The effect of T cell depletion from spleen cell allografts on graft-versus-host disease and long-term immune reconstitution in H-2 haplotype-identical murine combinations.

Graft-versus-host disease (GVHD) and states of immune reconstitution in allogeneic chimera mice across minor histocompatibility antigens were analyzed in excess of 9 months after injecting AKR/JSea (AKR) spleen cells into irradiated C3H/HeSlc (C3H) mice. When T cell-depleted AKR spleen cells were used as inoculum cells, neither graft failure nor GVHD was seen for 9 months postgrafting in the C3H mice irradiated with 660 rad or more. In an AKR - C3H (850 rad) model, Thy1.1+ or L3T4+ T cell depletion from donor AKR spleen cells abolished both acute and chronic GVHD in lethally irradiated C3H mice. Lyt2+ T cell depletion, however, resulted in acute and chronic GVHD in more than half of the recipient C3H mice. Moreover, actual existence of donor (AKR)-type T cells with L3T4 phenotype, but not Lyt2 phenotype, was always observed in the spleen of the C3H mice suffering from acute GVHD. In addition, the C3H mice that were irradiated with 850 rad, grafted with AKR spleen cells depleted of Lyt2.1+ T cells, escaped from acute GVHD and survived for more than 10 mo postgrafting, showed impaired activities of immune responses such as delayed footpad reaction to sheep red blood cells, antibody production tested by IgM plaque forming cells and reactivity to an intracellular bacterium. Listeria monocytogenes as compared with the C3H mice reconstituted with syngeneic C3H spleen cells or Thy1.1+ or L3T4+ T cell-depleted AKR spleen cells. These results suggest that L3T4+ T cells, rather than Lyt2+ T cells, contained in the grafted cells not only cause acute GVHD but also a long-term immunodeficient state (chronic GVHD) in recipient mice in the H-2-identical murine combinations examined here.

Combination chemotherapy for infections due to methicillin-resistant Staphylococcus aureus with combination therapy by cefuzonam and fosfomycin or minocycline in the urologic field.

To determine the bacterial and clinical effects of methicillin-resistant Staphylococcus aureus (MRSA) on urinary tract infection (UTI), postoperative wound infection, and bacteremia, 22 strains of MRSA from infected patients were examined; minimal inhibitory concentration (MIC), fractional inhibitory concentration (FIC) index, coagulase typing, and change in MIC in the combination of cefuzonam (CZON) and fosfomycin (FOM) or minocycline (MINO), and the clinical effects of the combination therapy of CZON+FOM or CZON+MINO were investigated in 23 patients. MIC distribution was assessed for 11 drugs: methicillin (DMPPC), cefazolin (CEZ), cefotiam (CTM), cefuzonam (CZON), minocycline (MINO), vancomycin (VCM), arbekacin (ABK), imipenem (IPM), fosfomycin (FOM), ofloxacin (OFLX), and clarithromycin (CAM). For VCM and ABK, MICs ranged from 0.2 to 12.5 micrograms/ml. MINO showed a wide range of MIC, from 0.05 to 25 micrograms/ml. All strains were less sensitive to other antimicrobials. This MIC distribution was assessed in categories by coagulase typing. For CAM, type II strains revealed > or = 100 micrograms/ml of MIC50 and MIC90 compared with 0.2 and 3.13 micrograms/ml in type VII strains. For mixed combinations of CZON and MINO at ratios of 10 to 1 and 40 to 1, the rates of blood concentration for drugs 10 and 120 min after the intravenous injection, MIC distribution was observed between MINO and CZON. For mixed combinations of CZON and FOM at ratios of 1 to 1 and 1 to 4, MIC distribution was more sensitive than for FOM or CZON alone. With respect to the clinical effects of combination therapy by CZON+MINO and CZON+FOM, of seven cases of UTI with CZON+MINO, MRSA was eliminated completely in 4 patients (57.1%). In all patients who received CZON+FOM, MRSA was completely eliminated by this treatment regimen. In 4 of 7 (57.1%) patients with would infection and bacteremia, MRSA was eliminated by the combination of CZON+FOM or CZON+MINO. These results suggest that CZON+FOM is an effective combination in treating UTI and other MRSA infections in urology.

Ofloxacin and fleroxacin enhance superoxide production in human polymorphonuclear leukocytes by increasing phosphorylation in the signal transduction pathway.

