A computer-controlled contracture correction device with low-load and continuous torque: an animal experiment and prototype design for clinical use.

The purpose of this study was to clarify the relationship between mechanical stress and tissue response of the contracted knee joint in rats and to propose a new design of contracture correction device for clinical use. Wistar rats were operated on to immobilize their knee joints with a procedure causing periarticular bleeding and were kept in flexed position for 40 days. At day 40, the immobilizing wire was removed, and after day 43, the contracted knee joint had been treated with tunable corrective devices secured by an external fixation method to the rear limb. These devices consisted of four types of motor-driving system which provided several different low-load and continuous stretch torques. Measuring the angle of maximum knee extension, its effectiveness was assessed comparing with a lower load and control group of natural recovery course. The device also had a cyclic joint movement within the acquired range of motion and an oval cam mechanism producing a small distraction force to the joint along its long axis. The results showed that an appropriate range of low-load continuous torque was more effective to correct joint contracture. On the basis of the animal experiment, a new computer-controlled, gas-driven contracture correction device was developed for clinical trial. It was concluded that mechanical application in a condition with low and continuous torque is a useful treatment for fixed joint contracture.

Induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro by hepatotoxin rubratoxin B.

To elucidate the mechanism of rubratoxin B toxicity, we investigated rubratoxin B-induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in mice and cultured cells; we also documented the involvement of stress-activated MAP kinases (c-Jun-N-terminal kinases [JNKs] and p38s) in this process. Rubratoxin B significantly (P<0.05) induced serum TIMP-1 levels in mice. Because TIMP-1 is thought to play a crucial role in the process of liver fibrosis, rubratoxin B may cause liver fibrosis. Rubratoxin B enhanced TIMP-1 secretion in HepG2 cells to a peak level of approximately 40 microg/ml. The amount of TIMP-1 mRNA increased with the duration of rubratoxin B treatment; and this hepatotoxin appears to induce TIMP-1 secretion through a transcriptional control mechanism. Unlike similar treatment with rubratoxin B and JNK inhibitor, concomitant treatment with rubratoxin B and p38 inhibitor increased rubratoxin B-induced TIMP-1 secretion, suggesting that p38s (but not JNKs) antagonize this process. In addition, treatment with p38 inhibitor slightly increased the amount of rubratoxin B-induced TIMP-1 mRNA, suggesting that p38s control rubratoxin B-induced TIMP-1 secretion chiefly post-transcriptionally. In this study, we showed that rubratoxin B induces TIMP-1 production in vivo and in vitro and that p38s antagonize rubratoxin B-induced TIMP-1 secretion.

Endothelin receptor antagonist prevents parathyroid cell proliferation of low calcium diet-induced hyperparathyroidism in rats.

Secondary hyperparathyroidism, one of the most frequently encountered disorders of the calcium homeostasis, is characterized by an increase in parathyroid epithelial (PT) cell number, which is crucial from a functional viewpoint. However, it is still unknown what factors are involved in PT cell proliferation. Endothelin-1 (ET-1), a vasoconstrictive peptide, has been shown to act as a mitogen in a variety of cell types. Rat PT cells are reported to synthesize ET-1 and possess its receptors. To test the hypothesis that ET-1 plays a role in PT cell proliferation, we used rat test subjects fed a low calcium diet for 8 weeks (low Ca rats). The number of the proliferating PT cells, measured by proliferating cell nuclear antigen immunostaining, was significantly increased, with striking immunoreactivity of ET-1 in the low Ca rats. An endothelin receptor antagonist, bosentan (100 mg/kg.day), prevented any increase in the proliferation of PT cells in the low Ca rats (14.3 +/- 2.7/1000 PT cells with no bosentan; 2.1 +/- 1.3 with bosentan; P < 0.01). These results indicate that ET-1 is involved in PT cell proliferation in vivo and suggest that blocking of ET receptors may become one of the important therapeutic strategies for preventing secondary hyperparathyroidism.

Idiopathic polypoidal choroidal vasculopathy in Japanese patients.

