Compressive force induces VEGF production in periodontal tissues.

During orthodontic tooth movement, the activation of the vascular system in the compressed periodontal ligament (PDL) is an indispensable process in tissue remodeling. We hypothesized that compressive force would induce angiogenesis of PDL through the production of vascular endothelial growth factor (VEGF). We examined the localization of VEGF in rat periodontal tissues during experimental tooth movement in vivo, and the effects of continuous compressive force on VEGF production and angiogenic activity in human PDL cells in vitro. PDL cells adjacent to hyalinized tissue and alveolar bone on the compressive side showed marked VEGF immunoreactivity. VEGF mRNA expression and production in PDL cells increased, and conditioned medium stimulated tube formation. These results indicate that continuous compressive force enhances VEGF production and angiogenic activity in PDL cells, which may contribute to periodontal remodeling, including angiogenesis, during orthodontic tooth movement.

Cyclical tensile force on periodontal ligament cells inhibits osteoclastogenesis through OPG induction.

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

Epstein-Barr virus-associated T-lymphoproliferative disease with hemophagocytic syndrome, followed by fatal intestinal B lymphoma in a young adult female with WHIM syndrome. Warts, hypogammaglobulinemia, infections, and myelokathexis.

A rare association of Epstein-Barr virus-associated T- and B-lymphoproliferative disease (EBV(+) T- and EBV(+) B-LPD) in a patient with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is reported. A 26-year-old Japanese female, who had been treated for WHIM syndrome since early childhood, developed hemophagocytic syndrome associated with EBV(+) T-LPD at the lymph nodes and spleen. The disease rapidly resolved in response to prednisolone therapy. However, 6 weeks later, fatal EBV(+) B lymphoma unresponsive to chemotherapy occurred in the intestine and other organs. Caution must be exercised that the patient with WHIM syndrome may be at risk for EBV-LPD.

Histopathologic findings of cornea verticillata in a woman heterozygous for Fabry's disease.

PURPOSE: To report the histopathologic findings of the cornea verticillata observed in a woman who was heterozygous for Fabry's disease. METHOD: A 67-year-old woman was found to have a whorl-like corneal opacity on her visit to the Department of Ophthalmology. Aichi Saiseikai Hospital. Her visit was because of a sudden loss of vision in her right eye owing to a central retinal artery occlusion in association with an ophthalmic artery occlusion. The patient died suddenly of an acute heart failure; with family consent, an autopsy was performed and the right eye was removed for histopathologic examination by light and electron microscopy. RESULTS: Low levels of alpha-galactosidase in the leukocytes together with the corneal finding led to the diagnosis of heterozygous Fabry's disease. Light microscopy revealed a 0.3- to 0.5-microm thick layer between the epithelial and Bowman's layers. Oil red O positive deposits were accumulated in the subepithelial layer, and the density varied in different regions. Electron microscopy showed that subepithelial layer differed in thickness, and the basal lamina reduplicated regionally. We were not able to determine the structure that correlated with the "ridge" in the central part of the cornea. CONCLUSION: The oil red O positive deposits and their variation in density in the subepithelial area of the cornea may have caused the characteristic whorl-like corneal opacity in this woman who was heterozygous for Fabry's disease.

Fibrous tumor of the breast in a postmenopausal woman receiving estrogen.

Fibrous tumor of the breast is a rare, benign stromal proliferation with atrophy of the epithelial component. Almost all patients who develop fibrous tumors are premenopausal. An unusual example of fibrous tumor of the breast is reported in a 62-year-old postmenopausal woman. The mass, first noted 1 year previously, progressively enlarged over the year. The patient noted a history of taking exogenous estrogens for 10 years. Intense estrogen administration during the year of enlargement may be associated with accelerated growth of the tumor. In addition, positive nuclear staining for estrogen receptor antibodies in stromal cells was demonstrated by immunohistochemical methods.

[Occurrence of BOOP outside radiation field after tangential radiation therapy for breast carcinoma].

