Lichen amyloidosus as a sweat gland/duct-related disorder: resolution associated with restoration of sweating disturbance.

BACKGROUND: Although a number of pathological processes resulting in amyloid deposition have been described in lichen amyloidosus (LA), no attention has been paid to the involvement of sweat glands/ducts in the pathogenesis of LA. According to recent studies, follicular structures are usually spared in serial histological sections of LA, and deposits of amyloid are likely to be confined to areas that display xerosis, suggesting that decreases in skin wetness by sweating disturbance seem to initiate LA. OBJECTIVES: To investigate whether sweating disturbance could represent an early event that triggers LA, and whether resolution of LA could be induced by restoring the sweating disturbance. METHODS: By using the impression mould technique, which allows an accurate quantification of individual sweat glands/ducts actively delivering sweat, we examined sweat responses to thermal stimulus in LA lesions before and after treatment with a moisturizer. RESULTS: Sweating disturbance was most profoundly detected in the 'hub' structure of the LA papule, and this disturbance due to leakage of sweat could be restored by short-term treatment with a moisturizer, particularly when used under occlusion. CONCLUSIONS: This study was limited by the relatively small sample size. Treatment of LA should be primarily directed at preventing leakage of sweat into the dermis or epidermis and therefore sweat delivery to the skin surface could be made easier.

Histological evaluation of skeletonized internal thoracic artery using ForceTriad™.

BACKGROUND: The internal thoracic artery (ITA) is a useful graft for coronary artery bypass grafting. Skeletonization, a technique that uses an ultrasonic scalpel, is increasingly used. However, the cost of an ultrasonic scalpel is extremely high. The purpose of this study was to determine whether a new electrosurgical cautery device (ForceTriad™) is as effective as an ultrasonic scalpel. METHODS: Bilateral ITAs were harvested from eight pigs using the skeletonizing technique. The ITA on one side was harvested with an ultrasonic scalpel and on the other side using the ForceTriad™. Macroscopic and histological examinations were performed in sixteen ITAs. RESULTS: No significant differences in the time required for harvesting were observed. The macroscopic findings revealed no significant change in any of the samples. The histological findings showed that the degree of thermal injury was similar. The normal structure was maintained in all samples. The ForceTriad™ costs US$ 226.82 less per patient than the ultrasonic scalpel. CONCLUSION: The new electrosurgical cautery device ForceTriad™ was less expensive, but it was equally effective. It appears that skeletonization performed with the new device is equivalent to that performed with an ultrasonic scalpel.

Prognostic value of perfusion MR imaging of high-grade astrocytomas: long-term follow-up study.

BACKGROUND AND PURPOSE: Although the prognostic value of perfusion MR imaging in various gliomas has been investigated, that in high-grade astrocytomas alone has not been fully evaluated. The purpose of this study was to evaluate retrospectively whether the tumor maximum relative cerebral blood volume (rCBV) on pretreatment perfusion MR imaging is of prognostic value in patients with high-grade astrocytoma. MATERIALS AND METHODS: Between January 1999 and December 2002, 49 patients (30 men, 19 women; age range, 23-76 years) with supratentorial high-grade astrocytoma underwent MR imaging before the inception of treatment. The patient age, sex, symptom duration, neurologic function, mental status, Karnofsky Performance Scale, extent of surgery, histopathologic diagnosis, tumor component enhancement, and maximum rCBV were assessed to identify factors affecting survival. Kaplan-Meier survival curves, the logrank test, and the multivariate Cox proportional hazards model were used to evaluate prognostic factors. RESULTS: The maximum rCBV was significantly higher in the 31 patients with glioblastoma multiforme than in the 18 with anaplastic astrocytoma (P < .03). The 2-year overall survival rate was 67% for 27 patients with a low (< or =2.3) and 9% for 22 patients with a high (>2.3) maximum rCBV value (P < .001). Independent important prognostic factors were the histologic diagnosis (hazard ratio = 9.707; 95% confidence interval (CI), 3.163-29.788), maximum rCBV (4.739; 95% CI, 1.950-11.518), extent of surgery (2.692; 95% CI, 1.196-6.061), and sex (2.632; 95% CI, 1.153-6.010). CONCLUSION: The maximum rCBV at pretreatment perfusion MR imaging is a useful clinical prognostic biomarker for survival in patients with high-grade astrocytoma.

Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases.

Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens-Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP-Pax6 transgenes into these Pax6(-) clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium.

[Aprotinin reduces bleeding during off-pump coronary artery bypass grafting in a patient on ticlopidine; report of a case].

A 65-year-old man was admitted to a local hospital with symptoms of unstable angina pectoris. He was administered ticlopidine before drug eluting stent (DES) stenting for 2 weeks. Coronary angiography showed 3 vessel diseases. He was then admitted to our hospital due to a sudden onset of unstable angina following shock during the percutaneous coronary intervention (PCI) procedure, emergency off-pump coronary artery bypass grafting (OPCAB) was thus performed. He received aprotinin 5 hundred thousand KIU just at the start of surgery and 5 hundred thousand KIU after undergoing anastomosis of the coronary artery. Postoperatively, only some minor bleeding was observed. Aprotinin reduces bleeding, the transfusion requirements of packed red blood cells, platelets, and the total blood units in patients on ticlopidine who undergo emergency OPCAB.

[Posterior ventricular septal perforation successfully repaired through right ventricular approach].

A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity.

BACKGROUND AND PURPOSE: On diffusion-weighted imaging (DWI), metastatic tumors of the brain may exhibit different signal intensities (SI) depending on their histology and cellularity. The purpose of our study was to verify the hypotheses (1) that SI on DWI predict the histology of metastases and (2) that apparent diffusion coefficient (ADC) values reflect tumor cellularity. MATERIALS AND METHODS: We assessed conventional MR images, DWI, and ADC maps of 26 metastatic brain lesions from 26 patients, 13 of whom underwent surgery after the MR examination. Two radiologists performed qualitative assessment by consensus of the SI on DWI in areas corresponding to their enhancing portions. We measured the contrast-to-noise ratio (CNR) on T2-weighted images and normalized ADC (nADC) values, and compared them with tumor cellularity. RESULTS: The mean SI on DWI and the CNR on T2-weighted images were significantly lower in well differentiated than in poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. The mean nADC value was significantly higher in well differentiated than poorly differentiated adenocarcinomas and lesions other than adenocarcinoma. All 3 small-cell carcinomas and 1 large-cell neuroendocrine carcinoma exhibited high SI on DWI. The nADC value showed a significant inverse correlation with tumor cellularity. There was no significant correlation between the CNR and tumor cellularity. CONCLUSION: The SI on DWI may predict the histology of metastases; well differentiated adenocarcinomas tended to be hypointense, and small- and large-cell neuroendocrine carcinomas showed hyperintensity. Their ADC values reflect tumor cellularity.

Hypoxic adaptation of the rat carotid body.

Three types of hypoxia with different levels of carbon dioxide (hypocapnic, isocapnic, and hypercapnic hypoxia) have been called systemic hypoxia. The systemic hypoxic carotid bodies were enlarged several fold, but the degree of enlargement was different for each. The mean short and long axes of hypocapnic and isocapnic hypoxic carotid bodies were 1.6 (short axis) and 1.8-1.9 (long axis) times larger than normoxic control carotid bodies, respectively. Those of hypercapnic hypoxic carotid bodies were 1.2 (short axis) and 1.5 (long axis) times larger than controls, respectively. The rate of enlargement in hypercapnic hypoxic carotid bodies was lower than in hypocapnic and isocapnic hypoxic carotid bodies. The rate of vascular enlargement in hypercapnic hypoxic carotid bodies was also smaller than in hypocapnic and isocapnic hypoxic carotid bodies. Thus, the enlargement of hypoxic carotid bodies is mainly due to vascular dilation. Different levels of arterial CO2 tension change the peptidergic innervation during chronically hypoxic exposure. The characteristic vascular arrangement was under the control of altered peptidergic innervation. During the course of hypoxic adaptation, the enlargement of the carotid bodies with vascular expansion began soon after the start of hypoxic exposure. During the course of recovery, the shrinking of the carotid bodies with vascular contraction also started at a relatively early period after the termination of chronic hypoxia. These processes during the course of hypoxic adaptation and during the course of recovery were under the control of peptidergic innervation. These findings may provide a standard for further studies of hypoxic carotid bodies.

Morphological changes in the rat carotid body 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia.