OBJECTIVE: To describe the vascular nature and clinical features of idiopathic polypoidal choroidal vasculopathy in Japanese patients. METHODS: Patients thought to have idiopathic polypoidal choroidal vasculopathy were examined with binocular ophthalmoscopy, slitlamp biomicroscopy with a contact lens, fluorescein angiography, and indocyanine green angiography. RESULTS: From January 1993 to December 1997, 35 eyes in 32 patients were diagnosed as having idiopathic polypoidal choroidal vasculopathy. Men were predominantly affected (22 patients [69%]). Most patients were unilaterally involved (29 patients [91%]) and elderly, with a mean age of 65.7 years (range, 44-82 years). Ocular manifestations were relatively mild, with serous or hemorrhagic detachments of the retinal pigment epithelium and neurosensory retina in the posterior pole. Most patients had a favorable course, although some experienced recurrence, and a few eyes developed disciform scarring. In all patients, indocyanine green angiograms demonstrated branching vascular networks with polypoidal dilations at terminals of the network beneath the retinal pigment epithelium. These lesions were mostly in the macula (33 eyes [94%]), with a few in the peripapillary area. CONCLUSIONS: Idiopathic polypoidal choroidal vasculopathy in Japanese patients differs from that in American patients. It seems that this disorder occurs in elderly Japanese patients and should be treated as a distinct clinical entity. It is probably a peculiar form of choroidal neovascularization beneath the retinal pigment epithelium. We propose the term "polypoidal choroidal neovascularization" for this disorder.

Sex difference in subunit composition of hepatic glutathione S-transferase in rats.

The activities of hepatic cytosolic glutathione S-transferases (GSTs) towards 1,2-dichloro-4-nitrobenzene in male rats were higher than those in females, however, the enzyme activities towards 1-chloro-2,4-dinitrobenzene were not significantly different between the two sexes. SDS-PAGE analysis of GSTs purified from male and female rat hepatic cytosols by affinity column chromatography showed that there was a significant difference in the subunit composition between the two sexes. With regard to the several isozymes of GSTs in male and female rats, isozymes with basic and neutral/acidic isoelectric points were separated into seven molecular species by chromatofocusing. These sex differences in the quantitative proportions of GST isozymes were also confirmed by immunotitration using anti-GST-BL and -AC antibodies. On the other hand, glutathione peroxidase (GSH-Px) activities in rat hepatic cytosol towards hydrogen peroxide and cumene hydroperoxide were markedly higher in females than in males. Of the two types of GSH-Px, selenoenzyme (Se-GSH-Px) and the Se-independent enzyme (non-Se-GSH-Px), the former was found to be mainly responsible for the sex difference in the enzyme activities. Moreover, the GSH-Px activity of GSTs, non-Se-GSH-Px, was also higher in females than that in males. Since GST isozymes of the BL type are known to possess GSH-Px activity towards cumene hydroperoxide, the increased activities of non-Se-GSH-Px in the female hepatic cytosol seemed to be mainly due to the increased transferase activities of the isozymes, GST-L2 and -BL.

Olfactory epithelium in young adult and aging rats as seen with high-resolution scanning electron microscopy.

The present study uses mainly scanning electron microscopy to demonstrate the three-dimensional internal cell structures of rat olfactory epithelial cells. The aldehyde-prefixed osmium-DMSO-osmium (AODO) method devised by Tanaka and Mitsushima (1984) was applied to the present study to disclose intracellular structures such as endoplasmic reticulum, mitochondria, Golgi apparatus, and lysosomes. The spatial distribution pattern of these structures in olfactory and supporting cells is discussed, paying special attention to the formation of lipofuscin-like granules present in aged rats.

Comparison of effects of Wasabia japonica and allyl isothiocyanate on the growth of four strains of Vibrio parahaemolyticus in lean and fatty tuna meat suspensions.

