Lymphatic Response Research Articles

Increased Lymphoscintigraphic Flow Pattern in the Lower Extremity Under Evaluation for Lymphedema

To analyze the clinical and scintigraphic features in four postoperative patients with lower limb edema. Four case reports are presented, and causes of increased lymphatic flow are discussed. Filtered 99mTc-sulfur colloid (0.1 mL; 20 MBq) was administered by subcutaneous injection into the second web space of each foot. Sequential local (inguinal) and whole-body imaging was performed periodically up to 24 hours after the injections. The patients were three women who were 40, 51, and 86 years of age and an 81-year-old man. Each patient had unilateral lower extremity swelling and had recently undergone an ipsilateral lower limb operation. One female patient had previously undergone proximal femoral vein ligation, and another female patient had venous insufficiency demonstrated by Doppler ultrasonography. The male patient had a history of severe arterial insufficiency, and the remaining female patient had no venous or arterial abnormalities. On lymphoscintigraphy, all patients showed increased lymphatic flow in the edematous lower limb. Only the male patient also demonstrated abnormal dermal backflow pattern. Increased lymphatic flow most likely is a normal response to lower limb edema in the presence of normal peripheral lymphatic structures. In the four described cases, a recent lower limb surgical procedure may have resulted in disturbance of normal proximal lymphatic channels. The role of sympathetic innervation of the peripheral lymphatic system is a potential factor determining lymphatic response to trauma or surgical intervention. Increased flow on lymphoscintigraphy may not necessarily represent normal flow, especially if other scintigraphic features of abnormal lymphatic function-such as dermal backflow pattern-are present.

Perilesional interleukin-2 in the VX-2 carcinoma in rabbits: A preliminary investigation

Immune system amplification by perilesional injection of interleukin-2 is a promising adjuvant approach for treating squamous cell carcinoma of the head and neck. A pilot study was designed to develop an animal model bearing squamous cell carcinoma in which to test the efficacy of perilesional interleukin-2. Rabbits were inoculated intramuscularly with the papilloma virus - induced squamous carcinoma VX-2 cell line. Tumor regression and host lymphatic response after perilesional interleukin-2 were measured. Variable responses were found. Growth of tumor cells implanted from cell culture was rapid in most animals. Tumor growth was prevented in animals receiving 10,000 units of interleukin-2 per injection initiated 9 days after tumor inoculation. This inhibition approached statistical significance when compared with growth of saline controls. Histologic responses consisted primarily of plasma cell and eosinophil infiltration. The intensity of the inflammatory response did not correlate with interleukin-2 dose. A trend toward enhanced tumor growth was seen with lower doses of interleukin-2 and when interleukin-2 therapy was initiated simultaneously with tumor inoculation. These findings suggest that high-dose recombinant interleukin-2 can prevent tumor growth if initiated after tumor inoculation. Whether this effect was caused by direct tumor cytotoxicity or mediated by the immune system is unclear. These preliminary results underscore the importance of understanding the effects of dose and schedule in the design of immunotherapy models before clinical use. (OTOLARYNGOL HEAD NECK SURG 1995;112:430-6.)

Perilesional interleukin‐2 in the VX‐2 carcinoma in rabbits: A preliminary investigation

Immune system amplification by perilesional injection of interleukin-2 is a promising adjuvant approach for treating squamous cell carcinoma of the head and neck. A pilot study was designed to develop an animal model bearing squamous cell carcinoma in which to test the efficacy of perilesional interleukin-2. Rabbits were inoculated intramuscularly with the papilloma virus-induced squamous carcinoma VX-2 cell line. Tumor regression and host lymphatic response after perilesional interleukin-2 were measured. Variable responses were found. Growth of tumor cells implanted from cell culture was rapid in most animals. Tumor growth was prevented in animals receiving 10,000 units of interleukin-2 per injection initiated 9 days after tumor inoculation. This inhibition approached statistical significance when compared with growth of saline controls. Histologic responses consisted primarily of plasma cell and eosinophil infiltration. The intensity of the inflammatory response did not correlate with interleukin-2 dose. A trend toward enhanced tumor growth was seen with lower doses of interleukin-2 and when interleukin-2 therapy was initiated simultaneously with tumor inoculation. These findings suggest that high-dose recombinant interleukin-2 can prevent tumor growth if initiated after tumor inoculation. Whether this effect was caused by direct tumor cytotoxicity or mediated by the immune system is unclear. These preliminary results underscore the importance of understanding the effects of dose and schedule in the design of immunotherapy models before clinical use.

