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In order to clarify the factors that lead patients in the terminal stage of malignant diseases to home care, we interviewed ten families of such patients. Among factors involving patients, a strong desire to stay at home and to spend time at home with the family were initially required. Adequate understanding of the patients and their diseases was also needed by families. Other factors include guaranteed medical services in emergencies and/or 24 hours/day 7 days/week care. Patients requested referrals to family physicians, visiting nurses or community health services to cover outpatient clinic functions. It is concluded that a strong desire to stay at home, adequate understanding by the family and guaranteed medical services in emergencies were three significant factors leading to home care of patients in the terminal stage of malignant diseases.

This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients.Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy.Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured.1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p0.05). 2) Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p0.01). The VAS score was significantly decreased after interview regardless of the presence or absence of odor stimulation (p0.0001).A reduction in state anxiety was observed. The effect of odor was not significant on the subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT.

Extensive allelotyping studies have implicated several tumor-suppressor loci on chromosomes 3p, 5q, 6q, 8p, 9pq, 10q, 11q, 14q, 17p, 18q and 19p in human kidney tumorigenesis. The PTEN (also called MMAC1 and TEP1) gene, a candidate tumor suppressor located at chromosome 10q23.3, is mutated in a variety of sporadic malignancies as well as in patients with Cowden disease. To investigate the potential role of the PTEN gene in renal tumorigenesis, we searched for abnormalities of the gene in 68 primary renal-cell carcinomas (RCCs) as well as in 17 renal carcinoma-derived cell lines, using DNA-SSCP, sequencing and microsatellite analysis. Five of 68 (7.5%) primary RCCs exhibited intragenic mutations (3 missense, 1 deletion and 1 splice-site), and 1 of 17 (5.9%) cell lines had an insertion mutation. Loss of heterozygosity of the PTEN gene occurred in 25% of primary RCCs, including the 3 cases with intragenic mutation and the 1 PTEN-mutated cell line. Clinical and histopathological examinations revealed that 4 of the 5 primary tumors with PTEN mutation were high-grade, advanced clear-cell RCCs with distant metastases or renal vein tumor invasions, resulting in poor prognostic courses. The other was a low-stage papillary/chromophilic RCC. Our data suggest that PTEN mutation is observed in a subset of RCCs and that, especially in clear-cell RCCs, it occurs as a late-stage event and may contribute to the invasive and/or metastatic tumor phenotype.

I reviewed the literature on dissociation and dissociative disorders from Pierre Janet to DSM-IV, and examined the current trends in research. Janet's theory on hysteria is multifaceted, and is based on three psychological models. Based on a hierarchical model, Janet related hysteric symptoms to the activities within the lower strata of mental hierarchy (automatisms psychologiques), which were demonstrably shown in somnambulism. A second model was based on the concept of a psychological system, which was hypothetically composed of ideas, images, feelings, sensations, and movements. According to this model, dissociation of psychological functions was fundamental to the mechanism of hysteria: loss of integration was thought to engender fixed ideas (ideas fixes) and to lead to the development of a system totally isolated from the whole personality system. Janet also attempted to explain various mental disorders using an economic model. He referred to a loss of equilibration between psychological force and psychological tension. Thus, an unexpected emotional experience was conceived to cause a consumption of reserved psychological force, which was in turn followed by exhaustion associated with hysteric symptoms. Whereas most current researchers regard Janet as the first to study psychological trauma as a principal cause of dissociation, I feel it is important to note that he also emphasized the role of stigmata, i.e., permanent traits of hysteric patients, which were represented as a suggestibility and a tendency toward a narrowing of the consciousness field. Discussion about dissociation and its relation to trauma all but disappeared after Janet. However, during the Second World War and post-war period, some psychiatrists began to pay attention to two emerging phenomena: a high incidence of dissociative symptoms such as fugue and amnesia among combatants, and traumatic neurosis frequently observed among ex-inmates of concentration camps. In the 1970s, interest in dissociation and trauma was revived in different areas: the feminism movement was linked with concerns about child sexual abuse, public curiosity about multiple personalities was heightened by novels and movies, and recognition of posttraumatic stress disorder (PTSD) among Vietnam War veterans. In 1980, dissociative disorders were finally adopted as a diagnostic category in the official nomenclature of DSM-III. Although current research on dissociation is being carried out in various fields, two basic assumptions, reflected in the definition of DSM-IV, can be made. One is the "trauma-genic hypothesis," and the other is the great importance attached to multiple personality disorder (MPD). According to the predominantly held view, dissociation represents a reaction to early traumatic experience, especially sexual and physical abuse in childhood. In contrast, some authors argue that the causality of childhood traumatic experience has not been empirically confirmed, and other factors such as the influence of the environment and the predisposition of patients should be taken into consideration. MPD, which was originally described as an unusual phenomenon in classical literature, is currently thought to be a common type of dissociation. However, the reported rapid increase in the number of MPD patients in North America may be partially due to over-diagnosis and inclusion of iatrogenic cases. Significance is also given to MPD in respect to classification of dissociative phenomena. According to the widely held scheme of a "dissociative continuum," which ranges from normal experiences such as daydreams to pathological states, MPD is placed at the extreme end of the continuum. Furthermore, most researchers tend to classify MPD as the severest dissociative disorder due to chronic trauma. On this point, there seems to be confusion about "extremity" and "severity" of MPD. I conclude that the trauma-genic hypothesis of dissociation and the overemphasis placed on MPD should be reexamin