Many antimicrobial agents including new quinolones (NQs) influence the cellular defense mechanisms such as polymorphonuclear leukocytes (PMNs), macrophages and lymphocytes. We examined the effects of NQs on superoxide (SO) production of PMNs following stimulation of phorbol myristate acetate (PMA). Ofloxacin (OFLX) and fleroxacin (FLRX) significantly augmented SO production of PMNs compared to lomefloxacin, sparfloxacin. Staurosporin and H-7, specific inhibitors of protein kinase C of SO production pathway in PMNs, inhibited augmented SO production by OFLX and FLRX in the concentration-dependent manner. NADPH oxidase activity was not influenced by OFLX in cell lysate assay system. These results suggest that OFLX and FLRX augmented PMN function through enhancing protein kinase activity, but not through direct enhancement of NADPH oxidase.

The hazards of alkaline disk batteries as foreign bodies in the nose.

This paper reports a case of intranasal chemical burn and septal perforation caused by an alkaline disk battery accidentally entrapped in the nasal cavity of a 3-year-old girl. The battery in the nasal cavity was removed after about 44 hours, but nasal septal perforation without nasal deformity occurred about 3 weeks after accident.

Olfactory evoked potentials produced by electrical stimulation of the olfactory mucosa.

We stimulated the olfactory mucosa electrically and elicited evoked potentials in rabbits. A bipolar stimulating electrode was placed on the olfactory region of the nasal mucosa via an anterior naris non-invasively. Evoked potentials were detected from the surface of a head. In most instances they were composed of triphasic negative-positive-negative peaks, the latencies of these peaks were about 25, 40, and 65 ms, respectively. This peak complex seemed to originate in the olfactory bulb. This method is non-invasive and is applicable to studying the olfactory system in animals and also in humans.

Modified combination chemotherapy of cisplatin and 5-fluorouracil in squamous cell carcinomas of the head and neck.

Randomized studies on the efficacy of two courses of different types of chemotherapy, including cisplatin and 5-fluorouracil (5-FU), were performed on 130 previously untreated cases with advanced squamous cell carcinomas of the head and neck. Cisplatin, followed by 120-hr continuous 5-FU infusion given in the conventional way, was administered to 60 patients (Group A), while cisplatin was administered 72 hr after the initiation of continuous 5-FU infusion in 70 other patients (Group B). The overall response rates (complete response plus partial response) were 58% in group A and 69% in group B, respectively. A superior complete response rate was obtained in cases receiving modified chemotherapy (10% in group A vs 20% in group B). There was no significant difference in the incidence of side effects between the two groups. These findings indicate that the modified cisplatin plus 5-FU combination chemotherapy tested here is more efficacious regimen than that of the conventional one to achieve high complete response rate and subsequently, to improve the survival of advanced carcinoma cases of the head and neck.

Three cases of inter-sterno-costo-clavicular ossification associated with tonsillar infection.

Three cases of inter-sterno-costo-clavicular ossification (ISCCO) associated with chronic tonsillitis are reported. Two cases had additional symptoms of pustulosis palmaris et plantaris (PPP). All the patients underwent tonsillectomy. The histological changes of the palatine tonsils of case 1 and case 2 were characterized by so-called focal small lacunar ulcers and periarteriolar fibrosis (onion-skin lesion). Some multinucleated giant cells were observed in case 2. Following tonsillectomy, symptoms in the clavicular region and the PPP improved. It is possible to consider that ISCCO is caused by focal tonsillar infection.

Chemiluminescence response of whole blood in patients undergoing urological operations.

Polymorphonuclear leukocytes (PMNs) are one of the most important components of the defence mechanisms against bacterial infection. The functions of PMNs are believed to be impaired in patients during the perioperative period. Bactericidal function of PMNs was investigated together with the luminol-dependent chemiluminescence (CL) reaction of whole blood in 23 patients, 12 undergoing open surgery and 11 undergoing endoscopic surgery. Blood samples were collected one day before surgery (day -1) and 2 hours (day 0), 24 hours (day 1) and 7 days (day 7) after surgery. Counts of whole white blood cells (WBCs), PMNs and lymphocytes were not different between the two surgery groups. CL responses in the open surgery group were increased on days 0, 1 and 7. In the endoscopic surgery group, CL response was increased on day 1, but not on day 0 or day 7. These results suggest that the PMN function during the perioperative period was not impaired, but increased just after surgery, mainly due to an increasing number of WBC caused by the surgical intervention.

