Influenza virus is a common respiratory tract viral infection. Although influenza can be fatal in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, its pathogenesis is not fully understood. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. In the present study, we investigated the role of Nrf2 in protection against influenza virus-induced pulmonary inflammation after cigarette smoke exposure with both in vitro and in vivo approaches. For in vitro analyses, peritoneal macrophages isolated from wild-type and Nrf2-deficient mice were treated with poly(I:C) and/or cigarette smoke extract. For in vivo analysis, these mice were infected with influenza A virus with or without exposure to cigarette smoke. In Nrf2-deficient macrophages, NF-κB activation and the induction of its target inflammatory genes were enhanced after costimulation with cigarette smoke extract and poly(I:C) compared with wild-type macrophages. The induction of antioxidant genes was observed for the lungs of wild-type mice but not those of Nrf2-deficient mice after cigarette smoke exposure. Cigarette smoke-exposed Nrf2-deficient mice showed higher rates of mortality than did wild-type mice after influenza virus infection, with enhanced peribronchial inflammation, lung permeability damage, and mucus hypersecretion. Lung oxidant levels and NF-κB-mediated inflammatory gene expression in the lungs were also enhanced in Nrf2-deficient mice. Our data indicate that the antioxidant pathway controlled by Nrf2 is pivotal for protection against the development of influenza virus-induced pulmonary inflammation and injury under oxidative conditions.

A topical application of a nonsteroidal anti-inflammatory drug (NSAID) may induct an adverse reaction of photoallergic contact dermatitis. The occlusive usage may provoke concomitant photoallergic sensitizations to an NSAID and other ingredients. We describe a 58-year-old woman with photoallergic contact dermatitis from ketoprofen and hydrogenated rosin glycerol ester in the applied compress. Our case indicates that photopatch testing with all ingredients is required to verify the actual photoallergen(s).

Primary effusion lymphoma (PEL) was once defined as a body cavity‐based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67‐year‐old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.

The biological, medical and environmental roles of trace elements have attracted considerable attention over the years. In spite of their relevance in nutritional, occupational and toxicological aspects, there is still a lack of consistent and reliable measurement techniques and reliable information on reference values. In this review our understandings of the urinary profilings of boron, lithium and strontium are summarized and fundamental results obtained in our laboratory are discussed.

Over the past decade we have successfully used inductively coupled plasma emission spectrometry for the determination of reference values for urinary concentrations of boron, lithium and strontium. Taking into account the short biological half-life of these elements and the fact that their major excretion route is via the kidney, urine was considered to be a suitable material for monitoring of exposure to these elements. We confirmed that urinary concentrations of boron, lithium and strontium follow a lognormal distribution. The geometric mean reference values and 95% confidence intervals were 798 μg/l (398–1599 μg/l) for boron, 23.5 μg/l (11.0–50.5 μg/l) for lithium and 143.9 μg/l (40.9–505.8 μg/l) for strontium. There were no discrepancies between our values and those previously reported. Our reference values and confidential intervals can be used as guidelines for the health screening of Japanese individuals to evaluate environmental or occupational exposure to these elements.

The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II-III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc.



Visual processing and its conscious awareness can be dissociated. To examine the extent of dissociation between ability to read characters or words and to be consciously aware of their forms, reading ability and conscious awareness for characters were examined using a tachistoscope in an alexic patient. A right handed woman with 14 years of education presented with incomplete right hemianopia, alexia with kanji (ideogram) agraphia, anomia, and amnesia. Brain MRI disclosed cerebral infarction limited to the left lower bank of the calcarine fissure, lingual and parahippocampal gyri, and an old infarction in the right medial frontal lobe. Tachistoscopic examination disclosed that she could read characters aloud in the right lower hemifield when she was not clearly aware of their forms and only noted their presence vaguely. Although her performance in reading kanji was better in the left than the right field, she could read kana (phonogram) characters and Arabic numerals equally well in both fields. By contrast, she claimed that she saw only a flash of light in 61% of trials and noticed vague forms of stimuli in 36% of trials. She never recognised a form of a letter in the right lower field precisely. She performed judgment tasks better in the left than right lower hemifield where she had to judge whether two kana characters were the same or different. Although dissociation between performance of visual recognition tasks and conscious awareness of the visual experience was found in patients with blindsight or residual vision, reading (verbal identification) of characters without clear awareness of their forms has not been reported in clinical cases. Diminished awareness of forms in our patient may reflect incomplete input to the extrastriate cortex.



