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Purpose: To evaluate the reproducibility of diaphragm position in our new breath-holding radiotherapy for abdominal tumors using image-guided radiation therapy (IGRT) and a voluntary breath-holding device, Abches., Materials and Methods: Patients treated with abdominal tumors using IGRT with Abches were enrolled. Twenty patients without dementia or severe lung disease were analyzed. Each fraction of all patients was set up with kV cone-beam CT with reference to the vertebral bodies. Before daily treatment, electronic portal imaging device (EPID) images of the diaphragm at breath-holding exhale phase were acquired. The difference in the diaphragm position relative to the vertebral body was analyzed by comparing EPID images and the digitally reconstructed radiograph of the planning CT. We evaluated the reproducibility of two axes: superior-inferior (S-I) and right-left (R-L) with the EPID measurements., Results: The 443 irradiation data sets were analyzed. The interfractional reproducibility of the diaphragm relative to vertebral bodies was 1.7 ± 1.4 mm in the S-I and 1.4 ± 1.2 mm in the R-L direction., Conclusion: This technique has good interfractional reproducibility and visibility of the diaphragm during irradiation. Its use is feasible in the routine clinical setting and irradiation.

The caring experiences of female families of persons with schizophrenia were described through exploring the families' descriptions of their experiences. Focus group interviews were conducted with 11 family caregivers. According to content analysis, the experiences revealed five major themes: early family experiences, family perceptions of illness and relatives with schizophrenia, family burden and suffering, family attitudes toward relatives with schizophrenia, and family thoughts about society and mental health resources. Also, the families had strength to overcome considerable adversity. It is needed for professionals to listen to family caregivers' narratives carefully and improve the support by focusing on accepting their experiences and histories with persons with schizophrenia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

People with mental disabilities tend to lack communication skills and have difficulty with interpersonal relationships. Interpersonal communication skills were examined in two people with Down Syndrome with regard to playing wadaiko (Japanese drum). Motion analysis compared single play and two-person play in which one participant was more skillful than the other. The effect of wadaiko play was quantified using two different methodologies: motion delay and hit-timing analysis and visual analog-scale (VAS) ratings before and after play. The motion analysis indicated that the study participants became mutually synchronized in playing wadaiko, and that a participant played more accurately when he played with a senior member. VAS ratings indicated that participants felt more positive after practicing wadaiko than before and self-confidence improved. Synchronized gestures of wadaiko performance may be an effective therapy for people with limited communication skills.

We present two cases of central venous catheterization (CVC) in which an ultrasound-guided in-plane approach was used. Case 1 was a 60-year-old man with acute myelogenous leukemia in whom a right supraclavicular CVC was performed. He had pancytopenia (leukocytes 2,000/μL; erythrocytes 350 × 10(4)/μL; platelets 5.6 × 10(4)/μL), and abnormal coagulability (prothrombin time-international normalized ratio 1.35). A linear array transducer was positioned cephalad to the right clavicle and rotated 30° clockwise. The 21-gauge needle was manipulated from outside of the transducer. A CV catheter (CV legaforce EX(®); Terumo Co., Japan) was placed and stitched near the right clavicle. The patient felt no discomfort caused by the catheter. Case 2 was a 64-year-old women with malignant lymphoma whose right internal jugular vein was surrounded by abnormally enlarged lymph nodes. CVC was performed by the in-plane supraclavicular approach, avoiding puncture of the lymph node. This novel CVC technique is useful to minimize the risk of complications and patient discomfort by indwelling catheter.

