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Biomedical subjects

C Petersen

Publications and source records attributed to C Petersen.

At least 91 records · Page 5Linked to original sources
PubMed1998

A novel multi-domain mucin-like glycoprotein of Cryptosporidium parvum mediates invasion.

Cryptosporidium parvum is a protozoan parasite which produces self-limited disease in immunocompetent hosts and devastating, persistent diarrhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence analysis of the gene encoding GP900, a previously identified > 900 kDa glycoprotein, predicts a mucin-like glycoprotein composed of distal cysteine-rich domains separated by polythreonine domains and a large membrane proximal N-glycosylated core region. A trinucleotide repeat composed predominantly of the triplet ACA encodes the threonine domains. GP900 is stored in micronemes prior to appearance on the surface of invasive forms. The concentration of native GP900 which inhibits 50% (IC50) of invasion in vitro is low picomolar; the IC50 for a recombinant cysteine rich-domain is low nanomolar. These observations indicate that GP900 is a parasite ligand for a host receptor involved in attachment/invasion and suggest that immunotherapy or chemotherapy directed against GP900 may be feasible.

Amino Acid Sequence↗
PubMed1998

Mouse Odf2 cDNAs consist of evolutionary conserved as well as highly variable sequences and encode outer dense fiber proteins of the sperm tail.

The outer dense fibers (ODF) of the mammalian sperm tail comprise a unique, specialized, and very prominent structure, consisting of nine fibers surrounding the axoneme. The ODF may play an important but as yet undefined role in sperm morphology, integrity and function. Study of the ODF is hampered by insufficient knowledge of their protein composition and the genetic regulation of their synthesis. We report here on the characterization of cDNAs encoding the Odf2 proteins of outer dense fibers of mouse sperm. We isolated two cDNA clones with variable 5' regions. Variability in sequence is restricted to specific regions in the N-terminal part of the encoded proteins, whereas the C-terminal part is highly conserved in Odf2 proteins both between species and within a species. This variability is confirmed at the protein level. The outer dense fibers could be detected immunologically in total sperm tails allowing a direct comparison of their length in relation to the length of the sperm tail. Odf2 transcripts could be demonstrated in testicular RNA and are restricted to germ cells. The start of transcription is in step 5 spermatids of tubular stage V and the RNA could be detected in the cytoplasm of differentiating spermatids in all subsequent tubular stages.

Amino Acid Sequence↗
PubMed1998

Comparison of the response of human FaDu squamous cell carcinoma in nude mice after hypofractionated-accelerated regimens and "curative" fractionation schedules.

BACKGROUND: It has been suggested that tumors respond differently after irradiation with 10 or more fractions than with less fractionated regimens and that extrapolation from experiments with only a few fractions to "curative" regimens may be invalid. To test this hypothesis, we compared hypofractionated-accelerated treatments with "curative" fractionation schedules in human squamous cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose necessary to control 50% of the tumors locally, were determined after irradiation under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10 fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS: TCD50 values of the hypofractionated regimens were not significantly different and varied from 41 to 46 Gy. The number of fractions given in the same overall time had no measurable effect on local tumor control. The TCD50 after 30 fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens. This effect was caused by a substantial increase of TCD50 with overall treatment time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of the present study compare well with our previous findings after different "curative" fractionation schedules in the same tumor. Thus, our study does not support that tumors respond differently after application of 10 or more fractions compared to less fractionated regimens. The biological mechanisms that govern the radiation response of FaDu tumors appear to be the same for hypofractionated-accelerated and "curative" regimens. Since only one tumor was investigated, these results cannot be generalized at the present time.

Animals↗
PubMed1998

Retroperitoneal ectopic neural mass: "abdominal brain"--presentation of two cases and proposal of classification of paraneuraxial neural ectopia.