直腸癌におけるリンパ系組織反応の有する臨床的意義に関する検討 原発巣からの距離（ｚｏｎｅ）別検討

腫瘍に対するリンパ系組織の免疫学的反応の場を腫瘍からの距離により4つのzone(zone1:腫瘍先進部,zone2:先進部よりやや離れた近傍領域,zone3:転移陰性1群所属リンパ節,zone4:転移陰性所属2,3群リンパ節)に分類した.zone1,zone2では各々リンパ球浸潤,リンパ濾胞(LF)が高度な群の生存率曲線が良好であった.zone3,4ではpara-cortical hyperplasia(PH),germinal center hyperplasia(GH)の高度群はそれぞれ良好な生存率曲線を示した.各症例が有する高度反応因子〔PH2,3,GH2,3,SH(sinus histiocytosis)2,3〕の数により,0,1因子〔NA(-)〕群と2,3因子〔NA(+)〕群に分けると,NA(+)群の生存率曲線は極めて良好であった.Coxの比例ハザードモデルを用いた多変量解析によるとNA,LFはリンパ節転移,深達度とともに予後への寄与度が高度であった.直腸癌症例のリンパ系組織に認める宿主側反応は,術後予後を予測する上で重要な意義を有することが示唆された.

Ploidy as a prognostic indicator in oesophageal squamous carcinoma and its relationship to various histological criteria.

One hundred surgically resected squamous cell carcinomas of the oesophagus were studied retrospectively to assess the significance of DNA aneuploidy as determined by flow cytometry using paraffin-embedded tissue. DNA aneuploidy was not an independent prognostic indicator but was found to be associated with tumour necrosis and host/tumour interface fibrosis. When tumours confined to submucosa or muscle wall were assessed, diploid tumours had a poorer survival rate than DNA aneuploid tumours. Other histological variables studied were tumour differentiation, depth of infiltration, glandular and small cell differentiation, lymphatic and vascular spread and host inflammatory response. These failed to show any significant association with ploidy.

Induction of Lymphatic Lesions by Brugia pahangi in Jirds with Large and Small Preexisting Homologous Intraperitoneal Infections

The effect of intraperitoneal (i.p.) infections induced by inoculations of 30 or 150 Brugia pahangi third-stage larvae (L3) on the development of infections and lymphatic lesions induced by subsequent homologous subcutaneous (s.c.) inoculations were compared in the present study. Lymphatic lesion severity, as judged by the numbers of lymph thrombi present, and lymphatic lesion scores were significantly reduced in both groups of jirds with existing i.p. infections. The numbers of adult worms that developed, locations of these worms, and the subsequent microfilaremias did not differ significantly between groups. All jirds with i.p. infections developed similar antibody titers to crude somatic adult antigen as measured by ELISA. These levels did not change following s.c. infections. Immediate and delayed footpad swelling responses were also similar in all groups. Results of these experiments support and extend previous studies indicating that i.p. infections of B. pahangi induce a hyporesponsive state in jirds to subsequent s.c. infections without significantly affecting the subsequent parasite burden. This effect appears to be independent of the numbers of L3 inoculated i.p. prior to lymphatic-induced infection. Circulating antibody titers and footpad swelling responses to B. pahangi antigen were not reduced in jirds with the hyporesponsive lymphatic inflammatory response and do not correlate with this condition.

Peripheral lymphatic responses to outflow pressure in anaesthetized sheep.

