Multiple lymphadenopathy as an initial sign of extramammary Paget disease.

Extramammary Paget disease (EMPD) often develops in external genitalia. Paget cells can, however, adopt an invasive phenotype and metastasize to regional lymph nodes and beyond, leading to poor patient outcomes. Based on this clinical observation, multiple lymphadenopathy may represent an initial sign of EMPD. To address the potential significance of multiple lymph node swelling in EMPD, we report two patients with cutaneous primary EMPD who showed multiple lymphadenopathy as an initial sign during the clinical course of the disease as well as tumour metastasis. Significantly, marked lymphatic vessel growth was observed in regional lymph nodes that underwent massive tumour cell invasion. Therefore, nodal lymphangiogenesis may promote tumour cell invasion and metastasis to distant organs, including the lymph nodes, emphasizing the clinical relevance of multiple lymphadenopathy.

Experience with injections of botulinum toxin type A into the detrusor muscle.

INTRODUCTION: We evaluated the effects of intra-vesical injection of botulinum toxin type A in the detrusor muscle in patients with neurogenic overactive bladder (OAB), patients with non-neurogenic overactive bladder and patients with interstitial cystitis. MATERIALS AND METHODS: Between January 2003 and December 2006 we treated 30 patients with 100 I. U. to 300 I. U. of botulinum toxin A in the detrusor muscle. Patients were clinically and urodynamically followed up for 4, 12 and 36 weeks thereafter. RESULTS: Neurogenic overactive bladder: of the 19 injected doses, 18 (94.7%) in 7 patients were judged as effective, and 1 (5.2%) of 200 U of BTX-A was judged as ineffective. Mean bladder volume increased from 137 to 396 ml. Non-neurogenic overactive bladder: of 7 injections, 6 (85.7%) were judged effective in 5 patients. Mean bladder volume increased from 149 to 322 ml. Interstitial cystitis: in all 4 patients the treatments were deemed ineffective. CONCLUSIONS: Injecting 300 units of BTX-A into 30 sites in the muscle located in the body of the bladder region is effective for neurogenic bladder patients with intermittent catheterization who have urge and reflective types of incontinence. Injections of 100 and 200 units of BTX-A to treat non-neurogenic overactive bladder with urinary incontinence provided together without retention. The optimal dose of BTX-A requires further investigation. Injection with 200 units of BTX-A was not useful against interstitial cystitis. None of the patients developed any adverse effects after injecting the bladder wall with BTX-A.

Clinical outcomes in older or younger patients with papillary thyroid carcinoma: impact of lymphadenopathy and patient age.

AIMS: To examine lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC) according to clinicopathological features and outcomes associated with the nodal status. METHODS: We reviewed 231 patients with PTC (> or =1.0cm) who underwent initial thyroidectomy with modified neck dissection. LNM was examined in the central and lateral compartment and risk factors for disease-free survival (DFS) were evaluated. Nodal status and outcomes were further evaluated in four subgroups, 19 older patients (> or =45years old) with palpable lymphadenopathy (PLA) and 134 without PLA, and 11 younger patients (<45years old) with PLA and 67 without PLA, because multivariate analysis revealed that age (p<0.05, Hazard ratio (HR) 3.51) and PLA (p<0.0001, HR 14.9) were risk factors for DFS. RESULTS: Central and lateral LNM were found in 176 and 151 patients. Seventeen exhibited skip metastasis. Recurrence and disease death occurred in 23 and 5. In analysis of the four subgroups, recurrence was significantly frequent in older patients with PLA than in younger patients with PLA or older patients without PLA (8/19 vs. 3/11 or 12/134). Younger patients without PLA did not exhibit recurrence. CONCLUSIONS: Prognosis is worse in older patients with PLA. Such patients should be treated carefully with a considerable treatment strategy.

Polyelectrolyte templating strategy for the fabrication of multilayer hemicyanine Langmuir-Blodgett films showing enhanced and stable second harmonic generation.

