Cutaneous metastasis of pancreatic carcinoma as an initial symptom in the lower extremity with obstructive lymphedema treated by physiotherapy and lymphaticovenous shunt: a case report, review, and pathophysiological implications.

Cutaneous metastasis from pancreatic cancer is relatively rare as an initial symptom, and it is generally localized on the periumbilical area that is known as Sister Mary Joseph's nodule. We report a rare case of a 49-year-old female who developed cutaneous metastasis of pancreatic cancer as an initial symptom. The patient was referred to our department for treatment of lymphedema due to surgical treatment of cervical cancer and underwent combined physiotherapy and, 2 months later, a lymph venous anastomosis (LVA) for treatment of the lymphedema. Two months after the operation, she developed erythema on her right leg which spread from the leg to the groin in series. This pattern corresponded to the direction of lymph drainage, which may have been enhanced by the conservative physiotherapy and LVA treatments. These facts suggest a possible relationship between cutaneous metastasis of carcinoma and treatment for lymphedema. Alternatively, the lymphedematous limb may be a privileged site for cancer growth, and metastatic seeding could have taken place from pre-existing hematogenous spread at the time of operation.

Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.

Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine. Acotiamide (0.3 and 1 µM) and itopride (1 and 3 µM) significantly enhanced the contraction of gastric body strips induced by electrical field stimulation (EFS), but mosapride (1 and 10 µM) did not. Acotiamide and itopride significantly enhanced the contraction of gastric body and antrum strips induced by acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also significantly enhanced the contraction of gastric body strips induced by ACh, but not that by CCh. In contrast, mosapride failed to enhance contractions induced by either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition of AChE, and the percentage inhibition of acotiamide (100 µM) against AChE activity was markedly reduced after the reaction mixture was dialyzed. In contrast, itopride exerted noncompetitive inhibition on AChE activity. These results indicate that acotiamide enhances ACh-dependent contraction in gastric strips of guinea pigs via the inhibition of AChE activity, and that it exerts mixed and reversible inhibition of AChE derived from guinea pig stomach.

The deficiency of immunoregulatory receptor PD-1 causes mild osteopetrosis.

Recently, the involvement of immune responses in metabolic bone disease and/or local bone destruction has received much attention. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a member of the immunoglobulin (Ig) superfamily, negatively regulates T cell activation. The deficiency of CTLA-4 induces profound osteopenia with an increase in osteoclastogenesis, suggesting the important role of activated T cells in osteoclastogenesis. Programmed death-1 (PD-1) is the newly identified immunoregulatory receptor, which also belongs to the Ig superfamily. Both CTLA-4 and PD-1 are induced on activated T cells, however, there are no reports linking PD-1 with osteoclasts. In the present study, we have examined the bone phenotype in PD-1-deficient mice PD-1-/- and the role of PD-1 in osteoclastogenesis and osteoclast function. Both trabecular and cortical bone mineral densities of tibia were significantly increased, as observed in peripheral quantitative computed tomography (pQCT), at 12 weeks of age in PD-1-/- mice. Histomorphometric analysis of the PD-1-/- mice and the age-matched controls at 12 weeks of age showed a 2-fold increase in bone volume (BV/TV) with a 55% decrease in osteoclast number (N.Oc/BS). Bone formation indices were similar in both groups. The number of soluble receptor activator of nuclear factor kappaB ligand (sRANKL)-induced osteoclast-like cells (OCLs) derived from the PD-1-deficient splenocytes was significantly decreased (by 25%). On the other hand, PD-1 deficiency did not affect the bone-resorbing activity of mature osteoclasts. Our results suggest that PD-1 deficiency reduces osteoclastogenesis resulting in an osteopetrotic phenotype. Identical members of the Ig superfamily, CTLA-4 and PD-1, which negatively regulate immune responses, may differentially affect osteoclastogenesis and bone remodeling.

Differences between proximal and distal portions of the male rabbit posterior urethra in the physiological role of muscarinic cholinergic receptors.

