Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease.

BACKGROUND: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined. METHODS: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients. RESULTS: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls. CONCLUSIONS: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.

Macroconidial development and germination in Trichophyton mentagrophytes.

Trichophyton Mentagrophytes was investigated for macroconidial development with particular emphasis on the conidial ageing by light and scanning electron microscopy. Macroconidial germination was also studied under various conditions. Sabouraud glucose agar supplemented with 3% NaCl was used to enhance production of macroconidia. After a long-term cultivation macroconidial compartments changed to spherical thick-walled structure. Some 12-month-old macroconidia were still capable of germination. A wide range of temperature (15-37 degrees C), and inoculum of less than 1 X 10(5) conidia per ml of rich media were appropriate for macroconidial germination. The germination process of macroconidia was highly tolerant to NaCl. A small fraction of the conidia were able to germinate even in distilled water without activation. Effect of freeze-thaw or ultraviolet irradiation on macroconidial germination was determined.

Immunohistological staining of antigens on semithin sections of specimens embedded in plastic (GMA-Quetol 523).

Glycol methacrylate-Quetol 523, introduced by Kushida (1977) for combined light and electronmicroscopy studies at low magnification, also permits application of immunofluorescence methods to semithin sections. To recover the antigenicity of proteins fixed with formaldehyde, abrupt dehydration before embedding and subsequent treatment of the semithin sections with protease were essential. Post-staining with suitable histological stains allows exact correlation of antigen localization with tissue structure.

[Evaluation of effectiveness of community mental health system in Kawasaki City--a comparison with national statistics].

UNLABELLED: The pioneering community mental health system of Kawasaki was evaluated by comparison with national statistics using the data from a citywide survey of patients with schizophrenia. METHOD: Subjects were citizens of Kawasaki who were receiving medical treatment for schizophrenia (ICD-9) in the city. All inpatients (565 cases) and a random sample of outpatients (685 cases; extraction rate was 1/3) who met the criteria were asked to complete the questionnaires by themselves. The responsible medical staffs of the subjects were also asked to complete the questionnaires. In order to calculate the total prevalence rate in the city, the number of patients who received medical treatment outside the city was estimated by extrapolation. RESULTS: Higher outpatient rate and lower inpatient rate of Kawasaki were indicated despite the almost equal prevalence (i.e. 32.7 per 10,000 population) compared to the national rate. The outpatient rate was 70.6% in Kawasaki, which was 16% higher than the national average. And the rate of outpatients with schizophrenia living alone in Kawasaki was three times higher. While national outpatient rates declined significantly when patients became 40 years old, such a decline was not evident in Kawasaki. On the other hand, as patients with schizophrenia got older, the rate of outpatients living alone or living with spouse increased in Kawasaki due to the change of caregivers' generation. CONCLUSION: The higher outpatient rate especially of people over 40 years old and the higher rate of patients who lived alone may be explained by the effective community care system in Kawasaki. However, more an intensive support system which provides' daily services such as home-help and group home services should be developed, as the living conditions of outpatients who lived alone were very difficult.

[A case of Kennedy-Alter-Sung syndrome associated with external ophthalmoplegia--therapeutic efficacy of fluoxymesterone].

We reported a case with Kennedy-Alter-Sung syndrome (KAS) associated with bilateral external ophthalmoplegia. The patient had movement disturbance of bilateral infra-oblique muscles. The doll's eye phenomenon was not noted. It was suggested that the external ophthalmoplegia was due to the involvement of the oculomotor nucleus that innervated infra-oblique muscle. The serum levels of testosterone and gonadotropin were high, suggesting that the feminization of KAS patients was caused by androgen insensitivity. The feminization of KAS patients is similar to the incomplete form of testicular feminization syndrome except that they do not have feminization of genitals. Therefore, we proposed that abnormalities of androgen receptors might play a role in the pathogenesis of KAS. Fluoxymesterone therapy significantly improved the muscle weakness of the extremities of the patient, even though the therapeutic efficacy was shown temporarily. The therapeutic efficacy of fluoxymesterone for muscle weakness supports our hypothesis.

[Pharmacokinetics of cisplatin and methotrexate in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure, undergoing combined hemodialysis and systemic M-VAC chemotherapy].

The pharmacokinetics of cisplatin and methotrexate were determined in a patient suffering from advanced ureteral tumor accompanied by chronic renal failure undergoing 4 consecutive cycles of M-VAC chemotherapy and hemodialysis. No significant difference was observed in t1/2, AUC or CLtot of total platinum between the patient with the chronic renal failure and patients with normal renal function. The AUC and CLtot of free platinum in the patient with the chronic renal failure were higher and lower, respectively, than in the patients with normal renal function. The free cisplatin rebounded remarkably after the end of dialysis, which may be partly attributed to an increase in the AUC and decrease in CLtot. However, the dialysis index was about 75 and 85% in the 3rd and 4th cycles, respectively. The t1/2 and CLtot of methotrexate in the patient with the chronic renal failure tended to be longer and smaller than those in patients with normal renal function, respectively. Seventy-two hours after administration, the methotrexate level was 0.02 microM, which was not at the high-risk level of high-dose therapy. After four cycles of M-VAC therapy, the rest of the right ureteral tumor was extirpated and the clinical response was CR. In conclusion, it is considered that cisplatin and methotrexate can be given to a patient with chronic renal failure. However, the cisplatin and methotrexate serum levels must be monitored, even after very low doses.

