from patients with a high level of serum IgE and from healthy donors were immortalized by Epstein-Barr virus. We examined IgE production of these B cells stimulated with IL-4. Supernatant IgE levels of patient's B cells cultured with or without IL-4 were higher than those of healthy donor's B cells. Our results indicated that B cells stimulated with IL-4 from patients produced IgE, germline C epsilon transcript, and S mu S epsilon recombination. The germline C epsilon transcript was dose-dependently induced in the presence of IL-4 and related to the supernatant IgE level. In B cell stimulated with IL-4 that were obtained from patients, (some of the) DNA near or within the I epsilon region was (already partly) unmethylated, unlike those from healthy donors, and there was a loss of methyl groups of the DNA upon the addition of IL-4 in B cells from both patients and normal donors. IgE synthesis of B cells stimulated with IL-4 in patients with a high level of serum IgE is due to an accessibility in the immunoglobulin heavy-chain isotype switch, and this may reflect the accessibility in synthesis of germline C epsilon transcript, which may be caused by the increase of opening chromatin structures because of their unmethylation in the I epsilon region.

Asthma↗

Genetic analysis of IgE and the IGHE, IGHEP1 and IGHEP2 genes in atopic families.

The familial occurrence of allergic diseases was studied in 478 individuals and their family members. The results showed that there was pronounced familial clustering. Total serum IgE concentrations of atopic patients and their parents were well correlated. Moreover, the concentration of specific IgE of the patients and their parents was also well correlated, suggesting that IgE production was genetically determined. To determine if major structural abnormalities of IGHE, IGHEP1 and IGHEP2 genes might lead to aberrant control and subsequent increase in IgE concentration, genomic DNAs from 55 individuals, i.e., 31 atopic patients and their family members, were examined. We detected the IGHE, IGHEP1 and IGHEP2 genes in all 55 leukocyte DNAs. We could not find any large deletions or duplications in the IGHE, IGHEP1 and IGHEP2 genes of atopic patients with high serum IgE concentrations.

Adolescent↗

Identification of monocyte chemotactic factors in supernatants of ovalbumin-stimulated lymphocytes from patients with atopic dermatitis who are sensitive to hen's egg.

Monocyte chemotactic activities in supernatants of ovalbumin (OA)-stimulated peripheral blood mononuclear cell (PBMC) cultures were studied in patients with atopic dermatitis (AD) who were sensitive to hen's egg. The monocyte chemotactic activities in hen's egg-sensitive AD patients were significantly higher than those of non-atopic healthy controls and patients with immediate allergic symptoms. However, the monocyte chemotactic activities were not detected in bovine serum albumin-stimulated PBMC culture supernatants in patients with AD who were sensitive to hen's egg, but not to cow's milk. Furthermore, there was significant correlation between the monocyte chemotactic activities and proliferative responses of PBMCs to OA in hen's egg-sensitive AD patients, whereas there was no significant correlation between the monocyte chemotactic activities and radioallergosorbent test values. These results suggest that PBMCs stimulated with food antigens produce monocyte chemotactic factors which relate to the pathogenesis of AD in food-sensitive AD patients and that the pathogenesis of AD may be related to cell-mediated immune responses.

Adolescent↗

Timing of onset of allergic symptoms as a response to a double-blind, placebo-controlled food challenge in patients with food allergy combined with a radioallergosorbent test and the evaluation of proliferative lymphocyte responses.

The timing of onset of allergic symptoms in a double-blind, placebo-controlled food challenge (DBPCFC) was combined with a radioallergosorbent test (RAST) and evaluation of proliferative responses of peripheral blood mononuclear cells (PBMCs) in 27 atopic dermatitis patients with hen's egg allergy. Of the 27 patients, 11 showed reactions within 2 h (immediate group), and 16 showed reactions after more than 2 h (nonimmediate group) after ingestion of hen's egg. The RAST scores for hen's egg in the immediate group were significantly (p < 0.01) higher than those in the nonimmediate group, while the proliferative responses of PBMCs to ovalbumin in the nonimmediate group were significantly (p < 0.01) higher than those in the immediate group. These results suggest that the RAST values are related to immediate allergic symptoms in DBPCFC and the proliferative responses of PBMCs are related to nonimmediate allergic symptoms in DBPCFC. The timing of onset of allergic symptoms in DBPCFC will render DBPCFC more useful in the diagnosis of food allergy, including the late-onset reactions to foods.