1. The aim of the present study was to elucidate functional differences between embryologically different portions of the posterior urethra of male rabbits in response to muscarinic acetylcholine receptor (mAChR) stimulation using in vitro isometric tension experiments and radioligand binding studies. 2. In the in vitro isometric tension experiments, carbachol, produced a dose-dependent contraction of the proximal portion under the resting state, but did not change the basal tone of the distal portion. Contraction of the proximal portion by 10(-5) M noradrenaline (NA) was dose-dependently enhanced by carbachol either in the presence or absence of NG-nitro-L-arginine (NOARG). In contrast, carbachol induced relaxation of the distal portion contracted by 10(-5) M NA, which was reversed to dose-dependent contraction in the presence of NOARG. 3. Both portions of the urethra had a similar number of [3H]-quinuclidinyl benzilate ([3H]-QNB) binding sites (195.3+/-74.1 fmols mg(-1) protein for the proximal portion and 146.5+/-8.5 fmols mg(-1) protein for the distal portion) with similar affinities (115.0+/-45.4 pM for the proximal portion and 79.9+ 2.9 pM for the distal portion). 4. The concentration-response curves to carbachol in both portions were shifted to the right in a parallel manner in the presence of pirenzepine (an M1 antagonist), 11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]-5, 11-dihydro-6H-pyrido-2,3-b)-(1,4)-benzodiazepin-6-one (AFDX-116, an M2 antagonist) and 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP, an M1/M3 antagonist). The pA2 values for pirenzepine, AFDX-116 and 4-DAMP were 7.5+/-0.1, 7.2+/-0.02 and 9.3+/-0.1 respectively for the contraction of the proximal portion, and 7.2+/-0.1, 7.1+/-0.2 and 9.1+/-0.2, respectively for the relaxation of the distal portion. 5. In conclusion mAChR subtypes distribute in a similar fashion throughout the length of the male rabbit posterior urethra with the discrepant responses to carbachol attributable to the differential involvement of the NO pathway in mAChR-generated reactions.

Splenectomy may improve the glomerulopathy of type II mixed cryoglobulinemia.

Many patients with type II mixed cryoglobulinemia have been shown to be infected with hapatitis C virus (HCV). Therefore, interferon-alfa has become the first choice of treatment for patients with HCV-associated cryoglobulinemia. However, the disease often relapses after the discontinuation of interferon therapy. The long-term effect of interferon therapy is controversial. Therefore, a more effective therapy needs to be developed. A 62-year-old Japanese woman was admitted to our hospital for the examination of abnormal liver function tests, severe edema, and purpura in her lower extremities. Glomerulopathy secondary to HCV-related cryoglobulinemia was suspected. Her serum creatinine was increased to 2.1 mg/dL. Interferon therapy was considered initially. However, because of pancytopenia caused by liver cirrhosis and splenomegaly, splenectomy was performed in February 1997, before the start of interferon therapy. Renal biopsy specimen taken at the time of the splenectomy showed typical cryoglobulinemic glomerulonephritis. Gradually, after surgery, the patient's thrombocytopenia and anemia improved, her proteinuria and hematuria were decreased, her cryocrit dropped from 15% to 5%, the Ccr increased from 21.1 mL/min to 48.8 mL/min, and the purpura in her lower extremities disappeared. A repeat renal biopsy performed in May 1998 showed marked histological improvement. Splenectomy is not widely accepted as a treatment for cryoglobulinemia. Our case suggests the possibility that the monoclonal-IgM component of the type II cryoglobulin may be formed in the spleen. In conclusion, splenectomy may be an effective therapy for cryoglobulinemia in patients with HCV-positive liver cirrhosis and pancytopenia secondary to splenomegaly.

Optimization of fermentation conditions for preparation of polygalacturonic acid transeliminase by Erwinia carotovora IFO3830.

This paper is concerned with optimization of the fermentation conditions for preparation of alkaline pectin lyase (poly-galacturonic acid trans-eliminase, PATE) by Erwinia carotovora IFO3830 (E.C.IFO3830). The orthogonal matrix method was adopted as the experimental design method for media. The effects of media composition on the growth rate of E.C.IFO3830 are in the order of pectin > KH(2)PO(4)/Na(2)HPO(4) > MgSO(4) > (NH(4))(2)SO(4) > glucose > L-glutamate sodium, and those on PATE activity are in the order of glucose > pectin > L-glutamate sodium > KH(2)PO(4)/Na(2)HPO(4) > MgSO(4) > (NH(4))(2)SO(4). The strain of E.C.IFO3830 grows quickly and easily near an initial pH of 7.0, and especially at the alkaline range of pH 7.0-8.0. The growth rate profiles indicate that E.C.IFO3830 grows very quickly; its generation time t(1/2) is about 0.2 h. The appropriate fermentation period is about 10-20 h for a high level productivity of biomass and 25-35 h for high productivity of PATE enzyme.

Optimization of fermentation reaction conditions for preparation of PATE enzyme by Erwinia carotovora IFO3830 by TFCCRD method.

