Reversible posterior leukoencephalopathy syndrome in a patient with severe uremic encephalopathy.

A 59-year-old male presented at our hospital with disturbance of consciousness. He had severe neurological disturbances associated with uremia caused by severe renal insufficiency. Cranial computed tomography (CT) was normal on admission. FLAIR-weighted MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe. Repeated hemodialysis resulted in improvement of the clinical symptoms and blood chemistry, and normalization of the MRI findings. Although the patient was discharged without neurological deficit, he had to be maintained on regular intermittent hemodialysis due to persistent renal failure. These reversible neuroradiological abnormalities may have been caused by reversible brain edema, but other pathoetiological factors should be also considered, such as abnormalities of cerebral metabolism and effects of uremic toxins.

Minimally required heat doses for various tumour sizes in induction heating cancer therapy determined by computer simulation using experimental data.

PURPOSE: Although induction heating cancer therapy (IHCT) using magnetic nanoparticles can be a promising approach to treatment-less multi-nodular cancers, the objective requirement for successful clinical application has not clearly been elucidated. We intended to define objective heat doses suitable for IHCT, especially focusing on the sizes of liver cancer nodules. MATERIALS AND METHODS: Alternating magnetic fields were applied to three human pancreatic cancer cell lines, the intercellular space of those cell pellets were filled with magnetic nanoparticles, and confirmed the cytotoxic effect of IHCT. Subsequently, the temperatures of liver cancer nodules in IHCT were simulated using a computer software program and the required heat dose for various sized tumours were determined. RESULTS: Heating the cancer cells up to 50 degrees C for 10 min was sufficient for complete cell killing and the heat dose of 1.7 W/g(tumour) is required for 10 mm tumour. Larger tumours require a smaller heat dose, e.g. 20 mm and 40 mm tumours require 0.7 W/g(tumour) and 0.6 W/g(tumour), respectively, whereas smaller tumours require large amounts of heat, e.g. 5 mm and 1 mm tumours require 5.1 W/g(tumour) and 105 W/g(tumour), respectively. CONCLUSIONS: Integrating the presently available technologies, including high-quality magnetic nanoparticles (1000 W/g(material)) and effective drug delivery systems (1-2 mg(material)/g(tumour)), treatment of a 10 mm tumour seems possible. Since treatment of smaller tumours less than 5 mm require substantial heat dose, researchers involved in IHCT should target cancer nodules of 10 mm or more, and develop a heat delivery system providing a minimum of 1.7 W/g(tumour).

Antitumor effect of new local hyperthermia using dextran magnetite complex in hamster tongue carcinoma.

OBJECTIVE: This study was performed to clarify the usefulness of Dextran magnetite (DM) for the oral cancer hyperthermia. METHODS: Tumors were induced in golden hamster tongue by 9,10-dimethyl 1-1,2-benzanthracene (DMBA) application. DM suspension was locally injected into the tumor-bearing tongue and tongues were heated up to 43.0-45.0 degrees C, by AC magnetic field of 500 kHz. RESULTS: The average time taken for the temperature to rise to 43.0 degrees C or above was 162 s (n = 17) at the margin of the tumor and 420 s (n = 17) at the center of the tumor. According to the tumor volume, the time required for an increase in the central temperature of tumor to 43.0 degrees C tended to be prolonged. Both temperatures could be maintained at approximately 43.0-45.0 degrees C for 30 min. The inhibition of the growth of tongue carcinoma in the four-time heating group was significantly greater than in the control group (P < 0.01). Moreover, the survival rate was significantly higher in the heated groups than in the control group (P < 0.01). Histological examination revealed a brown uniform DM accumulation at the stroma in the margin of the tumors. Many of tumor cells disappeared at the site adjacent to this accumulation. CONCLUSION: These results strongly suggest the usefulness of this local hyperthermic system in the oral region that is accessible to this treatment.

