A role for CXC chemokine receptor-2 in the pathogenesis of urogenital Chlamydia muridarum infection in mice.

We tested the hypothesis that a specific chemokine receptor, CXC chemokine receptor-2 (CXCR2), mediates acute inflammatory damage during chlamydial urogenital infection, which ultimately leads to the chronic sequelae of hydrosalpinx - a surrogate marker of infertility. Homozygous CXCR2 genetic knockouts (CXCR2-/-), heterozygous littermates (CXCR2+/-) or homozygous wild-type (wt) controls (CXCR2+/+) were infected intravaginally with Chlamydia muridarum. Although no change was observed in the infection in the lower genital tract based on CXCR zygosity, a delay in the ascension of infection into the upper genital tract was seen in CXCR2-/- mice. Significantly elevated peripheral blood neutrophil counts were observed in CXCR2-/- mice when compared with controls. Reduced rates of acute inflammatory indices were observed in the affected tissue, indicating reduced neutrophil extravasation capacity in the absence of CXCR2. Of note was a reduction in the postinfection development of hydrosalpinx that correlated with CXCR2 zygosity, with both CXCR2-/- (13%) and their CXCR2+/- (35%) littermates displaying significantly lower rates of hydrosalpinx formation than the wt CXCR2-sufficient mice (93%). We conclude that CXCR2 ligands are a major chemotactic signal that induces damaging acute inflammation and the resulting chronic pathology during the repair phase of the host response, but are dispensable for the resolution of infection.

A link between neutrophils and chronic disease manifestations of Chlamydia muridarum urogenital infection of mice.

Vigorous acute inflammatory responses accompany Chlamydia muridarum infections in mice and are positively correlated with adverse urogenital and respiratory tract infection outcomes in the mouse model. Thus, we tested the hypothesis that neutrophils induce an acute inflammatory insult that, in the repair phase, leads to the chronic sequelae of hydrosalpinx - a surrogate marker of infertility in the mouse model. To this end, we induced neutropenia in mice using a neutrophil-depleting monoclonal antibody during acute phases of C. muridarum urogenital infection only (days 2-21 postinfection). To prove induced neutropenia, peripheral blood was monitored for neutrophils during the treatment regimen. Neutropenic mice had a similar infection course as control mice, but had significantly reduced levels of certain histopathological parameters, reduced production of matrix metalloproteinase-9 (MMP-9) and reduced rates of hydrosalpinx following resolution of the infection. We conclude that neutrophils are a major source of MMP-9, a previously proved pathological factor in this model. Further, we conclude that acute inflammation in the form of neutrophils and neutrophil activation products are at least partially responsible for inducing the histological changes that ultimately result in fibrosis and infertility in the mouse model of chlamydial upper genital tract disease.

Stapediovestibular dislocation with pneumolabyrinth.

Traumatic luxation of the stapes into the vestibule is a rare entity, and the disease complicated with pneumolabyrinth is extremely rare. We report the case of a 72-year-old woman with pneumolabyrinth associated with a stapediovestibular dislocation. The patient presented with vertigo and nystagmus following penetrating trauma to the middle ear. High resolution computed tomography scans demonstrated air in the vestibule and dislocation of the stapes. Exploratory tympanotomy demonstrated oozing of the perilymph from the oval window and depression of the stapes into the vestibule. Pneumolabyrinth and stapes luxation detected by high resolution computed tomography should be predictive of a perilymphatic fistula.

Upregulation of MIP-2 (CXCL2) expression by 15-deoxy-Delta(12,14)-prostaglandin J(2) in mouse peritoneal macrophages.

A peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), has been reported to possess anti-inflammatory activity in activated monocytes/macrophages. In this study, we investigated the effect of 15d-PGJ(2) on the lipopolysaccharide (LPS)-induced expression of chemokine mRNAs, especially macrophage inhibitory protein (MIP)-2 (CXCL2), in mouse peritoneal macrophages. The inhibitory actions of the natural PPARgamma ligands, 15d-PGJ(2) and prostaglandin A1 (PGA1), on the expression of RANTES (regulated upon activation, normal T expressed and secreted; CCL5), MIP-1beta (CCL4), MIP-1alpha (CCL3), IFN-gamma-inducible protein 10 kilodaltons (IP-10; CXCL10) and monocyte chemoattractant protein-1 (MCP-1; CCL2) mRNA in LPS-treated cells were stronger than those of the synthetic PPARgamma ligands troglitazone and ciglitazone. However, 15d-PGJ(2) enhanced the expression of LPS-induced MIP-2 (CXCL2) mRNA. A specific PPARgamma antagonist (GW9662) had no effect on the inhibitory action of 15d-PGJ(2) and PGA1 in LPS-induced chemokine mRNA expression and on the synergistic action of 15d-PGJ(2) in LPS-induced MIP-2 (CXCL2) expression. Moreover, LPS itself reduced the expression of PPARgamma. Although the synergistic effect of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) mRNA expression was remarkable, the production of MIP-2 (CXCL2) in cells treated with 15d-PGJ(2) and LPS did not increase compared to the production in cells treated with LPS alone. The synergistic action of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) mRNA expression was dependent on the activation of nuclear factor-kappaB (NF-kappaB), and 15d-PGJ(2) increased the phosphorylation of p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in cells stimulated with LPS. These results suggest that the synergistic effect of 15d-PGJ(2) on LPS-induced MIP-2 (CXCL2) expression is PPARgamma-independent, and is mediated by the p38 and SAPK/JNK pathway in mitogen-activated protein kinase signaling pathways, which activates NF-kappaB. Our data may give more insights into the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ(2) on the expression of chemokine genes.

Elevated plasma osteopontin levels in patients with hepatocellular carcinoma.

OBJECTIVES: Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC). METHODS: We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed. RESULTS: Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells. CONCLUSIONS: These data propose elevated plasma OPN levels as a potential biomarker for HCC.

Upregulation of LPS-induced chemokine KC expression by 15-deoxy-delta12,14-prostaglandin J2 in mouse peritoneal macrophages.

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) was initially identified as a high affinity natural ligand for the peroxisome proliferator-activated receptor (PPAR)-gamma. Recent studies have shown that it has a potent anti-inflammatory effect by attenuating the expression of proinflammatory mediators in activated macrophages, mainly through the inhibition of nuclear factor (NF)-kappaB-dependent transcription of inflammatory genes. In this study, we investigated the synergistic effect of 15d-PGJ(2) on the expression of LPS-induced chemokine KC mRNA in mouse peritoneal macrophages. The time course of KC mRNA expression in cells stimulated with 15d-PGJ(2) plus LPS simultaneously (15d-PGJ(2)/LPS) showed similar patterns to the cells treated with LPS alone, and 15d-PGJ(2) had no effect on the stability of LPS-induced KC mRNA expression. Although NF-kappaB activity in cells treated with LPS was augmented by 15d-PGJ(2), pyrrolidone dithiocarbamate (PDTC) did not block the synergistic effect of 15d-PGJ(2) on LPS-induced KC mRNA expression. However, the synergistic effect of 15d-PGJ(2) was markedly inhibited when the macrophages were treated with a inhibitor of the mitogen-activated protein kinase (MAPK) signalling pathway, 2'-amino-3'-methoxyflavine (PD98059). Therefore, the mechanism of synergistic action of 15d-PGJ(2) on the expression of LPS-induced KC mRNA in mouse peritoneal macrophages is possibly related to the MAPK signalling pathway, not to NF-kappaB activation. These data may contribute to unravelling some of the different mechanisms contrary to the anti-inflammatory effect of 15d-PGJ(2).

Histopathologic characteristics of chronic sinusitis with bronchial asthma.