An encapsulated mass of brain tissue was found in the retroperitoneum of a fetus of gestational week 15 and a boy of age 3 years. The masses possessed fibrous tissue that bound them to the spine and intraspinal connective tissue, respectively, but there was no evidence of direct continuity of the ectopic brain tissue with the normal central nervous system. There was no dysraphism. In our fetal case, possible Foix-Alajouanine anomaly was additionally found. The ectopic neural tissue in the retroperitoneal region may be termed "abdominal brain." In the literature, an identical state has been described in the head (paracranial region) but there are no other records of the paraspinal region. Despite the different locations of the masses (head/paracranial or retroperitoneum/paraspinal), these ectopic brain masses should belong to the same disorder spectrum of the paraneuraxial neural ectopia, a new concept.

Cell Differentiation↗
PubMed1998

Diverse morphology of biliary atresia in an animal model.

BACKGROUND/AIMS: Extrahepatic biliary atresia can be simulated in Balb/c-mice which have been infected with rotavirus. Irreversible occlusion of the common bile duct is the result of an inflammatory process of the whole biliary tract. The observations in this animal model are similar to extrahepatic biliary atresia in newborn children. The present study describes the wide range of morphological findings in mice and compares the results with several classifications of extrahepatic biliary atresia in children. METHODS: Newborn Balb/c-mice were infected intraperitoneally with rhesus rotavirus; the pathological morphology of the extrahepatic bile ducts in 73 mice is described and illustrated by scanning electron microscopy. RESULTS: The extension and localisation of atresia varied from short to interrupted or long-segment atresia, with or without prestenotic dilatation. The gallbladder was small and atretic, or appeared hydropic due to atresia of the common bile duct. The wide range of pathomorphological findings is the final stage of an inflammatory process. The morphological changes of the extrahepatic bile ducts do not fit any pattern, and no classification is evident. CONCLUSIONS: Most types of extrahepatic biliary atresia in children can be mimicked in this animal model. Comparing these observations with different classifications of extrahepatic biliary atresia in children, it must be asked if any classification of the disease is justified, having regard only to pathomorphological findings in the extrahepatic biliary tract.

Animals↗
PubMed1998

Progress in developing animal models for biliary atresia.

Animal models for extrahepatic biliary atresia (EHBA) have failed to simulate the course of the disease. Until now only a few aspects of the entity could be investigated and no model was helpful in discovering the etiology of EHBA. Following the suspicion of a viral and hepatotropic infection, investigations in an infectious mouse model were continued. The results of previous and topical studies are summarized here. Infection of newborn Balb/c-mice with rhesus rotavirus (RRV) leads to cholestasis in 85% of the animals followed by a lethality of 90%. Preparation and histomorphological investigation of liver and ligamentum duodenale reveal EHBA of varying extent. Clinical course and morphological findings in mice are very similar to EHBA in newborn children and the results are presented in a chronological table. Hepatobiliary morbidity and lethality after RRV infection is higher in Balb/c-mice than in other mouse strains. This observation supports the suspicion that immunocompetence might be a determining factor in the etiology of EHBA. Initial therapeutic trials were made using this model by treating infected newborn mice with interferon-alpha (IFN). The prophylactic application of IFN protects the infected mice from cholestatic symptoms and appears to induce partial immunity. Their descendants are protected against the hepatotropic effect of RRV infection. Infected animals presenting with clinical signs of cholestasis can be treated successfully by IFN-therapy for one week. In the presented animal model. EHBA can be better induced and simulated than by any other method. As a first trial, a non-surgical and more etiologically orientated therapeutic method is tested in this model.

Animals↗
PubMed1998

Linear-quadratic analysis of tumour response to fractionated radiotherapy: a study on human squamous cell carcinoma xenografts.