A scanning electron microscope study of the human Bowman's epithelium.

The parietal epithelium of the Bowman's capsule in normal human kidney was studied by scanning electron microscopy. Stereoscopic scanning electron microscopy showed clearly that the Bowman's capsule, cut in half by a razor blade, was depressed hemispherically and coated with a flat layer of polygonal epithelial cells. The epithelial cell had a round, slightly elevated, and eccentrically located nuclear portion, and extended flat cytoplasmic layer from it toward the periphery. Tiny cytoplasmic projections, microvilli, were seen in varying degrees on the surface. One or two thin and long cilia were occasionally present around the nuclear portion.

The effects of cross-innervation on the myoglobin concentration of tonic and phasic muscles.

1. The myoglobin concentrations of m. soleus and m. flexor digitorum longus (F.D.L.) were estimated spectrophotometrically in normal cats.2. In another group of cats the nerves to m. soleus and F.D.L. were self-united in one limb and cross-united in the opposite limb and the myoglobin concentrations of m. soleus and F.D.L. in both limbs were estimated 6 months later.3. After self-union of the nerves the F.D.L./soleus myoglobin ratio was not significantly different from that of normal cats.4. After cross-union of the nerves the F.D.L./soleus myoglobin ratio was significantly greater than that of both normal cats and cats after self-union of their nerves.

The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages.

Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc gamma R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc gamma R on feline macrophage.

Unicompartmental knee arthroplasty for lateral gonarthrosis: midterm results.

Thirty-eight lateral compartment arthroplasties were performed in 22 years. Eighteen joints in 17 patients with an average age of 64.5 years were evaluated with minimum 5-year follow-up. Using the Hospital for Special Surgery knee score, 16 of 18 joints had satisfactory results in terms of function and pain relief. The average preoperative alignment on standing was 14.9 degrees of valgus angulation, which was corrected to 6.9 degrees of valgus. On radiographic analysis, no radiolucent lines were seen under the tibial component, but the femoral component was loose in 1 joint. Although 5 joints showed slight deterioration of osteoarthritic change in the medial compartment, lateral compartment arthroplasty is a reliable and successful option in the treatment of patients with a low level of physical activity.

Scanning electron microscopy of the glomerular filtration membrane in the rat kidney.

The rat kidney was perfused with saline and glutaraldehyde, treated with Murakami's tannin-osmium impregnation method, ethanol-freeze cracked and dried by the critical point method. Gold-palladium evaporated specimens were observed in a field-emission scanning electron microscope. The glomerular filtration membrane, fractured in different planes was observed with the following results: 1. Adjacent pedicles originate from different podocytes. No interpedicular bridges of apparent cytoplasmic nature could be found. 2. The basement membrane, in grazing fractures shows a horizontally layered architecture. 3. The attenuated endothelial sheet (lamina fenestrata) is divided into compartments, which we suggest should be called "areolae fenestratae", by cytoplasmic crests radiating from the nucleated portion of the endothelial cell. A crest also occurs along the cell margin, which contacts a similar crest at the margin of the adjacent cell. 4. The pores in the areolae fenestratae are variable in size (30-150 nm diameter). A knob-like projection from the apparently naked basement membrane is found in a portion of the pores. 5. Numerous microvilli may occur on the endothelium. Some of them anastomose and fuse with one another to form a net whose meshes appear identical with the endothelial pores. Domes and shelves formed of a fenestrated cytoplasmic sheet also occur above the ordinary level of the endothelial lining. A hypothesis implicating microvilli in the partial renewal of the endothelial sheet is proposed.

Effects of patient demands on satisfaction with Japanese hospital care.

OBJECTIVE: The objective of this study was to detect whether there was any difference among the characteristics of patient satisfaction between two patient emphasis groups: patients demanding technical elements of hospital care and patients demanding interpersonal elements. DESIGN AND SETTING: The sample for this study was drawn from in-patients discharged from 77 voluntarily participating hospitals throughout Japan. The relationship between overall satisfaction with hospital care and patient satisfaction, and the evaluation of a hospital's reputation, was explored by stepwise multiple regression analysis of 33 variables relevant to aspects of hospital care for each patient group. RESULTS: In the interpersonal emphasis (IE) group, 'nurse's kindness and warmth' was associated significantly with overall satisfaction, while 'skill of nursing care' and 'nurse's explanation' were significant predictors of overall satisfaction in the technical emphasis (TE) group. On the other hand, 'doctor's clinical competence', 'recovery from distress and anxiety', and items pertaining to the hospital's reputation were significantly related to overall satisfaction in both emphasis groups. CONCLUSION: For overall patient satisfaction, it is essential to satisfy specific items related to the aspect of hospital care emphasized by the patient. Specific significant predictors of overall satisfaction (e.g. 'doctor's clinical competence') were indispensable measures of professional performance in hospital care, irrespective of the patients' emphasis. A positive perception of hospital reputation items might increase overall patient satisfaction with Japanese hospitals.