Pathological study of naturally occurring adenocarcinomas demonstrating differentiation in ducks.

Case 1, a mucinous adenocarcinoma, was in the pancreas of a 5-year-old male mandarin duck. The tumour comprised a single layer of duct-like structures with abundant fibrous stroma. The neoplastic cells produced a large amount of mucin, and dense or moderately dense mucin granules were observed ultrastructurally. Case 2 was a 1-year-old male mandarin duck, which had a type II pneumocytoid carcinoma within the thoracic air sacs. Light microscopy revealed papillary growths composed of stratified neoplastic epithelium. At the ultrastructural level, the tumour cells had osmiophilic lamellar granules in the cytoplasm. Case 3, a ciliated cell adenocarcinoma with squamous metaplasia, was detected in the right lung of a 2-year-old male domestic duck (Anas platyrhynchos forma domestica). The neoplasm consisted of tubular structures with areas of squamous differentiation in places. The presence of cilia was confirmed by electron microscopy. The three adenocarcinomas appeared high-grade or moderate-grade malignant tumours in some aspects, but showed granules or cilia that are suggestive of their origin. The presence of cells retaining the capacity for differentiating into well-differentiated cells may be characteristic of sporadically occurring avian adenocarcinomas.

Clinical characterization of a case with familial hypobetalipoproteinemia caused by apo B-76, a new truncation of apolipoprotein B, combined with apo E2/E2 phenotype.

We report a 43-year-old Japanese man with hypobetalipoproteinemia likely due to apolipoprotein (apo) B-76, a new truncation of apo B, and with homozygosity for the apo E2 isoform. He had no history suggestive of fat malabsorption and no sign of neurological disorder. His fasting baseline serum low-density lipoprotein (LDL) cholesterol and apo B levels were approximately half of normal. His plasma apo E level was elevated and its phenotype showed the E2/E2 homozygote. SDS-polyacrylamide gel electrophoresis of delipidated LDL fraction revealed a new truncated apo B, designated as apo B-76 according to the centile system of nomenclature. The postprandial lipid metabolism of the patient showed an almost normal response after fat loading.

Serum uric acid and renal prognosis in patients with IgA nephropathy.

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.

Effect of apolipoprotein E3/4 phenotype on postprandial triglycerides and retinyl palmitate metabolism in plasma from hyperlipidemic subjects in Japan.

In a previous study it was shown that postprandial lipid metabolism is delayed in individuals with intra-abdominal visceral fat accumulation. Population studies have shown that as compared with individuals with apolipoprotein (apo) E3/3, those with phenotype apo E3/4 phenotype have higher plasma and low density lipoprotein (LDL)-cholesterol (C) concentration and increased susceptibility to coronary heart disease. The aim of the present study is to determine how apo E4 affects postprandial lipid metabolism by comparing individuals with apo E3/4 to those with apo E3/3 phenotype matched for abdominal visceral fat. Sixty-two Japanese subjects (41 male, 21 female) [average age 48+/-14 years; mean body mass index (BMI) 25+/-5.6 kg/m2] were recruited for this study. The subjects were divided into two groups: those with apo E3/3 (n=43) and those with apo E3/4 phenotype (n=19), as determined by isoelectric focusing (IEF). Visceral fat accumulation was analyzed as area of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fasting, an oral vitamin A and a fatty meal were administered to these subjects. The plasma triglyceride (TG) increased significantly hours after fat loading in both groups but the levels of TG were significantly higher in apo E3/4 than in apo E3/3 phenotype at 2, 4 and 6 h after fat loading. Plasma retinyl palmitate (RP) levels were also significantly higher in individuals with apo E3/4 than in those with apo E3/3 phenotype at 2, 4 and 6 h after fat loading. This investigation was then conducted in both genders separately, and found that these associations were statistically significant in men. Furthermore, after matching men for fasting TG levels, these associations did not persist for plasma TG levels at any time point, while plasma RP levels were still significantly higher in apo E3/4 group at 2 and 6 h after fat loading. These results indicate that in Japanese population especially for men apo E phenotype E3/4 is associated with an impaired postprandial TG-rich lipoprotein metabolism relative to apo E3/3 phenotype when matched for intra-abdominal visceral fat accumulation, which has a substantial effect on the metabolism of plasma TG-rich lipoproteins.

