The Presence of CA19-9 in Serum and Saliva from Lewis Blood-group Negative Cancer Patients

Eighteen cancer patients showed high levels of CA19-9 in sera, even though the blood-group phenotypes of their red blood cells were Le(a — b —). Seven of these patients (group I) were determined as Le(a — b —) from both red blood cells and saliva consistently, whereas eleven other patients (group II) secreted either Le^a or Le^b antigen in saliva and showed the expression of incompatible Lewis blood-group antigens. GDP-fucose: N -acetyl-glucosaminide a (1 × 4)-L-fucosyltransferase was demonstrated to be present in salivas from both group I and group II. These results suggest that a cancer-associated alteration of Lewis blood-group antigen expression occurs in cancer patients.     

A case of prostatic stromal tumor of uncertain malignant potential

Sarcomas and related proliferative lesions of specialized prostatic stroma are rare. Lesions have been classified into prostatic stromal tumor of uncertain malignant potential (P-STUMP) and prostatic stromal sarcoma based on the degree of stromal cellularity, presence of mitotic figures, necrosis, and stromal overgrowth. STUMPs are considered neoplastic, based on the observations that they may diffusely infiltrate the prostate gland and extend into adjacent tissues, and often recur. Although most cases of STUMPs do not behave in an aggressive fashion, occasional cases have been documented to recur rapidly after resection and a minority have progressed to stromal sarcoma. Here we describe a case of P-STUMP. A 57-year-old male went to his family doctor because of pollakisuria. Digital examination revealed abnormal findings in the prostate, then he was referred to our medical center. The mass was palpable in the left lobe of the prostate; it was elastic hard, surface smooth, about 2 cm in diameter. Serum PSA was elevated slightly (5.42 mg /dl). We diagnosed firstly leiomyosarcoma by transrectal ultra sound guided needle biopsy of the prostate. Then we performed radical prostatectomy. Finally we made the pathological diagnosis of P-STUMP. After 11 months, there is no sign of metastasis or recurrence.     

Intravenous Delivery of Liposome-mediated Nonviral DNA Is Less Toxic than Intraperitoneal Delivery in Mice

Suicide gene therapy has been shown to be an effective means of destroying pancreatic cancer cells. Liposomes have been described as having better efficacy in gene delivery, and an advantage of using liposomes as gene carriers is that they can be used repeatedly in vivo. The objective of this study is to compare the effect of gene delivery routes and to determine whether systemic delivery of the rat insulin promoter (RIP)–directed suicide gene construct would permit cell-specific gene delivery in vivo. Severe combined immunodeficient (SCID) mice were injected with liposome-RIP-TK (thymidine kinase) complex by either the intraperitoneal or the intravenous route. Twenty-four hours post gene delivery, mice received ganciclovir (GCV) treatment twice daily for 14 days. Mice were sacrificed at various time points. Complete necropsy and serum chemistry analysis were performed. Islet morphology was determined using hematoxylin and eosin (H&E) staining. Serum glucose and insulin levels were also determined. To determine the toxic effect on pancreatic islet cells, immunostaining of insulin-producing and glucagon-producing cells was carried out at each time point. H&E staining indicated that both intravenous and intraperitoneal liposome-RIP-TK gene expression had no effect in normal endocrine islet cells. Both gene-delivery routes in mice resulted in normal glycemia and serum insulin levels. The endocrine islets were intact, with a normal distribution pattern of insulin-producing beta cells and glucagon-secreting alpha cells. However, serum chemistry analysis revealed significantly elevated levels of liver enzymes; suggesting that possible liver damage had occurred with the intraperitoneal gene delivery of liposome-pRIP-TK. Intravenous liposome-mediated gene delivery had no effect on liver enzyme levels. Liposome-mediated gene delivery via intravenous injection was less toxic than intraperitoneal delivery. This gene-delivery route requires fewer liposome-DNA complexes and maintains normal liver function. Thus, intravenous delivery of gene therapy would be superior to intraperitoneal administration of gene therapy in mice.     

