To elucidate the mechanism whereby corticosteroids decrease the serum bilirubin concentration, changes in bilirubin metabolism were studied in patients with Gilbert's syndrome using a bilirubin load test and/or nicotinic acid test before and after corticosteroid treatment. Steroid administration increased hepatic clearance and uptake of bilirubin; the transfer rate for biliary excretion was unaffected. These results suggest that the main effect was enhancement of hepatic uptake or storage of bilirubin, which may be an important mechanism whereby corticosteroids reduce serum bilirubin concentrations in various liver disorders.

Adolescent↗

PubMedDate not supplied

A constitutional unconjugated hyperbilirubinemia combined with indocyanine green intolerance: a new functional disorder?

The kinetics of plasma clearance of indocyanine green and bromosulfophthalein were studied in 49 consecutive patients with chronic unconjugated hyperbilirubinemia. Forty-four patients had Gilbert's syndrome whereas five patients had impaired hepatic uptake of indocyanine green and virtually normal hepatic bromosulfophthalein uptake. There was no difference in bilirubin metabolism between the two groups. A family study of the patients with impaired indocyanine green uptake revealed that the defect appears to be transmitted as an autosomal dominant trait associated with inheritance of impaired bilirubin metabolism. These patients manifest a noval disorder of organic anion transport which, like Gilbert's syndrome, is also characterized by chronic milk unconjugated hyperbilirubinemia.

Adult↗

PubMedDate not supplied

The nicotinic acid test in constitutional conjugated hyperbilirubinemias and effects of corticosteroid.

The nicotinic acid test was performed in 5 patients with Dubin-Johnson syndrome, 5 with Rotor syndrome and 13 with Gilbert's syndrome. The increment in serum bilirubin concentration and bilirubin retention 5 hr later differed; the proportion of conjugated bilirubin in the increment of total bilirubin in Dubin-Johnson and Rotor syndromes was greater than in Gilbert's syndrome. These observations suggest that the nicotinic acid test reflects, in part, impaired biliary excretion of conjugated bilirubin. The results did not differentiate the two conjugated hyperbilirubinemias. The nicotinic acid test was also performed before and after corticosteroid treatment in four patients with Dubin-Johnson or Rotor syndrome. Although serum total and unconjugated bilirubin concentrations were reduced by corticosteroids, no significant change occurred in the parameters of the nicotinic acid test, suggesting that corticosteroids may enhance uptake of bilirubin without significantly altering biliary excretion of conjugated bilirubin.

Adrenal Cortex Hormones↗

PubMedDate not supplied

mRNA sequence for human cardiodilatin-atrial natriuretic factor precursor and regulation of precursor mRNA in rat atria.

The mammalian cardiac atrium has recently been shown to contain numerous peptides that exert marked effects on kidney function and vascular resistance. With one exception, the peptides have potent natriuretic and diuretic activities, and sequence similarities suggest that they may be derived from a common atrial natriuretic factor (ANF) precursor. The exception, cardiodilatin (CDD), differs from the ANF peptides in possessing potent vasorelaxant activity, but not natriuretic and diuretic activities. Here we report the cloning and sequence analysis of the cDNA for the human precursor protein (preproCDD-ANF) containing both the CDD and ANF sequences. The CDD sequence represents the N-terminal sequence preceded directly by a signal peptide, while the ANF sequence is present at the C-terminal end of the protein. Using hybridization analysis, we further show that the amount of rat preproCDD-ANF mRNA, which is synthesized selectively in the atria but not the ventricles, markedly decreases on water deprivation, suggesting that the water-electrolyte balance may be an important factor in the regulation of the expression of the preproCDD-ANF gene.

Amino Acid Sequence↗

PubMedDate not supplied

Cloning and expression of a cDNA encoding an endothelin receptor.

Endothelins are a newly described peptide family consisting of three peptides (ET-1, ET-2 and ET-3) which are the most potent vasoconstrictive peptides known. They are crucial in the regulation of vascular smooth muscle tone. The diverse functions of endothelins are thought to be mediated by interaction with many different receptors coupled to the inositol phosphate/calcium ion messenger pathway. However, because of the structural resemblance of the three peptides, the presence and nature of multiple endothelin receptors remain to be elucidated. We report here the cloning of a complementary DNA encoding a bovine endothelin receptor, which has a transmembrane topology similar to that of other G protein-coupled receptors and shows specific binding, with the highest selectivity to ET-1 in animal cells transfected with the cloned cDNA. This receptor messenger RNA is widely distributed in the central nervous system and peripheral tissues, particularly in the heart and lung. Our results support the view that there are other receptor subtypes.

Amino Acid Sequence↗

PubMedDate not supplied

Clinical pilot studies on pre-operative hyperthermic tumour ablation for advanced breast carcinoma using an 8 MHz radiofrequency heating device.