Morphological changes in the rat carotid bodies 1, 2, 4, and 8 weeks after the termination of chronically hypocapnic hypoxia (10% O2 for 8 weeks) were examined by means of morphometry and immunohistochemistry. The rat carotid bodies after 8 weeks of hypoxic exposure were enlarged several fold with vascular expansion. The carotid bodies 1 and 2 weeks after the termination of 8 weeks of hypoxic exposure were diminished in size, although their diameter remained larger than the normoxic controls. The expanded vasculature in chronically hypoxic carotid bodies returned to the normoxic control state. In the carotid bodies 1 week after the termination of chronic hypoxia, the density of NPY fibers was remarkably increased and that of VIP fibers was dramatically decreased in comparison with the density in chronically hypoxic carotid bodies. In the carotid bodies 2 and 4 weeks after the termination of hypoxia, the density of SP and CGRP fibers was gradually increased. In the carotid bodies 8 weeks after the termination of hypoxia, the appearance of the carotid body returned to a nearly normoxic state, and the density of SP, CGRP, VIP, and NPY fibers also recovered to that of normoxic controls. These results suggest that the morphological changes in the recovering carotid bodies start at a relatively early period after the termination of chronic hypoxia, and a part of these processes may be under the control of peptidergic innervation.

Peptidergic innervation in the rat carotid body after 2, 4, and 8 weeks of hypocapnic hypoxic exposure.

The distribution and abundance of neuropeptide-containing nerve fibers were examined in the carotid bodies of rats exposed to hypocapnic hypoxia (10% O2 in N2) for 2, 4, and 8 weeks. The carotid bodies after 2, 4, and 8 weeks of hypoxic exposure were enlarged by 1.2-1.5 times in the short axis, and 1.3-1.7 times in the long axis in comparison with the normoxic control ones. The enlarged carotid bodies contained a number of expanded blood vessels. Mean density per unit area (10(4) microm2) of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive fibers was transiently high in the carotid bodies after 4 weeks of hypoxic exposure, and decreased significantly to nearly or under 50% after 8 weeks of hypoxic exposure. Density of vasoactive intestinal polypeptide (VIP) immunoreactive fibers increased significantly in all periods of hypoxic exposure observed, and was especially high in the carotid bodies after 4 weeks of hypoxic exposure. Density of neuropeptide Y immunoreactive fibers was unchanged in the carotid bodies during hypoxic exposure. These characteristic changes in the density of SP, CGRP, and VIP fibers in the carotid bodies after 4 weeks of hypoxic exposure suggest that the role of these neuropeptide-containing fibers may be different in the carotid bodies after each of three periods of hypoxic exposure, and that the peptidergic innervation after 8 weeks of hypoxic exposure may show an acclimatizing state.

Changes in the peptidergic innervation in the carotid body of rats chronically exposed to hypercapnic hypoxia: an effect of arterial CO2 tension.

The abundance of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the carotid body was examined in chronically hypercapnic hypoxic rats (10% O2 and 6-7% CO2 for 3 months), and the distribution and abundance of these four peptidergic fibers were compared with those of previously reported hypocapnic- and isocapnic hypoxic carotid bodies to evaluate the effect of arterial CO2 tension. The vasculature in the carotid body of chronically hypercapnic hypoxic rats was found to be enlarged in comparison with that of normoxic control rats, but the rate of vascular enlargement was smaller than that in the previously reported hypocapnic- and isocapnic hypoxic carotid bodies. In the chronically hypercapnic hypoxic carotid body, the density per unit area of parenchymal NPY fibers was significantly increased, and that of VIP fibers was unchanged, although the density of NPY and VIP fibers in the previously reportetd chronically hypocapnic and isocapnic hypoxic carotid bodies was opposite to that in hypercapnic hypoxia as observed in this study. The density of SP and CGRP fibers was decreased. These results along with previous reports suggest that different levels of arterial CO2 tension change the peptidergic innervation in the carotid body during chronically hypoxic exposure, and altered peptidergic innervation of the chronically hypercapnic hypoxic carotid body is one feature of hypoxic adaptation.

Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse.