Several biophysical properties of four synthetic archaeal phospholipids [one polyprenyl macrocyclic lipid A and three polyprenyl double-chain lipids (B, C, D) bearing zero, one or four double bonds in each chain] were studied using differential scanning calorimetry, electron and optical microscopies, stopped-flow/light scattering and solid-state 2H-NMR techniques. These phospholipids gave a variety of self-organized structures in water, in particular vesicles and tubules. These assemblies change in response to simple thermal convection. Some specific membrane properties of these archaeal phospholipids were observed: They are in a liquid-crystalline state over a wide temperature range; the dynamics of their polyprenyl chains is higher than that of n-acyl chains; the water permeability of the membranes is lower than that of n-acyl phospholipid membranes. It was also found that macrocyclization remarkably improves the barrier properties to water and the membrane stability. This may be related to the adaptation of Methanococcus jannaschii to the extreme conditions of the deep-sea hydrothermal vents.

p300/CBP-associated factor (PCAF) is a histone acetyltransferase that plays an important role in the remodeling of chromatin and the regulation of gene expression. It has been shown to catalyze preferentially acetylation of the epsilon-amino group of lysine 14 in histone H3. In this study, the kinetic mechanism of PCAF was evaluated with a 20-amino acid peptide substrate derived from the amino terminus of histone H3 (H3-20) and recombinant bacterially expressed PCAF catalytic domain (PCAF(cat)). The enzymologic behavior of full-length PCAF and PCAF(cat) were shown to be similar. PCAF-catalyzed acetylation of the substrate H3-20 was shown to be specific for Lys-14, analogous to its behavior with the full-length histone H3 protein. Two-substrate kinetic analysis displayed an intersecting line pattern, consistent with a ternary complex mechanism for PCAF. The dead-end inhibitor analog desulfo-CoA was competitive versus acetyl-CoA and noncompetitive versus H3-20. The dead-end analog inhibitor H3-20 K14A was competitive versus H3-20 and uncompetitive versus acetyl-CoA. The potent bisubstrate analog inhibitor H3-CoA-20 was competitive versus acetyl-CoA and noncompetitive versus H3-20. Taken together, these inhibition patterns support an ordered BiBi kinetic mechanism for PCAF in which acetyl-CoA binding precedes H3-20 binding. Viscosity experiments suggest that diffusional release of product is not rate-determining for PCAF catalysis. These results provide a mechanistic framework for understanding the detailed catalytic behavior of an important subset of the histone acetyltransferases and have significant implications for molecular regulation of and inhibitor design for these enzymes.

A 79-year-old woman was admitted to our hospital with complaints of wheezing and dyspnea. Adenoid cystic carcinoma was diagnosed from the findings on biopsy specimens obtained by fiberoptic bronchoscopy. The tumor was resected and end-to-end anastomosis was performed. Precision analyses of lung sounds were conducted before and after the operation. During eupnea the tracheal sounds prior to operation contained an accentuated, high-frequency component at about 1,500 Hz. The tracheal sounds included a single monophonic wheeze during deep inspiration and 5 wheezes during forced expiration. By contrast, lung sounds in the chest wall were almost normal both before and after the operation. We concluded that increases in high-frequency components in tracheal sounds and the manifestation of various wheezes can be useful in diagnosing tracheal stenosis and/or tumors.