PURPOSE: To compare values for the alpha/beta ratio in experimental tumours irradiated either under conditions of clamping and short overall time or under more 'clinically realistic' conditions. MATERIALS AND METHODS: Human squamous cell carcinomas, FaDu and GL, were grown in nude mice. Alpha/beta values were determined from local tumour control data after treatment with single doses and 2, 4, and 8 fractions under clamp hypoxia in 3.5 days, using maximum likelihood analysis. Effective alpha/beta values (alpha/beta(eff)) were determined from treatment with 12, 30, and 60 fractions under ambient conditions in a constant overall treatment time of 6 weeks. RESULTS: After correction for an oxygen enhancement ratio of 2.7 the alpha/beta values were 15 Gy (95% CI 9; 24) for FaDu and 49 Gy (26; 122) for GL. In FaDu the TCD50 values after 12 to 60 fractions were not significantly different, the alpha/beta(eff) value was infinite (52; inf.). Unexpected from the high alpha/beta value, the TCD50 values of GL tumours increased from 37 Gy (28; 47) after 12 fractions to 59 Gy (52; 67) after 60 fractions: the alpha/beta(eff) value was 3 Gy (0.6; 12 Gy). CONCLUSIONS: The results support the view that mechanisms other than recovery from sublethal radiation damage and repopulation of clonogenic tumour cells may importantly impact on treatment outcome when the number of fractions is changed in clinical radiotherapy.

Animals↗
PubMed1998

[Complications in children with ulcerative colitis after total colectomy and J-pouch].

Our experience with proctocolectomy and the J-pouch procedure in eight children with ulcerative colitis is reported. The mean age at diagnosis was 8.4 years, and the mean time between diagnosis and colectomy was 2.2 years. We decided on a three-stage operation. The protective ileostomy was removed after approximately 4 months pouch-training. Two patients suffered pouchitis as a specific complication. An ileus occurred in two patients, one patient had a serious eosinophilic enteritis, and two children had multiple abdominal wall abscesses. All patients showed a significant increase in height velocity and the prepubertal patients experienced catch-up growth after the colectomy. All patients are continent during the day. Our experience suggests that proctocolectomy and the ileoanal-J-pouch procedure provide improved growth, continence and a low incidence of surgical complications.

Adolescent↗
PubMed1997

Ectopic neural tissue as an unusual cause of a retroperitoneal tumor.

In a 3-year-old boy an abdominal mass was palpated by chance, which consisted of cystic and solid structures and was shown on ultrasound scan and computed tomography to be located retroperitoneally. Intraoperatively, the cystic tumor contained clear, yellowish fluid and had a stalk leading to the interspinal space between L2 and L3. However, no signs of dysraphism, were found. Neuropathologic examination surprisingly showed non-neoplastic ectopic neural tissue, which has never been recorded at this extraspinal site before.

Child, Preschool↗
PubMed1997

New aspects in a murine model for extrahepatic biliary atresia.

The cause of extrahepatic biliary atresia (EHBA) remains unknown, and even an animal model is still lacking. Observations in a murine infectious model (newborn Balb/c mice infected with rhesus rotavirus group A [RRV]) reported extrahepatic biliary obstruction similar to findings in children who have EHBA. In the present study, this animal experiment was repeated, and the clinical and histomorphologic changes were observed over 3 weeks. Eighty-nine newborn mice were infected with RRV, and 67% showed signs of cholestasis and delayed growth. Eight of these animals recovered spontaneously whereas the others remained icteric. Fourty-six pups were prepared for microscopic examination following a 2-day interval. From the fifth day, the whole biliary tract showed edematous swelling with cellular infiltration. Ten days later, in the extrahepatic bile duct, a transformation took place in which concentric infiltration led to complete obstruction, sometimes with prestenotic dilatation. The intrahepatic changes showed reactive necrosis and proliferation of the small bile ducts. In one 19-day-old mouse, a ballooning dilatation was observed, similar to a developing choledochal cyst. Infection with RRV induces in newborn Balb/c mice a cholestatic clinical picture with different courses of the disease leading mostly to complete biliary obstruction and secondary hepatic changes similar to EHBA in children. This is the first animal model for EHBA with complete obstruction of the extrahepatic bile duct induced by infection. These findings present a new basis for further studies.

Animals↗
PubMed1997

Surgical therapy and follow-up of pancreatitis in children.