Lean tuna meat suspensions (LEAN), with a fat content of 0.006%, and fatty tuna meat suspension (FATTY), with a fat content of 3.0% were inoculated with four strains of Vibrio parahaemolyticus and wasabi (Wasabia japonica Matsumura) or allyl isothiocyanate (AIT) was added before incubation at 37 degrees C. During the incubation, viable Vibrio counts were determined on TCBS agar plates. Both LEAN and FATTY suspensions were inoculated with V. parahaemolyticus AOTO-81, (1.28+/-0.20) x 10(2) CFU/ml, followed by addition of 20 mg wasabi/ml, and incubation for 8 h. The viable Vibrio counts were (7.76+/-5.93) x 10(5) CFU/ml in LEAN and (3.50+/-2.65) x 10(1) CFU/ml in FATTY. When the same strain, at (1.18+/-0.22) x 10(2) CFU/ml, was incubated for 8 h with 50.9 microg AIT/ml, viable Vibrio counts were (4.79+/-1.78) x 10(4) CFU/ml in LEAN and (1.80+/-1.30) x 10(1) CFU/ml in FATTY. Growth of the other three strains with wasabi or AIT was shown to be less in FATTY than in LEAN. These results indicate that growth of V. parahaemolyticus is inhibited more in FATTY than in LEAN by wasabi and allyl isothiocyanate.

Extracellular soluble polysaccharide (ESP) from Aspergillus kawachii improves the stability of extracellular beta-gluocosidases (EX-1 and EX-2) and is involved in their localization.

Aspergillus kawachii produces two extracellular beta-glucosidases (EX-1 and EX-2) and one cell-wall-bound beta-glucosidase (CB-1), all of which are derived from the same bglA gene. Extracellular beta-glucosidases (EX-1 and EX-2) are stable in the crude solution form, but become unstable in the purified form under moderate conditions (pH 5.0 and 37 degrees C). Purified extracellular beta-glucosidases can bind to a mycelial cell wall fraction, even though these enzymes are released into the medium under solid culture conditions. A. kawachii produces an extracellular soluble the beta-glucosidases over the pH range of 3.0-7.0 and at temperatures below 50 degrees C. ESP directly interacted with the purified extracellular beta-glucosidases but did not affect the K(m) values of these enzymes. Moreover, ESP inhibited the adsorption of purified extracellular beta-glucosidases to the cell wall fraction and extracted them from it. These results that ESP plays important roles in the stability and localization of extracellular beta-glucosidases. ESP from A. kawachii directly binds to the enzymes and releases them to the medium from the cell wall layer and then stabilizes them.

Production and some properties of salt-tolerant beta-xylosidases from a shoyu koji mold, Aspergillus oryzae in solid and liquid cultures.

Beta-xylosidase production from a shoyu (soy sauce) koji mold, Aspergillus oryzae HL15, cultured in solid and liquid media was examined and some properties of the enzymes were studied. Three beta-xylosidases (Xy11, Xy12 and Xy13) were easily extracted with 0.5% NaCl from a solid medium and purified homogeneously on SDS-PAGE by chromatography. On the other hand, in a liquid medium, A. oryzae HL15 produced mainly cell-wall-bound beta-xylosidases which could not be extracted with 0.5% NaCl or any detergent. Cell-wall-bound beta-xylosidases, Xy11-CB and Xy12-CB, were liberated by digestion of mycelia with Yatalase and purified to a homogeneous state on SDS-PAGE by HPLC column chromatography. Four beta-xylosidases (Xy11, Xy12, Xy11-CB and Xy12-CB) exhibited not only high activity at high NaCl concentrations, but also similar properties; on the other hand, Xy13 differed in terms of thermostability and halophilic properties. The salt tolerance of beta-xylosidases in A. oryzae suggests that these enzymes are highly active and involved in releasing xylose in shoyu moromi mash.

Histology of the neobladder mucosa after sigmoidocolocystoplasty.

PURPOSE: The aim of this study was to examine the histopathology of neobladder mucosa biopsy specimens obtained routinely as part of postsigmoidocolocystoplasty (SCP) follow-up. METHODS: One hundred cases of SCP (mean age at surgery, 10.6 years) performed by the authors were examined for the presence of dysplasia or malignant changes in the mucosa of the neobladder using H&E and proliferating cell nuclear antigen (PCNA) staining. RESULTS: No dysplastic or malignant changes were identified in any case. Metaplasia was found in 5 cases and hyperplasia in 2. There were no major differences found on H&E and PCNA staining of specimens obtained after different periods of follow-up post-SCP; follow-up was short term (up to 5 years) in 44 cases, medium term (from 5 to 10 years) in 48 cases, and long term (over 10 years) in 8 cases. PCNA staining was significantly more intense in subjects who stopped regular bladder irrigations (BI) post-SCP and in subjects in whom bladder stones developed (P < .05; Welch's t test), compared with subjects who continued BI and subjects in whom bladder stones did not develop. CONCLUSIONS: After SCP, patients are advised to continue BI. Regular biopsies should be part of routine follow-up, especially in subjects with bladder stones.

