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If the zinc content of amigen was similar five years ago, ourpatient would have recovered following the administration ofapproximately 4 mg daily intravenously. When zinc is adminis-tered orally about 40 mg daily is required to produce the sameeffect. (100 mg of zinc sulphate heptahydrate contains 22 mgof elemental zinc.) It seems, therefore, that only about 10% ofzinc administered to patients with acrodermatitis enteropath-ica is absorbed by the gastrointestinal tract.

Shaare Zedek Hospital,Jerusalem 91-000.Israel S. FREIER

Department of Inorganic Chemistry,Hebrew University,Jerusalem E. JUNGREIS

BIOCHEMICAL TREATMENT OF CHOLERA

SIR,-In 1972 you drew attention to findings on the bio-chemical mechanism of fluid loss in cholera.’ It is now wellestablished that the exotoxin of Vibrio cholerce in the gutlumen stimulates the adenyl-cyclase system of intestinal muco-sal cells2 to increase their concentration of adenosine3’,5’-monophosphate4 (cA.M.P.) (see figure). It is this increasedintracellular CA.M.P. which appears to be the basic biochemicallesion, and subsequently leads to a net increase in water fluxfrom the mucosal cell to the gut lumen. 1 This knowledgeopens up possibilities of biochemical interference for thera-peutic purposes, since it seems reasonable to suppose that arti-ficial lowering of raised intracellular CA.M.P. levels should leadto a reduction in diarrhoea. However, this possibility has notbeen explored. An effective drug treatment for the diarrhoea ofcholera would be invaluable, for as the El Tor pandemic con-tinues, thousands of people die because they cannot be rehyd-rated quickly enough, or at all.

Inhibition of adenyl cyclase would be effective, and sincethere is some evidence that membrane-bound adenyl cyclase isthe molecular basis of the p-adrenergic receptor 7 p-blockingdrugs may be worth a trial. Prostaglandins can stimulateCA.M.P. formation, and inhibition of prostaglandin synthesis bysalicylates has already been suggested as a possible therapy.8The third point of attack on the chain is by activation of theenzyme phosphodiesterase which degrades CA.M.P. to 5’-A.M.P.

1. Lancet, 1972, ii, 167.2. Sharp, G. W. G., Hynie, S. Nature, 1971, 229, 266.3. Chen, L. C., Rhode, J. E., Sharp, G. W. G. Lancet, 1971, i, 939.4. Schafer, D. E., Lust, W. D., Sircar, B., Goldberg, N. D. Proc. natn. Acad.

Sci. U.S.A. 1970, 67, 851.5. Pierce, N. F., Carpenter, C. C. J., Jr., Elliott, H., Greenhough, W. B. Gas-

troenterology, 1971, 60, 22.6. Field, M., Plotkin, G. R., Silen, W. Nature, 1968, 217, 469.

This is more promising than the other methods because theactivity of this enzyme is the normal controlling factor in-fluencing intracellular CA.M.P. concentrations.’ The chemicalimidazole is a potent activator of phosphodiesterase.9 10

Although not available as a drug, its very close relative nirida-zole is a widely used and relatively safe anthelmintic whichmay well share the same properties.

Cholera is easily induced in laboratory animals and thereare plenty of human cases available for clinical trials-itwould be neither costly nor time-consuming to prove or dis-prove the efficacy of these drugs.North Hospital,P.O. Box 63,Chingola, Zambia GEOFFREY V. GILL

PARACRINE

SIR,-Unblessed by lexicographers, and with its originalmeaning" perverted, the term "paracrine" is gaining increas-ing currency among endocrinologists. Dr Grossman (April 3,p. 744) is right to draw attention to this semantic problem,which antedates my review (March 6, p. 529); I heard theword used in two recent symposia in which Dr Grossman wasa participant. I support his call for a term to describe therelease of locally acting substances from endocrine cells, but Iwould suggest that since "paracrine" is now being used in thissense, the redefinition which he advocates has already hap-pened. Since the English language (unlike French) alters byevolution rather than legislation, perhaps we need do no morethan accept the situation and hope that the lexicographers willrecognise usage as well as precedent when they acknowledgethe existence of the word.

Academic Unit of Gastroenterology,London Hospital,EIIBB . DAVID WINGATE

SIR,-Dr Grossman suggests that the word paracrinerequires redefinition from Feyrters original usage, which hedefines as para=additional.

Although Professor Feyrter (1895-1973) never proposed asingle definition for the actions of his "parakrine" cells, severalof his writings contain phrases which show he used the word,in its modern sense, to indicate that they "were to be regarded

7. Robison, G. A., Butcher, R. W., Sutherland, E. W. Cyclic AMP. New York,1971.

8. Bennet, A. Nature, 1971, 231, 536.9. Butcher, R. W., Sutherland, E. W. J. biol. Chem. 1962, 237, 1244.

10. Goodman, H. M. Biochim. biophys. Acta, 1969, 176, 60.11. Feyrter, F. Wien Z. inn. Med. 1946, 27, 9.

Biochemical pathogenesis of cholera, showing possible sites of pharmacological interference.Crossed lines indicate inhibition.