BACKGROUND: Acute and chronic pancreatitis in children differ from that in adults both from the etiology and the therapeutic approach. Within the frame of a blunt abdominal trauma-the most frequent cause in children-acute pancreatitis is often detected by emergency laparotomy and external drainage is recommended. Chronic relapsing pancreatitis, and particularly its hereditary form, is very rare in children and requires a different therapeutic concept. The results of surgical therapy for both forms of pancreatitis in childhood were evaluated in the present study. METHODS: Sixteen patients with acute and chronic relapsing pancreatitis were operated on in our facility between 1976 and 1988. Their history and postoperative course were analyzed in a retrospective study, including a final examination at the end of the follow-up period. RESULTS: Eight children with acute pancreatitis were operated on at an average age of 6 years and were followed up for an average of 7.5 years, with good results. The remaining children, aged between 3 and 14 years (average age of 9 years), were operated on for chronic relapsing pancreatitis. Our experience with early operative treatment, on average 2.7 years after onset of symptoms, is presented. Only three patients experienced a mild relapse during the follow-up period of 2-13 years (average of 5.4 years). CONCLUSIONS: For acute pancreatitis in childhood, operative treatment by inner drainage is necessary and effective only in case of complications, should conservative treatment fail. In children with chronic relapsing pancreatitis, the good exocrine and the normal endocrine function of the pancreas in these patients justified the early operation. Timely treatment is recommended in cases with typical changes of the pancreatic duct so as to shorten the relapsing clinical problems of the children and to maintain the function of the pancreas.

Abdominal Injuries↗
PubMed1997

Treatment of extrahepatic biliary atresia with interferon-alpha in a murine infectious model.

The etiology of extrahepatic biliary atresia (EHBA) in newborns remains unknown, although a first infectious animal model with complete obstruction of the common bile duct could be established. Intraperitoneal inoculation of newborn Balb/c mice with rhesus rotavirus induced cholestasis, leading, in most cases, to biliary atresia with lethal outcome, similar to EHBA in human newborns. The influence of interferon-alpha (IFN-alpha) on the hepatotropism of rotavirus infection was investigated in this animal model. Single-dose therapy with 10000 IU of IFN-alpha protected all rhesus rotavirus-infected pups from cholestatic disease. The same dose, injected 5 d after infection, had no protective effect. Starting with onset of cholestatic symptoms, the treatment with 10000 IU of IFN-alpha daily showed good results in 29 mice. Seventy-six percent of the mice recovered after 1 wk of therapy. Histologic investigation revealed normal findings in the hepatobiliary tract of clinically normal mice. Twenty-one percent of the descendants of infected and prophylactic IFN-alpha-treated mice showed cholestatic symptoms after infection with rhesus rotavirus (79% in an untreated control group) and a milder form of the illness. In conclusion, we found that prophylactic treatment with IFN-alpha prevented the hepatobiliary system of newborn Balb/c mice from severe damage by rhesus rotavirus in this artificially designed infectious model for EHBA. Infected and icteric mice, treated for 1 wk with IFN-alpha, had good prospects for recovery and prevention of complete and irreversible occlusion of the extrahepatic bile ducts. Infected and prophylactic IFN-alpha-treated dams gave good protection to their descendants. This means that EHBA in this model could probably be averted by maternal antibodies against rotavirus.

Animals↗
PubMed1997

The female pelvic floor: a dome--not a basin.