A 57-year-old man was referred and admitted to our hospital because of anterior mediastinal tumors and pericardial effusion. Although his condition had been diagnosed as thymic cancer by another hospital, a cytologic examination of pleural effusion specimens obtained a positive stain for chromogranin A, and yielded a diagnosis of thymic carcinoid tumor with multiple metastases. Despite irradiation and relief therapy, the patient died 8 months later. A histopathologic examination of the thymic tumor at autopsy revealed typical carcinoid patterns. The cytologic examination proved capable of accurately diagnosing the carcinoid tumor. Although such tumors are usually considered to have a good prognosis, unfavorable outcomes are also a possibility, as was demonstrated in this case.

Desmoplastic small round-cell tumor typically occurs in the abdomen of young men, but it can also develop at other anatomic sites and in older people, presenting greater diagnostic difficulties. We report a case of this tumor arising from the paratesticular region in a 43-year-old man. The tumor showed histologic, immunohistochemical, and ultrastructural evidence of multilineage differentiation, including epithelial, mesenchymal, and neuronal features. In addition, the presence of an EWS and WT1 chimeric messenger RNA was demonstrated by the reverse transcriptase-polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 and exon 9 primers, which revealed single polymerase chain reaction products with a junction of EWS exon 7 to WT1 exon 8. Our study demonstrates that desmoplastic small round-cell tumors of the paratesticular region share not only morphologic but also molecular genetic features with those of the abdomen and that reverse transcriptase-polymerase chain reaction analysis using paraffin sections is useful for a conclusive diagnosis.

Chromophobe renal cell carcinoma (RCC) is a newly established category of RCC composed histologically of characteristic "chromophobe" tumor cells. Although ultrastructural and immunohistochemical studies showed that these tumor cells present several features similar to those found in the intercalated cells of the collecting duct, immunohistochemical studies using antibody panels on a large number of cases are limited. We performed an immunohistochemical study of 21 Japanese cases of chromophobe RCC, along with cases of clear RCC and renal oncocytoma, to find hallmarks useful for precise differential diagnosis of these tumors. Chromophobe RCC was positive for epithelial membrane antigen but negative for vimentin. Cytokeratins did not show constant immunoreactivity in the three types of renal tumors. Furthermore, all of the chromophobe RCCs and renal oncocytomas were positive for E-cadherin but not for N-cadherin, whereas all of the clear RCCs were negative for E-cadherin, and 58% were positive for N-cadherin. The Ki-67 labeling indices were significantly lower in cases classified as (pT1) or Grade 2 chromophobe RCC than in cases of clear RCC. Immunoreaction for E-cadherin was demonstrated to be useful for distinguishing chromophobe RCC from clear RCC, and a low Ki-67 labeling index might indicate a favorable prognosis, as reported in several previous studies.

To clarify the process and mechanisms of the development and progression of peripheral lung adenocarcinoma, we investigated the relationships among the patterns of basement membrane (BM), stromal fibrosis, and the expressions of gelatinase A and tissue inhibitor of metalloproteinases-2 (TIMP-2) in 33 lesions of atypical alveolar cell hyperplasia (AAH) and 48 lesions of lung adenocarcinoma, including 24 lesions of bronchioloalveolar carcinoma (BAC). We found that the architecture of alveolar BM was intact in all 33 AAH lesions and 11 nonsclerosing BAC lesions that formed no central scar, suggesting that these lesions are early-stage intraepithelial neoplasia. The preexistent BM of the lung was disrupted, and the BM components around the neoplastic glands were disrupted or absent in the area of the central scar of some sclerosing BAC lesions with collapse fibrosis alone (2 of 4) and in those of all of the adenocarcinoma lesions associated with desmoplastic stromal fibrosis (nine sclerosing BAC and 24 non-BAC tumors). These results suggested that, in lung adenocarcinomas, destruction of the BM was correlated with the formation of a central scar, particularly with desmoplasia. It is likely that adenocarcinomas with a central scar are advanced and invasive cancers potentially having metastatic activity. The expression of gelatinase A and TIMP-2 was associated with central scar formation as well as with destruction of the BM components. Both the neoplastic and stromal cells expressed gelatinase A and TIMP-2 and probably play a role in tumor cell invasion.

