Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study.

AIM: To assess safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis for distal ulcerative colitis. METHODS: Granulocyte and monocyte adsorptive apheresis therapy (five aphereses for 5 consecutive weeks) was performed for 30 consecutive patients with active distal ulcerative colitis. Patient compliance, adverse effects and clinical symptoms were regularly assessed. RESULTS: Adverse effects were noted during nine (6%) apheresis sessions in eight patients; slight headache five, transient abdominal pain with tenesmus two, fever (38 degrees C) one and mild liver dysfunction one. None of these adverse effects was serious and all patients could complete five aphereses. Clinical symptoms (stool frequency and consistency, rectal bleeding, tenesmus and mucus in stools) significantly improved after the third apheresis. Clinical remission (normal stool frequency and no rectal bleeding) was achieved in 21 patients (70%) after five aphereses. The median Disease Activity Index score significantly decreased; from 6 [interquartile range (IQR): 4-7] to 2 (IQR: 1-3) (P < 0.0001). CONCLUSION: In the treatment of active distal ulcerative colitis, granulocyte and monocyte adsorptive apheresis is safe and well-tolerated. Granulocyte and monocyte adsorptive apheresis had a beneficial effect on clinical remission and symptoms. However, randomized-controlled trials would be necessary to assess a definite efficacy of granulocyte and monocyte adsorptive apheresis.

[Improved QOL with cancer chemotherapy in two patients with breast cancer suffering form carcinomatous pleurisy and carcinomatous peritonitis].

One of the breast cancer patients introduced here suffered from recurrent carcinomatous pleurisy and the other from recurrent carcinomatous peritonitis. The patient with recurrent carcinomatous pleurisy was a 47-year-old female with stage IIIa breast cancer. She underwent a standard mastectomy and, following surgery, radiotherapy (50 Gy) and CAF therapy (30 mg of ADM, 1,800 mg of futraful and 100 mg of CPA, administered p.o.). Dyspnea occurred 4 years after surgery. Pleural exudate cytodiagnosis proved positive and the patient was diagnosed with carcinomatous peritonitis. Continuous thoracic cavity drainage was carried out, and 30 mg of ADM was injected into the thoracic cavity. CAF therapy was performed. The dyspnea and thoracic effusion disappeared. At present, after one year and 7 months, the patient is receiving outpatient treatment and remains under observation. The patient with recurrent carcinomatous pleurisy was a 43-year-old female. The breast cancer was detected in a diagnosis of metastasis to the axillary lymph nodes. An increased CA15-3 level and ascitic retention were observed postoperatively at 5 months. Following administration of 600 mg of UFT and 1,200 mg of MPA, the ascites decreased and improvement of the thickened peritoneum was noted. The CA15-3 level was also lowered. It is anticipated that chemotherapy for carcinomatous pleurisy and carcinomatous peritonitis will contribute to an improvement in patients' QOL.

Influence of food consistency and dental extractions on the rat mandibular condyle: a morphological, histological and immunohistochemical study.

The purpose of this study was to investigate the relationship between food consistency and the growth of the mandibular condyle in rats. Secondly, the effect of dental extractions on cartilage of the mandibular condyle was examined in young adult rats fed foods of varying consistency. Thirty-six male Wistar rats were divided into four groups: (A) Solid diet--non-Extraction (non-Ext.) group; (B) Solid diet--Extraction (Ext.) group; (C) Powder diet--non-Ext. group; and (D) Powder diet--Ext. group. Extractions were performed at 12 weeks of age. The mandibular condyles were removed at 1, 4, and 8 weeks after the extractions. The shape of the mandibular condyles in the powder diet groups (C and D) was significantly narrower. In the Ext. groups (B and D), the thickness of the hypertrophic zone was reduced one week after the extractions. In the powder diet groups (C and D), the intensity of the staining of fibronectin decreased in the proliferative zone regardless of the extractions. In group B, a decreased intensity of this reaction was observed one week after the extractions. From these results, it appeared that food consistency and/or dental extractions affected the morphology of the mandibular condyle and the histological characteristics of the mandibular condylar cartilage.

Evanescent (tunneling) photon and cellular "vision'.

The existence of a rudimentary form of cellular 'vision' was discovered experimentally by Albrecht-Buehler. He found that Swiss 3T3 cells approached distant infrared light spots and suggested that the most likely explanation for this phenomenon involves the long-range processing of electromagnetic signals by the cells. In this paper, a theoretical possibility of this phenomenon is presented within the fully quantum theoretical framework of the electromagnetic field and water. By taking into account the usually neglected interaction between the electric dipole field of water molecules and the quantized electromagnetic field, the dynamically ordered region of water surrounding the cell up to the coherence length < 50 microns is shown to play the role of a nonlinear coherent optical device through which the cells receive electromagnetic signals from distant light spots. The electromagnetic signals for the cell Albrecht-Buehler found are shown to consist of evanescent photons (i.e. soft polaritons) tunneling through the dynamically ordered region of water between the cell and the distant light spot. In contrast to the (normal) vision of animals realized by receiving (normal) photons, cellular "vision' is found to be realized by receiving evanescent photons. It is also suggested that the existence of the dynamically ordered region of water realizing a boson condensation of evanescent photons inside and outside the cell can be regarded as the definition of life.