[The expression of ICAM-1 on head and neck squamous cell carcinoma cell lines].

Intercellular adhesion molecule-1 (ICAM-1) is one of the cell adhesion molecules. This molecule is a glycoprotein of about 90 KDa belonging to the immunoglobulin (Ig) superfamily and is widely expressed by hematopoietic and non-hematopoietic cells which play a role in the immune system. ICAM-1 is also a ligand or counter-receptor for the leukocyte integrin lymphocyte-function associated antigen-1 (LFA-1). We investigated the expression of ICAM-1 on the surfaces of cells from fifteen head and neck squamous carcinoma cell lines and the modulation of ICAM-1 expression by IFN-gamma, using an immunohistochemical stain. We categorized four types of stain degree. (-): < 10% of cells positive (+/-): 10-40% of cells positive (+): < 40-70% of cells positive (++): > 70% of cells positive Four cell lines showed (-) type. Three cell lines: (+/-). One cell line: (+). Seven cell lines: (++). The primary site of cell lines and the degree of ICAM-1 expression were not detectable. Connection between pathological differentiation and the degreed expression were not apparent, either. IFN-gamma up-regulated the degree of ICAM-1. All cell lines, when stimulated by IFN-gamma, showed (++) type.

[Experimental study on the effect of the topical application of steroids on olfactory disturbance in mice].

Although the topical treatment with steroids is the widespread method for olfactory disorders in human, the reports are limitted to clinical observations. The aim of this report is to evaluate the effect of topically applied of steroids in mice on the repairing course by the experimental olfactory disorders caused by zinc sulfate. The olfaction of mice was estimated by the record of behavioral task, using Cycloheximide, commonly used as repellent in rodents. When mice taste Cycloheximide for the first time, immediately the mice experience a very disagreeable taste leading to the simultaneous memory of the odor of Cycloheximide. Those who once experienced the taste and odor of Cycloheximide, will avoid simply by the odor next time. Two bottles were offered to mice, one containing distilled water and the other 0.01% Cycloheximide. When the mouse drank the distilled water, the response was interpreted as a correct response. When the Cycloheximide solution was chosen, an error. Twenty four mice were tested at ten times during a 10-minute trial, and the rates of correct response were counted. From the next day after the treatment of zinc sulfate, nasal application of 0.1% beta-methasone (group A), or nasal application of distilled water (group B) were applied to each group of twelve mice for five days. The results were as follows. 1. In the first experiment, the correct response was 85% (group A), and 80.8% (group B), however at the second trial, all responses were correct.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of turnover of olfactory epithelium in mice by using anti-BrdU monoclonal antibody].

Among nerve cells of vertebrates, the olfactory elements are uncommon in their capacity to turnover and to be replaced after injury. An autoradiographical and morphological observation has shown that degenerated olfactory nerve cells are reconstituted by a new population of neurons which originate from basal cells. However, an autoradiographic method requires a special isotope institute and it takes a long time for the final specimen to observe. Recently, a rapid technique without the radioisotope has been alternatively developed in which a thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), is incorporated into replicating DNA and subsequently localized using a specific monoclonal antibody. In the present study, cell dynamics of olfactory mucosa in mice were investigated by means of immunohistological technique. The results were as follows. 1. The labelled elements were concentrated at the basal layer of the epithelium, which were observed 5 hrs after the first injection of BrdU. 2. At 15 days after administration of BrdU, the labelled elements were located in the mid-layer of the epithelium, where can be recognized as the compartment of nerve cells. 3. After 30 days, the labelled cells disappeared from the epithelium. It indicates that the period of turnover in the olfactory epithelium of mice is within 30 days. 4. Fifteen days after axotomy of the olfactory nerves, two stained patterns which were numerously or sparsely labelled regions were observed. The former is considered that immature neurons predominantly exist, and the latter is the area which mature neurons abundantly locate. It is considered that this immunohistological approach is useful for the observation of the turnover of the olfactory epithelium.

Prevention of catheter-associated urinary tract infection by meatal disinfection.