Serum surfactant proteins-A and -D as biomarkers in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has a high mortality rate, and current therapies are only marginally effective. A serum biomarker that predicts clinical outcome would be useful to stage disease, indicate prognosis and the need for aggressive therapy, and help stratify patients for clinical trials. The goals of this study were to determine whether serum levels of surfactant protein-A (SP-A) or surfactant protein-D (SP-D) would distinguish between IPF and other types of interstitial lung disease and whether serum SP-A or SP-D levels predict outcome in patients with IPF. The authors found that serum SP-A and SP-D levels were significantly elevated in patients with IPF and systemic sclerosis compared to sarcoidosis, beryllium disease and normal controls, and that SP-D correlated with radiographic abnormalities in patients with IPF. In addition, the authors found that both serum SP-A and SP-D levels were highly predictive of survival in patients with IPF. This is the largest North American data set of surfactant protein measurements in idiopathic pulmonary fibrosis and the first report using multivariate analysis comparing serum surfactant proteins-A and -D to other commonly measured predictors of survival in idiopathic pulmonary fibrosis. Based on these results, the authors propose that serum surfactant proteins may prove to be useful biomarkers in patients with idiopathic pulmonary fibrosis.

The gluteal-fold flap for vulvar and buttock reconstruction: anatomic study and adjustment of flap volume.

The ideal skin-flap reconstruction provides functional preservation and a good cosmetic outcome in both the reconstructed site and the donor site. Although various flaps are used for reconstruction of the vulvar and buttock region, there are disadvantages associated with each. In 1996, Yii and Niranjan reported the gluteal-fold flap for vulvar reconstruction. As presently used, this flap is bulky, particularly in obese patients or when used for hemilateral reconstruction. Thinning the flap has been considered impossible because of the obscurity of the blood supply. In the study presented here, the pedicle vessels of this flap were studied in eight cadavers; the authors found that the flap is nourished by a direct cutaneous system of the internal pudendal artery and vein. Accordingly, adjustment of the flap volume was believed to be possible, with the exception of the adipose tissue containing the pedicle vessels. The authors have since used 14 thinned flaps for seven vulvar, one vaginal, and two buttock defects in 10 patients. All flaps survived completely. Good functional and cosmetic results were achieved with hemilateral or bilateral flaps in vulvar or buttock reconstruction. In the buttock in particular, the usefulness of this flap for anal and pelvic-floor reconstruction was demonstrated. The scar at the donor site, concealed in the gluteal fold, was acceptable. The gluteal-fold flap is very useful for various vulvar and buttock reconstructions because it can be adjusted to the required volume.

[Local staging with magnetic resonance imaging after neoadjuvant hormonal therapy for prostate cancer].

We retrospectively studied the staging accuracy of magnetic resonance (MR) imaging after neoadjuvant hormonal therapy (NAH) for 21 localized prostate cancers. MR imaging was performed using a 1.5-Tesla magnetic resonance system with a pelvic phased array coil. T2-weighted MR images were obtained on axial and coronal planes, and T1-weighted MR images using the dynamic technique with Gd-DTPA bolus enhancement were obtained in axial planes for each patient. On T2-weighted imaging, the signal intensity of the normal tissue in the peripheral zone became lower after NAH. Therefore, it was more difficult to detect residual malignant lesions in many cases than before NAH. The accuracy of T staging for prostate cancer after NAH in MRI was 71%. The accuracy, sensitivity, and specificity of the extracapsular invasion was 76%, 0% and 94%, respectively, and those of the seminal vesicular invasion 85%, 0% and 100%, respectively. While 2 of the 4 patients judged as downstaged cases in MRI showed corresponding pathological findings, 5 of the 21 cases (23.8%) were underdiagnosed. Local staging with only MRI for prostate cancer after NAH seems to have limits in applicability.

[Licorice-induced pseudoaldosteronism in a patient with a non-functioning adrenal tumor].