Segmental mediolytic arteritis is a very rare vascular disease which causes sudden intraabdominal hemorrhage. The disease is characterized by degeneration of the arterial media, followed by aneurysmal dilatation and rupture of the involved artery. Up to now, only 13 cases have been reported, and this unique disease is not fully recognized among general pathologists and physicians. Here, we present a case of segmental mediolytic arteritis involving the propria hepatic artery, which resulted in intraabdominal hemorrhage, and consequently hypovolemic circulatory disturbance. Histologically, the rupture focus showed degeneration and desquamation of the intima and media with fibrin-like material covering the exposed adventitia. Inflammatory infiltrates were only noted in the rupture focus as a secondary reactive change. Other than the rupture focus, there were two foci showing similar findings. This disease has rarely been reported and is seldom recognized as a cause of arterial rupture. In cases of sudden intraabdominal hemorrhage, segmental mediolytic arteritis should be considered as a possible cause in addition to atherosclerotic and mycotic aneurysm, traumatic injury and vasculitis syndromes.

HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes. Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAFII250 component of the general transcription factor, TFIID. The C-terminal domain of Tat binds to a site on TAFII250 that overlaps the histone acetyl transferase domain, inhibiting TAFII250 histone acetyl transferase activity. Furthermore, promoters repressed by Tat, including the MHC class I promoter, are dependent on TAFII250 whereas those that are not repressed by Tat, such as SV40 and MuLV promoters, are independent of functional TAFII250. Thus, Tat repression of MHC class I transcription would be one mechanism by which HIV avoids immune surveillance.

General transcription factor TFIID consists of TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s), which together play a central role in both positive and negative regulation of transcription. The N-terminal region of the 230 kDa Drosophila TAF(II) (dTAF(II)230) binds directly to TBP and inhibits TBP binding to the TATA box. We report here the solution structure of the complex formed by dTAF(II)230 N-terminal region (residues 11-77) and TBP. dTAF(II)230(11-77) comprises three alpha helices and a beta hairpin, forming a core that occupies the concave DNA-binding surface of TBP. The TBP-binding surface of dTAF(II)230 markedly resembles the minor groove surface of the partially unwound TATA box in the TBP-TATA complex. This protein mimicry of the TATA element surface provides the structural basis of the mechanism by which dTAF(II)230 negatively controls the TATA box-binding activity within the TFIID complex.

A unique aspect of the retrovirus life cycle is the obligatory integration of the provirus into host cell chromosomes. Unlike viruses that do not integrate, retroviruses must conserve an ability to activate transcription from a chromatin context. Human immunodeficiency virus (HIV)-1 encodes an unusual and an unusually potent transcriptional transactivator, Tat, which binds to a nascent viral leader RNA, TAR. The action of Tat has been well studied in various reductive model systems; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternary complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linked to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in NIH3T3 cells to a level similar to that observed for human cells. By using transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associated HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR.

The X-ray structure of a canonical GCN5-related N-acetyltransferase (GNAT), Serratia marcescens aminoglycoside 3-N-acetyltransferase, bound to coenzyme A (CoA) has been determined at 2.3 A resolution. The single domain alpha/beta protein resembles a cupped right hand wrapped around a cylinder and consists of a highly curved, six-stranded beta sheet of mixed polarity that is sandwiched between four alpha helices. The structure includes all four conserved GNAT motifs (C, D, A, and B) and represents the catalytic core of this large enzyme superfamily. Acetyl CoA recognition is mediated by a betaalpha structure derived from GNAT motif A, which presents an invariant Arg/Gln-X-X-Gly-X-Gly/Ala segment for hydrogen bonding with the cofactor. Motif B contributes acidic residues to the binding site for the positively charged antibiotic substrate.

Vagal paragangliomas are rare tumors and difficult to differentiate from carotid body tumors or schwannomas of the vagus nerve. We present a patient who could be preoperatively diagnosed as having a vagal paraganglioma by ultrasonography and color Doppler sonography.

This study examined (1) the direct effect of the duration of caregiving on caregiver psychological distress, and (2) two- or three-way interactions between duration, stressors (elderly's physical and cognitive impairments), and personal (caregiver's economic or work status) or social (informal or formal supports) resources. We interviewed 833 primary family caregivers of non-institutionalized frail elderly who had been selected through a screening process of all residents aged 65 and over (21,567 persons) in a suburban area of Tokyo. Caregiver psychological distress was evaluated by "Caregiving Burden Scale" as a caregiving-specific psychological measurement, and "Center for Epidemiologic Studies Depression Scale (CES-D)" as a general psychological measurement. The results were as follows. 1. For Caregiving Burden, duration showed a direct effect, as those who had been providing care for a longer duration of time reported higher burden. We found no interactions between duration, stressors, and resources on caregiving burden. 2. For CES-D, duration had interactions, but no direct effect. (1) Two-way interactions were observed between duration and caregiver's economic or work status, as caregivers with a low economic status or who were unemployed showed a stronger negative impact from duration of caregiving. (2) Three-way interactions were observed between duration, the elderly's ADL impairment, and informal support. Informal support, such as a secondary caregiver, buffered the negative impact of the elderly's ADL impairment in cases with a shorter duration of caregiving, but not for those with longer duration. (3) Three-way interactions were observed between duration, the elderly's cognitive impairment, and formal emotional support. Formal emotional support buffered the negative impact of the elderly's cognitive impairment for those with a longer duration of caregiving, but not for those with a shorter duration. These findings suggest that stress-buffering resources differ according to duration of caregiving.

