Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.     

Hepatocellular carcinoma with sarcomatous change. Clinicopathologic and immunohistochemical studies of 14 autopsy cases

Among 355 autopsy cases of hepatocellular carcinoma (HCC), 14 cases exhibited sarcomatous appearance (incidence, 3.9%). A clinicopathologic study was performed in these 14 cases, and the immunohistochemical localization of keratin (KRT), vimentin (VMT), albumin (ALB), fibrinogen (FBG) and alpha-fetoprotein (AFP) was also examined using the avidin-biotin complex method. Clinically, the HCCs with sarcomatous appearance were characterized by negative or low serum AFP levels and high incidence of extrahepatic metastasis. Grossly they were of infiltrative, mixed expansive and infiltrative, and pedunculated types. Histologically, the tumor consisted mainly of spindle-shaped cells and partly of multinucleated cells, and showed a sinusoidal growth pattern at the tumor-nontumor boundary. Immunohistochemically, tumor cells in the regions showing sarcomatous appearance were frequently found to be positive to KRT and VMT, whereas the percentage of positivity to ALB, FBG, and AFP were not significantly different from those in ordinary HCC. These results strongly suggest that the lesion showing sarcomatous appearance represents the sarcomatous change of HCC rather than being regarded as the complication of HCC and sarcoma.     

Effects of medium-chain triglycerides on brush border membrane-bound enzyme activity in rat small intestine

The effects of various types of dietary fat on brush border membrane-bound enzymes in rat intestinal mucosa were examined. Four groups of five rats were pair-fed defined diets for 10 d. The control group was fed a diet containing 57% sucrose and 2% corn oil as a fixed carbohydrate reference; the three experimental groups received diets containing 57% sucrose and 2% corn oil plus 13% fat in the form of medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) (either lard as a highly saturated fat or corn oil as a highly unsaturated fat). Feeding LCT compared to the control diet, decreased sucrase activity in mucosal brush borders of the duodenum and jejunum. In these segments of MCT-fed rats, sucrase activity was similar to that in the control animals. In another experiment, measuring immunoreactive sucrase-isomaltase in jejunal brush border membranes revealed that feeding a high corn oil diet, but not a high MCT diet, led to a reduction in the sucrase catalytic activity per unit weight of enzyme protein, suggesting that the degradation status of sucrase-isomaltase might be altered by the different types of dietary fats. With MCT feeding, jejunal alkaline phosphatase activity was enhanced to a large extent compared to the activity in other groups. Feeding MCT, compared to lard or corn oil, also increased microvillus phospholipids of the jejunal mucosa. These results suggest that MCT, unlike LCT, do not suppress the activity of mucosal microvillus membrane enzymes in rat small intestine.     

Purification, properties, and developmental changes of cellular retinol-binding protein, type II, in chicken intestine

Two distinct cellular retinol-binding proteins were detected in chicken small intestine. A predominant form was purified to homogeneity. The apparent molecular weight of this protein was estimated to be 17,200. This form was larger than a second minor form partially purified (molecular weight of 15,000). The absorption and fluorescence spectra of the bound retinol to the purified proteins were typical for the known cellular retinol-binding proteins. The results suggest that the purified binding protein corresponds to CRBP(II), previously identified in small intestine of rats and humans. To gain an insight into the possible role of CRBP(II) in chicken small intestine, the CRBP(II) contents in cytosols of small intestine of embryonic and post-hatch chicks were determined by enzyme-linked immunosorbent assay. The amount of CRBP(II) per unit DNA in small intestine was low at 15- and 17-day embryonic stage, but rapidly increased around the period of hatching. The increased level was still maintained in 6-week-old chicks, which accounted for 0.9% of total proteins in duodenum. The developmental pattern and the presence of abundant amount of CRBP(II) in chicken small intestine supports the hypothesis that CRBP(II) might play some role in the intestinal absorption of retinoids. Thus the involvement of a tissue-specific cellular retinol-binding protein in the intestinal absorption of retinoids appears to be common in mammalian and avian species.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Axonal dystrophy in the posterior column nuclei of young adult epileptics with chronic phenytoin intoxication

Axonal spheroids in the posterior column nuclei of phenytoin-intoxicated epileptics were classified according to their predominant subcellular components into six types, and their incidences were compared with those in controls. Spheroids from phenytoin-intoxicated epileptics showed significantly higher proportions of the tubulomembranous (TM) and layered membrane loop (LML) types in the gracile nucleus, appearance of the same types in the cuneate nucleus, and a significant decrease of the neurofilamentous (NF) type in both nuclei. The incidences of the complex body (CB) and granular material types and of the homogeneous dense-body (HDB) type, which appeared only in the gracile nucleus, showed no difference between the intoxicated patients and the controls. The NF, CB and HDB types were therefore considered to be nonspecific. It was thought that chronic phenytoin intoxication might induce dystrophic changes, such as those characterized by the presence of the TM and LML types, in the axon terminals of the gracile and cuneate nuclei, possibly due to some abnormalities of the axoplasmic transport system.     

Establishment and morphologic characterization of a cell line (DMBA-OC-1) from 7,12-dimethylbenz(a)anthracene-induced rat ovarian carcinoma

A new cell line (DMBA-OC-1) from 7,12-dimethylbenz (a) anthracene (DMBA) which induced ovarian carcinoma in rat was established and characterized. DMBA-OC-1 cells showed a paving-stone-like growth pattern at around the 10th to 20th passage, but at the point exceeding the 40th passage the cells showed a spindle form, having strong trends both towards flocculation and piling-up. Furthermore, diastase-resistant PAS-positive and hyaluronidase-digested Alcian blue positive substances were observed in cytoplasms. The cells also showed marked phagocytic activity. These findings suggest that DMBA-OC-1 cells are most likely the site of mesothelial cell origin.     

An autopsy case of Degos disease with neurological symptoms--neuropathological observations and increased platelet aggregation]

We reported clinical and neuropathological observations of a 41-year-old man with Degos disease. He first noted painless skin lesions over the upper extremities in January, 1982. Three years later he was diagnosed as Degos disease by skin biopsy, and treatment with aspirin was started. In September, 1985, he complained of paresthesia on his right arm, followed by a series of new neurological manifestations suggesting multifocal spinal cord lesions. On October 28, examination of admission showed papules with central umblication over the whole body except the head, face, palms, soles and scrotum. Neurological examination revealed no weakness, diminished right biceps reflex, exaggerated patellar reflexes and Achilles reflexes, left extensor plantar reflex, hypesthesia and hypalgesia to the level of Th8, mild left spastic gait, and retention of urine. In November, he had paraparesis, loss of vibration sense of lower extremities, hypesthesia and hypalgesia to the level of TH4, and weakness of right upper extremity. In December, he showed tetraplegia, left-sided facial palsy, and hypesthesia and hypalgesia to the level of C5. In January, 1986, he showed right facial palsy, left facial hypesthesia, pseudobulbar palsy. In February, he had bilateral abducens nerve palsy and hiccups. On February 18, he died of intracranial hemorrhages. He had episodic abdominal pain several times during admission. His condition deteriorated progressively in four months after the first manifestation of neurological symptoms, despite the therapy with heparin, urokinase, ticlopidine, dipyridamole, and prednisolone. Laboratory studies showed gradual increase of CSF proteins (from 156 mg/dl to 602 mg/dl) and extremely increased platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)     

A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound]

The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes.     

The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer

Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P<0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP<0.01 andP<0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P<0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P<0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.