Polyelectrolyte templating effectively suppresses the aggregation of cationic hemicyanine-based amphiphiles in monolayer Langmuir-Blodgett (LB) films leading to enhanced and stable optical second harmonic generation (SHG). The current study explores the impact of different polyelectrolytes (salts of poly(4-styrenesulfonic acid), deoxyribonucleic acid, and carboxymethylcellulose) on the mode of formation of multilayer LB films of the hemicyanine amphiphile and their SHG response. Pressure-area isotherms and Brewster angle microscopy reveal the impact of the polyelectrolyte complexation on the Langmuir films. Transfer ratios observed during film deposition, supported by electronic absorption spectra and atomic force microscope images of the multilayer LB films, suggest that the polyanions influence the deposition sequence, leading to significant variations in the SHG. Carboxymethylcellulose is identified as an optimal template that induces favorable z-type deposition, leading to the formation of stable multilayer films. These films exhibit the expected quadratic increase of SHG with the extent of deposition; significantly the film response is very stable under extended laser irradiation. It is proposed that structural adjustments of the sandwiched polymer layer lead to the observed deposition sequence and film stability. Polyelectrolyte templating is demonstrated to be a simple and effective strategy for the fabrication of multilayer LB films to elicit efficient quadratic nonlinear optical response.

Protection from photodamage by topical application of caffeine after ultraviolet irradiation.

BACKGROUND: Characterization of mechanisms that can reverse residual damage from prior skin exposure to ultraviolet (UV) would be of considerable biological and therapeutic interest. Topical caffeine application to mouse skin that had previously been treated with UV has been shown to inhibit the subsequent development of squamous cell carcinomas. OBJECTIVES: We used an established mouse photodamage model to investigate other possible effects of topical caffeine application after UV. METHODS: SKH-1 hairless mice were treated with ultraviolet B (UVB) followed immediately by topical application of caffeine or vehicle three times weekly for 11 weeks. RESULTS: Caffeine applied topically after UV treatment resulted in a significant decrease in UV-induced skin roughness/transverse rhytides as assessed by treatment-blinded examiners. Histologically, topical caffeine application after a single dose of UVB more than doubled the number of apoptotic keratinocytes as evaluated by sunburn cell formation, caspase 3 cleavage and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) staining. A trend towards decreased solar elastosis was noted in the caffeine-treated group although this was not statistically significant. Other histological parameters including epidermal hyperplasia, solar elastosis and angiogenesis were increased in mice treated with UV but topical application of caffeine did not alter these particular UV effects. CONCLUSIONS: These findings support the concept that topical application of caffeine to mouse skin after UV irradiation promotes the deletion of DNA-damaged keratinocytes and may partially diminish photodamage as well as photocarcinogenesis.

Hypothyroidism associated with anti-human chorionic gonadotropin antibodies secondarily produced by gonadotropin therapy in a case of idiopathic hypothalamic hypogonadism.

We report a 22-yr-old male patient with idiopathic hypothalamic hypogonadism who showed secondary resistance to gonadotropin (Gn) therapy over 3 yr after successful treatment with hCG combined with human menopausal Gn. The patient simultaneously developed subclinical hypothyroidism. Endocrine examination revealed low levels of testosterone (0.3 ng/ml), free T4 (0.91 ng/dl), and increased levels of TSH (31.1 microU/ml) in the serum. Serum autoantibodies to thyroid gland were all negative. Interestingly, thyroid function was improved after discontinuation of Gn therapy. In vitro assays by immunoprecipitation using 125I-hCG or 125I-TSH elucidated the presence of anti-hCG antibody in the serum 13 months after commencement of Gn therapy but anti-TSH antibody was not detected in the serum. Furthermore, the anti-hCG antibody specifically bound to hCG but not to other glycoproteins including TSH and FSH based on a competitive displacement assay. Bioassays using porcine thyroid cells revealed that the serum gamma-globulin fraction enables the suppression of cyclic AMP (cAMP) synthesis stimulated by TSH. Our findings suggest that anti-hCG and/or anti-idiotypic hCG antibodies induced by hCG therapy impaired TSH-dependent cAMP production through interfering with binding of TSH to its receptor, and this resulted in subclinical hypothyroidism in this patient.

A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20.