The present paper reports 2 cases of methamphetamine abuse. Following consecutive methamphetamine administration, the patients developed acute intoxication, during which time they showed a unique type of disturbance of consciousness: delirium and twilight state. In both cases, mental status changed, passing through three distinct stages: restlessness and insomnia, hallucinatory paranoid state, and disturbance of consciousness. A review of the literature suggests that disturbance of consciousness may occur occasionally during the course of amphetamine and methamphetamine intoxication, although these symptoms can be overlooked easily due to confounding symptomatology.

A 64-year-old woman had been feeding more than 60 pigeons in a coop in her back yard for 35 years. Diffuse reticulonodular shadows were found on a chest radiograph obtained as part of an annual check-up eight years before admission to the hospital. She was given a tentative diagnosis of idiopathic pulmonary fibrosis and was observed. She was admitted to our hospital because she noticed dry coughing and shortness of breath. A chest CT scan revealed segmentally distributed honeycombing and bronchi-bronchioloectasis. Tests for IgA and IgG antibodies to extracts of pigeon droppings in serum samples and in samples of bronchoalveolar lavage fluid were strongly positive, as were tests for lymphocyte blastogenic responses to samples of pigeon serum Examination of lung-biopsy specimens obtained by video-assisted thoracoscopic surgery revealed bronchiolitis, alveolitis, and honeycombing in a centrilobular distribution. The patient was given a diagnosis of pigeon-breeder's disease. Chronic hypersensitivity pneumonitis without acute episodes might be misdiagnosed as idiopathic interstitial pneumonia or bronchiectasis, as happened in this case. The possibility of chronic hypersensitivity pneumonitis should be considered when patients are suspected to have pulmonary fibrosis. It is important to obtain the detailed information on past or current avian contact, working history, and the home environment.

We used the MC3T3-E1 cell line, which originates from C57BL/6J mouse that is genetically type IIA secretory phospholipase A2 (sPLA2)-deficient, to reveal the type IIA sPLA2-independent route of the prostanglandin (PG) biosynthetic pathway. Kinetic and pharmacological studies showed that delayed PGE2 generation by this cell line in response to interleukin (IL)-1beta and tumor necrosis factor alpha (TNFalpha) was dependent upon cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2. Expression of these two enzymes was reduced by cPLA2 or COX-2 inhibitors and restored by adding exogenous arachidonic acid or PGE2, indicating that PGE2 produced by these cells acted as an autocrine amplifier of delayed PGE2 generation through enhanced cPLA2 and COX-2 expression. Exogenous addition or enforced expression of type IIA sPLA2 significantly increased IL-1beta/TNFalpha-initiated PGE2 generation, which was accompanied by increased expression of both cPLA2 and COX-2 and suppressed by inhibitors of these enzymes. Thus, our results revealed a particular cross-talk between the two PLA2 enzymes and COX-2 for delayed PGE2 biosynthesis by a type IIA sPLA2-deficient cell line. cPLA2 is responsible for initiating COX-2-dependent delayed PGE2 generation, and sPLA2, if introduced, enhances PGE2 generation by increasing cPLA2 and COX-2 expression via endogenous PGE2.

Based on a longitudinal study of a national representative sample aged 60 and over, we examined the impact of retirement on mental health and social well-being among elderly Japanese. From the baseline interviewees, we selected 178 study subjects who were full-time workers employed at least five days per week for at least six hours per day. At a follow-up survey three years after baseline, 34 had retired from their jobs and the rest still continued working. Mental health was rated from an aspect of depression, using a short form of the Center for Epidemiologic Studies Depression Scale. Social well-being was measured by two indicators: the degree of social participation and the frequency of meeting friends or neighbors. Multiple regression analyses were used to investigate the effect of retirement on mental health and social well-being, controlling for baseline health characteristics. Results showed there was no significant effect of retirement on either mental health or the degree of social participation. On the frequency of social contacts with friends or neighbors, however, the retirement x sex x age interaction contributed a significant effect. Early retirement among elderly men tended to decrease the frequency of social contrasts. This finding suggests that an extra-workplace social relationship should be recommended especially to middle-aged working men to prevent them from falling into social isolation after retirement.