Antigenicity and N-terminal amino acid sequence of a 35 kDa porin-like protein of Listonella (Vibrio) anguillarum: comparison among different serotypes and other bacterial species.

Listonella (Vibrio) anguillarum, an important fish pathogen, is divided into 10 serotypes according to O-antigens present on the outer membrane. However, the biochemical and immunological properties of porin proteins have not been reported. In this study, the antigenicity and N-terminal amino acid sequence of the 35 kDa porin-like-major outer membrane protein (Omp35La) were compared among different serotypes of L. anguillarum as well as other bacteria. In Western blotting analysis, antisera against Omp35La from strains of J-O-1, -2 and -3 serotypes could detect Omp35La, but not other proteins, in most L. anguillarum strains and isolated of the genera Vibrio and Photobacterium. This antigenicity of Omp35La is unrelated to the serotype and is conserved in related organisms. An N-terminal sequence showed identification with OmpF and OmpC of Escherichia coli and Salmonella typhimurium. However, this similarity was lower when compared to other human pathogens. Thus it was concluded that Omp35La does not contribute to the serotypes of L. anguillarum, although the N-terminal structure is well conserved among different serotypes.

Type VI collagen in mouse masseter tendon, from osseous attachment to myotendinous junction.

BACKGROUND AND METHODS: The association of masseter tendon type VI collagen with other extracellular matrix (ECM) components was examined from osseous attachment to myotendinous junction by immunohistochemistry and transmission electron microscopy with ATP treatment and enzyme digestion. RESULTS: In the tendon proper, fibrocytes extended their processes among bundles of striated collagen fibrils and associated with adjacent cells through amorphous materials, thus forming a three-dimensional network. The amorphous or filamentous material was observed around the fibrocyte cell body and along the cell processes, where the localization of type VI collagen was confirmed by immunohistochemistry using anti-type VI collagen antibody. After treatment with 20 mM adenosine 5'-triphosphate (ATP), 100 nm periodic fibrils, an aggregated form of type VI collagen, were formed in the place where amorphous or filamentous material was present before the treatment. In myotendinous junction, the ATP-aggregated periodic fibrils were observed to associate with the external lamina of the muscle cells as well as among junctional tendon collagen fibrils. In the tendon-bone boundary, ATP-aggregated periodic fibrils were observed around fibrocartilage-like cells in the uncalcifying area but not in the calcification front. Prolonged ATP treatment or hyaluronidase predigestion caused the formation of type VI collagen periodic fibrils in the area near the calcified matrix. CONCLUSIONS: The distribution of type VI collagen in mouse masseter tendon is different in different anatomical position. This may reflect the different functional demand for this collagen.

Type VI collagen periodic fibrils in the synovium of the mouse temporomandibular joint.

Immunohistochemical staining with anti-type VI collagen antibody was strongly positive in the intimal layer and moderately positive in the subsynovium. After treatment with 20 mM ATP, numerous structures with a periodicity of 100 +/- 10 nm (type VI collagen fibrils) appeared around the synovial cells. As the periodic dark bands were stained by ruthenium red, proteoglycan(s) or glycosaminoglycan(s) were probably associated with the type VI collagen fibrils. When the tissue was digested with testicular hyaluronidase before ATP treatment, the periodic fibrils were not found, and only a filamentous network of 100-nm interval was seen around the cells. Thus, type VI collagen is abundant in the synovium of the mouse mandibular joint and is associated with proteoglycans or glycosaminoglycans, which might have a role in its formation.

An ultrastructural study of extracellular fibrillar components of developing mouse mandibular condyle with special reference to type VI collagen.

The localization of type VI collagen was examined from birth to 8 weeks of age. Immunohistochemical staining with anti-type VI collagen antibody was strongly positive in the hypertrophic zone and moderately positive in the fibrous zone and the outer periphery of the proliferative zone, but negative in the inner area of the proliferative zone and mature zone. After ATP treatment, type VI collagen periodic fibrils with about 80-nm intervals were frequently observed but only in the fibrous zone. They occurred mainly in the superficial area of this zone, where striated collagen fibrils were sparse, while a few were noted in the inner area, where bundles of collagen fibrils were abundant. From these distributional differences of both components, a subzonation of the fibrous zone into superficial and inner area is suggested. Moreover, with ATP treatment there were fewer type VI collagen periodic fibrils formed with increasing age (8 weeks). Testicular hyaluronidase digestion before ATP treatment facilitated the formation of periodic fibrils, in all the ages examined, in the intercellular space and around the fibroblastic cells. The interaction of type VI collagen with other components such as collagen fibrils, glycosaminoglycans or proteoglycans may play a part in maintaining the structural integrity of extracellular matrix in the mouse mandibular condyle.