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 ( approximately 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region.

Analysis of HBV infection after blood transfusion in Japan through investigation of a comprehensive donor specimen repository.

BACKGROUND: To understand the risk of transfusion-transmitted viral infection, it is important to precisely assess cases of infection that follow transfusion. STUDY DESIGN AND METHODS: HBV infections noted after transfusion in 1997, 1998, and 1999 were analyzed. Transfusion in all these cases was performed before NAT was adopted for donor screening. To detect viral infection, PCR and serologic tests for HBV were performed retrospectively on all blood samples from implicated donors that had been stored in a frozen state after each donation. The concentration of HBV genome was measured in HBV-positive blood samples. RESULTS: One hundred three cases of HBV infection were analyzed; of these, only 16, including at least 10 infections due to window-period (HBsAg-positive by reverse particle hemagglutination assay) donations, were confirmed by further testing to be related to transfusion. The concentrations of HBV genome were very low in four blood samples (<50, 400, 500, and 800 genome equivalents/mL of plasma). CONCLUSIONS: The remaining risk of transfusion transmission of HBV infection before the adoption of NAT was mainly due to window-period donations, including one that was made before the HBV genome was detectable by PCR. However, it was determined that transfusion was not responsible in many cases for HBV infection after transfusion.

[Extragonadal germ cell tumor coexisted with renal cell carcinoma--a case report].

A patient was 31-year-old man with the chief complaint of 38 degrees C fever. He was pointed out left renal tumor by abdominal ultrasonography and computerized tomography (CT). CT revealed left infraclavicular, mediastinal and retroperitoneal lymph nodes swelling and left renal tumor. Serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG-beta) level were elevated. The diagnosis of extragonadal germ cell tumor and left renal cell carcinoma was confirmed pathologically by infraclavicular lymph node and renal biopsy. He was treated with 4 courses of BEP regimen and interferon-alpha, cimetidine therapy for 2 weeks preoperatively. After serum tumor markers were normal level, he underwent left radical nephrectomy and left infraclavicular, mediastinal and retroperitoneal lymph node dissection. The histology of all lymph nodes was necrotic tissue, but operation was incomplete. Therefore VIP therapy was performed postoperatively. This is the first case of extragonadal germ cell tumor coexisted with renal cell carcinoma in the world.

The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain.

We report here molecular cloning and expression analysis of the gene for a novel human brain link protein-1 (BRAL1) which is predominantly expressed in brain. The predicted open reading frame of human brain link protein-1 encoded a polypeptide of 340 amino acids containing three protein modules, the immunoglobulin-like fold and proteoglycan tandem repeat 1 and 2 domains, with an estimated mass of 38 kDa. The brain link protein-1 mRNA was exclusively present in brain. When analyzed during mouse development, it was detected solely in the adult brain. Concomitant expression pattern of mRNAs for brain link protein-1 and various lectican proteoglycans in brain suggests a possibility that brain link protein-1 functions to stabilize the binding between hyaluronan and brevican. The human BRAL1 gene contained 7 exons and spanned approximately 6 kb. The entire immunoglobulin-like fold was encoded by a single exon and the proteoglycan tandem repeat 1 and 2 domains were encoded by a single and two exons, respectively. The deduced amino acid sequence of human brain link protein-1 exhibited 45% identity with human cartilage link protein-1 (CRTL1), previously reported as link protein to stabilize aggregates of aggrecan and hyaluronan in cartilage. These results suggest that brain link protein-1 may have distinct function from cartilage link protein-1 and play specific roles, especially in the adult brain.

[Management of unilateral renal cystine calculi via percutaneous nephrolithotripsy in a child with a contralateral non-functional kidney--a case report].

A 2-year old boy visited our clinic with a chief complaint of high fever. A past history of acute renal failure due to cystine stones and cystinuria was expressed. Abdominal rentogenograms and CT demonstrated a right ureteral stone and a left renal stone. Furthermore renogram evaluation indicated non-function of the right kidney and dysfunction in the left kidney. Since right ureteral stone moved into bladder seven days post-admission, right ureteroscopy, left PNL, and cystolithotripsy were performed. Considering that right ureteral stenosis was determined by ureteroscopy, balloon dilation against the stenotic ureteral wall was performed. Left PNL and cystolithotripsy were successfully performed. No intraoperative complications occurred and no symptoms of signs of recurrence of the underlying metabolic disease were evident four months postoperatively.