We studied the influence of EIS on the respiro-circulatory condition of patients with portal hypertension. Subjects were fifty patients with portal hypertension who were successfully injected more than 5.0 ml of sclerotant into varices. A prospective randomized controlled trial was proposed to elucidate the effect of prophylactic administration of pure oxygen. Twenty-five patients inhaled pure oxygen (O2), remaining twenty-five patients did not during EIS. Respiro-circulatory function of patients was evaluated by monitoring O2 saturation, pulse rate and blood pressure during EIS. PaO2 was measured before and after EIS in seven patients without O2. EIS by the 5% ethanolamine oleate with iopamidol (EOI) was performed under X-ray monitoring. O2 saturation in patients without O2 inhalation was lowered, whereas that in patients with O2 inhalation was stable during EIS. O2 saturation during injection of EOI and after EIS in patients without O2 inhalation was significantly lower than that in patients with O2 inhalation. Pulse rate was significantly lower and a rise in blood pressure was smaller in patients given O2. No significant differences of PaO2 was noted before and after EIS. In conclusion, the monitoring of O2 saturation, pulse rate and blood pressure is necessary during EIS. Prophylactic administration of pure oxygen may be useful for prevention of hypoxic state and respiro-circulatory stabilization during EIS.

p300 is a nuclear phosphoprotein likely to be involved in the control of cell growth. Here we show that SV40 large T antigen (Tag) forms a specific complex with p300. In various Tag-expressing cell lines, the affinity of Tag for p300 was restricted to a newly identified unphosphorylated but ubiquitinated form of the protein. Further, Tag did not associate with p300 in an SV40 Tag-producing cell line (REV2) in which the original transformed phenotype (SV52) is reverted. Biochemical studies demonstrate that both the phosphorylation and the ubiquitination profile of p300 are altered in REV2 with respect to the wild-type fully transformed SV52 parental cells, wherein Tag-p300 complexes are readily detected. In contrast to Tag, the adenovirus early expression product E1a interacts with both phosphorylated and unphosphorylated forms of p300. In addition, when REV2 cells were infected with adenovirus, E1a-p300 complexes were detected, suggesting that the p300 expressed in REV2 has lost the affinity for Tag, but not for E1a. We then compared the ability of Tag and E1a to affect the transcription levels of the cAMP-responsive promoter (CRE), which is modulated in vivo by p300, in REV2 cells. We found that Tag repressed the CRE promoter in all of the cell lines in which Tag-p300 complexes were detected, but not in REV2 cells. In contrast, E1a efficiently inhibited CRE-directed transcription in this cell line. The data thus indicate that the different specificities exhibited by Tag and E1a towards the various forms of p300 are reflected in vivo as a difference in the ability of these viral oncoproteins to modulate the expression of CRE-containing genes.

We surveyed 22 patients (of whom 4 were women) with a history of antitussive drug abuse at a psychiatric hospital in the suburbs of Tokyo and at the Clinical Institute for Addiction Problems from 1 July 1986 to 30 June 1991. for changes in their pattern of abuse after the composition was altered. Here are our findings: 1) Researchers have long differed on whether ephedrine or codeine was responsible for the abuse of over-the-counter antitussive agents. The present study revealed that although codeine was still present in the new Bron syrup, its abuse was clearly on the decline in Japan, leading us therefore to conclude that psychological dependence on ephedrine was central to the spate of over-the-counter antitussive abuse observed in the 1980s. Although we cannot ignore the mellow feeling codeine creates, it is difficult to give it more central role in the abuse of such drugs. 2) Users were divided into two groups, one that had used other agents before using antitussives, and another that had never used any other agent but antitussives. A comparison of these two groups revealed clear differences in learning behavior, social adaptation, familial environment and delinquent tendencies, prior to their drug abuse. 3) After the composition was altered, abuse spread to Tonin syrup manufactured by another laboratory, Bron tablets, new Bron syrup and ephedrine tablets. Relatively recently, there have been some new cases of abuse of Bron tablets and an increase in the number of cases who continued to use Bron syrup even after its composition was altered. The Medical literature also reveals that in many countries the abuse of both codeine and ephedrine is becoming a social problem, and clearly either agent may be abused separately.

