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Our experience with four patients who underwent immediate reconstruction following total laryngopharyngoesophagectomy and extensive resection of the superior mediastinum is presented. The reconstructive procedures included free jejunal graft or microvascularly augmented gastric pedicle for esophageal reconstruction, pectoral fasciocutaneous or myocutaneous flap for tracheal reconstruction, and mesenteric flap connected with jejunal graft omental flap, or pectoral flap for protection of the great vessels and obliteration of the dead space in the cervical and superior mediastinal region. The reconstructive procedures were successful, and no pharyngocutaneous fistula, mediastinitis, or great vessel rupture was noted in any patient. There was one patient who developed lung edema and liver dysfunction postoperatively. Combinations of reconstructive procedures using well-vascularized soft tissues can be expected to provide well-tolerated reconstruction following extensive cervical and superior mediastinal resection.

Hepatitis B e antigen (HBeAg) is considered to be a major target for the immune response in chronic hepatitis B. The G-->A mutation at nucleotide 1896 may mediate viral escape by creating a TAG stop codon in the precore region, thus preventing HBeAg production. This mutation frequently evolves during HBe seroconversion if thymine, but rarely if cytosine, is present in position 1858. Applying a combination of polymerase chain reaction (PCR) and restriction enzyme action, we have studied the relation of the TAG mutation and the nucleotide (nt) 1858 variants to liver damage assessed by histology activity index (HAI) scoring in 175 chronic hepatitis B virus (HBV) carriers. A TAG mutation was found in 68 of 71 (96%) of HBeAg-negative carriers infected with a T-1858 strain, but not in any of 33 carriers infected exclusively with a C-1858 strain. Four patients showed a mutation of the precore start codon, and 2 had a TAA stop mutation at codon 2. HBeAg-positive infection with a mixture of wild-type and TAG mutant virus indicated active liver damage, because 8 of 9 (89%) of such patients had a Knodell HAI greater than or equal to 8. In HBeAg-negative stage, both inflammation and fibrosis were more pronounced in carriers infected with wild-type HBV compared with precore mutants. C-1858 strains were associated with more inflammation and fibrosis compared with T-1858 strains. C-1858 strains were found in 71% of northern European, 17% of southern European, 31% of African, 2% of Middle Eastern, and 10% of Far Eastern carriers. Analysis of these variants and mutants may prove useful for clinical evaluation and choice of therapy, and may be facilitated by the methods described. (Hepatology 1996 Sep;24(3):494-501)

The rectal and genital tract mucosae are considered to be major sites of entry for the human immunodeficiency virus (HIV) during sexual contact. We now demonstrate that vaginal epithelial cells can be infected by HIV type 1 (HIV-1) via a mechanism similar to that described for neuroglial cells and, more recently, for colorectal epithelial cells, involving initial interaction of the HIV-1 envelope glycoprotein gp120 with a cell-surface glycosphingolipid (sulfated lactosylceramide). A hyperimmune serum against gp120 was able to neutralize HIV-1 infection of vaginal epithelial cells. Site-directed immunization was employed to identify sites on gp120 recognized by antibodies neutralizing HIV-1 infection of vaginal and colonic epithelial cells. Hyperimmune sera were raised in monkeys against a series of 40 overlapping synthetic peptides covering the entire sequence of HIV-1 (HTLV-IIIB) gp120. Antisera raised against five synthetic peptides, corresponding to three relatively conserved regions and to the hypervariable region (V3 loop), efficiently neutralized HIV-1 infection of human vaginal epithelial cells in vitro. Similar results were obtained with the colonic cells. Hyperimmune sera to all five peptides have been shown earlier to neutralize HIV-1 infectivity in CD4+ T cells. These results have obvious implications for the design of mucosal subunit vaccines against sexually transmitted HIV-1 infections.

To improve hoarseness or misswallowing caused by unilateral recurrent laryngeal nerve paralysis, medialization of paralyzed vocal cord has frequently been performed. This method includes such techniques as injection method, insertion method, and arytenoid adduction, each presenting its merits and demerits. The insertion method which can be done while monitoring the patient's voice seems advantageous in that the technique is easy to perform and generally guarantees the voice improvement. Among insertion methods, Isshiki thyroplasty type I is the one most representative as well as popularized. However, since a silicone shim is inserted in this operation, it may be accompanied by the risks of carcinogenicity, foreign body reaction, and induction of collagen diseases of silicone. Therefore we planned to use a ceramic as a safe substitute instead of silicone. There has been no article reporting the use of ceramic in this type of surgery. We used a fibrin glue to fix the ceramic shim and for hemostasis, which was found very useful. Hitherto, 2 cases of unilateral recurrent laryngeal nerve paralysis underwent Isshiki thyroplasty type I using ceramic shim with satisfactory results.

Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a mildly immunosuppressed patient who had aplastic anemia were studied for human papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 DNA was identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH). In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although possibly another unidentified type of HPV in the lesion was suggested by the ISH findings. In the bladder transitional cell carcinoma, neither papillomavirus genus-specific (PGS) antigen nor HPV DNA was found.

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin-fixed, paraffin-embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV-positive and HPV-negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV-positive and HPV-negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

The renin-angiotensin system acts to constrict vessels and enhance renal retention of sodium and water to raise the blood pressure. Angiotensinogen (ang-n) is synthesized in the liver and released into the blood. It is cut by renin, which is produced by the kidneys, and becomes angiotensin I. Angiotensin I is cleaved by angiotensin converting enzyme (ACE) into angiotensin II, which is an active pressor substance. Recently, the presence of cardiac renin-angiotensin system has been reported in some animals [1,2,3] but it has not been investigated fully in the human heart. Angiotensin II appears to be a stimulus for cardiac hypertrophy [4]. In clinical studies, ACE inhibitor has been reported to cause regression of cardiac hypertrophy [5]. Bearing these findings in mind, we studied the presence of ang-n, renin mRNAs and ang-n protein in human autopsy hearts and discussed its relation to cardiac hypertrophy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Objective To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires. Design The VRQOL and VHI-10 questionnaires. Setting University hospital. Patients One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey. Main Outcome Measure Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires. Results The mean VRQOL scores for patients who had undergone radiotherapy (n = 63), chemoradiotherapy (n = 29), laser surgery (n = 14), or total laryngectomy (n = 27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively. Conclusion The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5 year old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1,10,19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40 to 80 fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma. Acta Pathol Jpn 41: 507 515, 1991.

Clinical data indicate that the recurring herpes simplex virus (HSV) from oro-labial lesions is HSV subtype 1 and that the virus from genital lesions is HSV-2. This suggests that HSV-1 and HSV-2 reside in latent forms in the trigeminal ganglia and sacral ganglia, respectively. However, the distribution of latent HSV-1 and HSV-2 infections in human spinal ganglia has not been fully examined. This report concerns the application of polymerase chain reaction (PCR) and in situ hybridization (ISH) to such a study. By using PCR and employing the respective primers, HSV-1 and HSV-2 DNAs were detected in 207 of 524 samples from 262 spinal ganglia (from the cervical to the sacral ganglia) examined on both sides. The percentages of HSV-1 and HSV-2 detected in a given set of ganglia were similar, indicating an absence of site preference. By ISH, few but positive hybridization signals were detected evenly in sacral ganglia sections. The data suggest that regional specificity of recurrent HSV infections is not due to regional distribution of latent virus, but that local host factors may be important for recurrences.

Rationale The purpose of this study was to assess the role of MIF in the pathogenesis of AR. Methods Serum MIF concentrations were measured by ELISA. In order to elucidate the cellular source of MIF at the site of allergic inflammation, we performed double immunostaining of biopsies of the nasal mucous membrane, with markers for MIF and for inflammatory cells. Results The mean MIF level in sera from AR patients was significantly higher than that in sera from healthy controls. Moreover, the levels were significantly correlated with the severity of the clinical symptoms. The majority of the MIF-positive cells at the site of allergic inflammation were eosinophils. Conclusions These data suggest that MIF plays a role in the initiation and maintenance of AR. Eosinophils formed by far the largest population of MIF producing cells, suggesting that they may be a major source of MIF at inflammatory sites in atopic disease.

Two cases of foreign bodies in the maxillary sinus are reported. The first patient was a 23-year-old male with a displaced tooth in the maxillary sinus for 6 years. The second patient was a 39-year-old male with many pieces of broken windshield glass in the maxillary sinus resulting from a traffic accident. In both cases, Caldwell-Luc operation was performed and the foreign bodies were removed.

We encountered 2 cases of tuberculosis of the parotid gland and 2 of cervical lymph nodes between 1986 and 1988.All diagnoses were confirmed by postoperative histological findings of tumor formation or metastatic lymph nodes. Since all cases exhibited a number of features in common, it may be possible to make a definite diagnosis without biopsy of the lesion.Drug therapy after surgical resection should be given for at least one year.