A 72-year-old man was diagnosed with hypertension, hypokalemia, and left adrenal tumor at another hospital, and was referred to our hospital on suspicion of primary aldosteronism. Investigations revealed low plasma aldosterone concentration, and the left adrenal tumor proved to be nonfunctioning, not hyperfunctioning. "Licorice" had been prescribed for the treatment of recurrent cramps in his calf. After stopping the licorice, his condition changed to normokalemia strongly suggesting that his pseudoaldosteronism had been caused by the drug. We reviewed 140 reports on licorice-induced pseudoaldosteronism in Japan, and found a second patient who might have suffered a similar coincidental nonfunctioning adrenal tumor.

New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue.

The possibility of dextran magnetite complex (DM) as a new hyperthermic material was examined in this study. DM suspension of 56 mg ml(-1) iron concentration was locally injected into the normal tongue of golden hamster. DM injected tongues were heated by 500 kHz alternating current (AC) magnetic field and its serial changes in temperature were recorded at 30-s intervals. The temperature of DM injected tongue was maintained at about 43.0-45.0 degrees C for 30 min by changing the AC magnetic field intensity. While temperature elevations of the contralateral tongue and the rectum were only of minor degree. In experiment on the extent of heating area, there was correlation between volume of black stain area and amount of the injected DM suspension (Y = - 18.1 + 1.94X, r = 0.931, P < 0.0001, n = 9 ). Histological examination after heating revealed brown uniform DM accumulation in the connective tissue between fibers of the tongue muscle. Except for vascular dilatations, no tissue damage was seen in the heated tongue. Thus, DM which has the possibility of selective and uniform heating in local hyperthermia might be useful for oral cancer therapy.

Serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis.

To find a less-invasive and lung-specific clinical biomarker, we measured serum levels of surfactant proteins A and D (SP-A and SP-D) by sandwich enzyme-linked immunosorbent assays in 42 patients with progressive systemic sclerosis (PSS) to evaluate their significance in relation to the presence of interstitial lung disease (ILD) and to assess their diagnostic merits. The patients were divided into two groups based on findings by chest computed tomography (CT): 30 patients with ILD (CT-positive ILD group), and 12 patients without any lung abnormalities (CT-negative ILD group). The CT-positive ILD group was further divided into two groups: 24 patients with ILD detectable by chest plain radiography (X-ray-positive ILD group) and six patients with ILD showing no abnormality (X-ray-negative ILD group). The levels of SP-A and SP-D in sera were significantly higher in the CT-positive ILD group than in the CT-negative ILD group. They were also significantly higher in the X-ray-positive ILD group than in the CT-negative ILD group. In the X-ray-negative ILD group, their levels were higher than those of the CT-negative ILD group. We next estimated sensitivity and specificity of SP-A, SP-D, and X-ray for detecting ILD on CT. Sensitivity of SP-D was high (77%) as well as that of X-ray (80%), whereas SP-A showed a low sensitivity (33%). Remarkably, five of six patients in the X-ray-negative ILD group showed SP-D concentrations over its cut-off level, thereby demonstrating that an SP-D assay contributes to the detection of ILD overlooked by X-ray. Moreover, a combination of X-ray and SP-D dramatically increases sensitivity to 97%. Specificity of SP-A, SP-D, and X-ray to the CT-negative ILD group was 100%, 83%, and 100%, respectively. In conclusion, this study indicates that elevated levels of serum SP-A and SP-D reflect well the presence of ILD and that the combination of SP-D and X-ray contributes to reduce the risk of clinicians overlooking ILD complicated by PSS, although a repetition in another set of subjects is needed to confirm these indications.

Structural transformation among the aggregate forms of bacteriochlorophyll c as determined by electronic-absorption and NMR spectroscopies: dependence on the stereoisomeric configuration and on the bulkiness of the 8-C side chain.

