Biomedical subjects
Publications and source records attributed to M Anderson.
An 8-week-old female cougar with a history of acute perineal swelling was determined to have a perineal hernia. The hernia was repaired with the conventional suture technique. This case represents an unusual perineal hernia, which may have been congenital.
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The mitochondrial DNA of the trypanosomatid Crithidia fasciculata consists of thousands of copies of a 2.5 kb minicircle and a small number of 37kb maxicircles catenated into a single enormous network. Treatment of C. fasciculata with the type II DNA topoisomerase inhibitor VP16 produces cleavable complexes of a type II DNA topiosomerase with both minicircles and maxicircles. A combined Southern and Western blot analysis of the cleaved DNA species released from the network by SDS treatment has identified topollmt, the kinetoplast-associated topisomerase, in covalent complexes with linear forms of minicircle and maxicircle DNAs. These results directly implicate topollmt in the topological reactions required for the duplication of the kinetoplast network.
A mouse strain with low lung tumor susceptibility (C3H) and a strain with high lung tumor susceptibility (A/J) were reciprocally crossed to produce C3A and AC3 F1 hybrid mice. Ki-ras oncogenes were detected in spontaneous and chemically induced lung tumors obtained from the C3A and AC3 mice. To further explore the genetics of the Ki-ras gene in mouse lung tumor susceptibility, the parental origin of Ki-ras oncogenes detected in lung tumors from the F1 hybrids was determined by a strategy based on a 37-base-pair deletion in the second intron of the A/J Ki-ras allele. Ki-ras oncogenes were derived from the A/J parent in 38 of 40 tumors obtained from C3A mice and 30 of 30 tumors from AC3 mice. The observation that the activated oncogene in hybrids originates from the susceptible parent suggests that the Ki-ras gene is directly linked to mouse lung tumor susceptibility. This finding may have implications for pulmonary adenocarcinoma development in humans, since Ki-ras oncogenes are detected in 35% of this human tumor type.
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The management of women with mild to moderately dyskaryotic cervical smears would benefit from a non-invasive test that predicts which women have high-grade cervical intraepithelial neoplasia. Detection of human papillomavirus type 16 (HPV16) DNA in cervical smears may be such a test. With the polymerase chain reaction (PCR), we estimated the amount of HPV16 DNA in cervical smears from 85 women referred for colposcopy because of abnormal cytology. An intermediate or high amount of HPV16 DNA predicted the presence of high-grade cervical intraepithelial neoplasia in a subsequent biopsy in almost 90% of patients irrespective of the cytological grade of the referral smear. This technique may allow early identification of those women with low-grade cytological abnormalities who have high-grade underlying cervical disease.
Murine trisomy 16 (mts16) placentas and fetuses, 17-day gestation age, were examined histologically and by magnetic resonance imaging at 9.4 T and compared with control littermate tissues. Placentas were studied by immunohistochemical methods, at 15-days gestational age, for expression of the major histocompatibility complex (MHC) class I H-2Kk cell surface marker. Immunohistochemical studies revealed a markedly increased expression of the MHC marker H-2Kk on cells in the labyrinth of the placenta of mts16. There were differences between the magnetic resonance (MR) images of the trisomic and normal placentas, which may be correlated with the increased expression of H-2Kk in the mts16 placental labyrinth. The decidual and labyrinthine components of the normal placentas showed similar high signal intensities (SI) while in trisomic placentas a marked high SI was characteristic only of the decidual region on proton spin density images. The MRI also revealed a smaller cerebellum in the ts16 fetuses. The potential effects of the compromised structure of the placental labyrinth and the overexpression of the H-2Kk marker on the mts16 neural and placental dysgenesis are discussed.
Gene expression of visna virus is highly restricted in monocytes, but is induced when monocytes differentiate into macrophages. A previous study on differential regulation of visna virus gene expression revealed that a specific AP-1 site in the long terminal repeat of the viral DNA is required for phorbol-ester-induced gene expression in macrophages (Gabuzda, Hess, Small, and Clements, Mol. Cell. Biol., 9, 2728-2733). In the present investigation, we examined the association of two DNA binding proteins, the proto-oncogene proteins FOS and JUN, with this AP-1 site in the visna virus LTR. We demonstrated that the concentrations of these two proteins and their mRNAs increased in U937 cells after phorbol ester induction. Furthermore, the binding of cellular proteins from the U937 nuclear extracts to this AP-1 site was significantly decreased in the presence of antibodies to JUN and FOS. In vitro-translated JUN protein also binds to this AP-1 sequence, and this binding is enhanced by the FOS protein. These results indicate that JUN and FOS are directly involved in the differential regulation of visna virus gene expression.