A 26-year-old male with chronic myelocytic leukemia was admitted for unrelated allogeneic bone marrow transplantation (BMT). After BMT, he developed swelling of biateral submandibular glands accompanied with pneumonitis possibly due to cytomegalovirus (CMV). Biopsy from the left submandibular gland showed giant cells with nuclear inclusion bodies that were positive for anti-CMV-IE monoclonal antibody, there fore cytomegalic sialoadenitis was diagnosed. The administration of ganciclovir resulted in resolution of the pnumonitis and submandibular gland swelling. Although cytomegalic sialoadenitis is not a life-threating complication in BMT patients, it should be noted that biopsy is very useful for the diagnosis of systemic cytomegalovirus infection.

A system for combined in vitro and in vivo culture of epithelial cells from distal human airways was established. Lung tissues that appeared to be generally normal were obtained from lungs removed surgically from patients with lung cancer. Small pieces of peripheral lung tissue were placed on culture dishes and cultured in F-12 complete medium containing serum and various growth factors, to obtain outgrown cells. For in vivo culture, rat tracheal grafts were de-epithelialized by freezing and thawing and were then used as culture vessels. Outgrown cells were harvested after 4 weeks of in vitro culture, inoculated into the denuded tracheal grafts, and then implanted into nude mice. For comparative purposes, bronchial fragments were also cultured in vitro and in vivo, by the same method. In vitro efficiency of colony formation was about the same for cells derived from peripheral lung tissue and from bronchial tissue (14.8 +/- 8.9% and 16.0 +/- 4.7%, respectively). Four weeks after implantation, the grafts were retrieved and processed for morphologic evaluation. By that time, grafts in both groups had totally re-epithelialized. Therefore, the growth potential of the cells derived from peripheral lung tissue and from bronchi in vivo appeared to be almost the same. Newly formed epithelial cells in grafts showed the same well-developed pseudostratified columnar form in both groups at 4 weeks. The time course of epithelial cell differentiation was also studied, with outgrown cells from lungs. Two days after implantation, undifferentiated cells were attached to the inner surface of the grafts as a single cell layer, and at 4 days, small cell nests containing mitotic cells were observed. At 1 week, the grafts were totally covered with undifferentiated cells. Over 2 to 3 weeks, differentiated cells (ciliated, secretory, and basal cells) appeared, and the epithelia had become fully developed by 4 weeks. As reported previously, cells that outgrew from lung explants were considered to be derived from bronchioles. Therefore, this system may be useful for studies of growth and differentiation of human bronchiolar epithelial cells under various conditions.

The literature on the psychiatric aspects of anabolic steroids (AS) abuse in the United States is reviewed. Since the 1980s the use of AS has become prevalent among adults and adolescents who are concerned with muscle size and strength, and the abuse of these agents is regarded as a serious drug problem. Researchers noticed that illicit, high-dose use of AS may produce not only somatic adverse effects but behavioral changes. Several studies using psychometry and questionnaires suggested that characteristic psychological phenomena such as increased aggression and irritability may be observed in AS abusers. Although the evidence determining the addictive potential of AS is limited, some authors provide evidence that the long-term use of AS may lead to a mental disorder which meets the DSM-III-R criteria of psychoactive substance abuse. Detailed case reports of AS-induced mental disorders are scarce, but characteristic symptoms, particularly major mood disturbances, have been recognized. Violent crimes committed by abusers taking large doses of AS have also been highlighted. In these cases the dangerous behavior appears to have been induced by aggression, grandiosity, and rage. This review indicates that empirical data specifying psychiatric effects of AS are not sufficient at present, and more attention needs to be paid to trends in AS abuse in Japan.

We performed a distal gastrectomy, including regional lymph node dissection, under laparoscopic observation followed by Billroth I. (B-I) anastomosis using autosuture in five patients with early gastric cancer. We had previously evaluated the technique for reconstructive surgery in animal experiments. Our method was determined to be safe without marked deformation caused by applying the autosuture for gastroduodenostomy. The wound was small, and an almost closed operation was possible. Furthermore, unlike endoscopic mucosal resection or laparoscopic partial resection, a major part of the regional lymph nodes can be extirpated; the lesion site may not be limited to the half of the stomach on the distal side. Our method of distal gastrectomy under laparoscopy is a potentially useful limited operation in patients with early gastric cancer.