CONCLUSION: These findings suggest that patients with both sinusitis and asthma present the histopathologic characteristic of a marked chronic inflammatory reaction, and that eosinophil infiltration may play a significant role in this marked inflammation of the sinus mucosa. OBJECTIVE: Chronic sinusitis and bronchial asthma are known to be closely related. However, the appearance of the mucosa in chronic sinusitis patients with asthma is somewhat different from that in patients without asthma. MATERIAL AND METHODS. We compared the sinus mucosal histopathologies of asthmatic patients with those of non-asthmatic patients. Fifty-three sinusitis patients with a diagnosis of asthma and 54 sinusitis patients without asthma, who served as controls, were enrolled in the study. All of these patients underwent endoscopic sinus surgery. The following seven light microscopic findings were compared in the asthmatic and non-asthmatic groups: the thickness of the basement membrane, goblet cell hyperplasia, subepithelial edema, submucous gland formation, eosinophil infiltration, lymphocyte infiltration and polymorphonuclear leukocyte infiltration. In addition, we explored a possible link between asthma and sinusitis by comparing the following factors in asthmatic and non-asthmatic patients: the presence of allergy, the degree of preoperative polyposis and the extent of preoperative disease as scored by means of ostiomeatal unit CT findings. RESULTS: No statistically significant differences were found between the two groups in terms of the presence of allergy, the degree of preoperative polyposis or the extent of preoperative disease. Basement membrane thickening, goblet cell hyperplasia and eosinophil infiltration were more prominent in the asthmatic compared to the non-asthmatic group (p <0.05).

A rapid three-dimensional measurement system for facial morphology by laser multi-slits.

A laser light-sectioning technique for measuring the three-dimensional shape of the face has been developed. Multi-slit lasers were used to minimize the recording time, and the accumulating technique of multiple images was used to reduce the memory size. The system can scan the entire human face within 6 seconds and develop a three-dimensional image in approximately 4 minutes. The accuracy of this system was found to be within a 0.4% relative error. The method has the advantages of being contact-free, rapid, automatic, and useful for three dimensional clinical assessment.

[A case of verrucous carcinoma showing a good partial response by C.P.E. (CDDP, PEP, etoposide) chemotherapy].

A 60-year-old woman was admitted to our hospital with a complaint of rough feeling on the oral mucosa and diagnosed as verrucous carcinoma with histopathological examination. She was treated with CPE chemotherapy, and showed a good response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia and anorexia. However, these were slight side effects. The patient is currently healthy with no recurrence after two years and 3 months. CPE chemotherapy is considered to be effective for a patient with verrucous carcinoma.

Ultrastructural study of mitochondria in oncocytes.

A number of mitochondria in oncocytes show pleomorphism by conventional electron microscopy. In an investigation of their stereostructure, specimens were obtained from 11 patients with Warthin's tumor, parts of which were used in the preparation of serial thin sections. It was revealed that cup-shaped and concentric ring forms of mitochondria resulted from invagination and that aberrant cristae such as the sheaflike and vesicular types were both derived from laminated cristae with vesicular structure.

Particle deposition efficiency of therapeutic aerosols in the human maxillary sinus.

The deposition efficiency of therapeutic aerosol particles in the human maxillary sinus is evaluated both in the human body and in a model cast of the upper airway. In the experiments, three sample materials, such as mono-dispersed polystyrene latex particles, aqueous glucose solution and pure water, in the range of particle diameter of from 0.5 to 15.8 microns, are employed in the model cast. The radioactive labelled aerosol particle is also used in the human body. From the results of the experiment, it is confirmed that even though the maxillary sinus is a closed hollow organ, aerosol flow is able to be induced only when the pressure gradient is applied between the nasal cavity and the maxillary sinus. In this case, the particle deposition is is explained in relationship to the inertia impaction of the aerosol particles on the inside wall of the maxillary sinus. The total deposition efficiencies and the deposited particle sizes in the sinus area for both experiments, with the model and in the human body, are almost the same at 3%, and 3-10 microns in diameter, respectively. A physical model for this particle deposition suggests that these experimental values change not only with the size distributions of therapeutic particles and the pressure gradient, but also with the diameter of the sinus ostium. Moreover, since the therapeutic particle might not enter the maxillary sinus when the diameter of the sinus ostium canal is less than 1 mm, some pretreatment to open the sinus ostium canal would be necessary before applying such aerosol therapy in practice.

[Clinical study on mandibular condylar fracture. 1. Retrospective study in 100 patients with 130 temporomandibular joint fractures with special consideration in the treatment for the various locations and forms of the fractures].

