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Biomedical subjects

C L Witte

Publications and source records attributed to C L Witte.

At least 73 records · Page 4Linked to original sources

Contribution of the liver to thoracic duct lymph flow in a motionless subject.

To ascertain the contribution of the liver to thoracic duct lymph (TDL) flow in a resting subject, afferent hepatic blood flow was temporarily interrupted in dogs by placing an atraumatic clamp across the hepatoduodenal ligament containing the hepatic artery, portal vein and 80% of hepatic lymphatic drainage. To circumvent extrahepatic splanchnic venous sequestration, a side-to-side portacaval shunt (S-S-PCS) was constructed prior to interrupting blood flow. Portal venous pressure, cervical TDL flow, and total protein content were serially monitored. TDL and total protein after S-S-PCS was comparable to that recorded in dogs without celiotomy (0.60 +/- 0.17 ml/min and 3.4 +/- 0.5g/dl, respectively). Interruption of hepatic blood flow was associated with a fall in TDL flow (0.38 +/- 0.8ml; p less than 0.001) and protein content (2.8 +/- 0.7g/dl; p less than 0.01) and TDL/plasma protein ratio (0.58 +/- 0.7 to 0.48 +/- 0.05; p less than 0.01). These data suggest that in the absence of supplemental fluid administration or other exogenous stimulation, hepatic lymph contributes one-third of resting TDL flow.

Animals↗

Documentation of an AIDS virus infection in the United States in 1968.

The acquired immunodeficiency syndrome was first recognized as a clinical entity in the United States in the early 1980s; however, the issue of when human immunodeficiency virus, the causative agent of the acquired immunodeficiency syndrome, was introduced into at-risk populations in the United States is unresolved. Previously, we reported the case study of a 15-year-old black male who was admitted to St Louis City Hospital in 1968 for extensive lymphedema of the genitalia and lower extremities. Chlamydial organisms were widely disseminated and isolated from numerous body fluids and organs. Over a 16-month clinical course his condition progressively deteriorated, and at autopsy there was widespread Kaposi's sarcoma of the aggressive, disseminated type. Recently performed Western blot and antigen capture assays on serum and autopsy tissue specimens frozen since 1969 have disclosed that this sexually active teenager was infected with a virus closely related or identical to human immunodeficiency virus type 1. The clinical and immunologic findings together suggest that an immunosuppressive retrovirus existed in the United States before the late 1970s.

Acquired Immunodeficiency Syndrome↗

Splenic salvage quantified by uptake of heat-damaged radiolabeled red blood cells. Experimental and clinical studies.

We evaluated a noninvasive radionuclide technique to quantify splenic trapping function, which is a key step in the disposition of blood-borne particulates such as poorly opsonized encapsulated microorganisms implicated in hyposplenic fulminant sepsis. Using computerized external gamma imaging, the percentage of splenic uptake of heat-damaged radiolabeled red blood cells was determined in adult Sprague-Dawley rats with eutopic (partial splenectomy) or ectopic (single or multiple autotransplantation) remnants or whole spleens, and in 14 patients with either an intact spleen or splenic remnants after treatment for trauma or hypersplenism. The masses of both eutopic and ectopic remnants correlated directly with the percentage of heat-damaged red blood cell uptake, but the percentage of uptake per gram was higher in eutopic remnants, paralleling more vigorous compensatory growth. In patients, the percentage of heat-damaged red blood cell uptake by remnant spleens was similar to that seen in the rats and, in addition, was supernormal in those with congestive splenomegaly. This noninvasive technique both provides a vivid biplanar image and quantifies blood-borne particle trapping, which is a key splenic function. A heat-damaged red blood cell uptake of less than 15 percent after splenic salvage suggests marginal splenic performance and continued vulnerability to overwhelming sepsis.

Animals↗

AIDS-Kaposi's sarcoma complex: evolution of a full-blown lymphologic syndrome.

An hypothesis is presented to explain the link between acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma (KS). According to this hypothesis, AIDS involves all four components of the integrated lymphatic system--lymphatics, lymph nodes, lymphocytes, and lymph--and thereby resembles various congenital and acquired lymphologic syndromes characterized by one or more of the following features: lymphostasis, angiogenesis, and fibrosis; depletion of immunocompetent cells and immunosuppression; opportunistic infections; and vascular neoplasms. A better understanding of the steps in the evolution of these processes and their interrelationships to the four components of the lymphatic system should provide insight into the immunopathogenesis of AIDS-KS as well as its detection and treatment.

Acquired Immunodeficiency Syndrome↗

Splenomimetic effect of Corynebacterium parvum in fulminant pneumococcemia.

The efficacy of Corynebacterium parvum to stimulate splenic growth and to boost host survival was examined by using adult Sprague-Dawley rats in a highly spleen-sensitive model of fulminant pneumococcemia. Rats were either treated (10 days or 1 hr before or 1 hr after) or not treated with C. parvum; were depleted of complement; underwent partial, total, or sham splenic resection; and then were challenged with either a low (2 X 10(2)) or a high (2 X 10(5)) dose of pneumococci. In the absence of C. parvum, survival (percent and duration) was lowest after total splenectomy and was proportional to remnant spleen weight after partial splenectomy. Although C. parvum treatment sharply increased splenic weight, nucleated cell numbers, and survival, the lowered mortality and improved survival time were independent of spleen weight. The rapidly acting, extrasplenic, splenomimetic protective effect of C. parvum suggests that this class of immunomodulators may be a useful adjunct in managing sepsis associated with defective or absent splenic function.

