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Biomedical subjects

B M Miller

Publications and source records attributed to B M Miller.

At least 37 records · Page 2Linked to original sources
PubMed1992

Analysis of radiation-induced micronuclei by fluorescence in situ hybridization (FISH) simultaneously using telomeric and centromeric DNA probes.

Fluorescence in situ hybridization using simultaneously a combination of DNA probes for the telomeric hexamer repeat (TTAGGG) and the centromerically repeated murine gamma-satellite DNA was applied to analyze the nature of radiation-induced micronuclei in mouse NIH 3T3 fibroblasts. After subtraction of spontaneously occurring micronuclei independent from the dose and time after irradiation, approximately 22% of the radiation-induced micronuclei did not reveal any hybridization signal. Approximately 17% showed one centromeric hybridization signal and about four telomeric signals, suggesting their origin from whole chromosomes. Almost 60% of radiation-induced micronuclei had telomeric signals only, suggesting their origin from acentric fragments. A fraction of micronuclei were found to contain two or more acentric fragments. Micronuclei derived from whole chromosomes or from multiple acentric fragments might, together with DNA synthesis in micronuclei, explain the occurrence of radiation-induced micronuclei with DNA contents greater than the largest chromosome arm.

Animals↗
PubMed1991

Application of the murine anti-Gd-2 antibody 14.Gd-2a for diagnosis and therapy of neuroblastoma.

We have tested the sialoganglioside monoclonal antibody Gd-2a for scintigraphic diagnostic and for immunotherapy in children with neuroblastoma stage IV. We could confirm tumor sites with Gd-2a scans in 1/2 children. Doses of 20-60 mg/m2 were administered daily for 5-10 days. 2/2 children with multiple tumor sites showed significant tumor regression. Four children, treated preventively, are still in clinical remission. One child showed tumor progression despite Gd-2a treatment. Adverse effects included itching, rashes, and pain.

Adolescent↗
PubMed1991

Classification of micronuclei in murine erythrocytes: immunofluorescent staining using CREST antibodies compared to in situ hybridization with biotinylated gamma satellite DNA.

Micronuclei (MN) in erythrocytes of mouse bone marrow cells were induced in vivo by the spindle poisons colchicine (COL) and vinblastine (VBL), by hydroquinone (HQ) and by the alkylating agent mitomycin C (MMC). Two different methods were applied to detect whole chromosomes with centromeric proteins or chromatin in MN to discriminate between spindle damaging or clastogenic activity of these chemicals. One method determined the fraction of MN with centromeric chromatin by immunofluorescent staining using antikinetochore antibodies (CREST staining). The other method applied non-radioactive in situ hybridization with a novel DNA probe. The fractions of MN that showed positive signals by either technique thus indicating with a high probability the presence of whole chromosomes instead of acentric fragments, were in good agreement for COL, VBL and HQ. After application of MMC, however, 4.5% of the MN were CREST-positive, while 29% gave a positive hybridization signal. The results suggest, that kinetochores may have lost certain centromeric antigens due to treatment with MMC so that MN containing whole chromosomes appear CREST-negative. The presented in situ hybridization scheme using satellite DNA is a more direct detection and is advantageous to the CREST staining technique in that it is unaffected by damage of kinetochore or centromeric function.

Animals↗
PubMed1990

Application of antikinetochore antibody staining (CREST staining) to micronuclei in erythrocytes induced in vivo.

Micronuclei (MN) can be formed by acentric chromosome fragments or whole lagging chromosomes. In order to discriminate MN produced by chromosome breakage from those arising from spindle malfunction a staining method using immunofluorescent kinetochore antibodies has been applied successfully in vitro. In the present study MN in polychromatic erythrocytes of mouse bone marrow cells induced in vivo by the spindle poison colchicine (COL) and the clastogen mitomycin C (MMC) were analysed after CREST staining. The staining method was modified by using pretreatment with detergents in order to allow a good penetration of the antibodies into the MN. About 66% of the MN induced by COL in contrast to only 4.5% of the MMC induced MN were CREST-positive. The preliminary results show that the CREST staining is also in MN induced in vivo capable of detecting the origin of MN and to discriminate between the spindle damaging or clastogenic activity of environmental agents. The method described will give supplementary information about MN, it cannot substitute for the common micronucleus test.

