Ethoxyzolamide Differentially Inhibits CO2 Uptake and Na+-Independent and Na+-Dependent HCO3- Uptake in the Cyanobacterium Synechococcus sp. UTEX 625.

The effects of ethoxyzolamide (EZ), a carbonic anhydrase inhibitor, on the active CO2 and Na+-independent and Na+-dependent HCO3- transport systems of the unicellular cyanobacterium Synechococcus sp. UTEX 625 were examined. Measurements of transport and accumulation using radiochemical, fluorometric, and mass spectrometric assays indicated that active CO2 transport and active Na+-independent HCO3- transport were inhibited by EZ. However, Na+-independent HCO3- transport was about 1 order of magnitude more sensitive to EZ inhibition than was CO2 transport (50% inhibition = 12 [mu]M versus 80 [mu]M). The data suggest that both the active CO2 (G.D. Price, M.R. Badger [1989] Plant Physiol 89: 37-43) and the Na+ -independent HCO3 - transport systems possessed carbonic anhydrase-like activity as part of their mechanism of action. In contrast, Na+-dependent HCO3- transport was only partially (50% inhibition = 230 [mu]M) and noncompetitively inhibited by EZ. The collective evidence suggested that EZ inhibition of Na+ -dependent HCO3- transport was an indirect consequence of the action of EZ on the CO2 transport system, rather than a direct effect on HCO3- transport. A model is presented in which the core of the inorganic carbon translocating system is formed by Na+-dependent HCO3- transport and the CO2 transport system. It is argued that the Na+-independent HCO3 - utilizing system was not directly involved in translocation, but converted HCO3- to CO2 for use in CO2 transport.

Quenching of Chlorophyll a Fluorescence in Response to Na+-Dependent HCO3- Transport-Mediated Accumulation of Inorganic Carbon in the Cyanobacterium Synechococcus UTEX 625.

In the cyanobacterium Synechococcus UTEX 625, the yield of chlorophyll a fluorescence decreased in response to the transport-mediated accumulation of intracellular inorganic carbon (CO2 + HCO3- + CO32- = dissolved inorganic carbon [DIC]) and subsequently increased to a near-maximum level following photosynthetic depletion of the DIC pool. When DIC accumulation was mediated by the active Na+-dependent HCO3- transport system, the initial rate of fluorescence quenching was found to be highly correlated with the initial rate of H14CO3- transport (r = 0.96), and the extent of fluorescence quenching was correlated with the size of the internal DIC pool (r = 0.99). Na+-dependent HCO3- transport-mediated accumulation of DIC caused fluorescence quenching in either the presence or absence of the CO2 fixation inhibitor glycolaldehyde, indicating that quenching was not due simply to NADP+ reduction. The concentration of Na+ required to attain one-half the maximum rate of H14CO3- transport, at 20 [mu]M external HCO3-, declined from 9 to 1 mM as the external pH increased from 8 to 9.6. A similar pH dependency was observed when fluorescence quenching was used to determine the kinetic constants for HCO3- transport. In cells capable of Na+-dependent HCO3- transport, both the initial rate and extent of fluorescence quenching increased with increasing external HCO3-, saturating at about 150 [mu]M. In contrast Na+-independent HCO3- transport-mediated fluorescence quenching saturated at an HCO3- concentration of about 10 [mu]M. It was concluded that measurement of chlorophyll a fluorescence emission provided a convenient, but indirect, means of following Na+-dependent HCO3- transport and accumulation in Synechococcus.

Eosinophilic spongiosis: a clinicopathologic review of seventy-one cases.

Eosinophilic spongiosis has a distinctive but not diagnostic histologic pattern of the epidermis. This pattern may be seen in a wide variety of clinical disorders. We have observed it most commonly in bullous pemphigoid, particularly the urticarial stage. In most biopsy specimens that show eosinophilic spongiosis, additional definable histologic criteria allow a specific clinical diagnosis to be made. Rarely, clinical correlation and immunofluorescent data may be needed for a precise diagnosis. The location of eosinophilic spongiosis within the epidermis is generally not helpful in making a definite diagnosis. The peripheral eosinophilia, found in 61% and 46% of our pemphigoid and pemphigus cases, respectively, may be an important laboratory parameter in the evolution of this distinctive histologic pattern. Eosinophilic spongiosis occurs in early pemphigus lesions. However, its presence does not necessarily herald pemphigus, as a similar histologic pattern can be seen in pemphigoid and other disorders.

Cutaneous malignant histiocytosis: a clinical and histopathologic study of eight cases, with immunohistochemical analysis.