We report three cases of bronchiolitis obliterans organizing pneumonia (BOOP) that occurred outside the radiation field after radiation therapy using tangential fields for breast carcinoma. All patients complained of a cough between 14 and 20 weeks after completion of radiation therapy. Fever also developed in two of the three. Chest radiography and computed tomography demonstrated peripheral alveolar opacities outside the radiation field on the same side as the radiation therapy. Laboratory data showed an increased level of C-reactive protein and an increased erythrocyte sedimentation rate. Bronchoalveolar lavage showed an elevated total cell count with a very high percentage of lymphocytes. Transbronchial lung biopsy revealed a histologic pattern consistent with BOOP. Treatment with corticosteroids resulted in rapid clinical improvement and complete resolution of the radiographic abnormalities. This pulmonary disorder appears to be induced by radiation, especially when a tangential field is employed for breast carcinoma, though the etiology has not been fully investigated. It is important to be aware of this type of pulmonary complication in patients given radiotherapy for breast carcinoma.

True exfoliation of the lens capsule following uveitis.

PURPOSE: To report a rare case of true exfoliation of the lens capsule following panuveitis, with slit-lamp photographs before and following the development of the true exfoliation. METHODS: Case report. Review of the history and clinical features of a 70-year-old woman who developed true exfoliation during the treatment for panuveitis. RESULTS: After 7 months of treatment for bilateral panuveitis with topical steroid and tropicamide, the patient developed a thin, transparent membrane arising on the lens surface in the right eye. A diagnosis of true exfoliation of the lens capsule was made. CONCLUSIONS: True exfoliation of the lens capsule following uveitis may occur due to the weakening of the anterior capsule by metabolic disorder caused by uveitis and precipitated by repeated mydriasis.

[Effective pentostatin-based treatment of adult T cell leukemia in a patient with severe arthritis].

We report a 48-year-old woman with adult T-cell leukemia who had refractory arthralgia, intense headaches, and fever. Leukemic cell infiltration of the cerebrospinal fluid was detected but no other acute signs were observed. Abnormal lymphocytes with lobulated nuclei were found in the synovial fluid, and a histologic examination revealed proliferation into the synovium. Because combination chemotherapy did not elicit a favorable response, the patient was treated with a pentostatin bolus injection. The articular symptoms disappeared and complete remission was obtained. Six months later, she experienced arthralgia again together with a gradual increase of abnormal lymphocytes in peripheral blood. Sixteen months later, the patient was given pentostatin and achieved a complete remission again. She is still free from relapse without further therapy after 36 months, and her articular symptoms have not returned either. There were no adverse effects due to pentostatin. The patient's serum IL-6 level was elevated, suggesting that IL-6 may play a role in arthropathy.

Acute lupus peritonitis successfully treated with steroid pulse therapy.

A 21-year-old man with systemic lupus erythematosus (SLE) who developed acute lupus peritonitis is described. Acute lupus peritonitis appeared during generalized lupus flare, with nausea, vomiting, frequent diarrhea, and abdominal tenderness with rebound and guarding. The patient was afebrile and had decreased bowel sounds. Abdominal ultrasonography and computed tomography revealed marked thickening of the gastric, duodenal, and jejunal walls, massive intraluminal fluid collection, and increasing ascites. Gastrointestinal endoscopy showed edematous mucosa with multiple erosions of the stomach and duodenum. The ascitic fluid was remarkable for low complement levels and elevated anti-DNA antibody. These manifestations of acute lupus peritonitis resolved after steroid pulse therapy with methylprednisolone. We should consider acute lupus peritonitis in a patient with SLE when abdominal symptoms are severe. Experience with our patient indicates that steroid pulse therapy is effective for this rare but severe manifestation of SLE.

[A case of acute myelogenous leukemia accompanied with myelofibrosis and megakaryocyte-like giant bizarre blasts].