Alkylating Agents↗
PubMed1990

Neonatal duodenal perforation.

Duodenal perforation in neonates is uncommon, and has been described rarely in the third part of the duodenum. Gastrointestinal perforations without an obvious cause have been labeled as "spontaneous." We report a case of perforation in the third part of the duodenum in a premature infant for which there was no obvious cause. In such "spontaneous" perforations, multifactorial etiology is likely and possible factors are discussed. The high mortality rate in such patients can be improved by early diagnosis and prompt resuscitation followed by surgery. Peritoneocentesis plays an important diagnostic role. It is also therapeutic in relieving the respiratory distress caused by free intraperitoneal air. The majority of duodenal perforations are amenable to primary closure at surgery and this should be the treatment of choice.

Duodenal Ulcer↗
PubMed1989

Failure of somatostatin or an analog to promote closure of end pancreatic fistulae.

Somatostatin has been reported to promote closure of pancreatic fistulae, but use of the analog SMS 201-995 (Sandoz, Inc.) has not previously been published. We used this analog to treat two patients with end pancreatic fistulae refractory to conventional therapy. One patient had disruption of a pancreaticojejunostomy after pancreaticoduodenectomy and the other had acute necrotizing gallstone pancreatitis and disruption of the pancreatic duct in the tail. SMS 201-995 (100-150 micrograms/d) abruptly decreased fistula output by 50% in both patients but further increases in dosage had no further effect on output. Neither fistula healed after 3-4 wk of therapy. Treatment with somatostatin or its analogs alone will not lead to closure of a pancreatic fistula complicated by factors such as distal obstruction, infection, or foreign body. Somatostatin may promote closure of lateral fistulae and may simplify the management of patients with high output fistulae.

Adenocarcinoma↗
PubMed1989

Suspect spindle poisons: analysis of c-mitotic effects in mouse bone marrow cells.

In the coordinated programme to study aneuploidy induction, sponsored by the Commission of the European Communities, 10 known or suspect spindle poisons (colchicine, econazole, chloralhydrate, hydroquinone, diazepam, thiabendazole, cadmium chloride, pyrimethamine, vincristine and thimerosal) were tested in mouse bone marrow cells for the induction of c-mitotic effects. Three criteria were chosen: changes of the mitotic index, induction of chromatid contraction and spreading and decrease of anaphase frequencies. Among the chemicals tested colchicine, econazole, chloralhydrate, hydroquinone and vincristine were found positive. Diazepam, thiabendazole, cadmium chloride, pyrimethamine and thimerosal revealed no induction of c-mitotic effects under the conditions tested. Mitotic block and subsequent chromosome malsegregation (non-disjunction) are related phenomena. The three criteria chosen are considered as an indicative pre-screening test for the aneuploidy inducing potency of a chemical in mitotic, but not in meiotic cells. The present experiments were also regarded as a dose-finding exercise for further in vivo studies.

Anaphase↗
PubMed1988

Intrapancreatic communication of bile and pancreatic ducts secondary to pancreatic necrosis.

An unusual complication of acute necrotizing pancreatitis occurred in which erosion of the intrapancreatic common bile duct and cephalic pancreatic duct formed a pancreaticobiliary cavity. This pancreatic process was observed to enhance during contrast computed tomography and was hypervascular during angiography, making preoperative diagnosis difficult. To our knowledge, the spontaneous development of such a cavity as a complication of acute pancreatitis has not been reported. The patient was successfully treated with pancreaticoduodenectomy.

Acute Disease↗
PubMed1988

Surgical versus endoscopic management of common bile duct stones.