Immunohistochemical study of Pneumocystis carinii infection in pigs: evaluation of Pneumocystis pneumonia and a retrospective investigation.

Infection with Pneumocystis carinii was demonstrated immunohistochemically in the lungs of pigs 15 to 75 days of age from a herd with epidemic pneumonia due to the organism. The distribution of the organism was centered on the airways, and extended progressively with age from the alveolar ducts to the alveoli. In a retrospective immunohistochemical study of 245 newborn to adult pigs which were necropsied between 1988 and 1995, P carinii infection was found in 87 pigs (35.5 per cent) aged between 17 days to seven months. In the pigs aged between one and three months the infection rate was 63.1 per cent. Pigs from herds in which suckler and weaner pigs shared the same air space were more heavily infected than those from the herds in which they were reared separately. There were no regional or seasonal variations in the level of infection, and the infection was not associated with any single disease.

Marked elevation in serum apolipoprotein E in a case of heterozygous cholesteryl ester transfer protein deficiency.

The subject was a 57-year-old Japanese woman with a body mass index of 21.2 kgm(-2). Her serum total cholesterol (TC), triglycerides (TG) and HDL-cholesterol levels were 7.11 mmoll(-1), 0.53 mmoll(-1) and 2.05 mmoll(-1), respectively. She had a marked increase of serum apolipoprotein (Apo) E concentration of 25 mgdl(-1) with normal concentrations of serum Apo A-I, A-II, B, C-II and C-III. Polymerase chain reaction-restriction fragments length polymorphism analysis of the cholesteryl ester transfer protein (CETP) gene from this subject revealed the heterozygous nucleotide change causing a Asp442 to Gly substitution (D442G) in the CETP protein. For comparison, 11 unrelated female subjects with this mutation (age, 57+/-5.1 years; BMI, 22+/-1.5 kgm(-2); TC, 7.23+/-1.16 mmoll(-1); TG, 1.44+/-0.80 mmoll(-1); HDL-C, 2.47+/-0.53 mmoll(-1)) were found to have a serum Apo E concentration of 7+/-1.5 mgdl(-1), about a third of the patient's concentration. The lipoprotein profile of the proband's serum analyzed by disk polyacrylamide gel electrophoresis showed a trace amount of VLDL. A vitamin A fat-loading test showed little increase in serum triglycerides and retinyl palmitate levels compared with control subjects at 2, 4 and 6 h after fat loading. Ultracentrifugation analysis of her serum revealed no detectable Apo E in the VLDL fraction but showed a large amount of Apo E in the HDL fraction, in contrast to a normal control, who had Apo E in the VLDL fraction as well as in the HDL fraction. Sequence analysis of the Apo E gene from the subject showed no nucleotide changes in exon 3 and exon 4, which code the mature Apo E protein, indicating there is no structural abnormality in the Apo E protein. Direct sequence analysis of the LDL receptor gene also did not show any nucleotide change. Based on these findings, it was hypothesized that the marked increase of Apo E in the patient's serum was caused by a decreased transfer of Apo E from HDL particles to TG-rich lipoproteins or impaired uptake of Apo E-containing HDL by LDL receptor or remnant receptor, due presumably to a dysfunction of these receptors in the patient.

Differential expression of lipoprotein lipase gene in tissues of the rat model with visceral obesity and postprandial hyperlipidemia.