A 45-year-old man was admitted with high fever and leukocytosis in August 1993. The diagnosis of acute myelogenous leukemia (AML; M2) was made on the basis of morphological, cytochemical and immunological characteristics of the blasts in the bone marrow. The induction therapy with BHAC, daunorubicin, 6-MP was unsuccessful in achieving remission; the bone marrow biopsy specimen revealed the proliferation of the remaining leukemic cells and massive fibrosis accompanied with unusual megakaryocyte-like giant bizarre cells. These megakaryocyte-like giant cells were positive for myeloperoxidase and CD34, but not GPIIIa and factor VIII, indicating that those were derived from myelogenous stem cells. Following the low-dose Ara-C therapy, improvement of fibrosis and disappearance of these giant cells were observed in the bone marrow. After the reinduction therapy with high-dose Ara-C and MIT against markedly increased blasts, the patient died of systemic fungal infection. The presence of myelofibrosis and giant atypical blasts might allow resistance to therapy and poor prognosis.

Small intestinal perforation due to cytomegalovirus infection in patients with non-Hodgkin's lymphoma.

We describe two patients with non-Hodgkin's lymphoma (NHL) who suffered cytomegalovirus (CMV)-related small intestinal perforations during the course of chemotherapy. Surgical specimens from both patients revealed histologic evidence of occlusive vasculitis and tissue destruction caused by CMV-affected cells in the submucosa and muscular walls, that may have played an important role in the pathogenesis of these perforations. Although such intestinal perforations are rare complications in NHL patients, CMV infection should be recognized as a primary etiological factor in acute abdominal crises when treating NHL patients with pharmaceutical agents including steroids. Emergency surgery and the anti-CMV agent, ganciclovir, would improve the prognoses of such patients.

Co-existence of PACAP and nitric oxide synthase in the rat hypothalamus.

The possible co-existence of pituitary adenylate cyclase-activating polypeptide (PACAP)-38 and nitric oxide synthase (NOS) in the rat hypothalamus was examined by a combination of PACAP-immunocytochemistry and NADPH-diaphorase histochemistry. Virtually all PACAP-38-immunoreactive neurones in the paraventricular and supraoptic nuclei exhibited NADPH-diaphorase activity. Since NADPH-diaphorase activity was identical to NOS-immunoreactivity in the magnocellular neurosecretory neurones, this finding indicates that the PACAP neurones synthesize NO.

[Clinical evaluation of diazepam suppository for premedication in children].

Anesthesiologists need a safe and effective premedication before general anesthesia and want to help decrease anxiety and minimize psychologic trauma to children. Therefore, we evaluated diazepam suppository (0.5 mg.kg-1 body weight) administered to 21 children before minor surgery under general anesthesia. We evaluated the sedative effect of the diazepam suppository (tablet) on the arrival at the operating room, during anesthesia induction and in the recovery room. On the arrival at operating room, 86% of children were sedated, and 65% of children could be induced smoothly under mask. There was no delayed emergence. Plasma diazepam level at induction was 376.5 +/- 28.4 ng.ml-1, which is the level needed for sedation. We conclude that diazepam suppository is a useful drug for premedication in children.

Selective accumulation and tumoricidal effect of cisplatin suspended in viscous ethyl oleate on hepatic cancers in animals after intraarterial infusion.

The selective accumulation and tumoricidal effects of cisplatin after intra-arterial infusion suspended in viscous ethyl oleate (VEO) on hepatic cancers of AH 272 tumor-bearing rats and VX-2 tumor-bearing rabbits were compared with those of cisplatin suspensions in ethyl oleate (EO) and Lipiodol Ultra Fluide (LP). The viscosities of VEO, EO and LP were 120, 4, and 21 centipoise (cp) respectively. Complete in vitro release of cisplatin from EO and LP occurred within 24 h, whereas only about 25% of cisplatin was released from VEO over the same period. When EO or VEO containing 3H-oleic acid were infused into the hepatic artery of rat liver inoculated with AH 272 tumor cells, radioactivity in the tumor site was higher than that in normal liver. In the case of cisplatin, concentration ratios after the infusion of EO and VEO were almost the same as those of oily carriers. Similar results were obtained in rabbit liver inoculated with VX-2 tumor cells. Cisplatin concentration in the tumor site seven days after intra-arterial infusion of VEO suspension was 5- and 1.7-fold higher, respectively, than that after EO and LP suspensions. The tumoricidal effect of cisplatin in VEO suspension on AH 272 tumor-bearing rats was higher than that after cisplatin solution and EO and LP suspensions, while VX-2 tumor growth was inhibited by the infusion of all cisplatin-containing oily carriers. VEO suspension thus appears very promising in intra-arterial infusion therapy.