The purpose of this study was to clarify the sense of coherence (SOC) and quality of life (QOL) of caregivers of persons with schizoprenia. Thirty-four families were investigated using the SOC-13, the 26-item World Health Organization Quality of Life, and an interview guide. Family caregivers in their 50s, 60s, and 70s with higher SOC scores showed higher QOL scores; older groups showed higher mean SOC and QOL scores; and a significant difference in the scores for the environment domain was observed among the 3 groups. SOC was considered to be influenced by the family caregivers' age, educational level, duration of ilness, and whether they live with the patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care practices; thus, primary care physicians have a significant opportunity to improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant new evidence has accumulated, and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading the strength of recommendation formulated for use in clinical practice. A total of 26 key recommendations, 10 for diagnosis and 16 for management, of patients with gout were evaluated, resulting in important updates for patient care. The presence of monosodium urate crystals and/or tophus and response to colchicine have the highest clinical diagnostic value. The key aspect of effective management of an acute gout attack is initiation of treatment within hours of symptom onset. Low-dose colchicine is better tolerated and is as effective as a high dose. When urate-lowering therapy (ULT) is indicated, the xanthine oxidase inhibitors allopurinol and febuxostat are the options of choice. Febuxostat can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. The target of ULT should be a serum uric acid level that is ≤ 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option. This article is a summary of the 2011 clinical guidelines published in Postgraduate Medicine. This article provides a streamlined, accessible overview intended for quick review by primary care physicians, with the full guidelines being a resource for those seeking additional background information and expanded discussion.

The caregiving experiences of husbands living with spouses with schizophrenia were described through exploring husbands' descriptions of their experiences. Twelve husbands participated in the study. According to content analysis, the husbands' experience revealed six major themes: identification and acceptance of the disease by the husbands, past and present experience with wives with schizophrenia, the roles and burdens of husbands, marital relationships and the presence of the wife for husbands, social resources, participation in the community and society, and perspectives on the future. Based on the bond of marriage established through living together and mutual trust between couples, the husbands aim to share life experiences with their wives., (Copyright © 2011 Elsevier Inc. All rights reserved.)

To identify and gain a better understanding of the cadherin-like receptor-binding site on Bacillus thuringiensis Cry toxins, it is advantageous to use Cry1Aa toxin, because its 3D structure is known. Therefore, Cry1Aa toxin was used to examine the locations of cadherin-like protein-binding sites. Initial experiments examining the binding compatibility for Cry1Aa toxin of partial fragments of recombinant proteins of a 175kDa cadherin-like protein from Bombyx mori (BtR175) and another putative receptor for Cry1Aa toxin, amino peptidaseN1, from Bo.mori (BmAPN1), suggested that their binding sites are close to each other. Of the seven mAbs against Cry1Aa toxin, two mAbs were selected that block the binding site for BtR175 on Cry1Aa toxin: 2A11 and 2F9. Immunoblotting and alignment analyses of four Cry toxins revealed amino acids that included the epitope of mAb 2A11, and suggested that the area on Cry1Aa toxin blocked by the binding of mAb 2A11 is located in the region consisting of loops2 and 3. Two Cry1Aa toxin mutants were constructed by substituting a Cys on the area blocked by the binding of mAb 2A11, and the small blocking molecule, N-(9-acridinyl)maleimide, was introduced at each Cys substitution to determine the BtR175-binding site. Substitution of Tyr445 for Cys had a crippling effect on binding of Cry1Aa toxin to BtR175, suggesting that Tyr445 may be in or close to the BtR175-binding site. Monoclonal antibodies that blocked the binding site for BtR175 on Cry1Aa toxin inhibited the toxicity of Cry1Aa toxin against Bo.mori, indicating that binding of Cry1Aa toxin to BtR175 is essential for the action of Cry1Aa toxin on the insect.

During cytokinesis, the central spindle, a bundle of interdigitated anti-parallel microtubules between separating chromosomes, recruits various cytokinetic regulator proteins to the cleavage region. Here, we show that the level of protein ubiquitylation is strikingly and transiently elevated in Aurora B kinase-positive double-band regions of the central spindle during cytokinesis. Two deubiquitylating enzymes UBPY and AMSH, which act on endosomes in interphase, were also recruited to the cleavage region. Whereas UBPY was detected only in the final stage of cytokinesis at the midbody, AMSH localized to a ring structure surrounding the mitotic kinesin MKLP1-positive region of the central spindle and midbody throughout cytokinesis. Depletion of cellular UBPY or AMSH led to defects in cytokinesis. VAMP8, a v-SNARE required for vesicle fusion in cytokinesis, localized to the central spindle region positive for ubiquitylated proteins, and underwent ubiquitylation and deubiquitylation by both UBPY and AMSH. Our results thus implicate the ubiquitylation/deubiquitylation of proteins including VAMP8 in cytokinesis.