Development of hemopoietic bone marrow within the ectopic bone induced by bone morphogenetic protein.

Neogenesis of hemopoietic bone marrow was observed in the ectopic bone induced by implantation of bone morphogenetic protein (BMP) into the muscle of mice. A bone rudiment-like cartilage was formed first, which was then replaced by bone through an endochondral ossification process. Bone marrow formation occurred after the invasion of blood vessels into the cartilage, with accumulations of small lymphocyte-like cells and the appearance of large hemopoietic stem cells around the blood vessels. The stem cells proliferated and differentiated to form hemopoietic bone marrow. This process was similar to the embryogenesis of bone and bone marrow, but the hemopoietic activity of the BMP-induced bone was transient. The bone marrow was converted to fatty tissue within 2 weeks of its appearance. This study showed that implantation of BMP in the ectopic sites offers a useful model to investigate the neogenesis of ectopic bone marrow and the regulation of its activity.

Quantum optical coherence in cytoskeletal microtubules: implications for brain function.

'Laser-like,' long-range coherent quantum phenomena may occur biologically within cytoskeletal microtubules. This paper presents a theoretical prediction of the occurrence in biological media of the phenomena which we term 'superradiance' and 'self-induced transparency'. Interactions between the electric dipole field of water molecules confined within the hollow core of microtubules and the quantized electromagnetic radiation field are considered, and microtubules are theorized to play the roles of non-linear coherent optical devices. Superradiance is a specific quantum mechanical ordering phenomenon with characteristic times much shorter than those of thermal interaction. Consequently, optical signalling (and computation) in microtubules would be free from both thermal noise and loss. Superradiant optical computing in networks of microtubules and other cytoskeletal structures may provide a basis for biomolecular cognition and a substrate for consciousness.

A correlative immuno-light and electron microscopic study on the type I collagen in the bone morphogenetic protein-induced cartilage.

Bone morphogenetic protein (BMP) partially purified from bovine bone was implanted into the thigh muscles of AKR-strain mice to induce an ectopic endochondral ossification tissue. The extracellular matrix components around the hypertrophic chondrocytes in the induced tissue were examined by electron microscopy and immunohistochemistry for type I collagen. At 14 days after implantation, chondrocytes became hypertrophic with calcifying matrix around them. Some hypertrophic chondrocytes showed no degenerative appearances. They were ringed by a pericellular matrix with no metachromasia which was distinct from the metachromatic cartilage matrix. The localization of type I collagen was demonstrated by immuno-staining in this matrix. Ultrastructurally, ring-shaped matrix consisted of interwoven collagen fibrils on which a D-periodic banding pattern could be discerned. Immunoelectron microscopy demonstrated immunoreactivity of type I collagen on these fibrils. These results suggest that some of the BMP-induced hypertrophic chondrocytes maintain their activity and produce type I collagen-rich matrix before their lacunae are eroded.

[Treatment of nausea and vomiting induced by a 24-hour i.v. infusion of cisplatin].

Nine advanced gastric cancer patients were given 17 courses of cisplatin administrations by means of a 24-hour intravenous infusion at a dose of 100 mg/m2. For an anti-emetic, 40 mg of metoclopramide was administered 5 times at 6-hour intervals, along with a 500 mg hydrocortisone administration at the start of the cisplatin infusion. Despite this preventative treatment, nausea and/or vomiting occurred in over one-third of all the courses. Thus, to combat this nausea and/or vomiting, a combination of lorazepam (1.5 mg/day, divided into 3 p.o.), dexamethasone (20, 10 and 10 mg by i.v. at 3, 8, and 24 hours, respectively, after start of the cisplatin infusion), and a 60 mg intravenous administration of metoclopramide (5 times at 6-hour intervals) was given, and it was found that this new method (Method IV) prevented both nausea and vomiting.

[Futraful and UFT, their metabolic characteristics].

Investigations were made in human on the metabolism of Futraful (FT) and UFT (combination of uracil and FT), both of which are anticancer agents of pyrimidine metabolism antagonist. As a result, it was demonstrated that from the metabolic view point, those drugs essentially have a tumor-selective toxicity. Next, the mechanism of the superior clinical anticancer effect of UFT, compared to FT, was investigated enzymatically, showing the inhibitory effect of uracil on the degradation of 5-fluorouracil generated from FT in the organs and tumor tissues. Discussions were also made for the further development of fluoropyrimidines.