Oily drug carriers in cancer chemotherapy. II. Preparation of viscous ethyl oleate for intraarterial infusion therapy and its disposition in rats and hamsters.

Viscous ethyl oleate (VEO) was prepared as an oil drug carrier by the addition of aluminum stearate or ethyl cellulose. Since the rate of shear of VEO containing aluminum stearate was greatly and nonlinearly changed against the shearing stress compared to that containing ethyl cellulose, the latter was used for subsequent microvascular and organ distribution experiments in rats and hamsters. For infusion into the carotid artery in hamsters, neat ethyl oleate (EO, 4cP) or VEOs of various apparent viscosities (40, 80, 120 cP-VEOs) embolized the vascular system in the cheek pouch, although arrival time to the site where the embolization was observed and the embolization period differed depending on the type of oily drug carrier. For infusion into the hepatic artery in rats, however, only 120 cP-VEO embolized the vascular system in the liver. After infusion of the oily drug carrier containing 3H-oleic acid into the artery of hamster cheek pouch and rat liver, 30-50% of the radioactivity was gradually eliminated within 48 h, whereas about 80% of the dose was rapidly eliminated after infusion to rat stomach and kidney. In addition, the amount of 120 cP-VEO remaining in each organ 48 h after infusion was higher than those of EO and 40 and 80 cP-VEOs. Histological observation after infusion in rat liver revealed that 120 cP-VEO slowly migrated from the artery or arteriole to the sinusoidal capillary region. These results suggest that 120 cP-VEO can be used as a drug carrier because of its function of vascular embolization and high retention in a targeted tissue.

Differential sensitivity of cardiac pacemakers to exogenous adenosine in vivo.

Adenosine exerts pronounced depressant effects on cardiac pacemakers. Previous studies in vitro have indicated that different pacemakers exhibit variable sensitivity to adenosine: ventricular greater than junctional greater than sinus node pacemakers. This study tested the hypothesis that ventricular pacemakers are more sensitive to adenosine than sinus node pacemakers in vivo in an experimental canine model and determined the mechanism involved in this phenomenon using specific pharmacological interventions. For this purpose, dogs with chronic atrioventricular block, stable ventricular escape rhythm, and bilateral stellectomy and cervical vagotomy were studied. Dose-response curves for negative chronotropic action of adenosine in the sinus node and ventricular pacemakers were obtained in group 1 under base-line conditions, during isoproterenol infusion, and after subsequent administration of propranolol; in group 2 before and after administration of quinidine; in group 3 before and after administration of aminophylline; and in group 4 before and after administration of 1,3-dipropyl-8-phenylxanthine amine congener (XAC). Adenosine exerted a dose-dependent negative chronotropic effect on sinus node and ventricular pacemakers. At all doses tested, this action was more pronounced in the ventricle. Isoproterenol accentuated the action of adenosine in the sinus node (by 60-138%; P less than 0.05) but suppressed it in the ventricle (-37 to 53%; P less than 0.05). These effects of isoproterenol were attenuated by propranolol. Quinidine suppressed the action of adenosine in the sinus node (-38 to -52%; P less than 0.05) but not in the ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence of hypovitaminosis D in patients with mitral ring calcification.