Ghrelin is a novel growth hormone-releasing peptide isolated from rat stomach. In the present study, we report expression of a ghrelin gene-derived transcript (GGDT) in the mouse testis. Analysis of GGDT cDNA revealed that the 68 bp sequence at the 5'-end was unique and the remaining 252 bp sequence was identical with the sequence encoded by exons 4 and 5 of mouse ghrelin gene. The 5'-unique sequence encoded 12 amino acid residues being in-frame with the C-terminal 42 amino acid sequence of mouse ghrelin. The 54-amino-acid polypeptide encoded by GGDT contained no apparent signal peptide sequence but possessed a nuclear localization signal-like sequence. Ghrelin mRNA was extensively expressed in the stomach, while GGDT was expressed only in the testis. The 5'-unique sequence of GGDT was identified between exons 3 and 4 of the ghrelin gene, indicating that GGDT was generated by alternative usage of the 68 bp exon as the testis-specific first exon. The GGDT expression in the testis was initiated and increased after 2 weeks of postnatal period. These results indicate that the expression of GGDT is regulated in testis-specific and developmental stage-specific manners.

Post-pubertal mucinous cystadenoma of the pancreas.

A 14-year-old patient with a mucinous cystadenoma of the pancreas (MCAP) is presented. She presented with a palpable left-sided abdominal mass and underwent a left hemipancreatectomy. MCAP occurs mostly in middle-aged women, and no post-pubertal cases have been reported to date in the English literature.

Organization of the mouse ghrelin gene and promoter: occurrence of a short noncoding first exon.

Ghrelin is a growth hormone-releasing peptide recently discovered in the stomach of rat and human as an endogenous ligand for growth hormone-secretagogue receptor. In the present study, a full-length cDNA for mouse ghrelin has been cloned from the stomach using the oligo-capping and rapid amplification methods, and the organization of its gene and promoter has been analyzed. The mouse ghrelin cDNA was 521 bp long, consisting of 44 bp 5'-noncoding region, 354 bp coding region encoding a pre-proghrelin composed of 117 amino acid residues and 123 bp 3'-noncoding region. The genomic sequence analysis has revealed that the mouse ghrelin gene consists of 5 exons and 4 introns. The first exon was revealed to be only 19 bp long presented at the noncoding region of cDNA. The identical 19 bp sequence was also found as the first exon at the 5'-end of full-length rat ghrelin cDNA obtained from the stomach. A TATA box-like sequence, TATATAA was localized 24 bp upstream of the transcription start site of the mouse ghrelin gene. The sequence of the 5'-promoter region of mouse ghrelin gene including the TATA-like sequence and short exon 1 was highly homologous to that of reported human ghrelin gene. These findings suggest that the structure of the promoter region including the short noncoding first exon and its transcriptional regulation are conserved among the mammalian ghrelin genes.

Natural history of sigmoid colon cancer: report of a patient observed for 4 years.

We report a case of sigmoid colon cancer that was left untreated for a period of 4 years, because the patient declined treatment. A 59-year-old man was found to have an early carcinoma of the sigmoid colon measuring approximately 12 mm in diameter. The lesion, initially a flat cancer, increased in height and became sessile 4 months later. Subsequently, the central portion of the lesion became ulcerated, leaving an elevated ring along its periphery. The lesion eventually evolved into an ulcerated, invasive cancer. This sequence has not been observed with colonoscopy before.

Metastatic gastrinoma to the liver 20 years after primary resection.

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up.

Detection of hepatitis B virus X-region DNA in liver tissue from patients with hepatitis C virus-associated cirrhosis who subsequently developed hepatocellular carcinoma.

The risk of hepatocellular carcinoma (HCC) in patients chronically infected by hepatitis C virus (HCV) is relatively higher in Japan than in Western countries. The presence of hepatitis B virus X (HBX)-DNA in the liver tissue samples obtained on enrollment from 69 patients with HCV-associated cirrhosis who were subsequently followed in our hospital was analyzed by polymerase chain reaction (PCR). During the follow-up period of 5.7+/-3.2 years (mean +/- SD), 52 (75%) of 69 patients developed HCC. The PCR analysis indicated that the HBX-DNA sequence was detected in 25 (48%) of 52 patients who developed HCC during follow-up, but in only 3 (18%) of 17 patients who did not (P<0.05). These results suggest that HBX, a hepatitis B viral product relevant to hepatocarcinogenesis, is involved in development of HCC in some patients chronically infected by HCV in Japan.