[Successfully treated case of cervical trachea injury caused by suicide].

A 52-year-old man stabbed in his neck and abdomen by a kitchen knife for the purpose of suicide. He was immediately transferred by ambulance car. Subcutaneous emphysema was not observed. Stabbed wounds were observed in the neck and the abdomen. Radiography and computed tomography showed subcutaneous and mediastinal emphysema. The patient was diagnosed as having trachea injury. After admission, emphysema progressed rapidly and respiratory distress appeared. The patient was orally intubated and emergency surgery was performed. The stabbed wound was found to extend to thyroid grand and cricotracheal ligament. After thyroidectomy, the injured trachea was repaired primarily. The course of the patient was almost uneventful, and was discharged on the 23th operative day. He was diagnosed as having alcoholism by a psychiatrist. The patient died due to suicide by hanging 16 months after surgery. Orotracheal intubation and primary suture were effective in a patient with trachea injury. Prevention of suicide is also important after leaving hospital in patients with history of suicide.

Spindle cell metaplasia arising in thyroid adenoma: characterization of its pathology and differential diagnosis.

Spindle cell metaplasia in thyroid adenoma or carcinoma is rare and its pathological features are not well characterized. Distinction of this entity from medullary or anaplastic carcinoma has an important clinical implication. We encountered a case of thyroid follicular adenoma associated with spindle cell metaplasia. It showed "tumor in tumor appearance" and neoplastic spindle cells were positive for thyroglobulin, thyroid transcription factor-1, vimentin and focally chromogranin A and somatostatin (SS). MIB-1 index was <1%. Ultrastructure of the spindle cells was reminiscent of follicular cell origin. From the findings from our case, spindle cell metaplasia appears to be a benign clinical entity, suggestive of multidirectional differentiation of follicular cells.

Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes.

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor kappa B kinase/nuclear factor kappa B system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.

Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients.

AIMS/HYPOTHESIS: We examined the pancreatic islet lesions in Japanese patients with Type II diabetes mellitus to determine if the damage was related to oxidative stress. METHODS: Morphometric analyses were performed on immunostained sections of the tail portion of the pancreas from 14 diabetic and 15 non-diabetic patients. Amyloid deposition and oxidative stress-induced tissue damage were evaluated by Congo-red staining and immunostaining. Resistance to oxidative stress was assessed from immunostaining results for Cu, Zn-superoxide dismutase (SOD). Expression of (pro)insulin mRNA was assessed by in situ hybridisation. RESULTS: The pancreas from diabetic patients had amyloid deposition in about 15 % of the islets, intensified reactions of 8-OHdG and HNE, as well as reduced expression of SOD. Islet volume density of beta cells and total beta-cell mass in the pancreas from diabetic patients were reduced by 22 % (p < 0.001) and 30 % (p < 0.05). Islet volume density and total mass of (pro)insulin mRNA-positive cells were similarly reduced in diabetic patients by 22 % (p < 0.001) and 39 % (p < 0.05), respectively. Islet volume density of A cells was increased by 20 % (p < 0.001) but total mass did not change. There were no changes in volume densities of islet, D and PP cells. Reduced beta-cell volume density correlated with increased positive staining of 8-OHdG. CONCLUSION/INTERPRETATION: Japanese Type II diabetic patients show a reduction of beta-cell mass and evidence of increased oxidative stress-related tissue damage that is correlated with the extent of the beta-cell lesions.

Malignant glomus tumor in the branchial muscle of a 16-year-old girl.

Malignant glomus tumor is an extremely rare neoplasm and its histological features are not well characterized. We report a 16-year-old female patient with a malignant glomus tumor. The patient was admitted to our hospital presenting with a mass in the right upper arm that she had noticed for the previous 6 months. Computed tomography and magnetic resonance imaging revealed an expanded mass involving the surrounding tissues. At surgery, an ill-defined and expanded mass was found, 5 x 4 x 3 cm in size, in the right branchial muscle. The tumor was extirpated, along with neighboring muscle tissues. Histologically, tumor cells were round to short-spindle shaped, forming solid sheets admixed with vessels of varying size. Their nuclei were uniformly oval to round, and their cytoplasms were slightly eosinophilic. The growth pattern of the tumor cells resembled that of glomus tumor, but mitotic figures were frequent (as high as 10 per 10 high-power fields). Immunohistochemically, the tumor cells were positive for vimentin and muscle actin, but negative for desmin. There were no areas typical of benign glomus tumor or sarcomatous change. These findings led us to a diagnosis of primary malignant glomus tumor arising de novo. There has been no recurrence or metastasis for 21 months after wide excision.

Enhanced in situ expression of aldose reductase in peripheral nerve and renal glomeruli in diabetic patients.