Workers at a cadmium recovery plant in Globe, Colorado, showed an increased risk of lung cancer, which some investigators have attributed to cadmium exposure. We conducted a cohort mortality analysis of this work force and a case-control analysis of the lung cancer cases within this work force in order to assess the probable causes of the lung cancer excess. The Globe plant began as a lead smelter about 1886, switched to arsenic production in 1920, and became a cadmium metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are three potential lung carcinogens found in this workplace. Industrial hygiene data collected from 1943 onward served as the basis for the National Institute for Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned cadmium exposure estimates to employees based on their work area in the plant and calendar time. Few exposure data existed for substances other than cadmium. Feedstock ore concentrations were used as a surrogate measure of air arsenic levels. The arsenic content of the fines used as feedstock prior to 1940 was considerably higher than that of the fines used after 1940. Smoking histories had been obtained previously for 45% of the workers. A case-control analysis of the 25 cases of lung cancer known to have occurred among these workers through 1982 was conducted using three controls per case, matched by closest data of hire and age at hire. Potential causal agents for lung cancer included cadmium exposure, cigarette smoking, and arsenic exposure. Exposure variables for each case and control included estimated cumulative cadmium exposure in milligram-years per cubic meter, cigarette smoking history, and plant arsenic exposure status at the time of hire. Estimated cumulative cadmium exposures of cases and controls did not differ overall or within the date-of-hire strata. Cases were more than eight times more likely to have been cigarette smokers than were controls. Lung cancer risk in this workplace was more closely related to the period of hire, not to the cumulative cadmium exposure. The period of hire appears to be a surrogate for arsenic exposure as related to feedstock. The measures used here seem to indicate that exposure to arsenic and cigarette particulates, rather than to cadmium particulates, may have caused the increased rate of lung cancer of these workers.
The simian immunodeficiency virus, SIVmac, causes disease affecting multiple organ systems in macaques similar to human immunodeficiency virus infection in humans. Molecularly cloned SIVmac with a strong lymphocyte tropism was used in pathogenesis experiments to correlate viral cell tropism with disease. In 5 animals, exhaustive analyses on viruses from tissues and identification of infected precursor cells were done at multiple times during infection to ensure the virus had not mutated into a macrophage-tropic variant. Viral replication was measured by infectivity, infectious center assays, and in situ hybridization. Lymphocytes produced most virus in tissues, indicating the virus maintained its cell tropism in vivo. Lymphocytes in bone marrow were latently infected and those in the spleen and lymph nodes were productively infected. The virus failed to replicate in the brain after intracerebral inoculation. SIVmac that maintained a strong tropism for lymphocytes and a corresponding poor tropism for macrophages can cause persistent infection and AIDS but not other diseases such as primary pneumonia and encephalitis in rhesus macaques.
Both CT and MRI may play an important role in the initial assessment and subsequent management of patients with gynecologic cancer. The different capabilities of these examinations make the choice of test dependent on what portion of the body is visualized (e.g., chest, upper abdomen, or pelvis) and what information is sought. Body imaging can be scheduled appropriately when the findings from the study will have a significant impact on patient management (e.g., operative versus nonoperative management, selection of treating physician, and initial modality of treatment). However, the limitations of each modality must be appreciated. In general, a negative CT or MRI will not exclude the possibility of small volume disease involvement, and a critical positive study should, when practical, be histologically confirmed. Neither test stands alone, but each plays a role when integrated with careful clinical history, physical examination, and other laboratory and radiologic examinations.
A case is reported of acute respiratory distress in an adult that was caused by a bronchogenic cyst. Bronchogenic cyst in an adult may be seen on chest X-ray and confirmed by computerized tomography (CT) scanning. Surgical excision can provide dramatic relief.
Visual fields were mapped with kinetic are perimetry in 23 migraine with aura subjects and, for comparison, in 20 migraine without aura subjects and in 21 non-headache controls. Central vision on the Amsler eye chart and visual perception threshold on a computer task were also investigated. Measures were obtained at least seven days after an episode of migraine. In addition, 10 of the migraine with aura subjects and 10 migraine without aura subjects were studied the day after an attack. The day after migraine with aura, visual sensitivity in the periphery of the visual fields was depressed, central vision was blurred, and visual perception threshold was elevated. These visual disturbances had resolved 7 to 10 days later. With the exception of a minor increase in visual perception threshold, vision was normal after attacks of migraine without aura. Residual effects of the migraine aura could mediate the subclinical visual disturbances which persist for at least one day after attacks of migraine with aura.