The multimodality treatment approach for advanced breast cancer provides survival advantages with decreased locoregional and distant recurrences, but these intensive anti-tumour treatments cause severe myelosuppression. Thus, in this study, the usefulness of pre-operative anti-tumour treatment without myelosuppression was investigated. Nine patients with advanced breast carcinoma underwent pre-operative hyperthermic tumour ablation (HTA) using an 8 MHz radiofrequency (RF) heating device (Thermotron RF-8) combined with a grounded needle electrode. The patients had a mean age of 58.3+/-13.9 years and included four patients with stage IIIA, two with stage IIIB and three with stage IV cancer. The target temperature was over 50 degrees C. They tolerated pre-operative HTA therapy well with no early or late complications. The initial mean tumour size was 122.1+/-71.5 cm3 and the post-HTA tumour size was 82.2+/-63.4 cm3; the reduction rate was significant (p = 0.000 293). After the pre-operative HTA, all patients underwent surgery with Level III nodal extirpation. Post-operatively, no locoregional recurrence was observed. Microscopic examination of the primary focus showed complete coagulation necrosis expanding for a diameter of 3.5-5.0 cm. Taken together, the pre-operative HTA was a safe, well-tolerated and effective treatment, achieving tumour reduction as well as complete coagulation necrosis that resulted in a large volume of destruction in breast cancer tissue.

Adult↗

PubMedDate not supplied

Relation between clinical and histologic outcome of intraperitoneal hyperthermic perfusion for patients with gastric cancer and peritoneal metastasis.

In 15 patients with refractory gastric cancer and peritoneal metastasis, the relationship among histologic outcome of intraperitoneal hyperthermic perfusion (IPHP), extent of peritoneal metastasis, and cause of death was studied. The IPHP treatment did not kill all the gastric cancer cells which had penetrated deeply into subperitoneal layers. In contrast, gastric cancer cells in the abdominal effusion and/or lavage vanished. Three patients with peritoneal metastasis, deeply invaded and spread all over the peritoneum, died of peritoneal recurrence and 1 died of pericardial metastasis. In the remaining 11 patients with a lesser extent of peritoneal metastasis, 5 are living without recurrence and among the other 6, 4 died of recurrence of the disease and 1 died of other causes.

Adenocarcinoma↗

PubMedDate not supplied

Complementary DNA sequences of renin. State-of-the-art review.

The primary structure of human renin precursor was deduced from its complementary DNA (cDNA) sequence. The predicted sequence consists of 406 amino acids with a pre- and a prosegment carrying 20 and 46 amino acids, respectively. A high degree of sequence homology, especially in the catalytically important region, was found upon comparison of the mouse and human renins. An overall homology, including presequence between the two renins, is 68.7%. Close similarities were also observed in the primary structure of renins and other aspartyl proteinases with defined three-dimensional structures, suggesting a tertiary structure for renin that is similar to the other enzymes. A bilobal model of the tertiary structure of human renin with two approximately equal domains separated by a cleft was constructed using the homology of amino acid sequence of renins and other aspartyl proteinases. These results indicate that human kidney renin is homologous with mouse submandibular renin in primary and tertiary structures, proteolytic processing, and catalytic apparatus with small differences. The major structural difference distinguishing the two renins was the presence of the two possible glycosylation sites in human kidney renin, which was not observed in mouse submandibular gland renin.

Amino Acid Sequence↗

PubMedDate not supplied

Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer.

In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer.

Aged↗

PubMedDate not supplied

Histologic evaluation of preventive measures for scald injury on the peritoneo-serosal surface due to intraoperative hyperthermic chemoperfusion for patients with gastric cancer and peritoneal metastasis.

To histologically assess the preventive efficacy of cimetidine against scald injury on the peritoneo-serosal surface during intraperitoneal hyperthermic chemoperfusion (IHCP) for advanced gastric cancer, a randomized histologic study using cimetidine, a histamine H2-receptor antagonist, was performed for 20 patients with advanced or recurrent gastric cancer and peritoneal metastasis. Cimetidine 50 mg/kg was administered intravenously to 10 patients just prior to the IHCP (cimetidine group), and the remaining 10 patients underwent the IHCP without cimetidine (control group). The background factors and IHCP treatments of these two groups were nearly the same. Although the antitumour efficacy of the IHCP was not histologically different between the two groups, the histological analysis revealed that the peritoneo-serosal surface in the cimetidine group was protected against scald injury, compared with the control group. This finding suggests that pre-IHCP cimetidine is of great benefit for protecting the peritoneo-serosal surface from scald injury due to IHCP.

Antineoplastic Agents↗

PubMedDate not supplied

Clinicopathologic characteristics and survival of elderly patients with gastric cancer.