To explore the relationships between polyol pathway-related enzymes and pathologic features, we examined the immunohistochemical expression of aldose reductase (AR) and sorbitol dehydrogenase (SDH) in the peripheral nerve and kidney tissues collected postmortem from diabetic patients and compared it with those from non-diabetic patients. Tissue AR protein concentrations were also quantified. In non-diabetic patients, AR distributed in pericytes, smooth muscle cells of endo- and epi-neurial microvessels, Schwann cells in the sciatic nerve, and tubular cells of the renal medulla. By contrast, positive SDH reactions were observed in tubular cells of the renal cortex but were faint in the sciatic nerve. Diabetic patients frequently showed dense AR expressions in the sciatic nerve. In nephropathic diabetic patients, the glomerular mesangial area showed diffuse positive reactions for AR. The severity of structural changes in glomeruli correlated with the intensity of immunoreactive AR (r2=0.626, P<0.01). AR contents in the renal cortex and sciatic nerve from diabetic patients were 1.5- and 1.8-fold greater than those from non-diabetic patients, respectively (P<0.05 for both). These findings are the first to demonstrate enhanced AR expressions in peripheral nerve and renal glomeruli in diabetic patients and its relevance to the characteristic pathology.

Effects of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy.

BACKGROUND: Nonenzymatic glycation of neural proteins and their end-products (advanced glycation end-products, AGE) have been implicated in the pathogenesis of diabetic neuropathy. We need a development of effective ant-glycation agents for future clinical use. MATERIALS AND METHODS: We examined the effects of OPB-9195 (OPB), a new inhibitor of glycation, on the peripheral nerve structure and function in diabetic rats. Eight-week-old Wistar rats were made diabetic by streptozotocin (40 mg kg(-1), i.v.) and OPB (60 mg kg(-1) day(-1)) was given by gavage for 24 weeks. Age- and sex-matched normal Wistar rats were used for comparison. RESULTS: During the experimental period, OPB treatment did not affect the reduced body weight, elevated levels of blood glucose and glycated haemoglobin in diabetic rats. At the end of the experiment, delayed tibial motor nerve conduction velocity was significantly improved (by 60%) in treated diabetic rats, with reduction of serum AGE levels. Expression of immunoreactive AGE in the sciatic nerve was reduced in treated diabetic rats compared with those in untreated rats. Sciatic nerve (Na+, K+)-ATPase activity was also restored in treated diabetic rats. On the cross-sectioned sciatic nerves, positive cells with oxidative stress-related DNA damage, as expressed by 8-hydroxy-2'-deoxyguanosine, were less in the peripheral nerve of treated diabetic rats compared with those of untreated rats. CONCLUSION: The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.

Solitary thyroid metastasis of renal clear cell carcinoma: report of a case.

A case of solitary thyroid metastasis of renal clear cell carcinoma is described. The patient was a 77-year-old Japanese woman, who was referred to our department after a thyroid tumor was identified in May 1999. She had a history of renal clear cell carcinoma of the left kidney, which had been partially resected 3 years previously. Ultrasound sonography demonstrated that a well-demarcated hypoechoic mass containing high-echo spots representing small calcifications, which measured 45 x 34 x 31 mm in size, occupied the left lobe. Computed tomography revealed a low-density mass containing small calcifications. The results of preoperative fine-needle aspiration cytology strongly suggested a clear cell carcinoma metastasizing to the thyroid. A left hemithyroidectomy was performed on July 27, 1999. A histological examination revealed that the neoplasm was composed of tumor cells with abundant clear cytoplasm and round nuclei. The histological characteristics of this thyroid tumor were virtually identical to the renal cell carcinoma resected 3 years previously. Thyroglobulin stained negatively in the clear cells of the resected thyroid tumor in an immunohistochemical analysis. Clinically, the thyroid gland is a rare site of tumor metastasis; however, we should also consider the possibility of metastasis in the case of thyroid tumor patients with a history of renal cell carcinoma.

Gastrointestinal stromal tumour of the rectum.

Gastrointestinal stromal tumour (GIST) has been immunohistochemically defined as the tumour lacking differentiation towards either leiomyomatous tumour or schwannoma. We report a 75-year-old man who underwent an abdominoperineal resection of a large submucosal tumour of the rectum. The excised specimen was revealed to be an elastic soft tumour, 8 x 7 x 6 cm in size, which histologically consisted of spindle-shaped cells without nuclear atypia. The mitotic count was fewer than 2 per 10 high-power fields. The tumour cells were positive for staining of CD34 and c-kit protein, while the lesions were negative for alpha-smooth muscle actin, HHF-35, neuron-specific enolase, and S-100 protein. The diagnosis of GIST was confirmed by immunohistochemical examination of the tumour. From these findings, the present case is thought to be potentially malignant, and a long-term follow-up observation is needed for the case.