Aims—To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL).

Methods—Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected.

Results—Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL.

Conclusions—The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.

Key Words: MALT lymphoma • stomach • transformation

BACKGROUND—It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been suggested, none of the lung proteins have been characterised. The purpose of this study was to determine the antigen to which the serum from patients with pulmonary fibrosis reacted.
METHODS—The anti-A549 cell antibody was characterised in a patient with CFA using Western immunoblotting and immunohistochemical staining of A549 cells. As we identified that one of the antibodies against A549 cells was anti-cytokeratin 8, the expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent assay to measure the levels of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD).
RESULTS—Initially two anti-A549 cell antibodies were detected in the serum of patients with pulmonary fibrosis, one of which was characterised as anti-cytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cytokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and pulmonary emphysema.
CONCLUSIONS—One of the anti-A549 cell antibodies in the serum of patients with CFA was against cytokeratin 8. The serum levels of anti-cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These results suggest that anti-cytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis.



It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19–9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC. © 1999 Cancer Research Campaign

OBJECTIVES—Memory impairment is not only the earliest clinical symptom but a central and prominent feature throughout the course of Alzheimer's disease. Alzheimer related pathological alterations in the medial temporal structures may account for the memory impairments in patients with Alzheimer's disease. The aim of this study was to elucidate the role of the medial temporal structures in memory impairment caused by Alzheimer's disease.
METHODS—Using high resolution MRI and a semiautomated image analysis technique, volumes of the medial temporal structures (amygdaloid complex, hippocampal formation, subiculum, and parahippocampal gyrus) were measured, and correlations between atrophy of each structure and memory dysfunction in patients with Alzheimer's disease were examined.
RESULTS—Patients with Alzheimer's disease showed poor performance on verbal and non-verbal memory tests, and MRI volumetry showed a significant volume reduction of the medial temporal lobe structures. Volumes of the amygdaloid complex and of the subiculum correlated with memory performance. Stepwise regression analyses disclosed that the volume of the right amygdaloid complex specifically predicted visual memory function and to some extent verbal memory function, and that the volume of the left subiculum specifically predicted verbal memory function. Atrophy of the hippocampus did not predict severity of memory impairment.
CONCLUSIONS—The presence of perihippocampal damage involving the amygdala proper, its surrounding cortex, and the subiculum further increased the severity of memory impairment attributable to hippocampal damage in Alzheimer's disease.



OBJECTIVE: To investigate the relation between atrophy of the hippocampus and parahippocampal gyrus (the % hippocampal area) and cerebral metabolic rate for glucose (CMRGlc) in Alzheimer's disease. METHODS: 13 patients with probable Alzheimer's disease by NINCDS-ADRDA criteria (six men; seven women, mean age 71 years, mini mental state 13.8 (SD 4.6)) and age matched controls were studied. T1 weighted MRI (0.5T) images were used for evaluation of the hippocampal area. With a digitiser system, a percentage of the hippocampal area to the brain (the % hippocampal area) was calculated. Eight patients received another T1 weighted MRI (1.5T) for further evaluation of the minimum thickness of the hippocampus. Regional CMRGlc (rCMRGlc) was measured using PET and the FDG technique. RESULTS: The hippocampal area in patients with Alzheimer's disease was significantly lower than that of controls (P < 0.01). All the cortical rCMRGlc values in patients with Alzheimer's disease were lower than those of controls (P < 0.01). A significant correlation (P < 0.05) was found between the % hippocampal area and rCMRGlc in the temporal lobe, temporoparieto-occipital (TPO) region, and frontal lobe in Alzheimer's disease. There was a significant correlation between minimal hippocampal thickness and ipsilateral TPO metabolism on both sides. CONCLUSION: The ipsilateral correlation between hippocampal atrophy and decreased TPO metabolism in Alzheimer's disease suggests a functional relation and the asymmetries show that Alzheimer's disease is an asymmetric disease in its early stages.