Transformation among the aggregate forms of bacteriochlorophyll (BChl) c characterized by the wavelength of the Qy absorption, i.e. the dimer (B675), B705, B720 and B745, was traced by electronic-absorption spectroscopy for each of the isomers including R[E,E], R[P,E], R[I,E], S[P,E] and S[I,E] suspended in the mixtures of methylene chloride and n-hexane. A combination of NMR spectroscopy determining the structural motifs and calculation of the shift of the Qy absorption reflecting the long-range transition dipole-transition dipole interactions among the macrocycles in the entire aggregate structures proposed the following models: B705d (B705d'), a linear array of straight (inclined) columns consisting of a pair of the piggyback dimers; B720d and B745d, an assembly of two and five shifted-inclined columns consisting of more than six piggyback dimers; and B720m and B745m, an assembly of one and two parallel stepwise stacking of approximately 30 monomers. Calculations of the steric energies rationalized two different pathways of transformations: the dimer-->B705d (B705d')-->B720d-->B745d for the R isomers; and the monomer-->(B720m)-->B745m for the S isomers. Addition of S[I,E] seems to trigger the B745d-->B745m transformation of the R isomers.

Serial changes in surfactant-associated proteins in lung and serum before and after onset of ARDS.

The goal of this study was to determine the changes that occur in surfactant-associated proteins in bronchoalveolar lavage fluid (BAL) and serum of patients at risk for ARDS and during the course of ARDS. We found that the concentrations of SP-A and SP-B were low in the BAL of patients at risk for ARDS before the onset of clinically defined lung injury, whereas the concentration of SP-D was normal. In patients with established ARDS, BAL SP-A and SP-B concentrations were low during the entire 14-d observation period, but the median SP-D concentrations remained in the normal range. Immunoreactive SP-A and SP-D were not increased in the serum of patients at risk for ARDS, but both increased after the onset of ARDS to a maximum on Day 3 and remained elevated for as long as 14 d. The BAL SP-A concentrations were significantly lower in at-risk patients who developed ARDS, and no patient with a BAL SP-A concentration greater than 1.2 microg/ml developed ARDS. On Days 1 and 3 of ARDS, the BAL SP-D concentration was significantly lower in patients who died, and the BAL SP-D concentration was significantly related to the PI(O(2))/FI(O(2)) ratio. Thus, surfactant protein abnormalities occur before and after the onset of ARDS, and the responses of SP-A, SP-B, and SP-D differ in important ways. The BAL SP-A and SP-D measurements can be used to classify patients as high or low risk for progression to ARDS and/or death after the onset of ARDS. Strategies to increase these surfactant proteins in the lungs of patients with ARDS could be useful to modify the onset or the course of ARDS.

[Effect of liarozole on the cell proliferation activity in the rat urinary bladder epithelium induced by N-butyl-N-(4-hydroxybutyl) nitrosamine].

INTRODUCTION AND OBJECTIVES: Recently, the chemopreventive effects of various drugs on N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat urinary bladder carcinogenesis have been reported. The aim of this study was to evaluate the effect of liarozole, an antitumor agent that inhibits the metabolism of retinoids, on the initial stage of BBN induced rat urinary bladder carcinogenesis. MATERIALS AND METHODS: Seven-week-old, male Wistar rats were used. The rats were divided into four groups. All groups except control were allowed free access to the drinking water containing 0.05% BBN. Groups Lz40 (n = 5) and Lz80 (n = 5) were administered the liarozole solution, twice daily by gavage (40 mg/kg/day and 80 mg/kg/day, respectively). Group BBN (n = 5) was given no liarozole. The control group (n = 4) received no carcinogen. At 9 weeks after the start of the experiment, all rats were killed by ether anesthesia and their urinary bladders were taken for evaluation. The urinary bladders were fixed in 10% buffered formalin, embedded in paraffin, sectioned, and immunohistochemical staining using anti-proliferative cell nuclear antigen (PCNA) antibody was performed by the avidin-biotin-peroxidase complex (ABC) method. We calculated the PCNA positive rate and compared among the four groups. RESULTS: The PCNA positive rate of group BBN was 23.5 +/- 3.7%. Compared with group BBN, the PCNA positive rate of groups Lz40 and Lz80 were statistically less (16.4 +/- 4.3% and 9.8 +/- 2.6%, respectively). Furthermore, the PCNA positive rate of group Lz80 was statistically less than that of group Lz40. CONCLUSION: The results indicate that liarozole may inhibit the activity of cell proliferation in the initial stage of BBN-induced rat urinary bladder carcinogenesis and may be dose-dependent.