Eight cases of autopsy-proved malignant histiocytosis (MH) are reported, in which cutaneous involvement was a prominent finding at initial clinical presentation. In two patients, the disease remained confined to the skin for significant periods before systemic dissemination appeared. Immunohistochemical analysis of cutaneous infiltrates of MH showed uniform negativity of the atypical cells for lysozyme, immunoglobulin light chain, glycogen, and chloroacetate esterase content. In five cases, cytochemical stains for acid phosphatase, butyrate (nonspecific) esterase, chloroacetate esterase, and peroxidase activity were performed on bone marrow aspirates containing malignant cells; all demonstrated diffuse positivity for acid phosphatase and nonspecific esterase, and negativity for peroxidase and chloroacetate esterase. Touch-imprint preparations of cutaneous lesions in one of these cases yielded identical results. These findings indicate that cytochemical methods are preferable to immunohistochemical technics in identification of histiocytic malignancies and that foci of skin involvement may provide a useful source for such diagnostic evaluation.

Tilorone hydrochloride in the treatment of T cell lymphoproliferative cutaneous disease.

Tilorone hydrochloride was used to treat eleven patients with T cell cutaneous disease ranging from pre-Sézary syndrome to tumor-stage mycosis fungoides. Cutaneous histologic study, Sézary counts, delayed skin tests, patch tests, and quantitative T cell counts were monitored. The study revealed that the response to tilorone depends in part on the type and stage of disease, as well as the characteristics and responsiveness of the individual lymphocyte population. Patients with pre-Sézary syndrome are most likely to benefit from tilorone. The effect of tilorone on the T cell population is manifested by changes in responses to patch and skin tests, as well as histologic improvement. Intact immune responses and elevated levels of IgE may be important prognostic clinical parameters in these patients. Tilorone is ineffective in patients with mycosis fungoides and advanced Sézary syndrome. Keratopathy can be a limiting but reversible complication of therapy. The drug may provide an effective therapeutic step in the treatment of early T cell cutaneous disease or an adjunctive therapy to leukapheresis and chemotherapy.

Epidermoid hidradenoma. A clinicopathologic study.

Clinical and histopathologic data in 8 cases of epidermoid hidradenoma are presented. Most of the tumors were in the head and neck, and most of the patients were middle-aged and older adults. Generally, the lesions were asymptomatic nodules that sometimes showed ulceration or rapid growth. Despite having some histologic atypia or focal mitotic activity, the tumors were found to be benign on long-term evaluation. This epidermoid variant should not be otherwise differentiated from the benign group of solid-cystic hydradenomas, because cytologic variability did not predict a significant change in prognosis.

Cutaneous clinicopathologic correlation of allergic granulomatosis.

Allergic granulomatosis is a distinct clinical syndrome occurring in adults with asthma, eosinophilia, and multisystem vasculitis. Atopy and drug sensitivity are other important features. The skin reactions are most commonly nodular and inflammatory lesions. A unique feature is the deep papulonodules, which may occur singly on the scalp or symmetrically on the extremities. Cutaneous findings may range from purpura to urticaria and ulceration. The most common histologic finding is the extravascular granuloma; however, necrotizing vasculitis of small vessels is seen, as well as periarteritis nodosa involving larger vessels of the skin. This varied histologic and clinical spectrum seen in patients with systemic allergic granulomatosis is a reflection of a unique host response to multiple antigens. The cutaneous findings imply that allergic granulomatosis probably represents a unique host response to the same causative and pathogenetic factors as are usually found in periarteritis nodosa and necrotizing vasculitis.

Surgical treatment of familial benign chronic pemphigus.

Familial benign chronic pemphigus (Hailey and Hailey disease) is a rare, recalcitrant, often disabling genodermatosis that may not respond to conservative dermatologic therapy. We describe herein five patients with intertriginous familial benign chronic pemphigus who underwent excision and split-thickness skin grafting. All were men whose duration of disease ranged from one to 38 years. Follow-up evaluations ranging from ten months to nine years revealed no recurrence in graft sites in three patients, mild recurrence in one patient after eight years, and one death from pulmonary embolus in the postoperative period. The occurrence of familial benign chronic pemphigus around graft edges was a universal, but relatively minor, problem. Surgical excision provided definite relief from an otherwise disabling disease in four of our patients and a satisfactory improvement in life-style.

Factitious lip crusting.

Four cases of factitious crusting of the lips in women are reported. Two of the women had hemorrhagic crusts, and two had keratotic yellow crusts. All four patients had personality disturbances. Biting, picking, or unconscious licking of the lips may be the underlying mechanism for trauma and crust formation. This entity should be distinguished from contact cheilitis, actinic cheilitis, infectious cheilitis glandularis, and cheilitis granulomatosa. Some cases of exfoliative cheilitis may also be factitious. The presence of bizarre hemorrhagic or keratotic crusts on the lips should alert the clinician to a possible factitious origin, and a psychiatric evaluation should be done.

Blue fingertips associated with myxedema.

A 42-year-old woman had blue telangiectases of the fingertips associated with myxedema. In addition to this clinical finding, the patient had abnormal Doppler ultrasound study findings analogous to those seen in peripheral vascular occlusion. With thyroid replacement therapy, the telangiectases disappeared, and a dramatic improvement was noted in the results of the Doppler studies. We believe that the clinical picture seen in our patient was caused by the deposition of mucin around small blood vessels.