Adolescent↗

Immunoglobulin secreting cells in lymphocytes of patients with IgA deficiency or hyper-IgA.

To assess the ability of immunoglobulin production in vivo, we enumerated the immunoglobulin secreting cells in the peripheral blood of patients with an IgA deficiency and of those with hyper-IgA-emia. All seven patients with primary IgA deficiency and two of the three patients with secondary IgA deficiency had low numbers of IgA secreting cells. In all five patients with hyper-IgA the number of IgA secreting cells was increased. Our results suggest that measurement of immunoglobulin secreting cells in PBMCs is useful in the assessment of ability of immunoglobulin production in vivo.

Antibody-Producing Cells↗

The lung in polyarteritis nodosa: a pathologic study of 10 cases.

Polyarteritis nodosa (PAN) is characterized by necrotizing arteritis of medium-sized and small arteries in various organs. Pulmonary artery involvement in PAN has been considered rare. Previously, it also has been thought that patients with PAN do not have interstitial pneumonitis and fibrosis. A detailed pathologic analysis of pulmonary diseases associated with PAN was made in 10 autopsy cases of PAN. Arteritis affecting bronchial arteries was present in seven patients (70%). The data obtained suggest that arteritis in the lung in patients with PAN is more common than has been recognized previously. Diffuse alveolar damage (DAD) involving all lobes bilaterally was present in five patients; it was acute in two patients and organizing in three. In the patients with organizing DAD the degree of fibrosis in the interstitium differed among the lobes, and the fibrosis was more severe in the lower lobe than in the other lobes. Two patients presented with interstitial fibrosis with honeycomb lung of the posterior and lateral basal segments of the lower lobes of both lungs; in one of these patients interstitial fibrosis was present in an area of organizing DAD. Five patients died of respiratory failure resulting from DAD. In conclusion, it is important to consider DAD and interstitial fibrosis as complications of PAN.

Adolescent↗

The role of T lymphocytes in patients with food-sensitive atopic dermatitis.

The role of T lymphocytes was assessed in patients with food-sensitive atopic dermatitis (AD). T lymphocytes plus monocytes responded well to ovalbumin or bovine serum albumin (BSA) in children with AD who were sensitive to hen's egg or cow's milk compared with healthy children and children with immediate allergic symptoms who are sensitive to hen's egg or cow's milk. The responding cells were shown to be predominantly CD4+ T lymphocytes. Interleukin-2 activity and interferon-gamma concentrations in culture supernatants of ovalbumin-stimulated peripheral blood mononuclear cells (PBMCs) from patients with AD who were sensitive to hen's egg were significantly higher than those of healthy children and patients sensitive to hen's egg with immediate symptoms. Expression of Fc epsilon R II on B lymphocytes in cultures of ovalbumin-stimulated PBMCs from patients with AD was significantly higher than that of healthy children, but it tended to be lower than that of patients with immediate symptoms. These results suggest that, in patients with AD who are food sensitive, CD4+ T lymphocytes stimulated by food antigens secrete lymphokines such as interleukin-2 and interferon-gamma that are secreted from TH1 clones in mice, and express Fc epsilon R II on B lymphocyte that is induced by interleukin-4 secreted from TH2 clones in mice. Taken together, cell-mediated immunity may also occur in addition to IgE-mediated hypersensitivity in patients with food-sensitive AD.

Antigens↗

Improvement of food-sensitive atopic dermatitis accompanied by reduced lymphocyte responses to food antigen following natural measles virus infection.

Five patients with atopic dermatitis (AD) who were sensitive to hen's egg were observed before and after natural measles virus infection. Within 4 weeks of natural measles virus infection, the eczematous lesions clearly improved in four of the five patients in whom neither offending foods were eliminated, nor anti-allergic drugs, systemic steroids and steroid ointment administered. This was accompanied by reduced proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA). Another patient showed a transient improvement of AD symptoms, from severe to mild, and thereafter returned to severe accompanied by increased proliferative responses of PBMCs to OA. Radioallergosorbent test (RAST) scores for hen's egg in all five patients did not change in each level in each patient, except the transiently decreased RAST scores for hen's egg in one patient, after the infection. Thus, in patients with AD who are sensitive to food, the improvement of AD symptoms that appeared within 4 weeks of natural measles virus infection was related to reduced proliferative responses of PBMCs to the food antigen following the infection.

