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Biomedical subjects

C J Frank

Publications and source records attributed to C J Frank.

At least 19 recordsLinked to original sources

Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases.

SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways.

Animals↗

Bilateral interconnected latissimus dorsi-gluteus maximus muscular cutaneous flaps for closure of subfascial infections in lumbar spinal surgery. A technical note.

STUDY DESIGN: A surgical technique for primary closure of postoperative subfascial infections is described. OBJECTIVES: To describe the methods and indications for the use of the interconnected latissimus dorsi-gluteus maximus flap. SUMMARY OF BACKGROUND DATA: Closure of subfascial postoperative infection can be complicated by soft tissue defects and retained implants. Healing by secondary intention is expensive and gives unpredictable coverage of retained hardware. METHODS: A bilateral interconnected latissimus dorsi-gluteus maximus flap was used to cover resultant soft tissue defects according to techniques previously described for the delayed primary closure of myelomeningocele defects. RESULTS: Stable, durable, drainage-free soft tissue coverage was obtained in all patients treated with this technique. CONCLUSION: The latissimus dorsi-gluteus maximus flap represents an effective, economical option for the treatment of patients with subfascial infection after instrumented spinal fusion surgery.

Fascia↗

Evidence that loss of chromosome 18q is associated with tumor progression.

Four sets of cell lines (UM-SCC-14A, -14B, and -14C; UM-SCC-17A and -17B; UM-SCC-81A and -81B; and UM-SCC-83A and -83B), established from primary and metastatic or locally recurrent tumors from four patients with squamous cell carcinoma of the head and neck, were examined for loss of heterozygosity (LOH) on chromosome 18q. Metastatic or recurrent cell lines from all four exhibited 18q LOH. UM-SCC-14A, -14B, and -14C, which were derived from locally recurrent (14A and 14B) and metastatic (14C) tumors, lost all of 18q. However, in the other three cases, there was a partial loss of 18q in the recurrent or metastatic tumor cell lines but not in the primary tumor cell lines from the same patient. To determine whether the cell lines accurately reflect in vivo loss of 18q, we analyzed matched sets of normal, tumor, and tumor cell line DNA from eight patients with squamous cell carcinoma of the head and neck, including the tumor tissue corresponding to UM-SCC-81B. Three of the additional seven tumors and cell lines had 18q LOH. For all eight cases in which tumor and corresponding cell line DNAs were analyzed, there was complete concordance between allelic loss in the tumor and allelic loss in the corresponding cell line. The common region of loss established by tumors and cell lines with partial loss includes 18q21-18qter. This region contains the putative tumor suppressor gene DCC and two Mad (Mothers against dpp)-related genes, DPC4 and MADR2, which are both components in a transforming growth factor-beta-like signaling pathway. Loss of 18q in metastatic and locally recurrent tumors, but not in primary tumors from the same patients, suggests that a tumor suppressor gene in this region may be important in the progression of squamous cell carcinoma.

Carcinoma, Squamous Cell↗

Identifying genetic changes associated with tumor progression in squamous cell carcinoma.

Tumor behavior is the result of specific genetic changes that alter gene expression. From our cytogenetic studies chromosome 18 loss emerged as a common genetic change in squamous carcinoma cell lines. In this report we summarize data that link loss of 18 to tumor progression and reduced survival, indicating that one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown in vitro were karyotyped either as short-term or permanent cultures. Loss of chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in approximately 63% of cultured tumors. Primary and secondary tumors from the same individuals sometimes differed in loss of 18 indicating that this genetic change is associated with tumor progression. Heterozygosity for DCC was present in only 3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from unrelated donors, which is consistent with LOH in roughly one half of the cases. Of 4 informative cases with normal and tumor tissue, LOH was observed in 2. Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis of tumor tissue and cell lines from the same patient gave identical results. There was an excess of deaths from cancer in the group with 18 loss (20/25) when compared with the group without (5/15). Loss of chromosome 18 appears to be a marker of tumor progression in SCC. It is likely that mutation affecting DCC or another gene on 18 affects tumor growth or spread, leading to more rapid progression and reduced survival.

Carcinoma, Squamous Cell↗

Raman spectroscopy of normal and diseased human breast tissues.

Raman spectra of histologically normal human breast biopsy samples were compared to those exhibiting infiltrating ductal carcinoma (IDC) or fibrocystic change. Experiments at 784 nm with CCD detectors reduced fluorescence interference and produced high SNR spectra with relatively low (10-200 mW) laser power. Sample to sample and patient to patient variation for normal specimens were less than 5% for the ratios of major Raman bands. The Raman spectra changed dramatically in diseased specimens, with much weaker lipid bands being evident. The spectrum of infiltrating ductal carcinoma samples is similar to that of human collagen. Differences between benign (fibrocystic) and malignant (IDC) lesions were smaller than those between normal and IDC specimens, but were still reproducible. Fiberoptic sampling through a hypodermic needle and with a remote probe were demonstrated. The possibility of rapid diagnosis with Raman spectroscopy is considered.