Complications after sigmoidocolocystoplasty: review of 100 cases at one institution.

BACKGROUND/PURPOSE: The aim of this study was to review complications after sigmoidocolocystoplasty (SCP) performed at a single institution from 1984 to 1997. METHODS: The medical records of 100 patients who underwent SCP were reviewed retrospectively. RESULTS: Mean age at SCP was 10.8 years. Urinary control was improved in 75 cases and unchanged in 25. Post-SCP complications included death, abdominal wound infection or dehiscence, adhesive bowel obstruction, vesical calculi, vesicocolonic anastomosis stenosis, metabolic acidosis, and transient renal hypertension. Fifty-one patients underwent ureteric re-implantation (URI) at the time of, or before, SCP, and 7 had recurrence of VUR post-URI (spontaneous regression in 6); 3 patients had new onset of contralateral VUR post-URI (spontaneous regression in 2). Transient pleural effusion was seen after reinsertion of ventriculo-pleural shunts to ventriculo-thoracic in 12 cases, but there was no incidence of infection. Squamous metaplasia of the bladder mucosa was identified in 5 patients on routine mucosal biopsy results but resolved in all cases after regular bladder irrigation was commenced. Preoperative constipation or fecal incontinence was better managed after sigmoidectomy in approximately one third of cases (38%). CONCLUSIONS: SCP with or without URI can improve the quality of life of patients with neurogenic or small-capacity bladder, but it can be associated with long-term complications. Regular bladder irrigation is recommended to maintain bladder mucosa integrity.

An immunohistochemical investigation of porcine epidemic diarrhoea.

A sudden outbreak of epidemic diarrhoea of piglets occurred in Japan, the principal features being watery diarrhoea, dehydration and high mortality in newborn animals. The microscopical lesions were villous atrophy in the small intestine, the villous enterocytes being vacuolated and cuboidal in shape. The villus-crypt ratio was severely reduced, varying from 1:1 to 3:1. Transmission electron microscopy showed numerous coronaviruses within the cytoplasm of enterocytes and among microvilli. Specific antigens of porcine epidemic diarrhoea (PED) virus were detected in the cytoplasm of enterocytes by the streptavidin-biotin (SAB) technique. Infected cells, which were most abundant in the villous epithelia of the jejunum and ileum, were present in small numbers in the large intestine, the crypt epithelia, the lamina propria and Peyer's patches. The study suggests that the SAB technique is useful for the diagnosis of PED.

Follow-up of clinical efficacy of iontophoresis therapy for postherpetic neuralgia (PHN).

A great variety of therapies have been attempted for PHN, including pharmacotherapy and physical therapy. However, there has been no decisive treatment, and reports of the clinical efficacy of all available therapies have been rather controversial. Almost all studies conducted so far have looked only at short-term therapeutic efficacy, and only a few investigators have conducted long-term observations or studies on long-term outcome. We followed up the clinical efficacy of iontophoresis therapy using lidocaine and methylprednisolone in 197 PHN patients. Monitoring conducted for an average of 4 years after completion of the treatment showed that pain remained unchanged or improved compared to pain observed upon completion of the treatment in 90.4% of patients. Although 42.6% of patients were still continuing some treatment, 90.9% were found to be able to take care of themselves. Findings obtained were reviewed and discussed from various viewpoints. Our findings showed that iontophoresis therapy is not only effective at the end of the treatment, but its efficacy is maintained over a long period of time, indicating that it is clinically very useful for the treatment of PHN.

A case of multiple symmetrical lipomatosis (Madelung's disease).

