Malignant lymphoma of the parotid gland with monoclonal cytoplasmic immunoglobulin

A 56-year-old Japanese man with a malignant lymphoma of the parotid gland was reported. The tumor was located in the superficial lobe of the parotid gland, and somewhat invaded the surrounding soft tissues, but the regional lymph nodes were not involved. Histologically, the tumor was composed of round cells with plasmacytoid configurations and small lymphocytes. The plasmacytoid cells showed eccentric nuclei with fairly marked irregularities and perinuclearr halos. In a large number of tumor cells, a monoclonal cytoplasmic immunoglobulin (CIg), IgG-Kappa type, was demonstrated by the PAP method. Ultrastructurally, some of the tumor cells showed well-developed endoplasmic reticulum. From these findings, this tumor was diagnosed as a diffuse B-cell lymphoma, mainly composed of lymphoplasmacytoid cells. And this tumor may bear a similar nature to an extramedullary plasmacytoma of the classical terminology. Malignant lymphoma of the parotid gland is rare but a case with the demonstration of monoclonal CIg is considered very rare.     

Analysis of recombinant human tumour necrosis factor-alpha-induced CD4 expression on human eosinophils.

We examined the hypothesis that one of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression. Human eosinophils were cultured with various concentrations of recombinant human TNF-alpha (rhTNF-alpha) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil-derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross-linking of CD4 on eosinophils. The rhTNF-alpha induced CD4 expression on human eosinophils in a dose- and time-dependent fashion; rhTNF-alpha-induced CD4 expression was significantly inhibited by 10(-6) M cycloheximide, 10(-8) M dexamethasone, or 10(-6) M herbimycin A. Recombinant human interferon-gamma inhibited rhTNF-alpha-induced CD4 expression in a dose-dependent manner. However, cross-linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF-alpha-induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity.     

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.     

Depolarization thresholds for hippocampal damage, ischemic preconditioning, and changes in gene expression after global ischemia in the rat

Induced ischemic tolerance in rat hippocampus was investigated in a forebrain ischemia model of repeated 4-vessel occlusion (4-VO). Ischemic insult variability was reduced by the use of dc potential measurements to determine the duration of ischemic depolarization in hippocampus. The results demonstrate a depolarization threshold for ischemic injury to CA1 neurons of 4-6 min and a window for optimal preconditioning of 2.5-3.5 min. Levels of induced mRNAs encoding hsp72 and several immediate-early genes were also shown to vary with depolarization interval. Immediate-early genes were maximally induced after depolarization periods inducing optimal preconditioning, while hsp72 expression increased with insult severity over the range leading to neuron loss. These results are similar to those obtained in gerbil studies indicating that preconditioning does not require large increases in hsp72 expression, and demonstrate the fundamental comparability of rodent global ischemia models when monitored by this approach.     

Immunohistochemical Heterogeneity Within Clinically Nonfunctioning Pituitary Adenomas

To investigate whether adenohypophysial hormone expression is heterogeneous within individual clinically nonfunctioning pituitary adenomas, immunohistochemical examinations were performed on tissues obtained by multiple sampling of 11 adenomas. Stained sections were assessed by morphometric image analysis as well as semiquantitative estimation under microscopy. All tumors except one were immunopositive for one or more gonadotropins. Results were divided into five grades based on the proportion of immunoreactive cells per section. Semiquantitative estimation showed only a one-grade difference among samples from the same tumor in four cases for FSHβ and in two cases for LHβ. These qualitative similarities between multiple samples were confirmed by morphometric image analysis. From the practical standpoint of making a diagnosis of nonfunctioning pituitary adenoma, it is not necessary to take into account immunohistochemical heterogeneity within an individual tumor, and immunohistochemical findings in a given sample obtained at surgery can be regarded as representative of the entire adenoma.     

Changes of hepatic vitronectin levels in patients with chronic hepatitis C treated with interferon alpha

Hepatic vitronectin expression was assessed in 27 patients with chronic hepatitis C before and after interferon alpha treatment and in 7 control patients. Before interferon therapy, vitronectin was localized in the hepatocytes and in the portal and central venous regions. A high correlation was found for the vitronectin expression level with the histological grading and staging scores in the hepatocytes as well as in the portal region. After interferon therapy, the hepatic vitronectin was significantly decreased in the sustained and transient responders, but it was not as markedly decreased in the nonresponders and the non-treated group. A good correlation was found for the vitronectin expression with the staging scores but not with the grading scores in the portal region. These findings suggest that hepatic vitronectin is influenced by interferon therapy and that it may play an important role as a hepatic adhesion molecule through the improvement of inflammation, necrosis and fibrogenesis.     