In order to evaluate the role of calcium regulating hormones in the pathogenesis of mitral ring calcification, we have studied the serum levels of PTH and vitamin D metabolites in aged females both with and without mitral ring calcification (MRC). In the patients with MRC (n = 17), significantly lower levels of serum total protein (6.6 +/- 0.2 in the MRC group vs 7.1 +/- 0.1 g/dl in the control group, mean +/- SEM), BUN (15.7 +/- 0.9 vs 18.3 +/- 0.9 mg/dl), creatinine (0.7 +/- 0.02 vs 0.9 +/- 0.02 mg/dl) and calcium (8.4 +/- 0.1 vs 9.2 +/- 0.1 mg/ml) were observed as compared with those in the controls (n = 32). Significantly higher PTH levels (0.57 +/- 0.07 vs 0.38 +/- 0.04 ng/ml) were found in the MRC group. Levels of all three vitamin D metabolites in the MRC group were significantly lower than those in the control group (25-OHD; 11.2 +/- 1.4 vs 19.6 +/- 1.2 ng/ml, 24,25(OH)2D; 0.7 +/- 0.1 vs 1.3 +/- 0.1 ng/ml and 1,25(OH)2D; 12.5 +/- 2.4 vs 43.0 +/- 3.5 pg/ml). The correlation coefficient between PTH and 1,25(OH) 2D was -0.382(n = 49, p less than 0.01). Thus, the significantly higher PTH levels in the MRC group might result in hypovitaminosis D. In conclusion, evidence of hypovitaminosis D in the patients with mitral ring calcification was demonstrated.

[Cerebral aspergillosis as a cerebral vascular accident].

Cerebral aspergillosis is one of the most common mycotic infections in the central nervous system causing different clinical features such as brain abscess, granuloma, meningitis, and encephalitis. Cerebral aspergillosis, however, may lead to a cerebral vascular accident such as intracranial hemorrhage or cerebral infarction. In this report, we present two patients with cerebral aspergillosis accompanied by intracranial hemorrhage. A total of 124 reported cases of cerebral aspergillosis are reviewed to ascertain the pathogenesis of the associated vascular lesion. The first patient was a 9-year-old girl, who developed drowsiness with a headache during the medical treatment for acute myelocytic leukemia. CT disclosed subarachnoid and intraventricular hemorrhage. The autopsy revealed that the aspergillus arteritis was the cause of repeated hemorrhage. The second patient was a 15-year-old boy with allergic purpura and renal failure, who suddenly developed a stupor with convulsive seizure. CT disclosed an intracerebral hemorrhage in the right parieto-occipital area. The patient gradually deteriorated and died in spite of the surgical removal of the hematoma. The autopsy revealed that the hemorrhage was caused by the aspergillus arteritis. Cerebral aspergillosis has two routes of infection to the central nervous system: hematogenous dissemination from the distant site (usually the lung) and direct extension from the contiguous site (usually the paranasal sinuses or orbit). The primary mechanism of neuropathology is different between these two types. Primary cerebral arteritis is most often seen in patients with the former type, whereas primary basal meningitis occurs in the latter. The incidence of clinico-pathological features is different between hematogenous dissemination type and direct extension type.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effect of fatty acids on the binding of androgen receptor and R1881.

Unsaturated long chain fatty acids are known to inhibit the binding between estrogen and estrogen receptor, or progesterone and progesterone receptor in rat uterus. The effects of long chain fatty acids on the binding between androgen receptor of castrated rat prostate and 3H-R1881 were studied. The binding was not affected by saturated fatty acids such as palmitic acid (16:0) or stearic acid (18:0). But unsaturated fatty acids such as oleic acid (18:1), arachidonic acid (20:4) and docosahexaenoic acid (22:6) inhibited the binding between androgen receptor and 3H-R1881. The inhibitory effect of arachidonic acid was dose dependent. Scatchard analysis showed that the addition of arachidonic acid markedly decrease the number of binding sites of androgen receptor. But the dissociation constant was not affected. The inhibitory effect of arachidonic was not a competitive one.