1. Lymph flow and pressure fluctuations were measured by cannulating popliteal efferent and distal hind-limb afferent lymphatic vessels in anaesthetized sheep. The cannula outflow height was raised above the vessels to increase lymphatic outflow pressure. 2. Lymph flow decreased non-linearly as the outflow was raised. The rate of decrease increased with increasing outflow height. 3. Lymphatic contraction frequency rose and stroke volume fell with increasing outflow height. 4. The calculated power necessary to move lymph along the cannula initially increased with outflow height but it reached a peak and was reduced again by raising the outflow further. Calculated lymphatic stroke work followed a very similar pattern. 5. Lymph flow was maintained up to a greater outflow height in afferent than in efferent vessels. Curves relating frequency, power and stroke work to outflow height were shifted to the right in the afferent lymphatics. 6. These results are consistent with an intrinsic lymphatic pump which can be stimulated by increasing pressure. At high pressures, however, the pump fails.

Nodular colonic mucosa of childhood: Normal or pathologic?

The small colonic mucosal nodules that have been referred to in the past as lymphatic nodular hyperplasia are felt to represent a normal response of the prominent colonic lymphatic tissue in children. To support this hypothesis, a prospective study of all air-contrast barium enemas, colonoscopies, and intestinal biopsies performed during 1 yr was carried out. During that year 48 patients had air-contrast barium enemas, and 21 of these 48 patients also had colonoscopy and mucosal biopsies. Greater than half of the children studied by air-contrast barium enema (26 out of 48) and colonoscopy (12 out of 21) had nodular colonic mucosa. These nodules were described at colonoscopy as being smooth surfaced, yellowish-white, 1–2 mm in diameter. There was no correlation between the presence or absence of these nodules with any symptom or symptom complex. The younger the patients, the more frequently these nodules were observed. No immunologic disorder was associated with the nodular colonic mucosa in the children that were tested. Nodular colonic mucosa in childhood should be considered a frequent finding indicative of normal lymphatic response to nonspecific stimuli, which may often be infectious in nature.

The response of lymphatic smooth muscles to vasoactive substances.

A study was made of the isotonic response of bovine mesenteric lymphatics to several physiological vasoactive substances. Contractions of lymphatic smooth muscles were induced by serotonin (5-HT), prostaglandin F2alpha (PGF2alpha), noradrenaline (NA), histamine, dopamine and acetylcholine (ACh). The smooth muscles were particularly sensitive to 5-HT. Excepting PGF2alpha no other substances could equal 5-HT in the magnitude of the maximum response. The majority of 5-HT receptors seemed to be the D receptors. The decreasing order of the contractile responses was as follows: 5-HT greater than PGF2alpha greater than NA greater than histamine greater than dopamine greater than ACh. The contractile response to ACh was observed only in specimens involving valvular region. It was very likely that, in the lymphatics, there were 2 kinds of receptors for catecholamines, i.e. alpha and beta receptors, and the stimulation of the former induced smooth muscle contraction and that of the latter relaxation. A difference was noticed between the responses of valvular and intervalvular segments to NA. Relaxations of lymphatic smooth muscles were induced not only by isoproterenol but also by adenosine and adenine nucleotides. The decreasing order of the relaxant responses was as follows: ISP greater than adenosine greater than ATP greater than ADP greater cyclic AMP greater than or equal to AMP. The relaxant responses to adenine nucleotides tended to reduce with decrease in the number of high energy phosphates.

Lymphatic tissue response in chickens treated with tri-o-tolyl phosphate.

Indices of immunologic response elicited by tri-o-tolyl phosphate (TOTP) in chickens were investigated. Histopathologic evaluation of lymphatic organs (spleen, cecal tonsil, bursa of Fabricius) and selected immuno-related visceral organs containing lymphatic infiltrations (liver, kidney, duodenum, pancreas) was conducted. Liver and spleen showed a consistent and definite increase of diffuse lymphatic tissue in TOTP-treated animals. Total plasma protein levels of treated animals were increased from 7 to 20% over 4-14 days after TOTP administration. A similar increased pattern was noted in gamma-globulin:albumin ratios of the treated group. The data suggested stimulation of immunologic response in chickens treated with TOTP.

