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The distribution of lectin receptors in the human tonsil was studied using 16 biotinylated lectins. The avidin-biotin-peroxidase complex (ABC) method was used on frozen and paraffin-embedded tissue sections. Cell suspensions were also analysed by dual flow cytometry using respective fluorescein isothiocyanate-conjugated lectins and phycoerythrin-labeled anti-CD3 and anti-human immunoglobulin. Frozen sections fixed with acetone and paraffin-embedded materials fixed in three solutions were compared for lectin affinity; ethanol-fixed sections gave best results followed by frozen and buffered formalin-fixed ones, then nonbuffered formalin. Con-A, RCA-1, LcH, WGA, MPA, PHA, PSA, PNA, SJA and GSA-1 reacted with all tissue components of the tonsil in immunohistochemical studies, but binding intensity was fixative dependent. Binding of Lotus and BPA to lymphocytes was limited to germinal center lymphocytes. Other tissue components were also reactive but staining intensity was weaker in Lotus compared with BPA. SBA and DBA did not react with lymphocytes, but reacted with macrophages/histiocytes, vascular endothelia, and epithelial cells. LBA and LPA were constantly negative with all tissue components irrespective of fixatives. Flow cytometric analyses showed that all but three (DBA, LBA and LPA) partially or totally stained lymphocyte surfaces. Lotus receptors were expressed exclusively on B-lymphocytes.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) were administered into the rat brain following unilateral fimbria-fornix transection. Both bFGF and NGF stimulated the sprouting of acetylcholinesterase (AChE) positive fibers in the hippocampus on the lesioned side. Furthermore, a small number of AChE-positive fibers were regenerated even when only the vehicle was administered. Rats treated with NGF as well as control group had only thin fibers, whereas those treated with bFGF had not only thin fibers but also thick fibers. These results indicate that intrinsic NGF is released and acts on damaged neurons directly, while bFGF acts them on directly and/or indirectly after brain injury.

Fifteen patients with Japanese cedar pollenosis were examined for lower airway function. Flow-volume patterns obtained from flow-volume and volume-time curves during the pollen season (March) and outside of the pollen season (June) were evaluated. In a previous report we classified maximal expiratory flow-volume (MEFV) curves in five patterns from A to E. In the present study, the patterns did not vary between the two periods except in one patient. Eleven patients out of 15 showed type E patterns, in which the flow-volume curve was concave along its entire course. In most of the patients with severe or moderate symptoms of allergic rhinitis only during the pollen season, the curve shifted to the right, but the parameters of the curves did not increase significantly outside of season. These findings suggest that patients with Japanese cedar pollenosis suffer from continuous latent peripheral airway obstruction. Extremely slight changes in the flow rate were detected by comparing the curves obtained during the two periods.

Lymphocyte adhesion molecules defined by anti-CD44 antibody (Hermes-3) may be involved in lymphocyte binding to high endothelial venules at sites where lymphocytes exist the blood. CD44 expression was immunohistochemically examined in 167 well characterized cases of malignant lymphomas (MLs). None of 12 nodal follicular lymphomas (FLs) were CD44+, whereas 3 of 4 extranodal ones showed distinct CD44 expression. In contrast to nodal FLs, 28 of the 38 (74%) nodal diffuse B-cell lymphomas were CD44+ (p < 0.0001). T-cell lymphomas showed a significantly higher expression of CD44 antigen than diffuse B-cell lymphomas in the nodal cases (p < 0.04), but not in the extranodal ones. In nodal diffuse lymphomas, 3 of 5 stage I lymphomas (60%) were CD44+ in contrast to 53 of 63 stage II-IV lymphomas (84%), but the difference was not statistically significant. Of 14 Hodgkin's diseases, 9 cases were CD44+ with no significant correlation with clinical stage. The data of flow cytometric analysis confirmed the results of immunohistochemical analysis. In conclusion, CD44 expression is relevant to primary sites of distinctive MLs originating in the mucosal regions (MALToma) and some histological subtypes, but the relation with clinical stage was not defined. Some other adhesion molecules or different mechanisms must also be taken into account concerning the genesis and the expansion of MLs.