Lower eyelid reconstruction with a cheek flap supported by fascia lata.

The use of a cheek rotation flap is a well-known method for reconstruction of a large defect of the lower eyelid. In this technique, a separate lining tissue supporting the cheek flap is required for full-thickness reconstruction. Previously, a chondromucosal graft or conchal cartilage has been used to support this flap. Recently, we have used a homologous or autologous fascia lata as support for the cheek flap instead of rigid tissues like cartilages. A fascia lata strip is fixed with tolerable tension to the medial canthal tendon and lateral orbital rim. The inner surface of the fascia and the cheek flap is lined with a buccal mucosa graft to decrease irritation of the conjunctiva and cornea. We present here seven patients in whom this procedure was used for lower eyelid reconstruction following resection of a malignant skin tumor. Based on follow-ups of 7 to 22 months, the functional and aesthetic results have been good in all cases. This procedure may be applicable for total or subtotal reconstruction of the lower eyelid.

Idiopathic retroperitoneal fibrosis with duodenal obstruction successfully treated with corticosteroids.

We report a case of idiopathic retroperitoneal fibrosis presenting with duodenal obstruction. A 55-year-old man suddenly developed severe epigastric pain and was admitted to our hospital. On abdominal computed tomography (CT), a large retroperitoneal mass was found. Hypotonic duodenography showed obstruction of the third portion of the duodenum. He was diagnosed as idiopathic retroperitoneal fibrosis and was treated with prednisolone. The patient improved dramatically. He has been well for twelve months without any further treatment.

Mass production of bacterial alpha 2,6-sialyltransferase and enzymatic syntheses of sialyloligosaccharides.

To supply alpha 2,6-sialyltransferase for the large-scale synthesis of sialoside, we investigated culture conditions for the production of sialyltransferase 0160. The addition of galactose and beef extract, and control of the pH of the culture medium were effective on the production of sialyltransferase 0160. The maximal enzyme productivity reached 550 units/L. Using a crude extract of Photobacterium damsela JT0160 cells as an enzyme source, enzymatic syntheses were performed with mono- and di-saccharides as the sialyl acceptors. It was clarified that a crude extract of P. damsela JT0160 cells can be used as an synthetic catalyst for the enzymatic synthesis of sialyloligosaccharides. Furthermore, the enzyme assay showed that sialyltransferase 0160 could transfer NeuAc to not only N-linked but also O-linked carbohydrate chains. These results indicated that an abundant supply of sialyltransferase 0160 and its broad specificity make possible the synthesis of sialoside on a large scale.

[A case of leiomyosarcoma of the testis].

A 64-year-old man presented with the painless hard swelling of left scrotal content. Left orchiectomy with high ligation of the spermatic cord was performed with clinical diagnosis of testicular tumor. Histopathologically, it was diagnosed as leiomyosarcoma arising from the spermatic cord. There has been neither local recurrence nor metastasis for 5 months after operation. This is the 20th case of leiomyosarcoma of the spermatic cord in Japan.

Design of macromolecular biological response modifier by immobilizing of D-glucose analogue of muramyl dipeptide on carboxymethyl-dextran having mannose branches.