OBJECTIVE: To assess the efficacy of cervical conization as primary management of cervical intraepithelial glandular neoplasia (CIGN). DESIGN: A multicentre prospective cohort study. SETTING: CRC Clinical Trials Unit, Birmingham. SUBJECTS: 84 women registered with the Unit between May 1986 and January 1989. After excluding 33 women, 51 who had been managed in accordance with the described protocol and had the presence of CIGN confirmed by central review of diagnostic histopathological material were included in the study. INTERVENTION/PROTOCOL: Women with CIGN diagnosed on a cervical cone specimen were managed in accordance with a specific protocol: (a) women with negative cone margins were managed conservatively and followed up with regular cervical cytological and colposcopic examinations; (b) women with involved cone margins were managed by hysterectomy. MAIN OUTCOME MEASURES: Presence or absence of CIGN at cone margins, results of cervical cytological examinations following conization, results of histopathological assessment of any surgical specimens taken after initial cone biopsy. RESULTS: Of the 51 women with confirmed CIGN, managed by conization, 14 (27%) were aged 30 or less and 15 (29%) were nulliparous. Thirty five women who had a cone biopsy showing margins free of CIGN have been managed by conization alone. After a median follow-up period of 12 months there is no apparent residual CIGN or invasive disease in this group. Thirteen women have had further surgical procedures (according to protocol) and two have had a hysterectomy for benign gynaecological disorders. Eight further procedures were carried out because the original cone biopsy had margins involved with CIGN, and only one of them was found to have residual CIGN. The other five procedures were carried out solely because of abnormal cytology, only one of them had a diagnosis of CIN 1. A total of 10 women had cytological abnormality following cone biopsy, one had CIGN, one had CIN 1 and a third had CIN 3. CONCLUSIONS: Our preliminary data suggests that when a diagnosis of CIGN is made upon a cone biopsy, further surgery is unnecessary in those women in whom the margins of the cone specimen are free of disease. Cytological and colposcopic follow up, including cytological sampling of the endocervical canal, is recommended for these women.
Twenty-one horses had a complete unilateral humeral fracture during race training or racing at a California racetrack during the period 24 February 1990 to 10 July 1991. Fractures occurred approximately equally in left and right limbs, and in males and females. Most fractures occurred during training, and in 2- and 3-year-old horses. Only 5 of 16 Thoroughbred horses with known racing records had previously raced more than once, and their mean time between races was less than the time between their last race and fracture (P = 0.07). Ten of 13 humeri studied further had gross evidence of periosteal callus bridging one portion of the fracture line, indicative of a pre-existing stress fracture.
Neurological disease resulting from lentivirus (including human immunodeficiency virus) infections is usually caused by a strain of virus that replicates productively in microglia in vivo and in macrophage cultures in vitro. We undertook this study using the model of simian immunodeficiency virus in macaques (SIVmac) to test the hypothesis that macrophage tropism is a prerequisite for neurotropism of the virus. Using molecularly cloned SIVmac239, a virus which is lymphocyte- but not macrophagetropic, we showed that this virus failed to infect brain after intracerebral (i.c.) inoculation into two macaques. Rather, these inoculations resulted in disseminated infection in lymphoid organs and the bone marrow. Two sequential passages of infected bone marrow cells inoculated i.c. into new macaques resulted in severe neurological disease and classical neuropathological lesions. Virus obtained from affected brain answered the hypothetical question: it was neurotropic and macrophagetropic. New findings in the study were that both lymphocyte- and macrophage-tropic viruses were present in the animals, but the viruses localized in different tissues: the lymphotropic virus in the spleen, lymph nodes, and plasma and the macrophagetropic virus in the brain and lungs. To determine whether the brain virus was preferentially neurotropic and whether it had neuroinvasive properties, infectious brain homogenate was inoculated into one animal i.c. and into two others peripherally. The i.c. inoculated animal developed fatal encephalitis 5 months later, and examination of tissues showed cell-free virus only in brain homogenates. Only microglia were infected despite persistent viremia and infection in bone marrow cells. The two macaques inoculated peripherally remained healthy and were euthanized at 6 months. Virus replication was detected only in the bone marrow cells and peripheral blood mononuclear cells. No infection in any macrophage population in visceral organs was detected, and the virus did not invade the brain. The strictly microglial specificity of this virus suggested that different macrophage populations in the body may select specific phenotypes of lentivirus from the quasispecies of virus in the bone marrow. This could provide the basis for specific disease affecting different organ systems.
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