Antigens↗

Delay lines and amplitude selectivity are created in subthalamic auditory nuclei: the brachium of the inferior colliculus of the mustached bat.

1. The biosonar pulse of the mustached bat, Pteronotus parnellii parnellii, consists of four harmonics of a constant-frequency component (CF1-4) followed by a frequency-modulated component (FM1-4). FM-FM combination-sensitive neurons in the auditory cortex and the medical geniculate body (MGB) show facilitative responses to certain combinations of FM components in a pulse-echo pair. They are tuned to particular delays of echo FMn (EFMn) (n = 2, 3, or 4) from pulse FM1 (PFM1). The neural mechanisms for creating their response properties involve delay lines, coincidence detection, and multiplication. Coincidence detection and multiplication take place in the MGB. It is not yet known where and how delay lines are created. The first aim of the present studies is to examine whether delay lines are created by subthalamic nuclei. FM-FM neurons are tuned to not only echo delays but also echo amplitudes. Therefore, the second aim of the present studies is to examine the extent to which amplitude selectivity is created by subthalamic nuclei. Responses of single nerve fibers to acoustic stimuli were recorded from the brachium of the inferior colliculus (BIC) using tungsten wire microelectrodes, and their response latencies and best amplitudes were measured. 2. All BIC fibers responded strongly to single tone bursts. No FM-FM combination-sensitive neurons were found in the BIC. The best frequencies of BIC fibers were predominantly within the frequency ranges of four harmonics of the species-specific biosonar pulse. 3. The response latencies of BIC fibers tuned to FM1 were more diverse (3.5-15.0 ms) than those of BIC fibers tuned to FMn (3.8-6.5 ms). This difference in latency distribution was independent of stimulus amplitude. These data are consistent with the theory that delay lines utilized by FM-FM neurons are created by neurons tuned to the "FM1 frequency," and indicate that the delay lines are mostly, if not all, created in a subthalamic nucleus or nuclei. 4. The best amplitudes of BIC fibers tuned to FM1 or CF1 were 63.2 +/- 4.5 (SE) dB SPL, and those of BIC fibers tuned to FMn or CFn were 48.2 +/- 10.7 dB SPL. The distribution of the best amplitudes of BIC fibers were very similar to those of FM-FM and CF/CF neurons in the MGB. These data indicate that the amplitude selectivity of thalamic FM-FM and CF/CF neurons is mainly a product of a subthalamic nucleus or nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Autopsy results of an elderly case of Parkinson's disease and aorto-esophageal fistula who died of a massive hematemesis during prolonged bed rest].

An 81-year-old female patient with an 8-year history of Parkinson's disease was hospitalized because of aspiration pneumonia. The clinical course of her pneumonia was prolonged because of dysphagia with a short period of remission, and she required a long period of bed rest. She received supportive nutrition via a nasogastric tube and many peroral medications that consisted of 3 anti-Parkinsonian drugs and 5 anti-bacterial or anti-tussive agents. Six months after admission, she vomited fresh blood through the nasogastric tube, then went into hypovolemic shock. Hemodynamic stability was temporarily achieved by blood transfusion. Gastroduodenal endoscopic examination could not reveal the exact bleeding site because of massive blood clots. Five days later, the patient died of a massive hematemesis. Autopsy revealed 2 chronic longitudinal ulcers, each 1.7 x 0.4 cm in size, in the upper portion of the esophagus. One of them had developed a fistula to the aorta. Neither esophageal carcinoma nor a foreign body was detected around the fistula. Atherosclerosis of the aorta was mild and the perforation channel was covered with the esophageal epithelium. The fistula was assumed to be a product of local esophageal injury due to drug retention.

Aged↗

[A 50-year-old man with metamorphopsia and optic nerve swelling].

