A case report of granulomatous orchitis--review of 20 cases in Japan

We report a case of granulomatous orchitis. A 31-year-old male complained of right lumbago and scrotal pain. The ultrasonographic finding was multiple hypo-echoic areas in the right testis as highly suggestive of testicular cancer. The diagnosis was made after orchiectomy. Granuromatous orchitis is a rare disease which true etiology remains obscure. Only 20 cases have been reported in Japan. The clinical, radiological and pathological features of 20 cases are presented and discussed. Patients' age ranged from 29 to 79 years, an average of 55 years. The left testis was involved in 7 patients, the right in 9 and 4 cases were bilateral. Ultrasonographic examination of the affected testis revealed hypoechoic mass, so little value in differentiating granulomatous orchitis from neoplasm. The correct diagnosis of granulomatous orchitis has never been made prior to surgery, because it clinically bears a lot of resemblance to testicular cancer. The diagnosis usually is made on histological examination. Orchiectomy is the main form of treatment to date, because antibiotics have little effect on the course of the disease and at the time of diagnosis, the testis is already destroyed and there is hardly any viable testicular tissue in the removed specimens.     

Sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery: A case report

We report a case of sporadic gastric carcinoid tumor successfully treated by two-stage laparoscopic surgery. A 38-year old asymptomatic woman was referred to our hospital for evaluation of a submucosal tumor of the stomach. Endoscopic examination showed a solitary submucosal tumor without ulceration or central depression on the posterior wall of the antrum and biopsy specimens were not sufficient to determine the diagnosis. Endoscopic ultrasound revealed a tumor nearly 2 cm in diameter arising from the muscle layer and a computed tomography scan showed the tumor enhanced in the arterial phase. Laparoscopic wedge resection was performed for definitive diagnosis. Pathologically, the tumor was shown to be gastric carcinoid infiltrating the muscle layer which indicated the probability of lymph node metastasis. Serum gastrin levels were normal. As a radical treatment, laparoscopy-assisted distal gastrectomy with regional lymphadenectomy was performed 3 wk after the initial surgery. Finally, pathological examination revealed no lymph node metastasis.     

Suspected case of primary malignant melanoma of the parotid gland

A patient presented with malignant melanoma of the parotid gland with no obvious primary lesions, which was treated by total parotidectomy with excision of skin. Despite radiotherapy for brain metastases and combination chemotherapy for lung and lymph node metastases, she died 13 months after the initial operation.     

Total Colectomy Improves Altered Distribution of Regulatory T Cells in Patients with Ulcerative Colitis

Background It is now generally believed that regulatory T cells (Tregs) play an important role in peripheral tolerance, and a defect in Tregs is considered one of the most important factors in the induction of various kinds of autoimmune disease including ulcerative colitis (UC). Here, we examined the change in frequency of Tregs phenotype in five patients with UC whose condition had not been controllable by conventional conservative therapy and who were scheduled for total colectomy. Aims The aim of this study was to elucidate the role of Tregs in the pathogenesis of UC in a clinical setting. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from five patients with UC, and the change in frequency of Tregs was analyzed by flow cytometry before total colectomy and on postoperative days 1, 7, and 20. Tregs were defined as CD4+ CD25+ CD45RA+ T cells, and data (%) were expressed as frequency of Tregs/CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) from healthy blood donors (n = 5) and from patients undergoing other types of major surgery (n = 5) were used as controls. Results Comparison with normal subjects showed that generation of Tregs was suppressed in UC patients before they underwent total colectomy (0.95 versus 5.06; P = 0.009). The frequency of Tregs increased shortly after total colectomy. The frequency at postoperative days 1, 7, and 20 was 3.81%, 8.13%, and 3.76%, respectively. There were significant differences in the change in frequency in the period before surgery and postoperative day 1, between postoperative days 1 and 7, and between days 7 and 20. Conclusions Elimination of targeted antigens residing in the colorectal mucosa by total colectomy improved the suppressed distribution of Tregs in UC patients. The present study provides the first direct clinical evidence that Tregs play a pivotal role in the pathogenesis of UC.     

Polymerase chain reaction-based subtyping of ureaplasma parvum and ureaplasma urealyticum in first-pass urine samples from men with or without urethritis

BACKGROUND: Our previous study suggested a significant association between Ureaplasma urealyticum and nongonococcal urethritis (NGU). However, association of the serovars of U. urealyticum with NGU remains unclear. A polymerase chain reaction (PCR)-based assay can distinguish 4 serovars of Ureaplasma parvum from each other and categorize 10 serovars of U. urealyticum into 3 subtypes: subtype 1 (serovars 2, 5, 8, and 9), subtype 2 (serovars 4, 10, 12, and 13), and subtype 3 (serovars 7 and 11). GOAL: The goal of this study was to determine which subtypes of U. urealyticum are associated with NGU as determined by PCR-based assay. STUDY: The prevalence of U. urealyticum subtypes in 106 ureaplasma-positive men with urethritis was compared with that in 30 ureaplasma-positive men without urethritis. RESULTS:: In men with nonchlamydial NGU and men with Mycoplasma genitalium-negative nonchlamydial NGU, only U. urealyticum subtype 1 (serovars 2, 5, 8, and 9) was detected significantly more often than in men without urethritis. CONCLUSION: This study suggests that subtype 1 of U. urealyticum (serovars 2, 5, 8, and 9) is associated with NGU independently of Chlamydia trachomatis or M. genitalium.     