Cytophagic histiocytic panniculitis with fever, cytopenia, liver failure, and terminal hemorrhagic diathesis.

We have seen five adult patients with a clinical picture of recurrent histiocytic, cytophagic panniculitis, cytopenia, abnormal liver function tests, and a terminal, febrile bleeding diathesis. Originally thought to have Weber-Christian disease, these patients, we believe, represent a unique syndrome: lobular, histiocytic, cytophagic panniculitis. Erythrophagocytosis and cytophagocytosis are readily observed, but the cells do not show malignant features. Histiocytosis can be found at times in the bone marrow, lymph nodes, liver, spleen, and serosal tissues, as well as in the skin and subcutaneous tissues. The terminal hemorrhage in these patients is characterized by features of pancytopenia, liver failure, and intravascular coagulation. This disease may be separated from malignant histiocytosis by the chronic course, the primary involvement of the adipose tissue, and the benign histiocytes in the infiltrate. It has some similarities to other regional histiocytoses such as sinus histiocytosis, intestinal histiocytosis, and splenic histiocytosis.

Ulcerative lichen planus. Follow-up of surgical excision and grafting.

Four patients with ulcerative lichen planus of the feet underwent total excision and split-thickness skin grafting of the affected areas. One patient underwent grafting in 1951, and remained free of recurrent ulcers for 26 years. Another, who had an 18-year follow-up after grafting, required an additional procedure. The possibility of squamous cell carcinoma in ulcerative lichen planus is considerable, lending further support to the concept that excision with grafting is the treatment of choice for these lesions.

Diagnostic value of tests of fibrin metabolism in patients predisposed to pulmonary embolism.

Blood tests for fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were performed in 100 patients at high risk for thromboembolism in order to assess the diagnostic value of these determinations in patients suspected to have pulmonary embolism. Tests were positive significantly less often in high-risk patients, and mean values were significantly lower, when compared with patients with established pulmonary embolism (P less than .001). However, no significant differences existed between high-risk patients and patients with deep venous thrombosis of the legs. Positivity rates and mean values were significantly higher in the presence of pulmonary embolism than in patients with deep venous thrombosis alone (P less than .05). Elevated FDP/fdp and SFC values are useful in the diagnosis of pulmonary embolism in high-risk patients; moreover, positive results in a patient with deep venous thrombosis suggests that pulmonary embolism has occurred.

Noninvasive diagnosis of deep venous thrombosis by phleborheography.

Phleborheography, a recently described noninvasive test for deep venous thrombosis, was compared with leg venography in 75 patients. Acute deep venous thrombosis was accurately diagnosed by phleborheography in 24 patients, with no false-positive diagnoses. External venous compression without thrombosis was diagnosed correctly in two patients. The remaining patients appeared normal or had chronic venous disease by phleborheography; however, 11 of these had acute deep venous thrombosis by venography, for a false-negative rate of 31%. Most undetected thrombi were in small calf veins. The specificity of phleborheography is thus 100%, but the sensitivity is only 69%. Similarly, its positive predictive value is 100% and the negative predictive value is 78%. When phleborheography shows acute deep venous thrombosis, this diagnosis may be accepted with confidence and therapy chosen accordingly, without venographic confirmation. Venography may still be required to withhold anticoagulation when phleborheography is negative.

Use of fibrinogen/fibrin degradation products and soluble fibrin complexes for differentiating pulmonary embolism from nonthromboembolic lung disease.

To help differentiate pulmonary embolism from other lung diseases, we measured the degradation products of fibrinogen and fibrin and soluble fibrin complexes in normal control subjects and patients with pulmonary embolism, lung cancer, pneumonia, chronic obstructive pulmonary disease, tuberculosis, asthma, and several miscellaneous disorders. A separate group of patients, who were suspected of having pulmonary embolism but had negative pulmonary angiography, were also tested. Many nonthromboembolic lung diseases frequently were associated with positive fibrinogen/fibrin degradation products or soluble fibrin complexes, but those with high positivity rates for one test tended to have low rates for the other test. Both fibrinogen/fibrin degradation products and soluble fibrin complexes were positive in 55 per cent of patients with pulmonary embolism but only in 4 per cent with nonthromboembolic conditions (P less than 0.001), in 7 per cent of patients with negative pulmonary angiography (P less than 0.001), and in none of the normal subjects (P less than 0.001). Both tests were negative in only 3 per cent of patients with pulmonary embolism but in 35 per cent of nonthromboembolic diseases (P less than 0.005), 54 per cent of those with negative pulmonary angiography (P less than 0.001), and 79 per cent of normal control subjects (P less than 0.001). The combination of fibrinogen/fibrin degradation products and soluble fibrin complexes is more valuable than either test alone in the diagnostic separation of thromboembolic from nonthromboembolic pulmonary diseases.