Biosynthesis of Vicia graminea lectin- and Vicia unijuga lectin-binding glycoproteins in human tumor and nontumor cells and an estimation of its epitope structure.

We investigated biosynthesis of Vicia graminea lectin (VGA)- and Vicia unijuga lectin (VUA)-binding (Vgu) glycoproteins, which are human malignant tumor-associated antigens, in cultured human tumor and non-tumor cells by pulse-labeling experiments with [35S]-methionine, followed by immunoprecipitation using immobilized VUA, SDS-PAGE and autofluorography. It was shown that Vgu glycoproteins synthesized by tumor cells were 15-30 times greater than those of non-tumor cells. It was also shown that about 40-70% of Vgu glycoproteins synthesized by non-tumor cells were secreted from the cells while more than 80% of the antigen synthesized by tumor cells was not secreted, and that Vgu glycoproteins consisted of multiple molecular species with the same epitope. To estimate the epitope structure of Vgu glycoproteins, in preliminary experiments we prepared sialoglycoproteins and/or sialoglycopeptides from purified human glycophorin A. Human glycophorins A(M) and A(N) (GPs-A(M) and A(N)) were treated with Clostridium perfringens neuraminidase to remove all sialic acid residues linked to carbohydrate chains, with Newcastle disease virus (NDV) to remove alpha2-3 linked sialic acid residues, and by Edman's degradation to eliminate N-terminal amino acid of GP-As. Partial or complete desialylation reactions resulted in disappearance of the reactivity of GP-A(M) and GP-A(N) with corresponding antisera and in appearance of reactivities with VUA and VGA. Elimination of N-terminal amino acid of GP-As also resulted in appearance of reactivities with VUA. These results show that sialoglycoproteins with similar serological properties of Vgu glycoprotein could be prepared from GP-As, and suggest that the epitope structure of Vgu glycoprotein may be related to the MN blood type-epitope structure and its sialic acid residues at N-terminal moiety of GP-As.

Effect of human hydrosalpinx fluid on in vitro mouse embryogenesis.

OBJECTIVE: Women with hydrosalpinx have an unfavorable pregnancy rate. As one approach to elucidate the effect of hydrosalpinx on uterine tubal functioning, we examined the effect of hydrosalpinx fluid on early embryo development in mice. METHODS: Hyperovulation was induced in ICR mice, and late 2-cell-stage embryos were harvested 42 hours after administration of human chorionic gonadotropin (hCG). Hydrosalpinx fluid was obtained from patients during surgery after informed consent was obtained. The embryos were cultured in 3 culture fluids: (1) mBWW medium containing 0.3% bovine serum albumin (positive-control medium) (BSA), (2) Ca2+, Mg2+-free phosphate buffered saline (negative-control medium) (PBS), and (3) 100% human hydrosalpinx fluid. The developmental status of the embryos 120 hours after hCG administration was examined. RESULTS: Embryogenesis from a 2-cell-stage embryo to a blastocyst was observed in 98.3% (118/120) of the embryos cultured in the mBWW medium, in 0% (0/120) of the embryos cultured in PBS, and in 98.3% (118/120) of the embryos cultured in 100% human hydrosalpinx fluid. CONCLUSION: In the micro-environment of human hydrosalpinx fluid, late 2-cell embryos of ICR mice developed normally to blastocysts. The present results also suggest that non-species-specific embryogenetic factors might be present in human hydrosalpinx fluid.

Acute myocardial infarction following toxic epidermal necrolysis?