Background: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis that is caused by mutations in the VPS13A gene. There are only few reports that studied clinical status of the obligate carriers of ChAc. Clinical courses with follow-up neuroradiological and neuropsychological evaluations in individuals with ChAc have been rarely reported., Methods: We followed an index patient with ChAc and evaluated the clinical features of the pedigree members. Genetic analyses of VPS13A and genes responsible for other neuroacanthocytotic and neurodegenerative diseases were performed., Conclusions: The index patient was homozygous for a 3889C>T nonsense mutation in the VPS13A gene and presented with a typical ChAc phenotype. Neuropsychological evaluation with brain imaging in the patient over 3 years revealed atrophy and a decrease in blood flow at the basal ganglia and frontal lobe, and impairment in cognitive function reflecting frontal lobe dysfunction in progressive manners. Four out of five heterozygous mutation carriers in the pedigree showed signs or symptoms potentially attributable to a heterozygous VPS13A mutation.

G-quenched MBs are devised from readily available starting materials and used for sequence specific DNA detection with high efficiency.

The deubiquitinating enzyme UBPY, also known as USP8, regulates cargo sorting and membrane traffic at early endosomes. Here we demonstrate the regulatory mechanism of the UBPY catalytic activity. We identified 14-3-3 epsilon, gamma, and zeta as UBPY-binding proteins using co-immunoprecipitation followed by mass spectrometric analysis. The 14-3-3 binding of UBPY was inhibited by mutating the consensus 14-3-3-binding motif RSYS(680)SP, by phosphatase treatment, and by competition with the Ser(680)-phosphorylated RSYS(680)SP peptide. Metabolic labeling with [(32)P]orthophosphate and immunoblotting using antibody against the phosphorylated 14-3-3-binding motif showed that Ser(680) is a major phosphorylation site in UBPY. These results indicated that 14-3-3s bind to the region surrounding Ser(680) in a phosphorylation-dependent manner. The mutation at Ser(680) led to enhanced ubiquitin isopeptidase activity of UBPY toward poly-ubiquitin chains and a cellular substrate, epidermal growth factor receptor, in vitro and in vivo. Moreover, addition of 14-3-3epsilon inhibited the UBPY activity in vitro. Finally, UBPY was dephosphorylated at Ser(680) and dissociated from 14-3-3s in the M phase, resulting in enhanced activity of UBPY during cell division. We conclude that UBPY is catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase.

A novel FRET based strategy for DNA sequence analysis utilising base-discriminating fluorescence (BDF) nucleoside, (Py)U/(2-Ant)U, as donor in the dual-labelled oligonucleotide probe is reported; a selective/specific emission from acceptor, was observed upon excitation at the donor, only when the opposite base of the "smart" fluorescently labeled BDF nucleoside, (Py)U/(2-Ant)U, is adenine on the complementary target sequence.

Mutations in vacuolar protein sorting 13A (VPS13A) gene are responsible for chorea-acanthocytosis (ChAc). We previously determined the full-length sequence and exon-intron structure of mouse VPS13A and generated a ChAc model mouse by using the gene targeting technique. In the process, we found diverse 5' and 3' transcript variants. Since ChAc is a rare neurodegenerative disorder, the mouse model should be useful for investigation of ChAc molecular pathogenesis, and the model's brain specific variants of VPS13A will be indispensable in these investigations. In the present study, we investigated mouse VPS13A transcript variants. We found brain-specific variants of mouse VPS13A, which may be involved in the brain-specific pathology of ChAc. In addition, we identified for the first time mouse VPS13C cDNA sequences and brain-specific variants of VPS13C.

Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. In this study, we produced an antibody against chorein and examined its protein-level expression and localization in mouse. Immunoblot analysis revealed that chorein was expressed in a gene dose-dependent manner in the VPS13A deletion-mice that we recently developed, which confirms the sensitivity of the antibody. Chorein was highly expressed in testis, kidney, spleen, and brain, and was expressed ubiquitously in various brain regions. Subcellular analysis of the brain showed high levels of chorein in microsomal and synaptosomal fractions. Immunohistochemically, chorein-like immunoreactivity was ubiquitously observed in the brain in the neuronal perinuclear region, cytoplasm and fibers. In testis and kidney, clear cell-specific patterns of chorein-like immunoreactivity were detected. Our findings provide basic information on chorein in vivo and may contribute to taking the first step toward understanding molecular pathogenesis of ChAc.

Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. Recently, using a gene-targeting technique to delete exons 60-61, we produced a ChAc-model mouse that corresponds to a human disease mutation. In this study, a comparative microarray analysis of gene expression in the striatum revealed an increased level of gephyrin gene expression in the ChAc-model mice compared with wild type mice. Since gephyrin is known as a GABA(A) receptor-anchoring protein, we compared the protein-level expression and localization of gephyrin and the GABA(A) receptor alpha1 (GABRA1) and gamma2 (GABRG2) subunits. Gephyrin and GABRG2 immunoreactivities in the striatum and hippocampus of the ChAc-model mice were significantly higher than those in the wild types. Our results suggest that chorein functional loss may lead to a compensatory upregulation of gephyrin and GABRG2 in the pathologic condition in ChAc.

Monoubiquitination of endocytosed cell surface receptors serves as a sorting signal for their trafficking from endosomes to lysosomes. The sorting of ubiquitinated proteins is executed by concerted actions of class E vacuolar protein sorting (Vps) proteins. Some proteins in the sorting machinery undergo monoubiquitination, suggesting that their functions are also regulated by ubiquitination. The Hrs-STAM complex, a class E Vps protein complex essential for the initial step of the sorting pathway, binds two deubiquitinating enzymes, UBPY and AMSH. Here we examined the effects of inactivating UBPY on protein ubiquitination at endosomes. Overexpression of a catalytically inactive UBPY mutant or depletion of UBPY by RNA interference resulted in the accumulation of ubiquitinated proteins on morphologically aberrant endosomes. Electron microscopy showed that they are aggregates of multivesicular endosomes. Among the sorting machinery proteins that undergo ubiquitination, Eps15 was monoubiquitinated at an elevated level in UBPY-inactivated cells. UBPY also deubiquitinated Eps15 in vitro, suggesting that Eps15 is a cellular substrate for UBPY. Furthermore, inactivation of UBPY caused the accumulation of Eps15 on the endosomal aggregates. These results suggest that UBPY regulates the level of protein ubiquitination on endosomes, which is required for maintaining the morphology of the organelle.

Study Objective: Abdominal aortic aneurysmectomy (AAAectomy) results in a general ischemia-reperfusion syndrome accompanied by an acute rise in pulmonary artery pressure (PAP). We examined whether ulinastatin, a urinary trypsin inhibitor, prevents ischemia-reperfusion injury and increase in PAP after aortic unclamping (XU) during AAAectomy., Design: Prospective study., Setting: Public, university-affiliated hospital., Patients: Sixteen patients (11 males and 5 females) scheduled for AAAectomy., Interventions and Measurements: The patients received 300000 IU of ulinastatin intravenously before XU (n = 8) or no additional treatment (n = 8) (control). Heart rate, central venous pressure, PAP, pulmonary arterial wedge pressure, arterial pressure, mixed venous oxygen saturation (Sv(O2)), and cardiac output were monitored. Arterial and mixed venous blood samples were analyzed for pH, Pa(CO2), Pa(O2), hemoglobin, and oxygen saturation, and the physiological shunt function (Qs/Qt) were calculated. Plasma concentrations of malondialdehyde, myeloperoxidase, granulocyte elastase, alpha1-antitrypsine, and thromboxane B2 and the stable hydrolysis products of thromboxane A2 were measured. Measurements were conducted before aortic crossclamping (XC) (baseline) and at 10, 30, and 60 minutes after XU., Main Results: A significant increase in PAP was observed 10 minutes after XU in the control group but not in the ulinastatin group. At 60 minutes after XU, Qs/Qt values had increased in the control group but had decreased in the ulinastatin group. There were no significant changes in malondialdehyde, thromboxane B2, granulocyte elastase, and alpha1-antitrypsine levels after XU in either group. A significant decrease in the plasma level of myeloperoxidase after XU was found in both groups., Conclusions: The present study demonstrated that ulinastatin prevents increase in PAP and shunting after XU during AAAectomy.