Immunoallergological studies were carried out to clarify the differences between 24 patients with drug-induced asthma (DIA) and 240 with non-drug-induced asthma (non-DIA). The mean values of age, skin reaction to Candida albicans (C. albicans), serum IgE levels, specific IgE antibodies to house dust (HD) and C. albicans, bronchial sensitivity and leukotriene B4 (LTB4) synthesis from peripheral venous blood in patients with DIA were not significantly different from those in patients with non-DIA. In contrast, the frequency of positive skin reaction to HD and histamine release from peripheral basophils by anti-IgE were significantly lower in DIA than in non-DIA. These results agree with the reports that DIA was often observed in non-atopic asthma. But, the mean value of serum IgE was very high in DIA as well as in non-DIA. This result suggests that IgE mediated reaction in DIA is important. Furthermore, the proportion of neutrophils in bronchoalveolar lavage fluid (BALF) was significantly lower in DIA than in non-DIA. Our findings suggest that a decrease of intrapulmonary neutrophils might play an important role in the pathophysiology of DIA.

The effects of long-term glucocorticoid therapy on chemical mediator and cellular reaction in the airways were examined in 69 patients with bronchial asthma. The histamine release induced by Ca ionophore A23187 from cells in the bronchoalveolar lavage (BAL) fluid of atopic asthmatics was significantly lower in the subgroup with steroid-dependent intractable asthma (SDIA) than in non-SDIA patients (p < 0.05). In contrast, histamine release in nonatopic SDIA patients did not differ from nonatopic non-SDIA patients. The release of leukotriene C4 (LTC4) was significantly lower in atopic patients with SDIA (p < 0.02). However, there was no significant difference in LTC4 release between nonatopic patients with SDIA and without SDIA. The proportion of BAL lymphocytes was significantly lower in atopic patients with SDIA than in those without it (p < 0.05), although there was no significant difference between the nonatopic patients with and without SDIA. These results show that glucocorticoids affect humoral and cellular events in the airways of atopic asthmatics more than in those of nonatopic asthmatics.

A total of 124 lesions from 1 to 6cm in diameter, including 31 cavernous hemangiomas, 32 metastases and 61 hepatocellular carcinomas (HCC) were analyzed to study the usefulness of magnetic resonance imaging (MRI) at 0.5 Tesla to differentiate focal hepatic lesions on the basis of qualitative criteria. Each focal hepatic lesion was assessed for shape, internal architecture and signal intensity relative to normal liver parenchyma. While all cavernous hemangiomas and metastases except one lesion could be detected, detection rate of HCC was significantly inferior to that of the other two diseases. A tumor capsule and a hyperintense focus on T1-weighted images were demonstrated in only HCC lesions in strong contrast with the other two diseases; however, metastases with slow-growing characteristics or subacute hematoma may appear as similar images. Cavernous hemangiomas appeared markedly hyperintense on T2-weighted images in 23 of 31 lesions, but one metastasis and one HCC had similar images. A multivariate analysis of several MRI resulted in the following mean discriminant scores: cavernous hemangioma, -1.2652; metastasis, 0.1830; and HCC, 0.7138. It appeared to be possible to differentiate the three diseases with 84.4 percent accuracy.

A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pellet (IL-2 mp), was developed by fusing IL-2 into a needle shaped collagen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL-2 in the serum became undetectable by 6h after a subcutaneous injection of 1 x 10(6) unit of IL-2 in phosphate-buffered saline (PBS). In contrast, after a single subcutaneous injection of IL-2 mp containing the same amount of IL-2, the concentration of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK activity and generation of IL-2 activated killer cells were observed in the spleen from day 1--day 3 after a single subcutaneous injection of IL-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adoptive immunotherapy by a single subcutaneous injection of IL-2 mp followed by intravenous injections of in vitro cultured IL-2 activated killer cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.

Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction.

The differences in physiological and safety conditions of one-man buses and two-man buses were examined from the view point of occupational fatigue. This survey consisted of a work load study which included a time study, study of subsidiary behavior, auditory task, memory test, Galvanic Skin Response (GSR) and physiological function tests and a self-administered questionnaire which involved items concerning safety and subjective fatigue complaints. The visual and postural restrictions in the one-man bus were greater than in the two-man bus. The mental capacity of the one-man bus drivers was found to be less. Greater mental fatigue and stress were observed in the one-man bus. More subjective fatigue complaints were observed in the one-man bus. More cases of near accidents were observed in the one-man bus. From these results it was concluded that the one-man bus caused bus drivers a greater mental and physical work load.

Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the human knee.