It is well known that muramyl dipeptide is a minimum required structure of bacterial peptidoglycan responsible for immunoadjuvant activity. Since mannose receptors exist on the surface of macrophages, polymers with branched mannose residues are expected to target moieties to macrophages. To achieve an efficient delivery of D-glucose analogue of muramyl dipeptide (GADP) via receptor-mediated endocytosis by mannose receptors on the surface of macrophages, GADP/carboxymethyl-dextran (CM-Dex)/Man conjugate was synthesized. Moreover, to study the effect of the introduction of mannose residues, we also synthesized GADP/CM-glucomannan (CM-GM) and GADP/CM-Dex conjugates. The immunological enhancement activities of their conjugates were evaluated by measurements of glucose consumption and beta-D-glucuronidase activity from macrophage-like cells. The GADP/CM-Dex/Man and GADP/CM-GM conjugates showed higher immunological enhancement activity than the GADP/CM-Dex conjugate. The immunological enhancement activity of GADP/CM-Dex/Man and GADP/CM-GM conjugates was decreased to the same level of immunological enhancement activity of GADP/CM-Dex conjugate under the presence of excess mannose. These results suggested that the introduction of mannose residues into GADP/CM-Dex conjugate could increase the affinity against macrophage and the immunological enhancement activity of GADP/CM-Dex conjugate itself.

Enzyme-linked immunosorbent assay using F(ab')2 fragment for the detection of human pulmonary surfactant protein D in sera.

We developed an enzyme-linked immunosorbent assay (ELISA) for detection of SP-D in serum using recombinant SP-D as a standard and horseradish peroxidase conjugated F(ab')2 fragment of mouse monoclonal antibody IgG to avoid the interaction of serum factors including rheumatoid factor. The use of F(ab')2 fragment dramatically decreased the value of serum SP-D concentration in rheumatoid arthritis patients without pulmonary complication to the close level of healthy volunteer. In contrast, the patients with collagen disease having interstitial pulmonary pneumonia exhibited consistently elevated levels of serum SP-D. The use of new ELISA with recombinant SP-D and F(ab')2 fragment of anti-SP-D monoclonal antibody gives a greater advantage for the accurate detection of SP-D in sera from patients with idiopathic pulmonary fibrosis, interstitial pneumonia with collagen disease and pulmonary alveolar proteinosis without interference of rheumatoid factor.

Targeted hyperthermia using dextran magnetite complex: a new treatment modality for liver tumors.

BACKGROUND/AIMS: Dextran magnetite complex (DM) is a colloidal suspension of subdomain magnetite particles ('magnetic fluid'). It has been reported that DM generates a great amount of heat in an AC magnetic field. MATERIAL AND METHODS: In this experimental study on Japanese white rabbits, a new treatment modality for liver tumors was examined in which the tumor is selectively heated with an intravascularly administered DM-containing embolic material followed by external application of an AC magnetic field. RESULTS: The heat generation of DM in vitro was found to be more than 3-fold greater than that with magnetite particles of 40-micron diameter. As a DM-containing embolic material, we developed a DM/Lipiodol emulsion. When DM/Lipiodol emulsion was injected into the hepatic arteries of the rabbits following VX2 tumor transplantation into the liver, embolization of the artery and selective heating of the embolized liver were successfully attained following exposure to a 100-kHz AC magnetic field of approximately 15000 A/m. Histological examination of the embolized liver disclosed that DM had accumulated in the hypervascular, viable part of the tumor. CONCLUSION: These results demonstrate the potential feasibility of using a DM-containing embolic material for targeted hyperthermia of liver tumors.

Culture of cells derived from the human sebaceous gland under serum-free conditions without a biological feeder layer or specific matrices.

We succeeded in serially culturing cells derived from human sebaceous gland (sebocytes) under serum-free conditions. Sebaceous glands were isolated from dispase-treated facial skin specimens and cultured using two different methods, explant culture and dispersed cell culture, in KGM. In both types of culture the sebocytes proliferated rapidly without a biological feeder layer or specific matrices. It was possible to cultivate the cells serially for at least three passages (explant culture) and six passages (dispersed cell culture), and to store the cells in liquid nitrogen with good recovery. Analytical thin-layer chromatography revealed that the cells synthesized a large amount of sebum-specific lipids, squalene and wax esters in vitro. Both testosterone and 5 alpha-dihydrotestosterone significantly stimulated the proliferation of the sebocytes. The methods presented here may permit a large series of studies on the function of sebaceous glands or cells derived from sebaceous glands.