Ligand-activated receptor tyrosine kinases undergo endocytosis and are transported via endosomes to lysosomes for degradation. This "receptor down-regulation" process is crucial to terminate the cell proliferation signals produced by activated receptors. During the process, ubiquitination of the receptors serves as a sorting signal for their trafficking from endosomes to lysosomes. Here, we describe the role of a deubiquitinating enzyme UBPY/USP8 in the down-regulation of epidermal growth factor (EGF) receptor (EGFR). Overexpression of UBPY reduced the ubiquitination level of EGFR and delayed its degradation in EGF-stimulated cells. Immunopurified UBPY deubiquitinated EGFR in vitro. In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR. Overexpression of Hrs or a dominant-negative mutant of SKD1, proteins that play roles in the endosomal sorting of ubiquitinated receptors, caused the accumulation of endogenous UBPY on exaggerated endosomes. A catalytically inactive UBPY mutant clearly localized on endosomes, where it overlapped with EGFR when cells were stimulated with EGF. Finally, depletion of endogenous UBPY by RNA interference resulted in elevated ubiquitination and accelerated degradation of EGF-activated EGFR. We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.

We analyzed the binding site on Cry1Aa toxin for the Cry1Aa receptor in Bombyx mori, 115-kDa aminopeptidase N type 1 (BmAPN1) (K. Nakanishi, K. Yaoi, Y. Nagino, H. Hara, M. Kitami, S. Atsumi, N. Miura, and R. Sato, FEBS Lett. 519:215-220, 2002), by using monoclonal antibodies (MAbs) that block binding between the binding site and the receptor. First, we produced a series of MAbs against Cry1Aa and obtained two MAbs, MAbs 2C2 and 1B10, that were capable of blocking the binding between Cry1Aa and BmAPN1 (blocking MAbs). The epitope of the Fab fragments of MAb 2C2 overlapped the BmAPN1 binding site, whereas the epitope of the Fab fragments of MAb 1B10 did not overlap but was located close to the binding site. Using three approaches for epitope mapping, we identified two candidate epitopes for the blocking MAbs on Cry1Aa. We constructed two Cry1Aa toxin mutants by substituting a cysteine on the toxin surface at each of the two candidate epitopes, and the small blocking molecule N-(9-acridinyl)maleimide (NAM) was introduced at each cysteine substitution to determine the true epitope. The Cry1Aa mutant with NAM bound to Cys582 did not bind either of the two blocking MAbs, suggesting that the true epitope for each of the blocking MAbs was located at the site containing Val582, which also consisted of 508STLRVN513 and 582VFTLSAHV589. These results indicated that the BmAPN1 binding site overlapped part of the region blocked by MAb 2C2 that was close to but excluded the actual epitope of MAb 2C2 on domain III of Cry1Aa toxin. We also discuss another area on Cry1Aa toxin as a new candidate site for BmAPN1 binding.

Chorea-acanthocytosis (CHAC) is a hereditary neurodegenerative disorder with autosomal recessive transmission, in which selective degeneration of striatum has been reported in brain pathology. Clinically, CHAC shows Huntington's disease-like neuropsychiatric symptoms and red blood cell acanthocytosis. Recently, we identified the gene, CHAC, encoding a novel protein, chorein, in which a deletion mutation was found in Japanese families with CHAC. In the present study, we have identified the mouse CHAC cDNA sequence and the exon-intron structures of the gene and produced a CHAC model mouse introducing no. 60-61 exon deletion corresponding to a human disease mutation by a gene-targeting technique. The mice began to show acanthocytosis and motor disturbance in old age. In behavioral observations, locomotor activity was significantly decreased and the contact time at social interaction test was decreased significantly in the model mice. In the brain pathology, many apoptotic cells were observed in the striatum of the mutant mice. In neurochemical determinations, the dopamine metabolite, homovanillic acid, concentration decreased significantly in the portion including the midbrain of the mutant mice. These findings are consistent with the human results reported elsewhere and indicate that the CHAC model mice showed a mild phenotype with late adult onset. The CHAC model mouse therefore provides a good model system to study the human disease.

