Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

Extremely Well Differentiated Papillary Adenocarcinoma of the Lung with Prominent Cilia Formation

We describe a 54-year-old woman with primary pulmonary adenocarcinoma showing a characteristic papillary architecture and prominent cilia formation. Immunohistochemically, the tumor cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and Leu Ml, and negative for lactoferrin and surfactant apoprotein. An ultrastructural study also indicated differentiation toward bronchial surface epithelial cells. To our knowledge, this type of neoplasm has not been reported as peripheral-type adenocarcinoma of the lung. Acta Pathol Jpn 42: 745–750, 1992.     

Squamous cell carcinoma of the thyroid--a report of three cases

Three cases of squamous cell carcinoma of the thyroid are reported herein. In all cases, the carcinoma occurred in old age and was characterized by a rapidly growing tumor, usually associated with dyspnea and dysphagia. The prognosis of all 3 cases was poor, with a mean survival of only 6.3 months. Although squamous metaplasia is an accepted etiology of this disease, clinical investigation of the cases presented here does not favor it in consideration of the clinical features of papillary carcinoma of the thyroid with squamous metaplasia. The histological findings of our cases revealed areas of cystic formation, suggesting that some of these carcinomas may be derived from remnants of embryonic origin.     

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.     

Refractory hemolytic uremic syndrome improved by plasmapheresis using cryosupernatant fraction as a replacement fluid: A case report

A 52-year-old woman who had had 6 months of chemotherapy using mitomycin C and cisplatin for cervical cancer presented with hemolytic uremic syndrome. Conventional plasmapheresis using whole-plasma fraction was ineffective. However, plasmapheresis using the cryosupernatant fraction dramatically improved symptoms of hemolytic anemia and thrombocytopenia in this case. The activity of factor VIII in the cryosupernatant fraction of plasma as a replacement fluid decreased after removal of cryoprecipitate, indicating effective removal of von Willebrand factor. The pathogenesis of her hemolytic uremic syndrome may have been associated with von Willebrand factor multimers contained in the cryoprecipitate of plasma. Similar use of the cryosupernatant fraction of plasma could not be found in other reports of cases of hemolytic uremic syndrome. Plasmapheresis using the cryosupernatant fraction of plasma may improve refractory hemolytic uremic syndrome.     

Hepatic infarction with portal thrombosis

A case of hepatic infarction with portal thrombosis is reported. A 63-year-old woman with liver cirrhosis and esophageal varices was admitted for treatment of the esophagel varices. Endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) were performed. Two months later, she experienced right hypochondralgia and right flank pain. Serum transaminase levels were suddenly elevated, and computed tomography scans of the liver showed multiple small nodular lesions. Her condition worsened, and she died of hepatic failure. Autopsy revealed splenic and portal vein thrombosis, multiple hepatic infarction, and evidence of chronic pancreatitis. We believe that liver cirrhosis and chronic pancreatitis were the main risk factors for the portal thrombosis, and the treatment for esophageal varices appeared to have triggered the thrombosis. The hepatic infarction was caused by the portal thrombosis.     

Long-term follow-up studies in 211 patients with tetralogy of Fallot after corrective surgery over 10 years

A total number of 427 patients with tetralogy of Fallot who underwent corrective surgery between 1960 and March 1990, in whom 211 patients who survived the surgery over 10 years were evaluated for the follow-up studies. Hemodynamic and cardiac function studies were carried out in 101 patients at the mean interval of 15.7 years (ranges 2 to 21 years). Three methods indicated that patients with muscle resection and pulmonary valvulotomy without patch enlargement (NP) had worse results than the groups with RV patch below valve (RP) and with transannular patch (TP). Also, Holter ECG revealed ventricular arrhythmias in patients with NP were more common than the groups with RP and TP. Sixteen patients (13 with NP, 2 with TP and one with RP) were required reoperation for residual ventricular shunt in 13, residual pulmonary stenosis in 11 and tricuspid regurgitation in 2. All of these 16 patients survived operation and obtained excellent clinical status. It is concluded that patients with TOF after corrective surgery should be carefully followed with short term interval to prevent sudden death and postoperative complications.     

Clinicopathologic and mucin histochemical analyses of 90 cases of ovarian mucinous borderline tumors of intestinal and müllerian types

Clinicopathologlc and mucin histochemical characteristics of 90 cases of ovarian mucinous borderline tumors (MBT) of Intestinal (IMET) and müllerian types (MMBT) were studied to determine whether IMBT and MMBT constitute distinct tumor subtypes. The IMBT (77 cases, 78 lesions) contained goblet cells, absorptive cells and endocrine cells, which represented Intestinal differentiation. The average diameter of IMBT was 13.4 cm. Five patients (6.5%) had stage III disease wtth pseudomyxoma perltonel and one of them died from tumor. Approximately 50% of IMBT demonstrated gastrointestinal characteistics on mucin histochemistry. The MMBT (13 cases, 14 lesions) consisted of mumus columnar cells and eosinophilic cells, with no Intestinal differentiation. MMBT accounted for 15.2% of MBT. MMBT averaged 8.4 cm in diameter, and 29% were associated with endometriosls of the ipsilateral ovary. All patients with MMBT had stage I disease, and none suffered from pseudomyxoma peritonel. All patients whose follow-up data were available were alive and well, without evidence of tumor recurrence. The mucin histochemical findings in MMBT resembled those of noml endocervix. Results of the present study suggest that IMBT and MMBT have different characteristics and constitute distinct subtypes of MBT.     

Development of GFAP-positive cells and reactive changes associated with cystic lesions in HTX rat brain.

HTX rat, a congenital hydrocephalic strain, develops ventricular dilatation and cystic cavities in the cerebral white matter after birth. To investigate the reactive changes in glial cells around these cavities, immunohistochemical staining for glial fibrillary acidic protein (GFAP), a specific marker protein of astrocytes, and bromodeoxyuridine (BrdU), a thymidine analogue, was carried out on 107 Wistar and HTX rat brains from birth to postnatal day (P) 26. Animals were divided into three groups: Group A, Wistar rats as normal controls; Group B, HTX rats with a normal structure or only mild ventricular dilatation without any lesion in the white matter; and Group C, HTX rats with severe ventricular dilatation and cyst formation in the white matter. Group B rats showed similar development of GFAP-positive (GFAP+) cells to that in Group A rats, both morphologically and quantitatively. On the other hand, Group C rats showed definite structural changes in GFAP+ cells around the cystic cavities from P5. These included enriched cytoplasm and thickened cell processes with increased GFAP expression, and enveloped most cyst walls from P10. However, quantitative examination of the percentage of GFAP+ cells in Group C rats showed a similar developmental profile to those in Group A and B rats. Furthermore, the labeling index of BrdU-positive cells, indicating S-phase cells, in the white matter in Group C rats showed a similar decreasing pattern to that in Group A and B rats from P1 to P26.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anorexia nervosa with neutropenia--response of neutrophils to G-CSF]

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.