Biopsy↗

Acetabular fractures.

Acetabular fractures are not uncommon injuries of the pelvis. They are most frequently associated with high energy trauma such as that seen in a motor vehicle accident. Management of patients with acetabular fractures includes careful attention to ATLS (advanced Trauma Life Support) protocols and delayed operative treatment of the acetabular fractures. Diagnostic evaluation with plain radiography and CT is used to plan the treatment approach. Treatment includes not only the recognition of the fracture but avoidance of early and late complications. Emergent treatment includes closed reduction of associated hip dislocations followed by skeletal traction. Delayed reconstruction at four days after the injury decreases intraoperative blood loss by allowing retroperitoneal hemorrhage to subside. Final outcome after acetabular trauma depends not only on the reconstruction of the fracture, but the avoidance of complications. Acetabular fractures are becoming an increasingly common orthopedic injury. Fractures of the acetabulum (or hip socket) are most commonly seen after motor vehicle accidents. Young patients (18 to 30 years old) are typically affected. A frequent mechanism of injury is a direct blow to the anterior aspect of the knee with the hip flexed such as a dashboard injury in an automobile accident. Other mechanisms of injury include direct blows to the lateral aspect of the hip as in a fall from a height or a side impact automobile collision.

Accidents, Traffic↗

Characterization of human breast biopsy specimens with near-IR Raman spectroscopy.

Breast biopsy samples were examined with Raman spectroscopy with laser wavelengths ranging from 406 to 830 nm. A combination of a single-stage spectrograph, band reject filter, and CCD detector permitted low laser powers and minimal risk of sample radiation damage. Spectra of formalin-fixed human tissue revealed Raman features for lipids and carotenoids. The best defined lipid features were observed for 782- and 830-nm laser excitation, while carotenoid features were strongest in the 488-515-nm range due to resonance enhancement. Comparison of the spectra with those of fatty acid esters revealed that the major lipid component is a derivative of oleic acid. Lipid and carotenoid Raman bands were superimposed on a luminescent background which was less prominent at longer laser wavelengths. A compact, portable, diode laser spectrometer was tested in a clinical setting with fiber optic sampling. The results indicate that substantial biochemical information is available from near-IR Raman spectroscopy and the technique may have clinical applications.

Biopsy↗

A viral subunit immunogen for porcine transmissible gastroenteritis.

An immunogenic component was isolated from both the Illinois (propagated in young swine) and the Miller (cell culture-adapted) strains of porcine transmissible gastroenteritis (TGE) virus. The viral subunit was released from the virion by sonication and was separated from intact virus and other viral components by isopycnic centrifugation. It had a buoyant density in sucrose of 1.02 g/ml. Further purification consisted of gel filtration through Sephadex G200, in which process the immunogen, with a molecular weight of approximately 25 000, was the last component to be eluted. A group of ten young, weaned swine, inoculated intramuscularly with two or three 1-mg doses of the viral subunit were protected against challenge with virulent TGE virus, probably by the induction of secretory IgA. The immunogen also induced a humoral immune response of variable magnitude (titers ranging from 8 to 5 625) in the animals. These antibodies are not believed to be directly related to protection against infection. They can, however, be easily identified by serologic procedures and may serve as a convenient indicator of responsiveness to the TGE viral immunogen.

Animals↗

Lactogenic immunity to transmissible gastroenteritis virus induced by a subunit immunogen.

A subunit prepared from transmissible gastroenteritis (TGE) virus and used to immunize 24 gilts prior to farrowing induced production of specific antibody in the serum and milk. Challenge of pigs, two to seven days of age and suckling on the vaccinated gilts, with the Illinois strain of TGE virus resulted in morbidity of 28% and mortality of 4% as compared with 100 and 73%, respectively, for control piglets. Piglets nursing on a sow which had been immunized approximately 10 months previously were not protected, indicating that lactogenic immunity may be of short duration. Revaccination of this animal resulted in an anamnestic response.

Animals↗

Contagious equine metritis: the present situation reviewed and a revised code of practice for its control.

This report contains details of the code of practice for the control of contagious equine metritis (CEM) during the 1979 breeding season. It was prepared under the guidance of a scientific committee established by the Horserace Betting Levy Board under the chairmanship of Sir David Evans, FRS. The code is similar to the one introduced for the 1978 breeding season but takes into account the experience gained during the past 12 months. Following discussions with colleagues in Ireland it has been agreed that a similar code of practice will be introduced in the United Kingdom and Ireland so as to facilitate a uniform policy for the control of CEM. A summary of this report will be circulated to thoroughbred mare and stallion owners.

Animals↗

The current position of A.I. in horse breeding.

This short review article describes the various techniques currently available for artificial insemination in the horse. The collection and use of raw and extended semen is discussed together with the more recent developments in freezing semen. The expected conception rates with both fresh and frozen semen are quoted. The possible benefits in disease control and stud management are discussed, as well as the difficulties in controlling the use of A.I. from the Breed Registration Authorities point of view.

Animals↗