Adjuvants, Immunologic↗

Lymphatics and blood vessels, lymphangiogenesis and hemangiogenesis: from cell biology to clinical medicine.

The past 15 years have witnessed an explosion of knowledge about blood vascular endothelium due in large part to in vitro growth of endothelial cells from both large blood vessels and capillaries. In contrast, little comparable information has accumulated on endothelium of lymphatics, which lie in intimate contact with parenchymal cells and drain excess fluid, macromolecules, particles, and immunocompetent cells in a continuous recirculation between tissues and bloodstream. While structural and functional differences between the two vascular systems have been described in vivo, in tissue sections, and in isolated preparations, similarities are notable in ultra-structure, biochemistry, physiology, and pharmacologic responsiveness, and these may predominate under pathologic conditions. In 1984, three separate groups described in vitro culture of lymphatic endothelial cells from collecting ducts and cavernous lymphangiomas. Lymphatic, like blood vascular, endothelium grows in confluent monolayers, "sprouts", synthesizes Factor VIII-associated antigen and fibronectin, and ultrastructurally shows Weibel-Palade bodies; overlapping intercellular junctions and anchoring filaments typical of lymphatic endothelium are also found. Genetic, congenital, and acquired disorders such as strangulating fetal nuchal cystic hygromas (Down and Turner syndromes), vascular tumors and dysmorphogenesis (Maffucci and Klippel-Trenaunay syndromes), Kaposi's sarcoma, lymphogenous and hematogenous spread of cancer, and parasitic infestations such as filariasis, share overlapping abnormalities in formation, growth, and/or neoplasia of lymphatics and blood vessels. In these and similar clinical disorders, confusion often exists as to the nature of the cell or tissue of origin, and insight into the role and control of hemangiogenesis and lymphangiogenesis is still in its infancy. Nonetheless, with the ever widening array of investigative techniques, it is not only timely but imperative to explore the endothelial biology underlying these inborn and acquired disorders.

Animals↗

Factor VIII-associated antigen in human lymphatic endothelium.

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

Antigens↗

Compensatory spleen growth and protective function in rats.

To quantify compensatory spleen growth after reduction in splenic mass and to determine the effect of age and vascular supply on remnant growth, we examined adult and weanling rats for remnant regeneration and adult rats for host protection against bloodstream pneumococcal challenge at intervals up to 180 days after partial resection or autograft implantation. In adults, subtotally resected spleens with remnant blood flow and segmental anatomy otherwise intact (eutopic remnants) displayed prompt but relatively limited gains in remnant weight and nucleated cell number, and growth after 60 days was minimal; survival after pneumococcal challenge was directly related to initial remnant weight and unrelated to length of postoperative interval. Splenic autografts (ectopic remnants), by comparison, underwent necrosis early after devascularization, recovered initial remnant weight slowly, fell far short of restoring original cellularity, and even 6 months after implantation barely attained initial size; moreover, host protection against pneumococcaemia was no different in rats with autografts than in those with no residual spleen. Remnants in situ (both partial resection and whole spleens) grew more vigorously in weanling than adult rats. The results suggest that splenic regeneration after either partial resection or implantation is much more limited than previously suggested, at least in disease-free rats, and is regulated by size and integrity of the initial remnant spleen, adequacy of vascular inflow, and age of the host. Whereas eutopic remnants provide protection against bloodborne pneumococcal challenge in proportion to initial residual size, ectopic remnants even with prolonged maturation fail to display immunoprotective function.

Age Factors↗

Immunoarchitecture of the regenerating rat spleen: effects of partial splenectomy and heterotopic autotransplantation.

To investigate the microstructure of in situ (eutopic) and autotransplanted (ectopic) splenic remnants, adult Sprague-Dawley rats were studied 60 days after subtotal (approximately 80%) splenectomy, total splenectomy followed by single or multiple remnant intraperitoneal autotransplantation, or sham operation. Total nucleated cell counts were determined in excised splenic remnants, and immunohistochemical staining using monoclonal antibodies to rat B- and T-cell antigens was performed in serial tissue sections. Immunoarchitecture of eutopic remnants was indistinguishable from that of intact spleens and total nucleated cell counts remained proportional to weight. In contrast, ectopic remnants showed sparsity and abnormal mixing of B and T lymphocyte subpopulations with widespread loss of follicles and periarteriolar lymphoid sheaths in addition to lower density and marked reduction of total nucleated cells. These findings provide immunohistologic evidence that preservation of intact vasculature is critical to splenic architecture, which may account in part for the demonstrable functional inferiority of ectopic remnants.

Animals↗

A technical modification to improve experimental production of hepatogenic ascites.

Constriction of the thoracic inferior vena cava is a useful experimental maneuver to reproduce massive ascites. Unfortunately, the margin of safety of this technique is narrow in that too much constriction overly restricts venous return with subsequent shock and death, and lesser constriction is often associated with extensive venous collateralization via the azygos system and failure to sustain hepatic congestion. By combining azygos vein ligation with 50% constriction of the supradiaphragmatic inferior vena caval circumference at the time of the initial thoracotomy, we have found that intense hepatic congestion is sustained and that dogs consistently develop massive ascites within 2-3 weeks.

Animals↗

Lymphangiogenesis and lymphologic syndromes.

A unifying concept linking disorders of lymphatic dysplasia, hyperplasia and neoplasia is presented. The central role of disturbed lymphangiogenesis is illustrated in a wide variety of lymphologic syndromes characterized by lymphedema, lymphangiectasia, lymphangioma, and lymphangiosarcoma.

Adolescent↗