From 1980 to 1991, Japanese patients aged over 49 years with gastric cancer underwent gastric resection in our hospitals. For various studies, two groups, 35 patients over 79 years (advanced age group) and 884 patients aged 50-79 years (mature age group) were prepared. A retrospective study was done with special reference to clinicopathological features and the prognosis. There were no differences in clinicopathological characteristics between the two groups, except for operative procedures and the size, histology and vascular involvement of the primary tumor. The survival rate for the advanced age group was higher than that for the mature age group, with a significant difference at p = 0.00556. However, the postoperative morbidity rate was 48.6% in the advanced age group compared with 5.1% in the mature age group. The most frequent complications were respiratory-related, that is, atelectasis, pneumonia or aspiration pneumonia. Based on these data, advanced age is not a contraindication for resection of a gastric cancer, but patients with serious pulmonary and/or cardiac diseases would not be candidates.

Aged↗

PubMedDate not supplied

Hyperthermia-induced antitumor activity in human gastric cancer cells serially transplanted into nude mice.

Hyperthermia-induced antitumor activity was assessed histopathologically and findings related to transplantation of human gastric cancer into nude mice were examined. Fragments of human gastric cancer were incubated at 37 degrees C to 47 degrees C for various durations of time, then were evaluated either histologically or with regard to delay in tumor growth and the rates of transplantation into nude mice. Fragments exposed to 39 degrees C for 30 min to 120 min and 41 degrees C for 30 min did not differ from findings in the controls concerning tumor growth and transplantability. In the case of 41 degrees C for 60 min or more, the rates of transplantation decreased significantly and there was a delay in tumor growth. At 43 degrees C for 120 min, 45 degrees C for 30 and 60 min, and 47 degrees C for 15 to 60 min, transplantability was nil. In the groups with a delay in tumor growth, there were irreversible changes in nucleic and cytoplasmic components, and in 6 groups with no evidence of transplantability, complete destruction of the glandular structure, pyknosis and karyorrhexis as well as disappearance of the cytoplasm occurred in almost all cases. Thus, the thermal dose of 43 degrees C for 120 min seems to be the minimally effective one for hyperthermia-induced tumoricidal activity.

Animals↗

PubMedDate not supplied

Mandibular lengthening by intraoral distraction using osseointegrated implants.

Mandibular lengthening by distraction osteogenesis is a new method for use in treating congenital deformities or postsurgical bone defects. However, the use of extraoral transcutaneous pins in the mandible has disadvantages, such as facial scars and facial nerve or inferior alveolar nerve injury. The purpose of this study was to establish a new approach to distraction osteogenesis in the mandible by using osseointegrated implants and an intraoral device. Ten adult canines were used for this experiment. After extraction of the teeth and placement of two titanium implants in the left mandible, connection of the intraoral distraction device to the abutments, and corticotomy in the medial portion between implants were performed. Distraction was done at the rate of 1 mm per day to elongate 10 mm in length. Radiographic and histologic examinations showed that successful mandibular lengthening was achieved. New bone was primarily formed by intramembranous ossification and partial endochondral ossification. Titanium implants placed for anchorage of the device remained stable during the course of mandibular lengthening. Study results suggest that the intraoral device using osseointegrated dental implants can be used as a mechanism for distraction osteogenesis in the mandible.

Animals↗

PubMedDate not supplied

Clinicopathologic characteristics of gastric cancer patients with cancer infiltration at surgical margin at gastrectomy.

Although curative surgery is desirable in patients with gastric cancer, tumors adjacent to the esophagogastric and/or gastroduodenal junctions present surgeons with some difficulty in estimating whether or not the lesion has infiltrated beyond the surgical margin. We report herein a retrospective analysis with respect to the clinicopathologic features of the primary lesion and margin positivity for tumor cells. Between 1982 and 1993, 861 gastric cancer patients underwent gastrectomy in our clinics. Of these, 340 had early cancer and the remaining 521 advanced cancer. Cancer infiltration at the surgical margin was determined macroscopically in the fresh resected specimen; re-resection was carried out immediately for positive cases and, subsequently, a rapid histologic examination at the newly-incised edge was carried out intraoperatively. Of the 340 patients with early cancer. 15 (4.4%) had a positive surgical margin which was directly resected successfully. Of the 521 patients with advanced cancer, 73 (14%) had a positive surgical margin and 28 of them had a microscopically negative surgical edge after re-resection; however, 8 others had a positive result at the newly-excised edge after re-resection, and the remaining 37 could not undergo re-resection because of their poor general condition and/or because the tumor had spread to other sites. The positive rate for the final surgical margin was 5.2% (45/861 patients). All of the patients with a positive margin and early cancer had a superficial or excavative type lesion, and 76.7% (56/73 patients) of those with advanced cancer had Borrmann's III or IV type lesion. These findings suggest that in such patients with a tumor adjacent to the esophagogastric and/or gastroduodenal junctions, particular attention should be paid to Borrmann's III or IV lesions in advanced cancer and to superficial or excavated type lesions in early cancer in order to reduce the frequency of positive surgical margin. Additionally, an immediate histologic examination after re-resection is extremely important.

Adenocarcinoma↗