Ligand-stimulated growth factor receptors are rapidly internalized and transported to early endosomes. Unstimulated receptors are also internalized constitutively, although at a slower rate, and delivered to the same organelle. At early endosomes, stimulated receptors are sorted for the lysosomal degradation pathway, whereas unstimulated receptors are mostly recycled back to the cell surface. To investigate the role of Hrs, an early endosomal protein, in this sorting process, we overexpressed Hrs in HeLa cells and examined the intracellular trafficking of epidermal growth factor receptor (EGFR) in EGF-stimulated and unstimulated cells. Overexpression of Hrs inhibited the trafficking of EGFR from early endosomes, resulting in an accumulation of EGFR on early endosomes in both ligand-stimulated and unstimulated cells. On the other hand, overexpression of Hrs mutants with a deletion or a point mutation within the FYVE domain did not inhibit the trafficking. These results suggest that Hrs regulates the sorting of ligand-stimulated and unstimulated growth factor receptors on early endosomes, and that the FYVE domain, which is required for Hrs to reside in a microdomain of early endosomes, plays an essential role in the function of Hrs.

A 58-year-old man was scheduled for laryngomicrosurgery for treatment of large laryngeal polyps. Although awake induction was initially attempted to prevent airway obstruction, his vocal cords could not be visualized. We therefore tried intubation with a Parker Flex-Tip (PFT) tube under the guidance of a bronchial fiberscope (BF). After inserting the BF, his trachea was intubated easily. The operation was performed without any complications. We conclude that a PFT tube is useful for endotracheal intubation in a patient with large laryngeal polyps.

Conjugation with ubiquitin acts as a sorting signal for proteins in the endocytic and biosynthetic pathways at the endosome. Signal-transducing adaptor molecule (STAM) proteins, STAM1 and STAM2, are associated with hepatocyte growth factor-regulated substrate (Hrs) but their function remains unknown. Herein, we show that STAM proteins bind ubiquitin and ubiquitinated proteins and that the tandemly located VHS (Vps27/Hrs/STAM) domain and ubiquitin-interacting motif serve as the binding site(s). STAM proteins colocalize with Hrs on the early endosome. Overexpression of STAM proteins, but not their mutants lacking the ubiquitin-binding activity, causes the accumulation of ubiquitinated proteins and ligand-activated epidermal growth factor receptor on the early endosome. These results suggest that through interaction with ubiquitinated cargo proteins on the early endosome via the VHS domain and ubiquitin-interacting motif, STAM proteins participate in the sorting of cargo proteins for trafficking to the lysosome.

The aim of this study is to investigate the efficacy of a structured intervention program in emotional and physical states of family caregivers for elderly. This program is a series of five weekly 90-minute sessions including psycho-education, problem-solving techniques, and relaxation training. Subjects were 56 primary caregivers looking after relatives with dementia or disability at home. Psychological inventories, i.e., Profile of Mood States (POMS) and General Health Questionnaire30 (GHQ-30) were administered at the period of 4 weeks before, pre-, post-intervention, and 2 months after intervention. They were taken a blood sample to measure natural killer (NK) cell activity at the 4 weeks before, pre-, and post-intervention. In the waiting list control group, there was no change in the POMS, the GHQ-30 and NK cell activity. The scores for depression, anger-hostility, tension-anxiety, confusion (POMS), and general illness, social dysfunction, anxiety and dysphoria, suicidal depression (GHQ-30) at the post-intervention decreased significantly when compared with pre-intervention scores. Moreover, there was persistence of the improvement during two months after intervention. Post-intervention NK cell activity was significantly higher than the pre-intervention. These results indicated that our program was effective in managing the stress of family caregivers.