Postprandial hyperlipidemia is frequently accompanied with intra-abdominal visceral accumulation in human subjects. We have found that the decreased lipoprotein lipase (LPL) mass and activity is negatively associated with the amount of visceral fat accumulation. Here, we studied the postprandial hyperlipidemia using the OLETF rat, a model with visceral obesity, in order to clarify the molecular mechanism causing postprandial hyperlipidemia accompanied with visceral obesity. At the same age of 32 weeks, the OLETF rats showed obviously higher plasma leptin, total cholesterol, triglyceride, and HDL-cholesterol levels than the control LETO rats, although the plasma glucose level was not significantly different. Fat-loading test revealed the delayed metabolism of exogenous fat in the OLETF rats compared to the LETO rats, similar to human subjects with visceral obesity. In the obese rats, plasma levels of LPL mass and activities were 60 and 49% of control rats. The expression of LPL gene was decreased in subcutaneous adipose tissues and skeletal muscle of OLETF rats to 40 and 52% compared to those of LETO rats. In OLETF rats, plasma tumor necrosis factor-alpha (TNF-alpha) and insulin levels were increased to 2.0- and 2.3-folds compared to those in control rats. Furthermore, plasma insulin and TNF-alpha levels in OLETF rats were negatively correlated with the expression levels of LPL gene in subcutaneous fat and muscle. These results indicate that decreased LPL mass and activity in the animal model with visceral obesity is possibly caused by decreased expression of LPL gene in tissues mediated by the increased levels of insulin and TNF-alpha. The different expression of LPL gene in tissues associated with the increased levels of insulin and TNF-alpha possibly elucidate the underlying mechanisms involving the postprandial hyperlipidemia observed in visceral obesity.

Intestinal spirochetosis in wild sika deer (Cervus nippon yesoensis) infected with Brachyspira species.

Seven adult free-ranging sika deer (Cervus nippon yesoensis) were examined by histology, immunohistochemistry and electron microscopy for intestinal spirochetal infection. Histologically epithelial and goblet cell hyperplasia and edema of the lamina propria mucosa with macrophage and lymphocyte infiltration were observed in the cecum and colon in 6 of the 7 deer. Numerous argyrophilic spirochetes were present in the crypts and some had invaded epithelial and goblet cells and caused degeneration. Immunohistochemically the organisms stained positively with polyclonal antisera against Brachyspira (Serpulina) hyodysenteriae and B. pilosicoli. Ultrastructurally they were 6-14 microm long, 0.2-0.3 microm wide and had 4-6 coils and 13 axial filaments per cell; such features were closely similar to those in the Brachyspira species. These results showed that the spirochetes were capable of inducing enteritis in deer and this intestinal spirochete infection might already be prevalent among wild sika deer in Japan. There is a possibility that this spirochetal colitis is a new syndrome in sika deer and that the same and/or similar spirochetes have infected ruminants, including sika deer and cattle.

Differential regulation of leptin receptor expression by insulin and leptin in neuroblastoma cells.

Leptin exerts its effects by interacting with specific membrane receptors (Ob-R). We studied the exact localization of long intracellular domain form (Ob-Rb) in human brain. In addition, we analyzed the regulatory features of Ob-Rb expression in two neuroblastoma cell lines. The Ob-Rb mRNAs were abundant in putamen, frontal lobe, medulla, cerebral cortex, cerebellum, thalamus, hippocampus, corpus callosum, caudate nucleus, and amygdala, indicating that Ob-Rb transcripts are expressed differently from that of other Ob-R isoforms. In SK-N-MC cells, the expression of Ob-Rb mRNA was induced by increasing doses of insulin, and the maximum amount of mRNA expression was 9.4-fold higher in the presence of insulin (100 nM for 24 h), compared to the absence of insulin. In IMR32 cells, the transcripts were increased 4.0-fold when cells were incubated with 1 nM of insulin for 48 h. In contrast, Ob-Rb expression in IMR32 cells decreased to 18% of control following a 24-h incubation period with 50 ng/mL of leptin, compared to incubation in the absence of leptin. These results indicate that expression of Ob-Rb is differentially regulated by inhibitory signals of energy balance in neuroblastoma cells. The identification of the novel regulatory mechanisms involving the Ob-Rb isoform by insulin and leptin now makes it possible to elucidate the underlying mechanisms involving increased food intake and uncontrolled energy balance associated with leptin resistance in obese individuals.

