THE ROLE OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN THE PATHOGENESIS OF COLLAGEN-INDUCED ARTHRITIS IN RATS

Collagen-induced arthritis was produced in rats by intradermal immunization with type II collagen and the expression and production of monocyte chemoattractant protein-1 (MCP-1) were examined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Northern blot analysis. Two to three weeks after the immunization, the hindfeet showed swelling and redness, followed by the development of severe arthritis, particularly in the ankle joints. During this period, prominent infiltration of neutrophils and macrophages was observed. Sandwich ELISA and Northern blot analysis revealed that MCP-1 concentrations in the joint lavages and MCP-1 mRNA levels in the joint tissues both peaked at 2 weeks after the immunization. By immunohistochemistry, various types of cells, particularly neutrophils, macrophages, synovial cells, and vascular endothelial cells, stained positively for MCP-1. Finally, injection of a neutralizing monoclonal antibody against rat MCP-1 significantly decreased the number of exudate macrophages in the lesions and reduced the ankle swelling by about 30 per cent compared with controls. These results suggest that MCP-1 plays a critical role in this model in the recruitment of monocytes and in the development of arthritis. © 1997 John Wiley & Sons, Ltd.     

Cardiac Pacemaker Regulated by Respiratory Rate and Blood Temperature

A new method using respiratory rate and temperature as the guides for optimal pacing is proposed. A pacemaker was fabricated which senses these two parameters simultaneously. The pacemaker functions by calculating the cardiac rate, which would be derived from the respiratory rate and the blood temperature. The higher of the two rates is adopted as the cardiac pacing rate, i.e., at which stimuli will be delivered. The operation was tested in a mongrel dog with complete atrioventricular block. After the induction of anesthesia, a thermistor temperature probe was inserted into right atrium and a respiratory rate sensor was attached around the chest. After administration of a pyrogenic drug, both respiratory rate and blood temperature increased. The pacing rate was increased from 178 beats/minute(bpm) at 36.4 degrees C, blood temperature, and 26.5 acts/minute(apm), respiratory rate, to 233 bpm at 40.1 degrees C and 40.0 apm. Cardiac output was increased from 2.15 liters/minute(l/pm) at the beginning to 2.50 l/pm at maximum. The transition of the guide from respiratory rate to temperature was observed at about 38 degrees C.     

Suppressive Effects of Eviprostat,a Phytotherapeutic Agent,on Lower Urinary Tract Symptoms in Prostate Cancer Patients Treated with Brachytherapy

Objectives: Eviprostat is an anti‐oxidant, anti‐inflammatory phytotherapeutic agent that is commonly used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia in Japan and Germany. Prostate cancer patients treated with brachytherapy generally have complaints of LUTS for several months postoperatively. Methods: We investigated the protective effects of Eviprostat against the development of LUTS in 37 patients, who had received ¹²⁵I prostate brachytherapy as monotherapy. These patients were divided into two groups, an Eviprostat‐treated group (n = 18) and an untreated control (n = 19), whose background had no significant difference. The group treated with Eviprostat was prophylactically medicated from 3 weeks preoperatively until 3 months postoperatively. Symptom scores and quality of life for urination were evaluated according to the International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC) on preoperative day 1, and postoperative months 1, 3 and 6. Results: Both the scores of IPSS and the levels of quality of life in EPIC were significantly worse at 1 month postoperatively compared to the pretreatment baseline, and thereafter progressively improved in both groups. Eviprostat‐treated patients showed significantly better recovery compared to Eviprostat‐untreated control at 6 months postoperatively, with respect to urinary summary score, urinary function and urinary irritation/obstruction subscales in EPIC. Moreover, the feeling of incomplete emptying in IPSS and the urinary irritation/obstruction subscale in EPIC were significantly improved at 3 months postoperatively compared to the peak impairment at 1 month in the Eviprostat‐treated group. Conclusions: It is possible that Eviprostat has the potential to ameliorate postoperative LUTS caused by brachytherapy.     

Impact of Living at the Japanese Antarctic Research Expedition Base on Urinary Status

Objectives

Urinary disorders are generally well understood, but there are few reports on the urinary status of people living in unusual climates such as the polar regions. We studied the impact of living conditions on the urinary status of members of the Japanese Antarctic Research Expedition.

Methods

This prospective study enrolled 12 consenting members of the wintering party stationed at the Syowa Station in Antarctica between November 2012 and March 2014. The subjects completed questionnaires (the International Prostate Symptom Score [IPSS], Overactive Bladder Syndrome Score [OABSS] and Pittsburgh Sleep Quality Index [PSQI]) and kept daily voiding dairies for 3 days consecutively every 2 months.

Results

Compared with baseline values, the mean scores on all the questionnaires decreased during the stay in Antarctica, from 3.42 to 2.31 for the IPSS, 1.25 to 0.986 for the OABSS, and 4.58 to 3.78 on the PSQI. A significant difference was noted in the scores of seven subjects with a 3 point or more decrease in IPSS score and five members with a decrease less than 3 points (?2.22 vs 0.448, P = 0.0416).