The fermentation conditions for preparation of polygalacturonic acid transeliminase (PATE) enzyme by Erwinia carotovora IFO3830 were optimized for seed ratio, vibration rate, and temperature by the TFCCRD method. The results indicated that the optimum fermentation conditions for E. carotovora IFO 3830 were that seed ratio, vibration rate, and temperature were 5% v/v, 113 min(-1), and 29 degrees C, respectively.

A Conjugative Plasmid Carrying the efe Gene for the Ethylene-Forming Enzyme Isolated from Pseudomonas syringae pv. glycinea.

ABSTRACT Previous work suggested that the efe gene encoding the ethylene-forming enzyme was present in the plasmids of three pathovars of Pseudomonas syringae including glycinea, phaseolicola (kudzu strains), and cannabina. However, no direct evidence to support this assumption had been presented. In the current study, we isolated the conjugative plasmid harboring the efe gene (ethylene plasmid) designated pETH2 from P. syringae pv. glycinea MAFF301683. pETH2 was detected by Southern blot hybridization using the efe probe, marked with the transposon mini-Tn5-Km1, and transferred into P. syringae Ni27(n), which does not produce ethylene. The transconjugant Ni27(n) (pETH2) produced ethylene at a level similar to pv. glycinea MAFF301683. In addition, the plasmid designated pCOR2, which encodes coronatine biosynthesis genes, was detected in the same strain. Although the molecular size of the plasmid pCOR2 was not easily distinguishable from pETH2, pCOR2 transferred independently into Ni27(n) and the transconjugants produced coronatine. These findings suggested that the efe gene has been horizontally dispersed among pathovars of P. syringae by plasmid-mediated conjugation in nature.

[Retroperitoneal ganglioneuroma: a case report].

A primary retroperitoneal ganglioneuroma was found incidentally in a 44-year-old man. Computed tomography revealed a homogeneous mass just above the right kidney. T1-weighted magnetic resonance imaging demonstrated the homogeneous mass, but T2-weighted imaging revealed a heterogeneous mass with a markedly high intensity area. The tumor was resected through a transabdominal approach. The resected specimen measured 11 x 9 x 4.5 cm and weighted 270 g. Histological examination showed that the lesion was a ganglioneuroma composed of mature ganglion cells and nerve fibers.

[A case of bilateral ectopic ureter in a male].

A 7-year-old boy was admitted for recurrent pyelonephritis. Intravenous pyelography IVP showed right hydronephrosis and normal left kidney and ureter. Cystourethroscopy revealed no ureteral orifices in the bladder but bilateral ureteral openings adjacent to the seminal colliculus. Right retrograde pyelography showed severe hydroureter and hydronephrosis. The diagnosis was bilateral ectopic ureteral opening into proximal urethra. His abnormality of ureteral opening was classified as type II in Thom's classification. Bilateral ureterocystoneostomy was performed. Only 3 cases of bilateral ectopic ureter in males have been reported in the Japanese literature.

[Multicentric Castleman's disease found by a renal sinus lesion: a case report].

A 79-year-old man complained of anorexia and weight loss. Computed tomography and magnetic resonance imaging showed a solitary mass in the left renal sinus. Left nephrectomy was carried out under a clinical diagnosis of renal pelvic tumor. The pathological diagnosis was plasma cell type of Castleman's disease. The patient suffered from lymph node swelling in the right neck at age 75 and the lymph node was resected. The pathological diagnosis was lymphadenitis but it proved to be plasma cell type of Castleman's disease. The patient also had had a lymphadenectomy in the supraclavicular fossa and in the supraorbital area at age 76. Both had been diagnosed as lymphadenitis pathologically but they proved to be plasma cell type of Castleman's disease. The final diagnosis was multicentric Castleman's disease. We reviewed multicentric Castleman's disease.

[Inverted Y ureteral duplication with a ureteral stone in atretic segment: a case report].

A 46-year-old male was admitted with the chief complaint of right side abdominal pain. A retrograde urogram disclosed right hydronephrosis and an anomalous branch in the shape of an inverted Y accompanied by a calculus on the right ureter. Extirpation of the calculus and vesicoureteroneostomy were performed just above the bifurcation. The anomalous branch was blind-ending.

[A case of staphylococcal enterocolitis caused by methicillin resistant Staphylococcus aureus].