Upregulation of Matrix Metalloproteinase in Tear Fluid of Patients with Recurrent Corneal Erosion

Purpose

To investigate gelatinase [matrix metalloproteinase (MMP)-2 and MMP-9] expression in the tear fluid of patients with recurrent corneal erosion (RCE).

Methods

Eleven patients with RCE, three patients with traumatic corneal erosion, and 10 control individuals were enrolled in this study. Tear samples from RCE eyes were obtained once, either at the time of recurrence (onset-phase samples, seven samples), or during the remission period (remission-phase samples, four samples). Tear samples from the nonaffected fellow eyes of the RCE patients were also examined once (fellow-eye samples, ten samples from ten patients). In addition, three samples from three patients with traumatic corneal erosion and ten samples from ten control individuals were obtained as well. Tear samples were collected by a modified Schirmer test I method and analyzed by gelatin zymography.

Results

Neither the active form of MMP-2 nor that of MMP-9 was detected in the samples from traumatic corneal erosion patients and control individuals. Both active MMP-2 and active MMP-9 were detected in all seven onset-phase samples. Active MMP-2 and active MMP-9 were detected in three of the four remission-phase samples. Although none of the ten fellow eyes had a history of RCE, active MMP-2 and active MMP-9 were detected in three fellow-eye samples.

Conclusions

Gelatinase expression was upregulated in the tear fluid of RCE patients. The presence of gelatinase in the affected eye during the remission phase as well as in the nonaffected fellow eye indicates that gelatinase expression in the tear fluid may be related to the recurrence of corneal erosion.?Jpn J Ophthalmol 2007;51:343–346 © Japanese Ophthalmological Society 2007

     

Mutation c. 1142 del G in the <Emphasis Type="Italic">PRPF31</Emphasis> Gene in a Family with Autosomal Dominant Retinitis Pigmentosa (RP11) and Its Implications

Purpose

To identify a mutation in the PRPF31 gene in a family (Family K) with autosomal dominant retinitis pigmentosa (adRP) linked to 19q13.4 (RP11) and to find the frequency of mutations in the PRPF31 gene among Japanese families with adRP.

Methods

Genomic DNA specimens were prepared from five symptomatic and two asymptomatic members of Family K and an additional 39 patients of 39 unrelated families with adRP. Coding regions of the PRPF31 gene were amplified by polymerase chain reaction. The amplicons were analyzed by a direct sequencing method.

Results

All seven family members had a heterozygous c.1142delG mutation in the PRPF31 gene, which was identical to the mutation previously reported in a different Japanese family. No other mutation was found in the PRPF31 gene among the 39 additional patients with adRP.

Conclusion

Although the frequency of mutations in the PRPF31 gene is about 2.5% in Japanese families with adRP, it is possible that c.1142delG is a common mutation among Japanese patients with adRP associated with mutations in the PRPF31 gene.?Jpn J Ophthalmol 2007;51:45–48 © Japanese Ophthalmological Society 2007

     

Analysis of quinolone resistance mechanisms in Neisseria gonorrhoeae isolates in vitro

BACKGROUND AND OBJECTIVES: Gonococcal fluoroquinolone resistance is now a significant problem in Japan. We generated gonococcal mutants resistant to norfloxacin in vitro from norfloxacin sensitive isolates and analysed the contribution of three known mechanisms of quinolone resistance in Neisseria gonorrhoeae. MATERIALS AND METHODS: Three clinical isolates of N gonorrhoeae susceptible to norfloxacin were exposed to increasing concentrations of norfloxacin. To identify mutations in the gyrA and parC genes of the gonococcal mutants, the quinolone resistance determining regions of the gyrA and parC genes were polymerase chain reaction (PCR) amplified and the PCR products were directly sequenced. Norfloxacin accumulation in the gonococcal cells was also measured. RESULTS: The MICs of norfloxacin for three variants containing a single GyrA mutation were 16-fold higher than that for their parent isolates. A variant showing reduced norfloxacin accumulation in the cells, without mutations in the GyrA or ParC proteins, was also less sensitive to norfloxacin, with a 16-fold increase in the MIC, compared with the parent strain. The MIC of norfloxacin for a variant which contained a single GyrA mutation with reduced norfloxacin accumulation in the cells was 128-fold higher than for the parent strain. A variant containing mutations in both GyrA and ParC proteins with reduced accumulation of norfloxacin in the cells showed a 256-fold increase in the norfloxacin MIC compared with the parent strain. There was no variant containing a ParC mutation without the simultaneous presence of a GyrA mutation. CONCLUSIONS: The results from this study suggest that not only a mutation in the gyrA gene but also reduced drug accumulation in cells contributes to the development of fluoroquinolone a mutation in the gyrA gene contributes to a high level of fluoroquinolone resistance in gonococci with decreases in accumulation in cells having an additional but lesser effect.


     

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome

Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB activity. These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB activation.