Increased in situ expression of nitric oxide synthase in human colorectal cancer.

There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

Rectal adenocarcinoid with lymph node metastasis.

We describe a case of a rare variant of a rectal carcinoid tumor that showed mucous gland differentiation accompanied by a lymph node metastasis with a histological appearance similar to that of the primary site. The tumor consisted of a typical argyrophilic carcinoid component and of goblet cell glands. The carcinoid component was positive for neuron-specific enolase, chromogranin A and synaptophysin. The goblet cells stained positively with periodic acid-Schiff (PAS) and alcian blue, and expressed carcinoembryonic antigen, but were negative for neuroendocrine markers. This case suggests that carcinoid tumor can differentiate towards mucus glands, which can also be found in the metastatic site.

Immunohistochemical assessment of proliferative activity in mammary adenomyoepithelioma.

AIMS: Two cases of adenomyoepithelioma of the breast were examined by immunohistochemistry to evaluate proliferative activity of epithelial and myoepithelial components. METHODS AND RESULTS: The tumours showed a bicellular pattern of gland-forming epithelial cells and proliferative myoepithelial cells with clear cytoplasm. They showed foci of monotonous growth of myoepithelial cells devoid of glands with low mitotic rate (1-2/10 high-power fields) and mild cytological atypia. Immunohistochemically, the glandular cells were positive for epithelial membrane antigen, cytokeratin (KL-1 and CAM5.2) and carcinoembryonic antigen, whereas tumour cells with clear cytoplasm were reactive with muscle-specific actin (MSA), alpha smooth muscle actin, vimentin, and S100 protein but negative for desmin. Proliferative activities assessed by MIB-1 (Ki-67)/MSA positive cell index were greater in myoepithelial cells in both cases (19.2% and 17.7%) as compared to those in epithelial cells (MIB-1/CAM5.2 index: 10.2% and 9.5%). CONCLUSIONS: These results might account for the previous findings that myoepithelial components predominate over the epithelial ones in an advanced stage of this tumour as well as in recurrent or metastatic lesions.

Crystalloid formation in gastrointestinal schwannoma.

We found intracytoplasmic crystalloids in two of six cases (33.3%) of gastrointestinal (GI) schwannomas. The crystalloid inclusions were periodic acid-Schiff (PAS) positive with diastase-resistance and stained blue with Masson's trichrome. They were needle-shaped and about 1 to 15 microm in length at microscopic levels. They had varying electron density revealed by electron microscopy and some of them showed distinct lattice structure with periodicity of about 9 nm. Survey of soft tissue schwannomas (n = 20) and S-100-negative GI stromal tumors (n = 41) did not detect such crystalloids. Although the origin and differentiation of GI stromal tumors (GISTs) have been a source of controversy, these intracytoplasmic crystalloids may be a marker for Schwann cell differentiation in some GIST.

Expression of nitric oxide synthase in macula densa in streptozotocin diabetic rats.

Renal haemodynamic changes are suggested to be an early sign of diabetic glomerulopathy. The juxtaglomerular apparatus relevant to the renin angiotensin system, known to be the site of nitric oxide (NO) production, is considered to play a role in the regulation of glomerular blood flow. This study was therefore designed to clarify whether in situ expression of nitric oxide synthase (NOS) is altered in the kidney of diabetic rats. Streptozotocin-induced diabetic rats with 6, 8, 12 and 32 weeks diabetes duration and age-matched normal control rats were used. The expression of a constitutive form of NOS (cNOS, neural type) and NADPH diaphorase activity in the renal cortex were studied immunohistochemically and histochemically. Diabetic rats had lower body weight and heavier kidney mass compared to control rats at each time point examined. Mean glomerular surface area was greater in 6, 8 and 12-week diabetic rats compared to age-matched control rats. cNOS reaction was localized in the macula densa and appeared less intense in diabetic rats compared to age-matched control rats. The mean number of macula densa cells positive for cNOS in each glomerulus and in each glomerular area was significantly lower in diabetic rats compared to control rats at any time examined. In contrast, NADPH diaphorase activity was detected in both juxtaglomerular arterioles and macula densa cells. The staining reaction of NADPH diaphorase in the arterioles remained positive but appeared less intense in macula densa cells in diabetic rats. These results suggest that NO production in macula densa cells may be reduced in diabetic rats, modulating the vasodilatory function of afferent arterioles. Further investigation on the changes in inducible NOS as well as endothelial cNOS are necessary to clarify mechanisms of haemodynamic changes in the diabetic kidney.

[A randomized controlled study of post-operative adjuvant therapy in non-small cell lung cancer].

