Costimulation and Autoimmune Diabetes in BB Rats

Costimulatory signals regulate T-cell activation. To investigate the role of costimulation in autoimmunity and transplantation, we studied the BB rat model of type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when 55–120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb) with different functional activities completely prevented diabetes in BBDP rats. Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes after treatment with polyinosinic-polycytidylic acid and an mAb that depletes Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes, whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no effect. In contrast, blockade of the CD134-CD134L pathway was highly effective for preventing autoimmune recurrence against syngeneic islet grafts in diabetic BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so. These data suggest that the effectiveness of costimulation blockade in the treatment of type 1 diabetes is dependent on both the costimulatory pathway targeted and the mechanism of induction, stage, intensity and duration of the pathogenic process.     

Organization of the trigeminal and facial motor nuclei in the hagfish, Eptatretus burgeri: a retrograde HRP study

We studied the trigeminal and facial motor nuclei of the hagfish by the retrograde HRP method. We distinguished 4 components in a single column of the motor nuclei of the trigeminal nerve and the facial nerve, viz., the pars magnocellularis of the trigeminal motor nucleus (mVm), the anterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp1), the posterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp2) and the facial motor nucleus (mVII). Although in Nissl preparations only the mVm could be distinguished from the rest of the nucleus, the boundaries of the other 3 components were clearly demarcated in HRP preparations. Intramuscular injections into two representative antagonistic jaw muscles revealed that there was no apparent topological organization of the neurons pertaining to the opening and closing muscles in the mVm and mVp1, but both antagonistic muscles were innervated bilaterally. Although the hagfish does possess a cartilaginous jaw, the organization pattern of the motor nuclei of the jaw muscles seems to be the most primitive of all living vertebrates.     

Abnormal fluorine-18-fluorodeoxyglucose uptake in benign esophageal leiomyoma

A benign esophageal leiomyoma with abnormally increased fluorine-18-fluorodeoxyglucose uptake on positron emission tomography (PET) was resected thoracoscopically. The tumor, of which the maximum standardized uptake value of the lesion was 4.7, was well defined and 38 mm in diameter. Neither mitotic activity nor degeneration was found histologically; and immunoreactivity for CD34, CD117, MIB-1, and glucose transporter-1 was negative immunohistochemically. A diagnosis of gastrointestinal stromal tumor was ruled out by an oncogenic kinase gene mutation study. This case cautions against PET-dependent evaluation for malignant potential of esophageal submucosal tumors.     

Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus

The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca²⁺-Mg²⁺ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl₂ (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.     

A new operational approach for the piriform sinus fistula

It has been well documented that piriform sinus fistulae often cause suppurative thyroditis; however, when a piriform sinus fistula does not present this symptom, making a correct diagnosis is very difficult. We have experienced 11 cases of a piriform sinus fistula. The conventional operational approach was performed in the initial eight patients, among which there were four recurrences in two patients. Therefore, a new operational approach was introduced for the three most recent cases and one recurrent case. First, the existence of the internal orifice of the fistula is confirmed with a laryngoscope, after which a transverse incision on the neck is made and the abscess dissected. The side wall of the piriform sinus is then opened with the help of a laryngoscope and the bottom part of the mucosa of the sinus transected with the internal orifice of the fistula, after which the fistula is removed en bloc with the bottom part of the sinus and abscess cavity. Using this operation, we experienced no complications and there has been no recurrence so far.This paper was presented at the 23rd Annual Meeting of Pacific Association of Pediatric Surgeons, June 1990 in Kona, Hawaii.     

Groove pancreatitis associated with true pancreatic cyst

We report a case of groove pancreatitis (GP) associated with a true pancreatic cyst. An 81-year-old man who had suffered epigastric pain for 4 months was referred to Saisekai Kure Hospital. Computed tomography and endoscopic retrograde pancreatography showed a cystic lesion in the groove area of the pancreas. Serum amylase elevation and imaging findings suggested GP due to the cyst. Six weeks of medical treatment did not improve the clinical symptoms. Therefore, pancreatoduodenectomy was performed. Histologic examination revealed a true cyst with intraluminal necrosis, which produced a protein plug that obstructed the Santorini duct. The parenchyma surrounding the groove area showed marked fibrosis and inflammatory cell infiltration. GP due to true pancreatic cyst was diagnosed. Although GP is usually caused by overconsumption of alcohol, which leads to changes in the pancreatic juice and the ultimate blockage of pancreatic outflow, the histologic features in our patient suggest that true pancreatic cyst stands as a secondary cause of GP.     

Two-level posterior lumbar interbody fusion for degenerative disc disease: improved clinical outcome with restoration of lumbar lordosis

BACKGROUND CONTEXT: Although posterior lumbar interbody fusion (PLIF) for degenerative lumbar diseases is routine, there are few reports on double-level PLIF. PURPOSE: To evaluate the clinical outcomes of double-level PLIF. STUDY DESIGN/SETTING: A retrospective study of operated cases in Gifu, Japan. PATIENT SAMPLE: Nineteen patients (8 men and 11 women, 59.5+/-10.2 years) who underwent double-level PLIF between 1996 and 2001. OUTCOME MEASURES: Operation time, blood loss, complications, the Japanese Orthopaedic Association (JOA) score for back pain and lumbar sagittal alignment were evaluated. METHODS: Patients were examined retrospectively at follow-ups of 3.6+/-1.7 years. Primary diseases were spondylolisthesis, spinal canal stenosis, degenerative scoliosis and herniated intervertebral disc. Fusion areas were L3 to L5 in 15 cases and L4 to S1 in 4 cases. RESULTS: The mean JOA score increased from an initial score of 12.9+/-3.5 to 21.3+/-4.9 at the final follow-up. There was a positive correlation (R=0.718, p<.001) between the increase in lordotic angle and the increase in the JOA score. Several parameters suggested that the surgical invasiveness was not minimal. CONCLUSION: Double-level PLIF provided satisfactory results and preserved lumbar spine lordosis.     

UFT for head and neck cancers: its tissue concentrations and effects on lymphocyte subpopulations

Summary UFT, a combination of the masked compound of 5-fluorouracil (FT-207) and uracil, was given to head and neck cancer patients for 1 week preoperatively and for 8 weeks postoperatively. Drug concentrations were examined in the surgically removed tissues. The concentrations of FT-207, 5-fluorouracil, and uracil were higher in tumor tissues than in normal tissues. The lymphocyte subpopulations were assessed by cytofluorometry with monoclonal antibodies. There was no evidence that adjuvant chemotherapy with UFT specifically suppresses immunocompetent cells. We therefore conclude that further clinical evaluation of adjuvant chemotherapy with UFT would be worthwhile.