Renal cholesterol embolism: analysis of two spontaneous autopsy cases

Two cases of spontaneous cholesterol embolism, which followed different clinical courses, acute and chronic renal failure, are presented and histopathological lesions are compared. Both cases were diagnosed as cholesterol embolism post-mortem. Case 1 (a 66-year-old man) had acute onset of illness with fever, leucocytosis and renal failure, diagnosed as vasculitis, and died of rupture of an abdominal aortic aneurysm. Case 2 (an 84-year-old man) had eosinophilia of unknown aetiology for 7 years with intermittent worsening of renal function and died of sepsis. Case 1 had diffuse cholesterol crystal emboli in the interlobular arteries and arterioles of the kidney, but case 2 had patchy cholesterol emboli in the interlobular arteries of the kidney. The aorta of case 1 was diffusely ulcerated, which is in contrast to that of case 2, who had limited ulceration in thoracic aorta, which might have contributed to the long duration of illness. Immunohistochemically, the number of macrophages and T cells that infiltrated around cholesterol emboli in the arteries was more in case 1 (macrophages 27.7, T cells 36.1/mm(2)) than in case 2 (2.7, 1.38/mm(2)). Focal interstitial inflammation occurred in both cases. In case 1, marked tubulitis was observed. Case 2 had rather severe atrophy of the tubules and fibrotic interstitium where mast cells were rich (31.9/mm(2)). The number of B cells and eosinophils was few in case 2 (11.35, 0.7/mm(2)) compared with case 1 (101.9, 16.15/mm(2)). These results suggest that in acute lesions of renal cholesterol embolism, macrophages and T cells accumulate around cholesterol crystals and cause tubulointerstitial inflammatory lesions with other inflammatory cells. In chronic lesions, macrophages, T cells and mast cells are the major inflammatory cells present in the interstitium.     

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.     

K-ras gene mutation enhances motility of immortalized airway cells and lung adenocarcinoma cells via Akt activation: possible contribution to non-invasive expansion of lung adenocarcinoma

Point mutations of the K-ras gene, which are found in 10 to 30% of lung adenocarcinomas, are regarded as being an early event during the carcinogenesis. Autonomous vigorous motility of neoplastic cells, as well as growth and survival advantages, are considered to be necessary for cancer development and progression. The present study describes the contributions of the K-ras gene mutation and its downstream pathway via phosphatidylinositol 3-OH kinase (PI3K)-Akt to the cell motility in an immortalized human peripheral airway epithelial cell (HPL1D) and lung adenocarcinoma cells (A549, H820, TKB6, and TKB14). We have also evaluated the relationship between pathological events and the K-ras-Akt pathway using surgically resected lung tumors. The HPL1D cells transfected with the mutated K-ras gene (HPL-V12) showed a significant increase in cell motility compared to those transfected with empty vector (HPL-E) or wild-type K-ras gene (HPL-K). The enhanced motility in the HPL-V12 cells was markedly reduced by either treatment with inhibitors of ras, PI3K, and/or MEK, or by transfection with the dominant-negative mutant Akt (dnAkt). The lung adenocarcinoma cells bearing the K-ras gene mutation (A549 and H820) showed consistently higher levels of cell motilities than those without the mutation (TKB6 and TKB14), and the motility of A549 and H820 cells were significantly inhibited by dnAkt transfection. These results suggest that the K-ras gene mutation could enhance the motility of neoplastic cells through a pathway involving PI3K-Akt. Actually, among the surgically resected lung tumors, the adenocarcinomas with the K-ras gene mutation tended to show a higher frequency and intensity of immunoreactivity for phosphorylated Akt (p-ser473Akt) than those without the mutation, supporting the in vitro observation that the mutated K-ras can activate the PI3K-Akt pathway. Immunoreactivity for p-ser473Akt was also seen in the pre-malignant and early lesions at a frequency similar to that in the advanced lung adenocarcinomas,. No correlation was seen between p-ser473Akt immunoreactivity and lymphatic/organ metastasis or prognosis. These results taken together suggest that the K-ras-Akt pathway might facilitate the motility of neoplastic cells during the early period of carcinogenesis in lung adenocarcinomas, and may contribute to their non-invasive expansion along the alveolar septa, rather than invasion or metastasis.     

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis

BACKGROUND: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS: A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS: Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.     

Propagation of tonic posturing in supplementary motor area (SMA) seizures

We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary motor area (SMA) seizures based on ictal encephalographic (EEG) findings and ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the vertex for the scalp recording or in the area over and/or adjacent to SMA for epicortical recording and (2) ictal motor semiology characterized, as previously reported, by sudden and a brief tonic posturing of extremities and trunk mainly occurring during sleep without loss of consciousness. In 50% (5/10) of the patients, tonic posturing began in one part of the body and moved to other part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1-M1. The sequential propagation of tonic posturing may represent the somatotopic organization within the SMA proper.