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A patient is described who presented with a disturbance of body cognition confined to the left side of the body. She showed difficulties in naming the left fingers and in moving the named left fingers. She also showed great difficulty in pointing to named parts of the body with her left hand. Earlier in the course of the disease she showed a personification phenomenon of the left hand. Brain MRI showed involvement of the entire corpus callosum, probably due to occlusion of a branch of the anterior cerebral artery. It is speculated that this syndrome is caused by disconnection of the right hemisphere from the left hemispheric body schema.

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In right middle cerebral territory infarction a new sign, excessive closure of the right eye ipsilateral to the lesion and mild closure of the left eye on command, was noted. The excessive ipsilateral eye closure was not observed on spontaneous eye closure.

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Fifteen patients with epilepsy and hypergraphia were compared with 32 patients with epilepsy but without hypergraphia. The number of previous psychiatric episodes, the number of Washington Psychosocial Seizure Inventory (WPSI) items indicating emotional maladjustment, and the number of CT scan abnormalities were significantly greater in the hypergraphic patients than in the non-hypergraphic patients. Cognitive performance, EEG laterality and the scores of WPSI items related to the psychological stress of seizures did not differ significantly between the two groups. Hypergraphia reflects changes in emotional responsiveness secondary to organic temporal lobe lesions.

A patient with MRI confirmed lesions in the corpus callosum and the left cingulate gyrus had a rare syndrome of crossed avoiding reaction of the left hand. With the right hand she could reach a stimulus object in whatever space it was presented. With the left hand, however, she could not mobilise it to reach a stimulus presented in the right hemispace relative to her body axis. In the left hemispace relative to her body axis her left hand reached an object without any difficulty. This left unilateral difficulty in the right unilateral space may be related to a unique spatial function that controls manual space, which is represented differentially in the two hemispheres. In the left hemisphere this function covers bilateral hemispace and is operated by the right hand. In the right hemisphere this function covers only the left hemispace and is operated by the left hand.

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Two different neurobehavioural abnormalities have been reported under the term hypergraphia. One has been described in temporal lobe epilepsies and the other in the acute stage of strokes of the right cerebral hemisphere. The latter type of hypergraphia in a patient with a metastatic brain tumour confined to the right hemisphere is reported. Such hypergraphia is a general right hemisphere sign that is not peculiar to strokes in the acute stage and the writing behaviour is inattentive.

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A unique behavioural syndrome in humans followed two separate strokes involving both parietotemporal regions. The behavioural alterations resemble those of Denny-Brown and Chambers' monkey with bilateral ablation of the parietal lobe which were characterised by strong withdrawal or refusal to be touched on the limbs and head. In both humans and animals, touch on the limbs or head elicited exaggerated withdrawal movements and refusal to be touched on the lips and tongue resulted in difficulty in feeding. These behavioural alterations can be interpreted as loss of exploratory activities towards extrapersonal space, or more positively, as rejection of contact with the environment. This rejection behaviour in which tactile, visual, and/or gustatory exploration tendencies are altered, is a counterpart of human frontal lobe syndrome and human Klüver-Bucy syndrome.

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A new right hemisphere symptom is reported. Five stroke patients with lesions in the perisylvian cortico-subcortical or thalamic region of the right hemisphere produced linguistically correct but semantically loose writing. The behaviour was initiated by subtle prompting and continued semiautomatically. A possible mechanism underlying this hypergraphia is discussed.

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Twenty-four right-handed, right hemiparetic patients with Broca's aphasia were examined for their singing capacity. Twenty-one (87.5%) produced good melogy. Twelve of these (57%) produced good text words while singing. It is speculated that the right hemisphere is dominant over the left for singing capacity. The relationship between melodic and text singing was also discussed.