Multiple symmetrical lipomatosis (Madelung's disease) is a rare disease with multiple symmetrical unencapsulated fatty accumulation diffusely involving the neck, the shoulders and the upper extremities (Kohan et al. Otolaryngol. Head Neck Surg. 1993;108:156-159). We describe a 48-year-old Japanese man with a history of alcoholism and liver cirrhosis who reported gradually enlarging masses in his cervical region for 4 years. MRI revealed large masses suggesting lipomas in the neck. The patient underwent a two-stage lipectomy. This patient is the 13th case reported in Japan since 1978, though over 200 cases have been reported since 1846 in Europe, most of them from the Mediterranean (Kitano et al. ORL 1994;56:177 180; Kaku et al. Endocrinol. Diabetol. 1997;4:103-106).

[Vascular endothelial growth factor promotes experimental choroidal neovascularization in monkey eyes].

PURPOSE: To evaluate the effect of vascular endothelial growth factor (VEGF) on experimental choroidal neovascularization (CNV) in monkey eyes through clinical, morphometric, and histological observations. METHOD: CNV was induced in both eyes of 6 rhesus monkeys by intense photocoagulation by red krypton laser. Immediately after photocoagulation, 2.5 micrograms of exogenous human VEGF was injected into the vitreous of the left eye in each animal. The right eyes served as controls. The eyes were enucleated 3 days to 12 weeks after photocoagulation and were examined by light and electron microscopy. RESULTS: VEGF-treated eyes developed remarkable serous retinal detachment around the sites of photocoagulation with manifest CNV one week after photocoagulation. Although there was no difference in the incidence of CNV between the treated and control eyes, the treated eyes showed more intense leakage of fluorescein from the CNVs for up to 4 weeks after treatment. Morphometrically, the CNVs were significantly larger and continued to grow longer in the treated than in the control eyes after one week of photocoagulation. Histologically, newly formed vessels with a distinct lumen were present in the treated eyes after 3 days of photocoagulation. CONCLUSION: Intravitreal injection of human VEGF promotes experimental choroidal neovascularization in monkey eyes.

[An experience of dissecting cerebral aneurysm of the anterior cerebral artery].

Intracranial dissecting aneurysms have been reported occasionally in recent years. However, excluding dissecting aneurysms which extend from the proximal intracranial carotid artery, dissecting aneurysms arising merely in ACA are found only rarely. We are reporting here a case of a 42 year-old gentleman who did not present any particular causative etiology such as trauma or other basic diseases causing arteritis. Our patient is the 8th case, as far as we could find in the literature, in which the dissection of the arterial wall originated at the ACA. The patient was thought to have a tiny saccular aneurysm at the A 1-2 junction of the right ACA associated with vasospasm in the distal ACA on the angiogram. The patient had motor weakness on the left side and headache as well as a low density area in the territory of the ACA on the CT scan. A craniotomy was performed verifying the aneurysm to be dissecting in type without any sign of recent subarachnoid hemorrhage in the surrounding structures. No aggressive surgical treatment such as trapping of the aneurysm was done because the collateral blood circulation in that territory of the distal right ACA seemed to be poor and the patient no longer had neurological deficit at the time of operation. The patient was treated successfully with antiplatelet therapy. On the follow-up angiogram performed 3.5 months after the onset of the illness, we noted the disappearance of the abnormal angiographical findings of the dissecting aneurysm and distal arterial narrowing (pearl and string sign).(ABSTRACT TRUNCATED AT 250 WORDS)

[Care networks of visiting nurse agencies before the long-term care insurance act].

PURPOSE: To describe how organizational background impacts on care networks of visiting nurse agencies. METHODS: A questionnaire was sent to all visiting nurse agencies (3,178) in Japan, and 1,548 responded. Questions were asked about the agency's background, management system, and cooperation with other community care agencies. FINDINGS: Seventy-nine percent of visiting nurse agencies were affiliated to medical organizations consisting of hospitals, clinics, or medical nursing facilities, The exceptions cooperated with various types of community service agencies, including home care agencies, assisted device agencies, housing improvement agencies, or volunteer services. The visiting nurse agencies had more frequent contact with housing improvement agencies when home care aid agencies were included within the same organizations. The results suggest that visiting nurse agencies can be divided into two types with reference to the long-term care insurance system. One has strong cooperative relationships with hospitals, and the other with community care agencies.