Seventy one patients with thyroid tumors received surgical treatment in our hospital from April 1985 to March 1988. 1) The pathological diagnosis in 39 patients (55%) was benign tumor (22 adenomatous goiters, 15 follicular adenomas, 2 cysts) and in 32 patients (45%) it was malignant tumor (27 papillary carcinomas, 3 follicular carcinomas, 1 malignant lymphoma, 1 squamous cell carcinoma). 2) For the preoperative diagnosis, delayed scintigraphy with 2a1T 1 C 1 and fine needle aspiration biopsy were quite useful in differentiating malignant thyroid tumors from benign ones. 3) Intraoperative frozen sections were helpful when the preoperative diagnosis was incorrect. 4) Cervical lymph node metastases were found in 75% of the patients with papillary or follicular carcinomas. 5) When cervical lymph node metastasis was obvious clinically, radical or modified neck dissections were performed. In patients without clinically apparent metastases, local neck dissection and sampling of the internal jugular chain were performed. When microscopic metastases were found in frozen sections, appropriate neck dissections were added.

Twenty-five patients with cancer of the head and neck were treated with high dose 5-FU infusion alone or as part of multimodal cancer treatment program. The infusion dose was 1500mg/24 hours for 120 hours via a peripheral vein. The courses were repeated at 2-3 week intervals. The tumor response and clinical effect of 5-FU high dose chemotherapy were evaluated in 12 patients who received 5-FU infusion alone. In the 10 patients with previously untreated epidermoid cancer, tumor response was apparent in 6 (1 had complete response and 5 partial response). In 9 of the 10 epidermoid cancer patients 5-FU was clinically effective and proved to be useful in further treatment as a part of multimodal therapy. Mild leukopenia, stomatitis, diarrhea and vasculitis/pigmentation were prominent side effects, but they could be tolerated by all 25 patients, even those with far-advanced cancer. This chemotherapy could be combined with radiotherapy. The results demonstrate that 5-FU alone in high dose infusions can play a role in preoperative induction chemotherapy and in multimodal cancer therapy.

The authors describe a patient who presented with recurrent chest pain during chemotherapy with 5-fluorouracil (5-FU).A 69-year-old man with metastatic lung carcinoma received 5-FU 1500mg/day by continuous infusion for 5 days. He developed chest pain during the second and third courses of 5-FU infusion, but there were no ischemic changes on the electrocardiogram.Cardiotoxicity as a rare side effect of 5-FU therapy has been reported, but its etiology remains unclear. The ischemic chest pain and EGG changes observed in most cases suggest that coronary artery spasm may be the cause of 5-FU cardiotoxicity. Although cardiotoxicity is a rare complication of 5-FU therapy, the authors think it is advisable to stop the treatment when chest pain occurs.

Two cases of unusual foreign bodies (crabell) in the bronchus are reported.The first patient was a 29-year-old male who aspirated a crabshell into the bron-chus when he was eating a crableg. Bronchoscopy was carried out but removal of the foreign body was difficult as the crabshell had many spikes which stuck into the wall of the bronchus.The second patient was a 51-year-old male who aspirated a crabshell into the bronchus in the same way. In this case, after removing some of the stuck spikes, we could easily take out the remaining fragment.Some clinical features of this bronchial foreign body (crabshell) and technique of removal are discussed.

A review of 20 malignant parotid tumors experienced at Department of Otolaryngology, Hokkaido University Hospital during 10 year period of 1976 through 1985 was performed retrospectively.Thirty five percent of these cases was adenocarcinoma, while malignant mixed tumor 20 percent.Nine out of these 20 cases had their initial treatment at our clinic, whereas the other 11 had previous surgical treatment and /or radiation therapy. Seven died of distant metastasis either in the lung or in the brain.It seemed evident that facial nerve involvement was suggestive of their poor prognosis in view of the fact that facial nerve of these 7 patients had invariably affected at their first visit to our clinic.