New high performance SAW convolvers used in high bit rate and wideband spread spectrum CDMA communications system.

New surface acoustic wave (SAW) convolver structures with high conversion efficiency and self-temperature compensation characteristics have been developed. Strong piezoelectric substrates, regardless of temperature coefficients of delay (TCD), can be used in these convolvers. New demodulation techniques using the developed SAW convolver for high bit rate and wideband spread spectrum code division multiple access (CDMA) communications have also been developed. I- and Q-channel demodulation data can be derived directly from binary phase shift keying (BPSK) or quadri-phase shift keying (QPSK) CDMA signals. In an experiment using a 128 degrees YX-LiNbO(3) substrate, CDMA signals of 9 Mbps (megabits per second) with 60 Mcps (megachips per second) spread by 13-chip Barker code and 11 Mbps with 140 Mcps spread by 25-chip Shiba's code were clearly demodulated, demonstrating the effectiveness of these techniques for use in future CDMA communications.

Myofibroblastoma of the neck in a heifer.

A 1.5-year-old Holstein heifer had a subcutaneous tumor mass (20 cm diameter) on the ventral portion of the neck, and the tumor was diagnosed as a locally invasive myofibroblastoma. It consisted of moderately cellular fibrous tissue, and the interlobular septum of the thymus was invaded by tumor cells. The neoplastic cells were positive for alpha smooth muscle actin and vimentin, but not for desmin. Electron microscopy disclosed the presence of moderately developed rough endoplasmic reticulum and microfilaments with focal densities.

A novel frameshift mutation in exon 6 (the site of Asn 291) of the lipoprotein lipase gene in type I hyperlipidemia.

A new heterozygous lipoprotein lipase gene defect has been identified in a type I hyperlipidemic patient at the position of notable amino acid Asn 291. The patient is a 33-year-old male. His body mass index (BMI) was 18.5 kg/m2. The total cholesterol (TC), triglycerides (TG) and high density lipoprotein-cholesterol (HDL-C) concentration from his fasting plasma were 4.8, 11.9 and 0.4 mmol/l, respectively. The lipoprotein lipase (LPL) activity and mass in the postheparin plasma (PHP) from the patient were 0.58 mmol/ml/h (normal range: 7.7+/-2.6) and 244 ng/ml (normal range: 192+/-30), respectively. The hepatic lipase activity of the PHP from the patient was 10.6 mmol/ml/h (normal range: 9.9+/-3.6). DNA analysis of the LPL gene revealed that this patient had a heterozygous one nucleotide deletion of A coding Asn 291, resulting in a premature termination of the LPL protein at amino acid residue 303. The other abnormality in the LPL gene of the proband was an amino acid residue 194 defect (Ile194-->Thr), which is known to cause a defective enzyme. A medium-chain triglyceride (MCT) loading test was conducted to find how this triglyceride affects plasma lipoprotein metabolism in this patient in a short term (Fig. 3). The plasma total cholesterol (TC) or high density lipoprotein (HDL)-C levels did not change significantly after oral administration of a fatty meal containing long chain triglycerides (LCT) or MCT. The plasma TG level, on the other hand, increased from 11.9 to 19.2 mmol/l (+61%) at 6 h after loading a fatty meal containing LCT, whereas the plasma TG levels tended to even decrease at 6 h after oral administration of an MCT, tricaprin (from 11.6 to 10.5 mmol/l (-9.4%)). These results suggest that MCT, as opposed to LCT, is useful for treatment of type I hyperlipidemia with a novel mutation at the notable amino acid Asn 291 of the LPL gene.

Delayed post-prandial lipid metabolism in subjects with intra-abdominal visceral fat accumulation.