Nasal continuous positive airway pressure changes blood pressure "non-dippers" to "dippers" in patients with obstructive sleep apnea

To evaluate the circadian pattern of blood pressure (BP) and the effects of nasal continuous positive airway pressure (CPAP) on patients with obstructive sleep apnea (OSA), we examined 24-hour BP in 38 male OSA patients with and without nasal CPAP. We measured the BP at 30-min intervals during daytime (800 to 2200) and nighttime (2200 to 800) hours. A "dipper" was defined as a patient who showed an average reduction of at least 10 mm Hg systolic and 5 mm Hg diastolic between daytime and nighttime values. The subjects were predominantly "non-dipper" (22 of 38 patients, 58%). Daytime hypertension (>160/95 mm Hg) was present in 11 of 38 patients (4 "dippers" and 7 "non-dippers"). After nasal CPAP treatment for 3 days, the average BP decreased significantly during the day and night in all subjects (p<0.05). Fifteen of 22 subjects who were "non-dippers" before treatment reversed to become "dippers." And daytime hypertension was detected in only 5 of these patients during nasal CPAP treatment (4 "dippers" and 1 "non-dipper"). These results showed that the "non-dipper" status was common in patients with OSA, and that nasal CPAP restored the normal circadian "dipper" pattern. We suggest that nasal CPAP may contribute to an improved prognosis in patients with OSA because of a reduction in cardiovascular risk factors in "non-dipper" with severe OSA.     

Urinary incontinence after non-nerve-sparing radical prostatectomy with neoadjuvant androgen deprivation

OBJECTIVES: The impact of non-nerve-sparing retropubic radical prostatectomy (RRP) for prostate cancer combined with neoadjuvant androgen deprivation on urinary control is not well documented. We examined the incidence and severity of urinary incontinence after such therapy and determined the etiologic factors causing this complication. METHODS: We examined the postoperative continence status of 104 consecutive patients admitted to the National Cancer Center Hospital who underwent RRP with wide resection of the pelvic nerves after neoadjuvant androgen deprivation. Incontinence was scored according to the number of pads used daily by the patient for urinary leakage. The severity of incontinence was analyzed according to patient age, weight of resected specimen, status of cancer stage, duration of neoadjuvant androgen blockade therapy, preoperative length of membranous urethra, and duration of urethral catheterization after surgery. We also measured the configuration and diameter of the reconstructed bladder neck by retrograde cystourethrography. RESULTS: In 104 patients examined, the percentage of patients who became dry postoperatively was 22% at 1 month, 47% at 3 months, 69% at 6 months, and 78% at 1 year. Of 81 patients who became dry postoperatively at any interval, 22 (27%) became continent within 1 month of RRP, 49 (61 %) were continent within 3 months, 71 (88%) became continent by 6 months, and another 10 (12%) became continent between 6 and 12 months postoperatively. Of 48 patients who were followed up for more than 1 year and for whom continence status at 1 month after surgery was available, all patients who used 1 to 2 pads per day (13 of 13) at 1 month after surgery regained continence by 1 year after surgery. However, only 62% of patients (16 of 26) who required more than 3 pads per day at 1 month after surgery became dry by 1 year after surgery. Only age (older than 70 years) and large prostate size (weight of surgical specimen more than 40 g) temporarily influenced the recovery of urinary continence after surgery. Dilation of the bladder neck evaluated by retrograde cystourethrography was prominent in severely incontinent patients in the immediate postoperative period. CONCLUSIONS: Our experience in patients who undergo non-nerve-sparing RRP after neoadjuvant androgen deprivation closely matches published surveys of patient-reported complications. Postoperative incontinence is not a major contraindication for non-nerve-sparing RRP after neoadjuvant endocrine therapy. Dilation of the bladder neck affected the recovery from incontinence, highlighting the importance of adequate reconstruction of the bladder neck.     

Prediction of viability of ischemically damaged canine pancreatic grafts by tissue flow rate with machine perfusion.

We studied the viability of canine pancreatic grafts using a short-time perfusion technique with an organ perfusion machine, "ORPH3000C". The following parameters were examined during perfusion of warm ischemically damaged grafts: Amylase, lipase, and insulin levels in the perfusate after 1-hr perfusion showed no significant correlation with warm ischemic time (WIT), and these indices could not be used to assess graft viability. Tissue flow rate (TFR) at the end of perfusion was significantly decreased with prolonged WIT. TFR correlated with the percent decrease in tissue SOD activity, thus TFR was a reliable predictor of reperfusion injury. Histological studies showed no findings attributable to warm ischemic injury before 1-hr perfusion. After 1-hr perfusion, the grafts were allotransplanted and the relation between TFR and endocrine function of the transplanted grafts was examined. TFR correlated with K value calculated from IV-GTT performed on day 5 postoperatively, suggesting that TFR is a predictable index of isolated pancreatic graft viability. Using TFR levels, this method allowed us to select only grafts with good function prior to transplantation. This technique appears to be of use for pancreatic transplantation from cadaver donors after cardiac arrest.