It is being reported that human papillomavirus (HPV) has been implicated in the pathogenesis of various neoplastic lesions of the genital organs. To investigate the etiological role of HPV and its types in nasolaryngeal papillomas, we retrospectively analyzed HPV genomes by nucleic acid hybridization methods ; for detecting DNA and mRNA, we employed the recently developed non-radioactive (digoxigenin labeled) DNA probes and compared the results by radioisotope methods.In total, 43 cases of papillomatous lesions were examined. They were verruca vulgaris of the nasal vestibule (Nr=2), nasal inverted papilloma (IP, Nr=26), and laryngeal papilloma (Nr=15).HPV types examined were type 2, 6, 11, 16 and 18.Two cases of verruca vulgaris were shown to contain HPV-2 DNA and its mRNA by in situ hybridization. HPV-11 DNA was detected in 3 cases (12%) of nasal inverted papilloma whereas HPV-16 was detected in 1 case (4%) ; the latter case was associated with squamous cell carcinoma.These results suggest that HPV may be implicated in the development of IP, and HPV-16 may play an important role in the malignant transformation of IP. In the cases of multiple laryngeal papilloma (Nr=8, one juvenile type and 7 adult type), either HPV-6 or HPV-11 was detected at the high rate (6/8, 75%). The presence of the HPV genomes provides strong evidence for the HPV etiology of these laryngeal papillomas. Whereas in the cases of adult single laryngeal papilloma (Nr=7), HPV was not detected.Technically, the sensitivity of digoxigenin (DIG) labeled DNA probe was almost same as 35S labeled probe by dot blot hybridization, thus we applied DIG labeled probe to Southern blot hybridization with low background. By in situ hybridization using digoxigenin labeled probes, the rates of HPV detection were almost equal to those by 35S labeled probes. But non-specific reaction was occasionally found in DIG-labeled probes. However, the pretreatment of DNase orRNase markedly diminished non-specific binding to the nucleic acids. Thus, DIG-label was shown to be excellent substitutional method for radioisotope.

Onuf's nucleus, located in the anterior horn of the sacral spinal cord, has been shown to innervate the striated muscles of the urethral and anal sphincters and is known to be well preserved in patients who have motoneuron disease. To answer the question whether the nucleus is also safe from motoneurotrophic virus infections, we examined the spinal cords of 3 individuals who had suffered severe poliomyelitis. In 2 of these which were acutely fatal cases, all motoneurons were damaged by neuronophagia, but Onuf's nucleus escaped the inflammatory degeneration. In a chronic case, neuronal loss in the anterior horn with replacement by gliosis was prominent below the thoracic cord down to the sacral cord, but Onuf's nucleus was well preserved. Thus, Onuf's nucleus appears to differ from other motoneurons with regard to susceptibility to poliovirus infection.

Thirty-four patients underwent thyroid surgery for papillary and follicular adenocarcinomas in the period from 1985 to 1989. Fourteen patients were treated with local neck dissection and 20 patients, with modified or radical neck dissection. Cervical lymph node metastasis was found in 25 patients (74%). Our recent policy for lymph node dissection is as follows: When deep cervical lymph node metastasis is clinically demonstrated, radical or modified neck dissection is performed. In patients without clinically demonstrated metastasis, local neck dissection and sampling of the internal jugular chain are performed. When microscopic metastasis is found in frozen sections, modified neck dissection is added. Thus we could select patients for modified neck dissection and choose appropriate neck dissection for more complete cancer clearance without losing postoperative functions.

It is often difficult to decide whether to restart an oral diet during acute hospitalization. We investigated retrospectively the predictive factors for successful oral intake after discharge from an acute care hospital or transfer to a recovery rehabilitation hospital. A total of 45 inpatients were enrolled, presenting with dysphagia due to various diseases during hospitalization in an acute care hospital. Between October 2011 and December 2012 the patients were examined with a videoendoscopic examination of swallowing (VE). We classified the feeding procedure after discharge from the hospital into three groups-the first group (group 1) had no oral intake limitation, the second group (group 2) had limited oral intake, and the third group (group 3) had no oral intake ability. We then assessed the factors of age, sex, VE score, and functional independence measure (FIM) score to compare the activities of daily living (ADL) between group 1 and group 2 + 3. FIM score consists of motor and cognitive scores. We observed a statistically significant difference in age, VE score, motor FIM score and cognitive FIM score in a univariate analysis (p = 0.03, p = 0.0036, p = 0.0019, p = 0.0125). The VE score also showed a statistically significant difference in a multivariate analysis (p = 0.0396), indicating that the VE score was an independent variable related to prediction of the feeding procedure. A VE score of 4 as the cut-off point between group 1 and group 2 + 3 provided a specificity of 0.944 and a positive predictive value of 0.923. On the other hand, a VE score of 9 as the cut-off point between group 3 and group 1 + 2 provided a specificity of 0.969 and a positive predictive value of 0.857. These results indicate that the VE score is a useful tool for the prediction of successful oral intake after discharge from an acute care hospital. In addition, age and ADL are also useful predictive factors for the feeding procedure.

Macrophage migration inhibitory factor (MIF) plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-IIC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We found that MIFTg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIFTg mice and significantly increased numbers of CD69+ T cells were detected in the spleens of these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with agr;-galactosylceramide (alpha-GalCer). Further, repeated administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play an ameliorating role upon stimulation with alpha-GalCer in the inflammatory process in MIFTg mice.