BACKGROUND: Individuals with obesity, in particular those with intra-abdominal visceral fat accumulation, are known to have various complications, such as hyperlipidaemia, impaired glucose tolerance, hyperinsulinaemia and hypertension, leading to the development of coronary heart disease. Post-prandial hyperlipidaemia has repeatedly been shown to be an independent risk factor for coronary heart disease. The aim of the present study was to investigate post-prandial lipoprotein metabolism in subjects with excessive visceral fat accumulation. MATERIALS AND METHODS: Eighty-three patients (52 men, 31 women) [average age 48 +/- 14 years; mean body mass index (BMI) 25 +/- 5 kg m-2] were recruited to the study. Visceral (or subcutaneous) fat accumulation was analysed as areas of fat deposition by computerized tomography at the umbilicus level. After a 12-h overnight fast, oral vitamin A and a fatty meal (40 g m-2 fresh cream containing 50 000 units m-2 vitamin A) were administered to these subjects. The concentration of retinyl palmitate (RP) was measured by high-performance liquid chromatography. RESULTS: The visceral fat area (V) was positively correlated with plasma triglyceride (TG) 0, 2, 4 and 6 h after fat loading and with plasma RP 0, 4 and 6 h after fat loading. The BMI did not show any correlation with plasma TG and RP at any point. The visceral fat area was positively correlated with the RP area under the curve (AUC) in the serum from the subjects [V vs. RP AUC: n = 83, r = 0.327, P = 0.013]. The BMI of the subjects did not show any correlation with the RP AUC (r = 0.021, P = 0.85). CONCLUSION: These results suggest that post-prandial lipid metabolism is impaired in subjects with intra-abdominal visceral fat accumulation, irrespective of BMI, leading to the development and progression of coronary atherosclerosis.

Effect of troglitazone on plasma lipid metabolism and lipoprotein lipase.

AIMS: To clarify how troglitazone, an insulin-sensitizing agent, affects lipid metabolism and postheparin plasma lipoprotein lipase (LPL). METHODS: Fifteen patients (3 male, 12 female) (the average age 62+/-7 years; the mean body mass index (BMI) 25+/-3 kg/m2 ) were recruited for this study. The serum lipids and postheparin plasma lipoprotein lipase (LPL) mass before and 4 weeks after oral administration of troglitazone (200 mg day-1 ) were measured. A mouse preadipocyte cell line, 3T3-L1, was incubated with troglitazone and LPL enzyme protein mass in the culture media was measured by an enzyme linked immunosorbent assay. A reverse transcription polymerase chain reaction (RT-PCR) using primers specific for the carboxyl terminal 135 amino acid of mouse LPL cDNA was used to evaluate the effect of troglitazone on expression of LPL and Northern blot analysis carried out to determine expression of LPL. RESULTS: The average levels before treatment of fasting serum total cholesterol, triglycerides, high density lipoprotein cholesterol, plasma glucose and glycohaemoglobin A1c were 5.6+/-0.9, 1.8+/-1.0, 1.5+/-0.5, 8.1+/-1.7 mmol l-1 and 7.8+/-1.6% respectively. Four weeks after treatment, those levels were 5.4+/-0.9, 1.2+/-0.3 (P=0.004), 1.6+/-0.5 (P=0.02) mmol l-1, 7.7+/-2.3 mmol l-1 and 7. 3+/-0.6% (P=0.01), respectively. The postheparin plasma LPL mass increased from 226+/-39 to 257+/-68 ng ml-1 (P=0.03) during that period. The LPL mass in the media of 3T3 L1 cells cultured in the presence of 10, 20 or 30 microm of this compound increased in a dose dependent manner. RT-PCR revealed that the area of the bands of the RT-PCR products on 1.5% agarose gel analyzed with NIH image from the cell extracts cultured in the presence of 10 microm troglitazone was significantly larger (P=0.0069) than that in the absence of this compound. Northern blot analysis revealed that in the cultured 3T3-L1 cells, the expression of LPL was enhanced in the presence of 10 microm troglitazone. CONCLUSIONS: Troglitazone improves plasma triglyceride-rich lipoproteins metabolism by enhancing the expression of LPL in adipocytes.

Propagation characteristics of longitudinal leaky SAW in Al-grating structure.