The efficacy of postoperative adjuvant chemo- and chemoimmunotherapy in non-small cell lung cancer was evaluated in a multicentric prospective randomized study. From September 1987 to June 1990, resected lung cancer patients were randomly stratified into three groups. Group A received 2 courses of chemotherapy with CDDP and VDS following operation. Group B was administered UFT daily for 1 year after 2 courses of CDDP. Group C received intrapleural administration of OK-432 after lung resection, then UFT and OK-432 once every 2 weeks for 1 year. Out of 94 cases, analyses were carried out on 87 of eligible cases. The five-year survival rate was 56.8% in stage I (43 cases), 73.3% in stage II (12 cases), 18.8% in stage IIIA (24 cases), 50% in stage IIIB (2 cases) and 33.3% in stage IV (6 cases). The five-year survival rate in group A was 32.2%, 55.2% in group B and 53.9% in group C, and no statistical difference was recognized between 3 groups. But in the cases of noncurative resection, the 5-year survival rate was significantly low in group A compared with Group B or C. Similarly, the cases with low-grade TP (<6.0 g/dl) or low response of PPD skin reaction (< 12mm) showed a significantly low 5-year survival rate only in group A. From these results, it was suspected that aggressive chemotherapy provides no benefit for postoperative lung cancer patients with advanced disease.

Transient abnormal myelopoiesis accompanied by hepatic fibrosis in two infants with Down syndrome.

Two necropsy cases of Down syndrome are reported. These showed transient abnormal myelopoiesis accompanying characteristic hepatic sinusoidal fibrosis. Numerous megakaryocytes were found in the liver of one case, but not in the other. Only eight cases of Down syndrome with simultaneous occurrence of hepatic fibrosis and transient abnormal myelopoiesis have been reported. The cases described here showed slight fibrotic changes in the hyperplastic bone marrow, which were not found in the previously reported cases of transient abnormal myelopoiesis.

Cystic pancreatic glucagonoma in contact with insulinoma found in a hypoglycemic patient.

Cystic glucagonoma in contact with insulinoma was found in the pancreas of a 28-year-old female patient with characteristic hypoglycemic syndrome. Among six tumors in total detected in the tail of the resected pancreas, the largest solid tumor (2.5 cm in diameter) consisted mostly of insulin-containing cells with conspicuous amyloid deposition. Contiguous to this tumor, the second largest nodule, measuring 1.8 cm in diameter, showed cystic changes and consisted of glucagon-containing cells. High concentration of immunoreactive glucagon was demonstrated in the cystic fluid. In addition to the cystic changes of endocrine pancreatic tumors, simultaneous occurrence of glucagonoma in contact with insulinoma appears to be extremely rare and repeated episodes of hypoglycemia may contribute to its pathogenesis.

Effect of aminoguanidine on functional and structural abnormalities in peripheral nerve of STZ-induced diabetic rats.

Nonenzymatic glycosylation of structural proteins and the formation of advanced glycosylation end products (AGEs) have been involved in the pathogenesis of diabetic complications. We examined the effect of aminoguanidine, a potent inhibitor of AGE formation, on functional and structural abnormalities in peripheral nerve of streptozocin-induced diabetic rats. Diabetic rats were treated with daily injections of 25 mg/kg body wt s.c. aminoguanidine (AG)-sulfate for 16 wk and compared to untreated diabetic rats. AG treatment improved motor nerve conduction velocity in 12- and 16-wk diabetic rats despite no changes in body weight, blood glucose, and HbAIc levels. AG treatment inhibited an accumulation of fluorescent AGE in diabetic nerves, and morphometric analysis of the sural nerve showed a partial effect on myelinated fiber size and axonal atrophy. These findings suggest that AG may have a beneficial effect on diabetic neuropathy and nonenzymatic glycosylation of peripheral nerve proteins.

Primary alveolar soft-part sarcoma of stomach.

A case of primary gastric alveolar soft-part sarcoma is presented. The tumor was found in the gastric remnant of a 67-year-old male who had undergone partial gastrectomy due to hemorrhagic gastric ulcer 13 years before. It was located mostly in the submucosa arising from the muscularis propria. The large eosinophilic cells showed the characteristic alveolar compartmentalization and contained intracytoplasmic periodic acid-Schiff-positive granules and typical crystals. Numerous electron-opaque secretory granules in the tumor cell cytoplasm, in addition to crystals of 9 nm periodicity, were confirmed at the ultrastructural levels. Immunostaining failed to detect muscle-related antigens. In contrast, methionine-enkephalin and neuropeptide Y appeared positive in the tumor cells. Interstitial spindle cells showed an occasional positivity to S-100. This is the first case of such a tumor occurring in the gastrointestinal tract, and the findings suggest that gastric alveolar soft-part sarcomas may have a different origin from those arising in the skeleton.