Clinical retrospective investigation was conducted on mandibular condylar fractures of 100 hospitalized cases at the Department of Oral Surgery, Kyoto University Hospital during the period from 1973 to 1983. The following results were obtained, 1. There were 74 males and 26 females. The age of the patients at the time of injury ranged from 4 to 78 years old. The average age was 28.1 years old. 2. Twenty-six patients were treated within a week of injury, 22 cases within 2-weeks and 33 cases were treated after more tham 3 weeks. 3. Of the 100 cases, 70 were unilateral fractures and 30 were bilateral. The incidence of the concomitant fractures of the mandible were higher in bilateral than in unilateral condylar fractures. 4. On fracture level and form 130-site in 100 patients were divided according to the classification of Maclennan and Kubo. Dislocated and high condylar fractures were most frequently observed. 5. Surgical reduction was mainly achieved in low neck fracture, and the contrary conservative treatment was observed in the higher level fracture. On the other hand condylectomy was infrequently indicated in the dislocated head fracture.

[Clinical study on mandibular condylar fracture. 2. Long-term follow-up study in 48 patients with 66 joints].

Sixty-six joints in 49 patients with mandibular condylar fracture were investigated by means of long-term follow-up observation. The group of patients consisted of 39 males and 10 females with ages from 15 to 75 years. The classification of the fractures was follows: MacLennan type 1; four, type 2; four, type 3; 39, and type 4; 39 joints respectively. Treatment was as follows: 25 joints were by conservative therapy, 31 joints were by surgical fixation, and 10 joints condylectomy. The follow-up period of observation ranged from 18 months to 10 years and one month an average of five years and seven months. Clinical assessment was based upon Nakatomi's dysfunction index on mandibular condylar fracture, of which the criteria are as follows; Excellent (No clinical dysfunction sign on the TMJ), Fair (Slight pain, noise, and limited range of motion of the mandible, but clinically no affected mastication), Poor (Moderate dysfunctioned jaw), and Failure (Severe dysfunctioned jaw). 23 joints in 18 patients were ranked as having excellent results. 31 joints in 22 patients were assessed as fair. Ten joints in seven patients were defined as poor, and the remaining two joints in two patients were failures. The overall success rate was 81.7%. There are no statistical differences between patient's groups based on age, sex, uni/bilateral modality, with/without other concomitant fracture, surgical/conservative procedure, location and form of fractures, and duration of period from injury. These results indicated that the conservative procedure would be the first choice as a reasonable and less invasive procedure for functional repair of mandibular condylar fracture. On the other hand, as most patients had some dysfunction sign on the TMJ after mandibular condylar fracture, a more appropriate treatment, surgical or otherwise, should be found.

Microsurgical treatment of patients with vestibular and cochlear symptoms.

Eighteen patients with vertigo, tinnitus, and various hearing disturbances were treated by posterior fossa exploration and microvascular decompression of the eighth cranial nerve; they were followed for more than 3 years. After successful decompression of the eighth nerve from offending vessels, the attacks of vertigo disappeared in 11 patients, improved markedly in 3 patients, and improved mildly in 4 patients. The tinnitus vanished in three patients and decreased in nine. The hearing disturbance improved in only five patients and worsened in three. Because of the satisfactory improvement of the attacks of vertigo, which are the most distressing symptoms for patients, we recommend surgical exploration for patients with severe symptoms of vestibular disturbances.

[Compound therapy including PSK for malignant head and neck cancer].

The effect of protein-bound polysaccharide preparation, PSK was studied in 44 cases with head and neck cancer. 1) Eight cases with laryngeal cancer received radiation therapy and PSK as immunotherapy, and eight cases as control received radiation alone. During radiation, the mean values of peripheral lymphocyte counts showed statistically significant difference (P less than 0.05) between the cases with immunotherapy and those without immunotherapy. 2) Twenty-eight cases received adjuvant immunochemotherapy with Carboquone and PSK. 22 out of 28 evaluable cases in the group received adjuvant immunochemotherapy were judged as effective. These studies suggest that PSK is one of the valid immunopotentiators.

Malignant fibrous histiocytoma of the temporomandiblar joint. Report of a case.

A case of malignant fibrous histiocytoma of the temporomandibular joint in a 21-year-old Japanese female was presented. The patient died of the tumor with local aggressive growth but without any organ metastasis, despite the intensive treatment including radical operation of the tumor, irradiation, and chemotherapy. This case suggested that radical curative operation was the only method of the treatment for this tumor. The clinicopathological features of the tumor are discussed, making reference to the malignant fibrous histiocytoma.