The charts of all patients with common bile duct (CBD) stones admitted to Virginia Mason Medical Center between January 1, 1981 and July 31, 1986 were reviewed to define current methods of management and results of operative versus endoscopic therapy. Two hundred thirty-seven patients with CBD stones were treated. One hundred thirty patients had intact gallbladders. Of these patients, 76 (59%) underwent cholecystectomy and common bile duct exploration (CBDE) while 54 (41%) underwent endoscopic papillotomy (EP) only. Of the 107 patients admitted with recurrent stones after cholecystectomy, all but five were treated with EP. The overall mortality rate was 3.0%. Complications, success, and death rates were all similar for CBDE and EP, but the complications of EP were often serious and directly related to the procedure (GI hemorrhage, 6; duodenal perforation, 5; biliary sepsis, 4; pancreatitis, 1). Patients undergoing EP required significantly shorter hospitalization than those undergoing CBDE. Multivariate analysis showed that age greater than 70 years, technical failure, and complications increased the risk of death, regardless of procedure performed. Twenty-one per cent of those undergoing EP with gallbladders intact eventually required cholecystectomy. The conclusion is that the results of EP and CBDE are similar, and the use of EP has not reduced the mortality rates of this disease.

Adult↗
PubMed1987

Intrapartum rupture of the falciform ligament and umbilical vein. A rare cause of hemoperitoneum in the newborn.

Intra-abdominal hemorrhage in the newborn is uncommon, but it must be considered in the first 48 hours of life in the infant with pallor, anemia, abdominal distension, and shock. The injured liver is the most common source of bleeding, with the spleen and kidney less often involved. In the case presented, the hallmarks of intra-abdominal hemorrhage were evident. Exploratory laparotomy revealed intraperitoneal bleeding emanating from the disruption of the umbilical vein and its enveloping falciform ligament. There was no other site of intra-abdominal bleeding and there were no intrinsic abnormalities of the umbilical cord or the placenta. Disruption of the intra-abdominal umbilical vein represented the sole source of intra-abdominal bleeding in this patient. The case is reported to document disruption of the intra-abdominal umbilical vein as a rare cause of neonatal hemoperitoneum.

Adult↗
PubMed1985

Further studies on the influence of chemical form and dose on absorptions of Np, Pu, Am and Cm from the gastrointestinal tracts of adult and neonatal rodents.

Absorption of isotopes of the actinide elements Np, Pu, Am and Cm from various organic media and/or in combination with plant or animal ligands or tissue is compared with their absorption from an inorganic nitrate medium. Gastrointestinal (GI) transport of 238Pu, 239Pu, 241Am and 244Cm at high concentrations from citrate medium by adult rats and/or mice was higher than from nitric acid medium. Neptunium-237 absorption, however, was not increased by citrate; probably because its oxidation state was reduced from 237Np(V) to 237Np(IV) by the medium and by the GI content. Increasing the mass of the 237Np dose resulted in increased absorption. Neither incorporation of 238Pu in rat liver nor retention of 238Pu oxide in rat lungs enhanced absorption when those Pu-containing tissues were administered intragastrically to either adult or neonatal rats. Ranking of GI absorption of the various forms of Pu gavaged in these studies suggests that transport is in the order: Pu citrate greater than Pu phytate greater than biologically incorporated Pu greater than Pu nitrate.

Actinoid Series Elements↗
PubMed1984

The use of 2-substituted 5-nitroimidazoles in the treatment of chronic murine Trypanosoma brucei infections with central nervous system involvement.

Chronic infections of Trypanosoma brucei GVR 35/2 in mice, normally relapse after conventional chemotherapy because infective trypanosomes in the brain escape the action of the drug and are able to multiply and eventually re-establish a parasitaemia. However, if treatment consists of a single dose of 1 x 20 mg/kg suramin followed 3 or 4 days later by a 2-substituted 5-nitroimidazole, given intraperitoneally, either as a single dose or as a course of daily injections, relapses rarely occur and the majority of the mice are permanently cured. The minimum effective levels for the three 5-nitroimidazole compounds (Merck Sharp and Dohme, Rahway, NJ, USA) were two doses of 10 mg/kg of L611,744; four doses of 10 mg/kg of MK 436; and three doses of 10 mg/kg of L634,549. Generally it was more effective to divide a given total dose into two or more daily doses, rather than to give the 4-nitroimidazole as a single treatment. The effective dose levels are low enough to be of practical significance and, if the 5-nitroimidazoles were ever licensed for humans, might well prove to be an alternative to melarsoprol treatment for the elimination of trypanosomes from the central nervous system.

Animals↗
PubMed1984

Gastrointestinal absorption of metals (51Cr, 65Zn, 95mTc, 109Cd, 113Sn, 147Pm, and 238Pu) by rats and swine.