BACKGROUND: Classically and based on necropsy observations, the muscles of the pelvic floor (the levator ani and coccygeus muscles) have been described as having the shape of a basin. In a previous study by Hugosson et al. (1991), magnetic resonance imaging revealed the dome shape of the pelvic floor in live subjects when muscular tonus is present. METHODS: The normal anatomy and the dynamic movements of the female pelvis were examined with magnetic resonance imaging including conventional and fast sequences. Six nulliparous and six parous healthy women without signs or symptoms of pelvic relaxation were studied in the supine position at rest, during voluntary pelvic contractions and during bearing down. RESULTS: The levator ani muscle was dome-shaped at rest. During voluntary pelvic contractions the muscle straightened, becoming more horizontal and during bearing down it descended, becoming basin-shaped. The width of the genital hiatus was the same in both groups at rest and it widened during bearing down in all but two 3-para women. The bladder base was lifted upward and forward during voluntary pelvic contractions but during bearing down it descended. The rectum at rest had a posterior angle which decreased during voluntary pelvic contractions and increased during bearing down. CONCLUSIONS: MRI of the female pelvis is valuable in anatomic and dynamic analysis in healthy women and offers new information about the female pelvic floor. The female pelvic floor is shaped like a dome-not like a basin.

Adult↗
PubMed1997

[Surgical treatment of chronic pancreatitis in children].

Chronic relapsing pancreatitis and its hereditary form are very rare in children. Our experience with early operative treatment in nine children is presented. The good exocrine and endocrine function of the pancreas in these patients justifies early operation when typical changes of the pancreatic duct are present since it shortens the relapsing clinical course and maintains good function of the pancreas.

Adolescent↗
PubMed1996

Cryptosporidiosis among patients infected with human immunodeficiency virus. Factors related to symptomatic infection and survival.

The authors reviewed the medical records of 194 human immunodeficiency virus (HIV)-positive patients newly diagnosed with cryptosporidiosis and all 3,564 patients with newly diagnosed acquired immunodeficiency syndrome (AIDS) at San Francisco General Hospital for the period 1986-1992. The study was designed to address three questions: 1) How do AIDS patients who present with cryptosporidiosis differ from other patients with AIDS? 2) What factors are associated with survival among AIDS patients with newly diagnosed cryptosporidiosis? 3) Does a diagnosis of cryptosporidiosis impact survival after AIDS diagnosis? A total of 194 cases of cryptosporidiosis among HIV-infected patients were identified during the study period. Of the 194 patients, 109 (56%) had no prior diagnosis of AIDS. These 109 patients represented 3.1% of the 3,564 newly diagnosed cases of AIDS in the same period. Among the 134 patients with CD4 T-lymphocyte counts performed within 3 months of Cryptosporidium diagnosis, 34 (25%) had CD4 counts greater than 209 cells/ml. In a multivariate conditional logistic regression model, the incidence of Cryptosporidium was related to ethnicity (for blacks vs. whites, matched odds ratio (OR) = 0.15, 95% confidence interval (CI) 0.03-0.73), CD4 count (for a CD4 count of < or = 53 cells/ml vs. > 53 cells/ml, matched OR = 12.60, 95% CI 4.01-39.61), and age (for a 10-year increase, matched OR = 0.51, 95% CI 0.27-0.98). Two factors measured at the time of Cryptosporidium diagnosis were identified as being independently associated with survival (p < 0.001) in the proportional hazards model: CD4 count < or = 53 cells/ml versus > 53 cells/ml (relative hazard = 6.18, 95% CI 2.99-12.76) and hematocrit < or 37% versus > 37% (relative hazard = 2.27, 95% CI 1.22-4.22). The median durations of survival in the four subgroups of Cryptosporidium-infected patients defined by these two variables differed significantly from each other (range, 204-1,119 days). Cryptosporidiosis as an initial AIDS-defining diagnosis was associated with an elevated relative hazard of death in comparison with other AIDS-defining diagnoses (relative hazard = 2.01, 95% CI 1.38-2.93). These data identify the groups of HIV-infected individuals at risk for presentation with symptomatic Cryptosporidium infection; the distinct survival patterns among subgroups of those patients already infected with this parasite; and the survival of AIDS patients with newly diagnosed cryptosporidiosis relative to patients with other AIDS-defining conditions. Such information is necessary for the design of prospective studies, the development of prophylactic strategies, the evaluation of candidate therapies, and the provision of prognostic information to patients.

AIDS-Related Opportunistic Infections↗