The incidence of catheter-associated urinary tract infections (UTIs) becomes higher with prolongation of the indwelling period of a catheter. As to the entry of bacteria, ascending UTIs have now attracted attention. In the present study. the metal area was examined bacteriologically and the possibility to use antiseptics for blocking the route of developing infections was investigated. The subjects included 72 patients with an indwelling, urethral catheter inserted post-operatively. These patients were divided into three groups treated with once or twice daily application of povidone-iodine or once daily application of povidone-iodine cream. In these groups, the relation between changes in isolation of bacteria from the meatal area and the incidence of UTI was evaluated. It was found that reduction in bacterial count by antisepsis is effective to prevent ascending UTIs. Moreover, once daily application of povidone-iodine was proven to be effective in male patients. The effective antisepsis in females was twice daily application of povidone-iodine.

Testicular injury induces cell-mediated autoimmune response to testis.

Studies on testis autoimmunity are needed for a better understanding of immunological male infertility. Evidence has accumulated that the delayed type hypersensitivity (DTH) response plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis. We report here that an antigen-specific DTH response to autologous testicular cells (TC) could be induced by bilateral testicular injury (trauma) in mice. Pretreatment of traumatized mice with a high dose of cyclophosphamide (CY) enhances the DTH response in a dose-dependent manner. The DTH response induced by testicular injury reaches its peak on the ninth day. We have shown that the local passive transfer of the footpad reaction to normal recipients by T cells further defines the DTH reaction. These characteristics resemble those of the previously reported DTH response to syngeneic TC induced by subcutaneous immunization with viable syngeneic crude TC. Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Secretion of a fibronectin-like substance from head and neck carcinomas.

The secretion of a fibronectin-like substance in culture supernatants of cell lines of head and neck squamous cell carcinomas was observed. Culture supernatants of some tumor cells had a high cell-attachment activity. Enzyme-linked immunosorbent assay with an antifibronectin antibody showed that the supernatant with cell attachment activity contained fibronectin. Furthermore, the cell attachment activity was clearly inhibited by the addition of a monoclonal antibody to fibronectin. These findings strongly suggest that the fibronectin produced by cancer cells is one of the potent mediators of the cell attachment.

Deletion of Mls-reactive T cells in H-2-compatible but Mls-incompatible bone marrow chimeras.

The cellular basis of tolerance induction to Mls-encoded antigens in radiation bone marrow (BM) chimeras has been investigated in two H-2-compatible strain combinations of AKR/J (H-2k, Thy-1.1, Mls-Ia) and C3H/He (H-2k, Thy-1.2, Mls-IIa). Sequential appearance of host- and donor-derived T cell subsets and T cell receptor gene messages occurred in the peripheral lymphoid organs of both irradiated AKR/J mice reconstituted with C3H/He BM cells (C3H/He-AKR/J chimera) and irradiated C3H/He mice reconstituted with AKR/J BM cells (AKR/J-C3H/He chimera). A large number of cells expressing T cell receptor gamma genes were detected in spleen on day 21 after reconstitution, while the normal level of alloreactivity was first detected in the spleen on day 56 after reconstitution in correlation with the appearance of appreciable levels of Thy-1 high cells and T cell receptor alpha and beta gene transcripts. T cells bearing V beta 6, that is strongly correlated with reactivity to antigens encoded by the Mls-Ia genetic locus, were virtually abolished in spleen on day 56 in both C3H/He-AKR/J chimera and AKR/J-C3H/He chimera. Furthermore, expression of V beta 3 gene transcripts, that are important for recognizing Mls-IIa, was undetected either in the peripheral lymphoid cells of AKR/J-C3H/He chimera or in those of C3H/He-AKR/J chimera. These results suggested that clonal elimination of self-reactive T cells bearing V beta 3 or V beta 6 was induced by both host-derived radioresistant cells and donor-derived repopulating cells in the thymus of radiation BM chimeras.

Subdural hematoma associated with dural metastasis from paranasal sinus cancer: a case report and review of the literature.

We report a 72-year-old woman who developed a subdural hematoma following dural metastasis from paranasal sinus carcinoma. Subdural hematoma with malignant neoplasm is a serious condition seen only in advanced stages. The prognosis is poor, but appropriate measures can help the patient. Head and neck surgeons should note this unusual clinical entity.