We report a 50-year-old male having metamorphopsia associated with retinal edema. He was well until one month prior to the present admission when he developed occipital headache and backache. Three weeks later, he noted a sudden onset of twisting of visual images. On admission, he was in no acute distress with well preserved general conditions. Only neurological abnormalities were bilateral papilledema, retinal edema and horizontal nystagmus with a rotatory component. Routine blood chemistries were unremarkable. The CSF contained 28 cells/cmm with 60% consisting of large atypical cells. Cranial CT scans revealed no mass, however, the magnified orbital CT showed bilateral swelling of the optic nerve. He was treated with ventriculoperitoneal shunt and Ommaya tube placement through which methotrexate, cytarabine and prednisolone were administered. He was also treated with systemic cisplatin, mitomycin-C and 5-fluorouracil. With these therapy, his headache, metamorphopsia and papilledema improved. He was discharged for out-patient follow-up, however, he had to admitted again because of progressive difficulty of gait and loss of appetite. On admission, he complained of severe backache, and his gait disturbance appeared to be in part due to his backache. A slight weakness was noted in all four limbs with loss of deep reflexes. Mentally he was alert and cranial nerves appeared intact without papilledema. But nuchal rigidity was noted. Cranial CT scan revealed attenuation of all the cortical sulci and marked diffuse low density changes in the cerebral white matter, and his chest film revealed a ring-shape shadow in his left lung field. He deteriorated progressively with terminal gastrointestinal hemorrhage. He expired three weeks after his second admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[A 93-year-old woman presenting consciousness disturbance, left hemiplegia, and respiratory distress].

We present a 93-year old female who abruptly developed left hemiplegia on the way to the wash room. She was admitted to another hospital where her consciousness deteriorated and artificial respiration was necessary. She was transferred to our hospital 20 days after the onset of her stroke. On admission, her BP was 60/40 mmHg, and wheezing râle was heard in both lung fields. No heart murmur was present. She was in comatose state, but a small amount of spontaneous movements were present in her eyelids and the jaw. Neurologic examination revealed no papilledema, small non-reactive pupils with the right side being slightly larger than the left, absence of ocular movements, and loss of oculocephalic response and corneal reflex. An intratracheal tube was in situ, and the observation of the pharynx was impossible. No stiff neck was present. No spontaneous movement was observed in her limbs which were flaccid, and all the deep reflexes were lost except for jaw jerk which was weakly positive. Cranial CT scans revealed low density areas in the right anterior and middle cerebral artery territories with patchy areas of high density being consistent with a hemorrhagic infarction. In addition, a small high density mass lesion was noted in the left frontal lobe adjacent to the falx, which was thought to be a small meningioma. Her clinical course was complicated by pneumonia, hypotension and cardiac failure. She expired 2 months after the onset of her stroke. Postmortem examination revealed an extensive hemorrhagic infarction involving the territory of the right internal carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A 81-year-old man with dementia, gait disturbance, hemiparesis, and sympathetic apraxia].

We present a 81-year old male who developed dementia, gait disturbance and right hemiparesis. He was well until the age of 74 when he developed a hemorrhagic infarction in the right occipital region, which left him left homonymous hemianopsia. One year later he had one TIA attack consisting of dizziness, headache, and some clouding of consciousness. At that time, atrial fibrillation was found. At age 79, he was attacked by right hemiparesis. Cranial CT scans revealed a lesion consistent with a hemorrhagic infarct in the left middle cerebral artery territory. Two months prior to his final admission, he had a gradual onset of forgetfulness, labile affect, nocturnal agitation and hallucination which were followed by gait disturbance and urinary incontinence. On admission, he was alert but moderately demented. In addition he showed difficulty in repetition, limb kinetic and ideomotor apraxia of the left hand indicative of sympathetic apraxia, and constructional apraxia bilaterally. Granial nerves appeared intact except for left homonymous hemianopsia. His gait was wide-based and small stepped. No weakness or ataxia was noted. Deep reflexes were diminished on the left side. Plantar reflex was equivocally extensor of the left. Light touch and pain was slightly diminished on the right side. Cranial CT scans revealed a large low density area in the left fronto-temporo-parietal region. Also ventricular dilatation, diffuse low density change in the subcortical white matter, and diffuse cortical atrophy were seen. His clinical course was complicated by melena, anemia, pneumonia, cardiac failure and renal failure. He expired 2 months after his admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