Conclusion

This is the first survey of the urinary status of people living in a polar environment. The findings obtained by questionnaires and voiding dairies indicated that urination and sleep status did not worsen during the stay in Antarctica.     

Clinical Guideline for Female Lower Urinary Tract Symptoms

The “Japanese Clinical Guideline for Female Lower Urinary Tract Symptoms,” published in Japan in November 2013, contains two algorithms (a primary and a specialized treatment algorithm) that are novel worldwide as they cover female lower urinary tract symptoms other than urinary incontinence. For primary treatment, necessary types of evaluation include querying the patient regarding symptoms and medical history, examining physical findings, and performing urinalysis. The types of evaluations that should be performed for select cases include evaluation with symptom/quality of life (QOL) questionnaires, urination records, residual urine measurement, urine cytology, urine culture, serum creatinine measurement, and ultrasonography. If the main symptoms are voiding/post‐voiding, specialized treatment should be considered because multiple conditions may be involved. When storage difficulties are the main symptoms, the patient should be assessed using the primary algorithm. When conditions such as overactive bladder or stress incontinence are diagnosed and treatment is administered, but sufficient improvement is not achieved, the specialized algorithm should be considered. In case of specialized treatment, physiological re‐evaluation, urinary tract/pelvic imaging evaluation, and urodynamic testing are conducted for conditions such as refractory overactive bladder and stress incontinence. There are two causes of voiding/post‐voiding symptoms: lower urinary tract obstruction and detrusor underactivity. Lower urinary tract obstruction caused by pelvic organ prolapse may be improved by surgery.     

Ultrastructural evidence for eosinophil-mediated destruction of Angiostrongylus cantonensis transferred into the pulmonary artery of non-permissive hosts

Ultrastructural and cytochemical analyses were carried out on cellular reactions to the young adult worms of Angiostrongylus cantonensis surgically transferred into the pulmonary arteries of permissive (rat) and non-permissive (rabbit and guinea-pig) hosts. In permissive hosts, no appreciable cellular reactions could be found around worms throughout the course of the observations. By contrast, the infiltration of neutrophils along with eosinophils was observed around worms in non-permissive hosts even at early stages (days 2 to 4). At day 7 and later, the prominent degranulation (solubilization of the whole granule or the matrix alone with preserved crystalloid, tubulovesicular structure formation, and vacuole formation containing lysosomal contents, etc.) of eosinophils, and subsequent release of the lysosomal contents on to the worm surface were noted. Discharge of large amounts of peroxidase on to the worm surface was also demonstrated. The worms were thus damaged and their cuticular fragments were frequently found removed. In addition to this, degenerative changes, such as lipid-droplet and vacuole formations, were detectable in the hypodermis, somatic musculature and intestine of the parasites transferred into the non-permissive hosts, as early as day 4 after transfer. These data suggest that eosinophils would serve as a potential effector cell for killing of pulmonary arterial A. cantonensis in non-permissive hosts.     

Ultrastructural and morphometric analyses of eosinophils from the cerebrospinal fluid of the mouse and guinea-pig infected with Angiostrongylus cantonensis

Guinea-pigs infected with Angiostrongylus cantonensis developed pleocytosis and eosinophilia in the cerebrospinal fluid (CSF) at day 12 post-infection (p.i.), showing a peak response at day 20 p.i., followed by a gradual reduction. Ultrastructural observations on CSF eosinophils from infected mice and guinea-pigs revealed various signs of eosinophil degranulation after day 14 p.i., suggesting the exocytosis of lysosomal material. Morphometric analysis indicated that CSF eosinophils after day 22 p.i. contained fewer granules as well as smaller granules than those at days 14-20 p.i. These data suggest that CSF eosinophils release granule constituents into the outside of the cells and these secretion products could interact with the intracranial worms and are probably related to worm death. As degenerative atrophy or partial loss of Purkinje cells and the spongy vacuolation of the white matter were noted in the cerebellum of infected mice, it was suggested that CSF eosinophils could be a possible cause of neurological disorders in angiostrongyliasis cantonensis.     

Blood Coagulation and Vascular Integrity: Effects of Heparin

The administration of large and repeated doses of heparin to normal ratsresulted in increased output of red blood cells into the lymph, comparable tothat associated with x-ray induced thrombocytopenia. A considerable lapse oftime was observed between the inhibition of blood coagulation and the increase of vascular permeability to red blood cells. The latter was not decreasedby return of the blood clotting to normal.

Submitted on March 21, 1962 Accepted on July 4, 1962     

Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro

Summary We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5 J/cm²UVA), topical PUVA (0·3% 8MOP plus 200mJ/cm²UVA) or UVB (80mJ/cm²) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean± SD) were 69·3 ± 26.9%, 76·3 ± 31·3% and 83·8 ± 18·5%. respectively. Secondly, we investigated the effect of PUVA (0·001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm²UVA) and UVB (10, 30, 50, or 100 mJ/cm²) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.