To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we evaluated the lesion size, growth fraction, and p53 overexpression of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classified as showing low grade or high grade atypia. AAH-like carcinoma, presumably very early stage BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive of malignant potential and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determined immunohistochemically in terms of the Ki-67 labeling index. The overexpression of p53 was evaluated by assessing the nuclear accumulation of immunoreactive p53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of p53 in AAH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-like carcinoma, and overt BAC represent different categories, although the cellular events occurring in these lesions presumably represent a continuous spectrum of the changes that are reflected in the cytomorphology and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representing different steps toward overt BAC.

The prospective association of social integration reported in 1987 with change in activities of daily living (ADL) over three years was examined in a cohort of 2200 Japanese elderly, aged 60 years and over. Social integration data was obtained from a national survey which measured both the quantity and frequency of attachment. Social ties were classified into five types: spouse, child(ren) living together, child(ren) living separately, friend, neighbor, and community group. Eight potential confounding variables--age, educational attainment, existence of chronic diseases, subjective well-being, drinking, sleeping hours, cigarette smoking, and exercise--were controlled using logistic regression analysis for each sex. Men who attended community group meetings more frequently had significantly less decline in ADL during the follow-up period for those who were ADL unimpaired at the baseline survey, and were also significantly more improved for those who were ADL impaired people at the baseline survey. Trends for women were not significant.

A case of adrenal cyst with an immunohistochemical evidence of mesothelial origin is presented. A 73-year-old Japanese woman was referred to our hospital with a complaint of left flank pain. The diagnosis of left adrenal cyst was made based on the radiographic and hormonal examinations. The adrenal cyst was removed surgically. Histological examination revealed that the cyst was lined with either a single layer of squamous or cuboidal cells. In immunohistochemistry testing, the cells were positive for keratin and carbohydrate antigen 125, while they were negative for epithelial membrane antigen, vimentin, desmin, and factor VIII related antigen. Thus, the present case was classified as epithelial cyst of mesothelial origin.

To examine the clinical characteristics of methamphetamine (MAP) psychosis in Japan, we evaluated 104 patients with MAP psychosis (80 men and 24 women) admitted to the closed psychiatric units of Tokyo Metropolitan Matsuzawa Hospital between 1988 and 1991. There has recently been a steep increase in the number of admissions for MAP psychosis, reflecting the growth of the epidemic of MAP abuse in Japan. Although more than half of the patients were discharged within one month, 16 patients were hospitalized for more than 3 months. Most of the patients showed paranoid psychotic state similar to schizophrenia, consistent with previous reports. Despite the abstinence from MAP and antipsychotic medication, psychotic symptoms tended to persist in some of the patients. The etiological role of MAP psychosis in the development of long-lasting psychotic state was discussed.

A TATA box-binding initiation factor, TFIID, plays a central role in the transcriptional regulation by activators. Using anti-TFIID tau (a TATA box-binding component of native TFIID) immunoaffinity chromatography, nine polypeptides (230, 110, 85, 62, 58, 42, 28, 22, and 21 kDa) were identified as native Drosophila TFIID components that are tightly associated with TFIID tau. To verify the functional activity of the purified TFIID complex, template DNA and other transcription factors were reconstituted with purified TFIID bound to the antibody-Sepharose matrix. Immobilized TFIID mediated not only basal transcription but transcriptional activation by upstream stimulatory factor (USF). On the other hand, recombinant TFIID tau immobilized on the same antibody-Sepharose matrix could not mediate activation by USF. These results suggest that one or more of these additional polypeptides are required as functional TFIID subunits for activator-dependent transcription in conjunction with TFIID tau. As further evidence of the relevance of the Drosophila TFIID components identified in this analysis, including the previously unrecognized p230 (Dynlacht, B. D., Hoey, T., and Tjian, R. (1991) Cell 66, 563-576), protein blot analysis showed that TFIID tau interacts specifically and exclusively with p230. This suggests that p230 is an integral subunit of TFIID and that it may play a major role in tethering other subunits to TFIID tau.

We have constructed the Bonse-Hart type Ultra-small-angle X-ray Scattering (USAXS) instrument to study large-scale density fluctuations in colloidal and polymer systems. Our USAXS instrument has very high small-angle resolution up to 8 micrometers. The USAXS curves from polymer latex dispersions at very low ionic strength showed clear Bragg peaks, indicating that the ordered structure of latex particles was formed even inside dispersions by the electrostatic interactions between the particles. The lattice system and lattice constant could be precisely estimated. The time evolution of the USAXS curve reflecting the ordered structure formation was also examined. The microdomain structure of polymer alloy systems and microcrystalline structure of polypropylene film were also investigated. The USAXS technique enables us to investigate submicron structures in various systems which could not be studied by other techniques