[Platelet aggregation and coenzyme Q10 content in platelets in cancer patients].

Platelet aggregation, plasma beta-thromboglobulin (beta-TG) concentration and coenzyme Q10 content in serum and platelets were measured in 45 patients with unresectable carcinoma of the lung and in 7 patients with metastatic pulmonary tumor before and after receiving chemotherapy. A significant increase in the plasma beta-TG concentration in cancer patients (47.4 +/- 18.7 ng/ml) was observed (p less than 0.001) compared to the controls (30.3 +/- 9.2 ng/ml). Serum coenzyme Q10 content was lower in cancer patients (0.42 +/- 0.19 micrograms/ml) (p less than 0.05) compared to the controls (0.57 +/- 0.24 micrograms/ml). The reason of decrease in serum coenzyme Q10 content in cancer patients was difficult to explain. No significant difference of the coenzyme Q10 content in platelets (1 X 10(8) cells) was observed either cancer patients (12.5 +/- 2.8 ng) or the controls (12.6 +/- 2.1 ng). No significant correlation was noted among platelet aggregation, plasma beta-TG concentration and coenzyme Q10 content in serum and platelets. Administration of either vindesine or KW2083 did not influence the coenzyme Q10 content in platelets. These results suggest that ATP synthetic pathway by oxidative phosphorylation in platelet be maintained in cancer patients, although a significant increase of plasma beta-TG concentration appears to be associated with an acceleration in the metabolic turnover of platelet.

Comparison of 3D FLAIR, 2D FLAIR, and 2D T2-weighted MR imaging of brain stem anatomy.

BACKGROUND AND PURPOSE: Although 3D FLAIR imaging visualizes detailed structures of the brain stem, it has not been used to evaluate its normal anatomy. The purpose of this study was to evaluate whether 3D FLAIR images can provide more detailed anatomic information of the brain stem than 2D FLAIR and 2D T2WI. MATERIALS AND METHODS: We prospectively evaluated MR images in 10 healthy volunteers. 3D and 2D FLAIR images, 2D T2WI, and DTI were obtained on a 3T MR imaging scanner. A VISTA technique was used for 3D FLAIR imaging. White matter tracts and nuclei of the brain stem were determined on 3D and 2D FLAIR images and 2D T2WI by referring to anatomic atlases and DTI color maps. The subjective assessment of the visibility by using a 4-point grading system and the contrast ratio of the structures on 3D and 2D FLAIR images and 2D T2WI were evaluated. RESULTS: The visibility of the SCP and MCP, DSCP, CST, and CTT was higher on 3D FLAIR images than on 2D T2WI and 2D FLAIR images. The contrast ratio for the CST, SCP, MCP, DSCP, and CTT was significantly different on 3D FLAIR images and 2D T2WI and on 3D FLAIR and 2D FLAIR images; there was no significant difference in contrast ratio for the SCP at the pons on 3D FLAIR and 2D T2WI. CONCLUSIONS: 3D FLAIR images provide detailed anatomic information of the brain stem that cannot be obtained on 2D T2WI and 2D FLAIR images.

Neuromuscular blockade by vecuronium during induction with 5% sevoflurane or propofol.

This randomized trial investigated whether 5% sevoflurane potentiated neuromuscular blockade by vecuronium. General anaesthesia was induced with 5% sevoflurane in oxygen in 16 patients or with propofol in 16 patients. After loss of consciousness, vecuronium was administered to all participants at randomly assigned doses of 25, 30, 35 or 40 µg/kg. Neuromuscular blockade was assessed by use of acceleromyography to measure responses to train-of-four stimuli in the adductor pollicis and corrugator supercilii muscles. Maximum blockade was significantly more intense in the adductor pollicis among patients in the sevoflurane group than in the propofol group, whereas there was no significant between-group difference at the corrugator supercilii muscles. In both groups, maximum blockade at the corrugator supercilii was significantly less intense than that achieved at the adductor pollicis. In the dose-response analysis, the 50% and 95% effective doses were lower for sevoflurane than for propofol in both muscles, although this did not reach statistical significance. It is concluded that induction of general anaesthesia with sevoflurane might provide improved conditions for intubation and reduce airway problems.