Cumulative Fatigue Symptoms Index (CFSI) is used for workers' subjective assessment of feeling of fatigue and of symptoms. Until now, this index has been used in the analysis of members of the same occupation. The purpose of this study is to examine fatigue symptoms in workers and to assess by CFSI the effect of regular physical exercise. Study participants were an exercise group (n = 67) and a non-exercise group (n = 115) of older workers, aged from 30 to 69 years. The CFSI questionnaire was distributed to all participants and the former group (exercise) answered two descriptive questions concerning the aim and subjective effects of physical exercise. As a result, it was found that mental fatigue symptoms decreased in the exercise group even after considering the differences in managerial position, subjective senses on health and marital status which are related to degree of feelings of fatigue. Weakened vitality was significantly less in the exercise group than the non-exercise group. Therefore, we concluded that weakened vitality would be needed to be regarded on an assessment scale for effects caused by exercise. It has also been considered that we should investigate general fatigue in assessing physical fatigue relating to one's lifestyle.

The case of a 63-year-old man with acrosyringeal adenomatosis (eccrine syringofibroadenoma of Mascaro) is reported. Asymptomatic papular lesions had appeared on the dorsum of both of his feet 30 years earlier, then extended gradually and symmetrically to his hands, arms, legs, trunk, and auriculae. Although his hair, teeth, and nails were normal, he had glaucoma, chronic sinusitis, chronic otitis media, chronic pancreatitis, and gastrointestinal polyposis. No similar symptoms were found in the family history. Histopathologically, proliferations of pale epithelial cells extended from acrosyringia into the dermis, forming interconnected epithelial cords, within some of which were ductal structures. A syringoma and syringoma-like structures were closely associated with these lesions. Enzyme-histochemical, immunohistochemical, and ultrastructural studies supported the concept that this case represents a benign tumor derived from the acrosyringium, which is different from eccrine poroma. Acrosyringeal adenomatosis seems to be a more appropriate name for such a lesion than does eccrine syringofibroadenoma (Mascaro).

The presence of thyroid hormone autoantibodies was investigated in a 48-year-old non-goitrous woman with high levels of serum total T3 and free T3. Her other thyroid function tests were normal. The presence of thyroid hormone autoantibodies were assessed in serum, acid-charcoal treated serum, IgG fractions and in a purified IgG fraction. the IgG fraction was separated from serum by a protein A-Sepharose CL-4B column chromatography and purified by gel filtration chromatography using Sephacryl S 200. Sera from normal individuals were used as controls. The results showed that the increased serum total and free T3 levels were caused by the presence of anti-T3 IgG autoantibodies. The results also indicate that protein A column chromatography is useful as a screening method for gross qualitative analyses of thyroid hormone autoantibodies.

A 48-year-old non-goitrous woman, who had undergone cardiac surgery for mitral stenosis under the extracorporeal circulation, showed high levels of serum T3 and free T3 in a recent follow-up study, employing antibody coated-bead RIA for T3 and -Amerlex M particle RIA for free T3. However, other thyroid function tests (T4, free T4, TSH and TBG) were normal. We suspected that thyroid hormone autoantibodies (THAA) in her serum interfered with T3 and free T3 analyses. The presence of THAA was demonstrated by the use of various procedures as follows. Firstly, the patient's serum was directly incubated with 125I-T3 or -T4 analog which did not bind to TBG, followed by B/F separation with polyethyleneglycol, counting the precipitates. Secondly, after the serum was treated with an acid-charcoal solution to remove circulating thyroid hormone, the measurement of THAA was made as stated above. Normal sera were used as controls. Both the non- and acid-charcoal-treated sera showed much higher percentages of 125I-T3 analog precipitation as compared with controls. In the case of 125I-T4 analog, there was no difference between them. In the third study, the presence of IgG antibodies that bound T3 but not T4 was investigated. The IgG fraction of the patient's serum was separated employing a Protein A-Sepharose CL-4B column chromatography. Then, the prepared IgG fraction was purified by a technique of gel filtration chromatography (Sephacryl S 200). Non-purified and purified-IgG fractions both revealed higher binding percentages of 125I-T3 analog than the control IgG fraction and non-IgG fraction of the patient. Furthermore, a good dose response was observed between the binding percentage of 125I-T3 analog and each dose of the patient's serum or IgG fraction. From these observations, it was clarified that this woman had anti-T3 IgG autoantibodies using a Protein A column chromatography with confirmation of gel filtration chromatography.