New orientations for longitudinal leaky SAW with small propagation losses and high velocities in lithium niobate (LN) and lithium tantalate (LT) have been found. Their velocities are 6100 to 6500 m/s in LN and 5200 to 5800 m/s in LT. Their propagation losses are almost negligible only in the case of an Al-grating structure. For example, the Al thickness relative to the SAW wavelength must be 8.4% for 171 degrees YZ'-LN; for 133 degrees YZ'-LT, the value must be 9.2%. These propagation properties were obtained by using a simulator that combined both finite-element and analytical methods. These results were also well confirmed by measuring the impedance responses of one-port SAW resonators.

Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase manifesting as acute renal damage.

A 32-year-old man who had had frequent gouty arthritis over the past 17 years, was admitted for acute renal failure. Acute renal failure was improved rapidly after medication was resumed and the patient was sufficiently hydrated. The hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in the patient had been reduced to about 30% of the normal control. Therefore we considered that this patient suffered from a partial deficiency of HPRT. A point mutation of HPRT gene 68G (guanine) to T (thymine) was detected. This is a mutation that has not been previously reported. Familial analysis indicated that his mother and sister were heterozygotes.

Malignant insulinoma with extensive liver metastases presenting as disturbance of consciousness.

A 56-year-old man was referred to our hospital for evaluation of episodic disturbance of consciousness. Hypoglycemic symptoms were noted and Whipple's triad was satisfied. The 75 g OGTT and the glucagon test revealed a high baseline insulin level and hyperreactivity to glucagon. A pancreatic tumor and liver metastases were found by abdominal computed tomography (CT). Based on the finding of liver biopsy, the final diagnosis was malignant insulinoma with liver metastasis. He selected conservative treatment and no hypoglycemic crisis has occurred for one year since discharge. Early diagnosis and long-term follow-up is necessary since this tumor is slow growing.

[Renal damage in a chronic active hepatitis C patient receiving interferon-alpha therapy].

A 68-year-old male patient with chronic active hepatitis C was treated with interferon-alpha (IFN-alpha) for a period of 5 months. The patient responded well to the IFN therapy showing substantial improvement in liver function and disappearance of HCV-RNA. However, one year after the treatment he was found to have developed proteinuria and showed a reduction in Ccr. Renal biopsy findings were as follows: Light microscopy showed diffuse expansion of mesangial cells with a focal/local increase in cellularity accompanied by capillary loop thickening. Splitting of the basement membrane was also present. An immunofluorescent study showed that IgA was localized predominantly in the peripheral capillary wall. Electron microscopy showed that there was mesangial cell interposition between the peripheral capillary wall and endothelial cells. Furthermore, endothelial cells were expanded and numerous platelets were seen in the capillary lumen. These findings were compatible with focal MPGN accompanied by activation of endothelial cells. These histological data suggest two clinical disease entities: late-onset renal damage induced by IFN-alpha alone, and HCV-induced renal damage possibly modified by the direct effect of IFN-alpha on the endothelium. The present case suggests that IFN therapy for HCV may produce a particular type of renal damage, under the influence of either IFN or HCV infection, and/or both.

Acute renal failure after binge drinking of alcohol and nonsteroidal antiinflammatory drug ingestion.

A case of reversible acute renal failure (ARF) following binge drinking together with the transient use of a nonsteroidal antiinflammatory drug (NSAID) is described. After binge drinking. the patient experienced hyperdipsia, and the volume of his urine decreased. Subsequently, he took an NSAID to relieve systemic joint pain associated with low grade fever, and then he had complete anuria. One day after taking the NSAID, he visited our hospital, and was found to have severe renal dysfunction accompanied by severe liver damage (blood urea nitrogen and creatinine concentrations were 57 and 5.4 mg/dl, respectively). The impaired renal function progressed over the first three hospital days, as reflected by an elevated creatinine concentration to 11.6 mg/dl. Nine treatment sessions of hemodialysis were, therefore, required to recover the loss of renal function. The present case suggests that binge drinking may be a potential risk factor for ARF in the presence of NSAIDs.