We describe a 29-year-old woman with rheumatoid arthritis who suffered an acute myocardial infarction 70 days after an initial presentation with toxic epidermal necrolysis (TEN). The trigger for the TEN was probably an over-the-counter anti-influenza treatment containing tipepidine hibenzate. Although the patient had familial hypercholesterolemia, we believe that thrombocytosis, induced by the inflammatory response and metabolic stress resulting from the TEN, may also have played a significant role in the pathogenesis of the myocardial infarction. Although TEN manifests itself principally as a skin disease, the potential for systemic morbidity, including cardiovascular abnormalities, should also be remembered.

Amidolytic activities and prostate-specific antigen in human seminal plasma.

The amounts of protein measured by absorbance at 280 nm, succinyl-L-alanyl-L-alanyl-L-prolyl-L-leucine-p-nitroanilide (Suc-Ala-Ala-Pro-Leu-pNA), D-valyl-cyclohexyl-alanyl-L-arginine-p-nitroanilide (Val-CHA-Arg-pNA), and glutamyl-L-phenylalanine-p-nitroanilide (Glu-Phe-pNA) amidolytic activities, and prostate-specific antigen (PSA) were measured in human seminal plasma (HSP) samples separated from the semen of 46 cases, including 13 cases of azoospermia and 33 cases of normozoospermia showing either good or poor quality of liquefaction. There was a highly significant correlation between the concentrations of all amidolytic enzyme activities studied and the concentration of PSA in HSP samples (p<.01). The HSP sample volume showed a relatively good negative coefficient of correlation to all items measured (p<.01) with the exception of protein concentration. The Suc-Ala-Ala-Pro-Leu-pNA, Val-CHA-Arg-pNA, and Glu-Phe-pNA amidolytic activities in azoospermia HSP samples were 2.33. 1.68, and 1.43 times higher, respectively, than those of normozoospermia samples showing good quality liquefaction. After the addition of morphologically purified human sperm to HSP sample of azoospermia cases, the Suc-Ala-Ala-Pro-Leu-pNA amidolytic activity in the HSP sample of azoospermia was not decreased for up to 18 h incubation, while the number of motile human sperm gradually declined, and no motile human sperm were detected after 18 h of incubation. The high Suc-Ala-AlaPro-Leu-pNA amidolytic activity in HSP samples of azoospermia cases did not result from a lack of motility.

[Examination for indication of systematic biopsy for diagnosis of prostate cancer].

BACKGROUND: Systematic biopsy has been commonly used for detection of prostate cancer. Nevertheless, as this examination occasionally gives patients severe complications it is necessary to give careful consideration for application of this examination. Thus, we analyzed retrospectively 145 cases who underwent transrectal ultrasonography (TRUS) guided systematic biopsy to evaluate the application of systematic biopsy, correlating with the findings of digital rectal examination (DRE), prostate specific antigen (PSA), the findings of transrectal ultrasonography (TRUS) and the results of biopsies. METHODS: Between May, 1995 and May, 1997, 143 patients who were suspected to have prostate cancer with either of PSA and DRE, and 2 patients who received visual laser ablation of prostate (VLAP), underwent TRUS guided systematic biopsy of prostate. We evaluated diagnostic efficacy of PSA, DRE, TRUS, prostate-volume-specific PSA, and PSA density (PSAD). RESULTS: Sensitivity, specificity and positive predictive value (P.P.V.) are 78.4%, 62.8% and 53.5% for DRE, 100.0%, 4.4% and 41.8% for PSA, 88.2%, 60.0% and 52.9% for TRUS, 87.8%, 72.1% and 64.2% for prostate-volume-specific PSA, 100.0%, 30.6% and 45.4% for PSAD, respectively. Ten of 69 patients (14.5%) whose PSA levels were 4.0 to 10.0 ng/ml were diagnosed as cancer, and positive for both or either of DRE and TRUS. Twenty-seven who were negative for both of DRE and TRUS were not diagnosed as prostate cancer. Using the combination of prostate-volume-specific PSA, DRE and TRUS, we could eliminate 29 non-cancer men (21.5%) whose PSA level was greater than 4.0 ng/ml from systematic biopsy. CONCLUSION: On the diagnosis of prostate cancer, the combination of prostate-volume-specific PSA, DRE and TRUS is very useful to exclude unnecessary systematic biopsy, if an urologist could be used to and trained for DRE and TRUS.