Adult and neonatal rats and neonatal pigs were gavaged with solutions of metal radionuclides to determine gastrointestinal absorption. Zinc-65 and technetium-95m were well-absorbed by both age groups; chromium-51, cadmium-109, tin-113, promethium-147, and plutonium-238 were not. The quantities of the poorly absorbed metals that were absorbed by neonates were between 4 and 100 times higher than those absorbed by adult rats. Autoradiograms prepared from the entire small intestine of the neonatal rat showed that 109Cd was retained in the duodenum. In contrast, measurements in the piglets showed much higher 109Cd retention in the ileum than in the duodenum. Autoradiograms and radiochemical measurements of 147Pm and 238Pu in both neonatal rats and swine showed the highest level of retention in the ileum. The results indicate that, for most of the metals studied, absorption from the gastrointestinal tract is substantially higher for neonatal than for adult rats.

Age Factors↗
PubMed1984

Leupeptin's effect on organ weight, RNA, DNA, and protein content after long bone fracture in the rat.

Long bone fracture in the rat is accompanied by enhanced urinary nitrogen loss reflecting changes in protein synthesis and breakdown. The effects of leupeptin, an inhibitor of lysosomal proteases, were assessed on organ weights, RNA, DNA, and protein content after injury in the rat. Two groups of 8-week-old rats were studied: The first group received left femoral fracture. Half of these received leupeptin (25 mumole ip/day), and the remainder received saline. The second group served as uninjured pair-fed controls, with half receiving leupeptin and half receiving saline. On Days 0, 1, 2, 4, and 7 after injury, animals were sacrificed and organs were removed for determination of weight, RNA, DNA, and protein content. All injured rats lost weight, with maximum loss occurring on Day 4. Food intake was also reduced. Pair-fed rats lost the same amount of weight as injured ones, and leupeptin could not prevent whole body weight loss. Expressed as percentage of total body weight, livers from leupeptin-treated injured rats weighed 10% greater than saline-treated ones on Days 2, 4, and 7 after injury (P less than 0.05). No differences occurred in RNA, DNA, or protein contents. Diaphragms similarly weighed 10, 20, and 30% greater on Days 2, 4, and 7 after injury, respectively, in leupeptin-treated rats (P less than 0.05). In addition, the RNA and DNA contents of diaphragms were 96 and 88% greater, respectively, in treated rats than in controls (P less than 0.05) on Day 4. It is concluded that leupeptin causes a relative increase in the weights of livers and diaphragms after injury, and causes a marked increase in the RNA and DNA contents of diaphragms.

Animals↗
PubMed1984

Absorption and distribution of cadmium in mice fed diets containing either inorganic or oyster-incorporated cadmium.

To determine the absorption, organ distribution, and retention of organically bound cadmium (Cd) and the effects of dietary zinc (Zn) on Cd metabolism, groups of mice were fed five different diets. The organic Cd used in the diets was in the form of lyophilized oyster (Crassostrea virginica) that had accumulated radiolabeled 109Cd through a plankton food chain. The mice were fed either a standard basal mouse diet (AIN-76) or diets containing five or eight times the Zn concentration of the basal diet. The source of Zn was either oyster tissue or ZnCO3. The concentration of organic and inorganic Cd provided a dose of approximately 0.4 mg/kg. Diets prepared from oyster tissue probably contained all of the Cd and 85% of the Zn in organic form. Diets prepared with inorganic metals contained about the same Cd and Zn concentrations as the diets prepared with oyster. There was very little difference between the retention of Cd by mice that ingested organic (oyster bound) Cd and those fed inorganic Cd (CdCl2). However, when the Cd retained in the intestine was excluded, retention of organic Cd was significantly greater than that of inorganic Cd. The organ distribution of Cd differed significantly according to the chemical form of Cd fed (organic or inorganic) and the Zn level in the diet. The kidneys of mice fed organically bound Cd retained a higher percentage of the metal than the kidneys of those fed inorganic Cd. On the other hand, the livers of animals fed a low-Zn diet retained a higher percentage of the Cd than the livers of those fed a high-Zn diet, regardless of the dietary source of Cd.

Absorption↗