Evidence of Functional Microenvironments in Lymphatic Tissue Response to Antigen

Experiments with young and aged mice support the concept that the reticular stroma of the spleen, possibly interacting with other humoral factors, is essential for the expression of immunocompetent precursors directed towards the production of 7S antibody.

Response of lymphatics of canine hind limb to sympathetic nerve stimulation.

1. The changes in lymphatic pressure in a limb whose circulation was temporarily arrested with a pneumatic cuff have been studied.2. Stimulation of the lumbar sympathetic chain caused an increase in lymphatic pressure. It has been shown that this is a primary not a secondary phenomenon, due to an active lymphomotor mechanism.3. The increase of lymphatic tone is proportional to the rate of stimulation; peak values are reached between 5 and 9 impulses/sec.

The immune response to sheep erythrocytes in the mouse. I. A study of the immunological events utilizing the plaque technique.

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1-2 days and 2-3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2-3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

RESPONSE OF THE SUPERFICIAL LYMPHATICS OF THE ARM OF INTACT MAN TO SYNTHETIC VASOPRESSIN.

SummaryPreliminary studies indicate that PLV-2 and Lys-Vp, 2 synthetic vaso-pressins, increase the rate of lymph flow in the superficial lymphatics of the forearm. The mechanism by which these polypeptides influence the rate of lymph flow is unknown.

Vascular and Lymphatic Responses in Injury

Vascular and Lymphatic Responses in Injury

Benign subpleural lymph node appearing as a pulmonary "coin" lesion.

A peripheral, pulmonary lymph node large enough to appear on chest roentgenograms as a coin lesion is unique. The pulmonary lymph nodes are situated in the parenchyma of the lung adjacent to the larger bronchi and tend to lie in the angles between the bronchial branches, usually extending only as far peripherally as the third bronchial branching. Most lymph tissues found beyond this point consist simply of aggregations of lymphoid cells and can not be regarded as normally occurring structures or true lymph nodes. They are generally caused by a response of the lymphoid tissue to infections, inhalation of irritating substances, or other noxious stimuli (1, 2). Miller, in his text on The Lung, (1) noted a definite increase in the pulmonary lymphoid tissue of older persons and attributed much of this increase to prior inhalation of carbon or other irritating particles rather than to past infections. The hyperplastic subpleural lymph node in the following case probably represents such a lymphatic response to the inhalation of anthracotic particles. This benign peripheral node appeared on the scout chest roentgenograms as a noncalcified, noncavitary, solitary pulmonary nodule. Case Report Mr. S. A., a well developed 58-year-old office worker, was hospitalized on Dec. 10, 1959, because of persistent epistaxis following an upper respiratory tract infection. Hemostasis was obtained by the insertion of anterior and posterior nasal packs, and the bleeding did not recur. Chest roentgenograms made on admission (Fig. 1) revealed a discrete, circumscribed area of increased density, 1.2 cm. in diameter, without calcification or cavitation, situated in the lateral basal segment of the lower lobe of the right lung. There was a calcific infiltrate in the right upper lobe. The patient gave a history of a chronic nonproductive cough often interrupting his sleep. He stated that he habitually smoked one and one-half packs of cigarettes daily. Physical examination of the chest was negative. There was slight digital clubbing. Intradermal tests with blastomycin and coccidioidin antigens and sputum examinations and cultures for M. tuberculosis were negative. A surgical consultation was obtained and a thoracotomy was recommended. It was subsequently performed without difficulty. A sharply defined, apparently encapsulated tumor, 1.2 cm. in diameter, was resected. Microscopic examination showed the subpleural mass to be a well circumscribed, hyperplastic lymph node with a rim of cortical follicles and a medullary portion containing a large amount of carbon pigment (Fig. 2). Comment In this patient the peripheral, pulmonary lymph node probably became hyperplastic in response to the presence of anthracotic particles. The hazard of carcinoma in the pulmonary coin lesion, particularly in men past the age of forty, has necessarily resulted in the resection of benign, asymptomatic lesions discovered on scout chest roentgenograms (3–5).