Recently, the frequency of methicillin resistant Staphylococcus aureus (MRSA) infection has been increasing. We experienced a case of postoperative enterocolitis due to MRSA. The patient was an 81-year-old male with benign prostatic hypertrophy. Urine leakage from the penrose drain tube appeared 1 day after suprapubic prostatectomy. We had used intravenous infusion of antibiotic agents including cefodizine (CDZM), imipenem (IPM/CS) and cefmetazol (CMZ). He developed severe diarrhea, high fever, oliguria, leg edema and ascites 24 days after the operation. MRSA was detected from his feces. Toxic shock syndrome toxin-I (TSST-I) was produced by this bacteria the coagulase type of which was type II. The patient was treated with oral vancomycin (1 g/day), to which this bacteria showed sensitivity and the patient showed, improvement, including symptoms, leucocytosis and serum CRP level 12 days after administration of vancomycin.

[Giant epidermal cyst in the perineum extending into the pelvic space in the patient with polycystic kidney disease: a case report].

A 75-year-old man with autosomal dominant polycystic kidney disease was admitted to our hospital with the chief complaint of a giant mass in the left side of the perineum that had gradually developed in size during the previous 20 years. Palpation revealed a neonatal head-sized cystic mass with no tenderness. Magnetic resonance imaging (MRI) demonstrated a well-circumscribed homogeneous mass extended to the dorsal side of the bladder. It was excised surgically without any injury of rectum or urinary tract. The resected specimen was 23 x 18 x 12 cm in size and 1.2 kg in weight. The pathological diagnosis was epidermal cyst. Cases with an epidermal cyst extending into the pelvic space are extremely rare with few cases having been reported in the world.

[Primary sclerosing lipogranuloma of the male genitalia: report of three cases].

Recently, genital sclerosing lipogranuloma having no history of trauma and foreign body infusion are more common in Japan. We report three cases recently encountered in which tumors were diagnosed as sclerosing lipogranuloma on histological examination. In case 1, lipid analyses of the tissues by infrared absorption spectrometry proved that it was endogenous in origin.

[Prostatic cancer presenting as palpable lymph node metastasis--report of three cases].

Three cases of prostatic carcinoma with palpable metastatic lymph nodes are presented. In case 1, the intrapelvic lymph node metastases were recognized as an abdominal mass. In case 2 and 3, non-regional superficial lymph node metastases were palpable. Orchiectomy and anti-androgen therapy were effective in all cases.

[Rectal involvement by prostate carcinoma: a report of three cases].

We reported 3 cases of rectal involvement by locally invasive prostate carcinoma which caused an urethrorectal fistula in case 1 and a rectal stenosis in case 2 and 3. Discriminating between primary rectal carcinoma and prostate carcinoma locally invasive to the rectum is very important because of distinct differences in treatment and prognosis. To confirm the tumor origin, tumor markers, proctosigmoidscopy, computerized tomography and biopsy with immunohistochemical staining for prostate specific antigen were useful.

[Three cases of cystic testicular disease: simple cyst of the testis, cyst of the tunica alubuginea and mature cystic teratoma].

We experienced three cases of cystic testicular disease including simple cyst of the testis, cyst of the tunica alubuginea and mature cystic teratoma. Cystic testicular diseases have been considered rare, but increasing usage of ultrasound in the diagnosis of scrotal diseases has made them more common. Ultrasonography seemed to be useful to distinguish nonneoplastic testicular cysts (simple cyst of the testis, cyst of the tunica alubuginea) from cystic lesions of solid testicular tumors.

[The correlation of the severity of stress urinary incontinence with static and stress urethral pressure profiles].

The urethral pressure profile (UPP) at rest and under stress was recorded by means of double lumen microtip transducer catheter in 58 females with stress urinary incontinence (SUI). The patients were divided into three groups including mild to moderate SUI patients (n = 29, group 1), severe SUI patients (n = 16, group 2) and very severe SUI patients (n = 13, group 3) according to a one-hour pad test. The functional urethral length (FUL) was divided into four equal lengths and the pressure transmission ratio (PTR) was calculated for each quartile for each female. We examined the correlation of the severity of SUI with urethral pressure parameters: maximum urethral closure pressure (MUCP) at rest and functional urethral length (FUL) at rest and PTR. SUI patients showed a negative association between the severity of SUI and MUCP, but no significant differences in the FUL were seen between the different groups. PTR was shown to be similar in order for all groups of SUI patients showing a linear decrease in the value of the PTR along the FUL. However, we found a negative association between the severity of SUI and PTR (P < 0.05) at the middle part of the FUL (Q3). These findings indicate that there are more defective distal sphincter mechanisms in severe SUI patients than in mild to moderate SUI patients. There was an overlap between the different groups in both MUCP and PTR at the middle urethra (Q3), suggesting that other parameters are related with the severity of SUI.