916

as acting solely on their immediate neighbours in gut and pan-creas".’ For instance (19532) he used the word anliegenden(neighbouring) in referring to their site of action and in thesame paper stated that the principles of the islet cells "sowohlin die Ferne wie an Ort und Stelle [locally] wirken". In 19663 3he wrote: "ein parakrine, also seitliche Beeinflussung derTatigkeit der epithelialen Deckzellen". Here seitliche can onlymean neighbouring.To acknowledge Feyrter’s prescience in this matter does not

detract from the significance of Dr Grossman’s comments, butI submit that redefinition of the excellent word paracrine is notrequired.

Royal Postgraduate Medical School,Hammersmith Hospital,London W12 0HS A. G. E. PEARSE

IgM RECEPTORS ON CELLS IN HODGKIN’SDISEASE

SiR,—Receptors for IgM antibody complexed with the oxred cell have been described on human T lymphocytes. Mac-rophages may also have receptors for IgM-antigen com-plexes.5 6 Normal mouse thymocytes are cytotoxic towardscells infected with murine sarcoma virus (M.s.v.) in the pre-sence of IgM antibody.7 We here present evidence of IgM-re-ceptor cells in Hodgkin’s disease.

In 32 patients with Hodgkin’s disease, unexpectedly highlevels of complement (C3d) rosettes were observed on 5 occa-sions in lymphoid-cell suspensions. The use of control ox redcells sensitised with IgM antibody gave clear evidence that in3 cases the sampled tissue contained IgM-receptor-bearingcells, in blood (case 1), lymph-node (case 2), and spleen (case3). The receptor profiles were:

2 other cases had a similar receptor profile with 40% and30% of cells probably expressing IgM rather than E.A.c. recep-tors. Each of the 5 individuals had substantial numbers ofphagocytes in the cell suspensions (15, 11, 30, 11, 19% respec-tively). In a previous study normal T lymphocytes formedrosettes with IgM-coated cells, provided they were cultured for24 hours in a medium containing little or no free IgM.4 In thecases reported here, rosettes were formed after 10 minutes’ in-cubation at 37°C of IgM-sensitised red cells and lymphoidcells, followed by centrifugation and 2 hours’ incubation at4°C. After formation these rosettes were stable to quitevigorous agitation and incubation at 37°C. Under these con-ditions, lymphocytes from normal blood, spleen, lymph-node,or tonsil show only occasional IgM rosettes.

Thus, the IgM rosetting, encountered in 5 of the 32 patientswith Hodgkin’s disease is highly abnormal, and we wonderwhether IgM rosetting is a marker of T-lymphocyte imma-turity in such cases. We have not yet found evidence of IgMrosetting in other lymphomas.

Department of Pathology,University Medical School,Teviot Place,Edinburgh EH8 9AG

J. A. HABESHAWA. E. STUARTA. E. DEWARG. YOUNG

1. Pearse, A. G. E. Brit. J. Hosp. Med. 1974, p. 697.2. Feyrter, F. Uber die peripheren endokrinen (parakrinen) Drüsen des

Menschen; p. 27, Vienna, 1953.3. Feyrter, F. in Handbuch der Allgemeinen Pathologie edited by F. Büchner,

E. Letterer, and F. Roulet; vol. VIII, no. 2, p. 345. Berlin, 1966.4. Moretta, L., Ferrarini, M., Durante, M. L., Mingari, M. C. Eur. J. Immun.

1975, 5, 565.5. Lay, W. H., Nussenzweig, V. J. Immun. 1969, 102, 1172.6. Rhodes, J. Nature, 1973, 243, 527.7 Lamon, E. W., Whitten, H. D., Lidin, B., Fudenberg, H. H. J. exp. Med.

1975, 142, 542.

SURFACE FILAMENTS ON CANCER CELLS

SIR,-Professor Gabbiani and his colleagues’ report an in-creased amount of contractile proteins in cells from skin’andbreast cancers, and a network of microfilaments projectingfrom the cell surface. Some non-malignant cells also have fila-mentous projections, and we reasoned that the excess of fila-ments at the surface of cancer cells should be manifest as a dis-proportionate increase in size of the filamentous areas. Wetested this by measuring the relative lengths of filamentous andfilament-free regions on tracings of the cell perimeter.

Cells grown on coverslips were obtained from cultures maintainedat a cancer chemotherapy service. They were derived originally fromsurgical specimens and when expedient were accompanied by cellsgrown from a biopsy specimen of nearby normal tissue. Cancerous andnormal cells were either stained by Giemsa stain or shadow cast forexamination by light microscopy,2 and the image was projected ontowhite paper at a distance of 5 m. The outline of the cell perimeter wastraced in pencil using a continuous line for filament-free areas and abroken line to indicate filamentous areas. A geographer’s ipsometerwas then used to trace the perimeter of the cell and the lengths occu-pied by a particular surface measured. Some of the coverslip prepara-tions were prepared for survey by scanning electron microscopy.

Measurements of cell populations from four differenthuman cancers and their normal cell counterparts are shownin the table. A comparison of the variance within each groupof normal cells using Student’s test showed a p value >001,Within each group of cancer cells p was <0.001. Comparingthe difference in mean values of normal and cancerous groups

1. Gabbiani, G., Trenchev, P., Holborow, E. J. Lancet, 1975, ii, 796.2. Markham, R., Blackwell, P. M., Usher, G. Pathology, 1975, 7, 45.

Scanning electron micrographs of cultured normal (a) and cancer (b) ceJ1Ifrom human ovary to illustrate increased filament-bearing surfaa acancer cell. (Reduced to half from x500).