The fibrous components of the metacarpophalangeal (MP) joint including the palmar plate, the collateral ligament and the dorsal plate were studied with particular attention paid to the fibrous structure of the fibrous tendon sheath and the deep transverse metacarpal ligament. The tough fibrillar structure around the MP joint, especially the force nucleus, consisted of three types of mixed fibers: the fibrous tendon sheath of the A1 pulley, the deep transverse metacarpal ligament, and the palmar plate. The tendon sheath was located on the ulnar side in the index and middle fingers, on the central position in the ring finger, and on the radial side in the little finger. These fibrous connections among the fingers formed a transverse arch in the hand. The palmar plate of the MP joint was relatively rigid and appears to function as a cushion when flexed. A fold-like protrusion of the synovial layer of the palmar plate of the MP joint had a meniscoid function, which was larger than that of the proximal interphalangeal joint. The capsule of the MP joint was thicker at the dorsal area, forming a dorsal plate, which is a sliding floor of the extensor mechanism and has a meniscoid function for joint congruity. The main lateral stabilizer consisted of collateral ligaments and accessory collateral ligaments anchored to the palmar plate. These structures act together as a "phalangeal cuff", connecting the proximal phalanx to the metacarpal head and sta

To test transdifferentiation of retinal pigment epithelial (RPE) cells in suspension culture, chick embryonic RPE sheets and dissociated RPE cells were cultured for two months in a non-adherent dish for suspension culture. RPE cells, isolated as a sheet, aggregated immediately and remained the same size with their differentiated characteristics for two months. The presence of basic fibroblast growth factor (bFGF) at concentrations of 10 ng/ml or higher induced the formation of a spherical lentoid structure which was positive for crystallin and bFGF receptor. In contrast, dissociated RPE cells did reaggregate but did not develop the lentoid structure even in the presence of bFGF. The transdifferentiation of RPE cells to the lentoid structure in this study was in contrast to their transdifferentiation to the retina, as reported in a previous study.

To study the expression of the amiloride-sensitive sodium channel, a putative mechano-receptor in the rat eye, reverse transcriptase-polymerase chain reaction and in situ hybridization were done. The gene for the alpha subunit of the amiloride-sensitive sodium channel was shown by polymerase chain reaction to be expressed in mRNA isolated from the whole eye tissue. In situ hybridization demonstrated that the gene was expressed in basal layers of the corneal and conjunctival epithelium, ciliary epithelial cells, lens epithelial cells at the equator, retinal and iris pigment epithelial cells, ganglion cells and cells in the inner and outer nuclear layers of the retina. The results suggest that the amiloride-sensitive sodium channel plays a role in maintaining sodium balance as well as in possible mechanosensation in these ocular tissues.

We studied the magnetic resonance imaging (MRI) of 120 knees in 86 rheumatoid arthritis (RA) patients and of 14 unaffected knees in 12 control cases. We also developed a scoring system as a quantitative analysis method. We divided the MRI into 10 items, and classified the severity of the symptoms into 4 grades (score 0 to 3). The average total score increased according to the radiographic grade. Soft tissue lesions were clearly detected, even in the early stages of RA. Items such as synovial proliferation showed a high score even in the early stages, suggesting that it was the initial symptom of RA. The score also showed a correlation with the inflammatory signs. These results suggest that this scoring system is very sensitive and yields a good reflection of RA activity. We demonstrated that this system is simple and convenient for routine diagnostic use. We further demonstrated that it is useful for following the advancement of RA and for evaluating the response to treatment.

Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.

To determine the allergens of mite allergic rhinitis, we studied 31 patients with mite allergic rhinitis by skin tests and nasal provocation tests (15 for skin and 16 for nasal tests) using 6 fractions of Dermatophagoides pteronyssinus (Dp) extract differing in molecular weights (15, 25, 32, 53, 95 and 190 kDMW). In skin testing, patients showed intense positive reactions to the fractions of 15, 25, 32, 95 and 190 kDMW, among which the most patients showed positive reactions to the fractions of 15 and 25 kDMW. Significant differences were found in patients' positive reactivity among each fraction and between low (15 and 25 kD) and high (95 and 190 kD) molecular weight fractions as well. In nasal provocation tests, patients showed intense positive reactions to the fractions of 15, 32, 53 and 95 kDMW, especially to the fractions of 15 and 95 kDMW. Furthermore, the insidence of positive reactions to the 15 kDMW fraction was significantly higher than that to any other fraction in the skin tests (P < 0.05). From these results, the low molecular weight fraction, 15 kDMW, is considered to be the main allergen of this mite and the high molecular weight fractions, 95 and 190 kDMW, may also be considered to be allergens of this mite.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.