1109
history of breast cancer who were premenopausal, so menopausal status is not a confounding variable in our study. An additional factor affecting Kd could be receptor protein structure. Multiple polymorphisms of ER and PR have been identified, and the results presented here suggest that some women with a family history of breast cancer might inherit a variant receptor gene with
an altered Kd. The same inherited structural also induce familial breast cancer susceptibility. abnormality might
Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY 10029, USA
Fig 1-ERKd and PRKd (mean and SE)
in breast tumours.
Numbers of cases indicated above SE bar Values nanomolar Kd values.
as
square-roots of
history. Breast tumour ER, ERKd, PR, and PRKD concentrations were measured with a Rianen Assay Systems kit (DuPont). There was a significant reduction in ERKd and in PRKD in the tumours of women with a family history of breast cancer. The results are expressed as the square-roots of nanomolar values, to normalise variances (fig 1). There was no significant association of ER or PR with family history (fig 2). 15 women had a first-degree family history of breast cancer in mother, daughter, or sister. The other women had affected aunts or cousins. There was no significant difference in the proportion of women with or without a family history who were premenopausal (23% and 19%, respectively). Although Kd values are estimated in several laboratories, little has been published about their character or clinical usefulness.5 In one study, postmenopausal patients with high Kd values tended to have shorter recurrence-free survival.6 Since Kd reflects binding affinity between receptor and ligand, the "true" Kd value should be identical within the same tissue in the same species. But the observed Kd depends on assay method6 and receptor phosphorylation.7 Menopausal status also affects Kd because of high endogenous oestrogen and progesterone levels in premenopausal women.6 However, there was no significant difference in the proportion of women with or without a family
Fig 2-ER and
PR.
STEVEN LEHRER EVA LEVINE PENNY SAVORETTI JOAN CROPLEY SWAN N. THUNG H. K. SONG LYNDA MANDELL BRENDA SHANK
1. McGuire WL, Chamness GC, Fuqua SAW. Estrogen receptor variants in clinical breast cancer. Mol Endocrinol 1991; 5: 1571-77. 2. Fuqua SW, Hill SM, Chamness GC, et al. Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. J Natl Cancer Inst 1991; 83: 1157-60. 3. Lehrer S, Sanchez M, Song HK, et al. Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer. Lancet 1990; 335: 622-24. 4. Callahan R, Campbel G. Mutations in human breast cancer: an overview. J Natl Cancer Inst 1989; 81: 1780-86. 5. Witliff JL. Steroid receptor analyses, quality control, and clinical significance In: Donegan WL, Spratt JS, eds. Cancer of the breast, 3rd ed. Philadelphia: Saunders, 1988: 303-55. 6 Thorpe SM, Rose C. Biological and clinical relevance of Kd values for estradiol binding in primary breast cancer tumors. Eur J Cancer Clin Oncol 1988; 24: 1163-70. 7. Dayani N, McNaught RW, Smith RG. ATP mediated receptor interconversion as a model of estrogen receptor action: isolation of the factor which converts the non-estrogen binding form of the receptor to the low affinity binding form. J Steroid Biochem 1988; 30: 219-24.
Gene therapy for cancer SIR,-Dr Gutierrez and colleagues’ review (March 21,
p
715)
useful introduction to some of the gene therapy ideas circulating in cancer research. However, in the context of tumourcell-targeted gene therapy, insufficient emphasis was given to the important point that the genes must either reach all the target cells or destroy indirectly those tumour cells they cannot reach. Tumour-suppressor genes, MHC genes, and the varicella-zoster virus thymidine kinase gene proposed for virus-directed enzyme prodrug therapy (VDEPT)* have no "bystander effect" and influence only the tumour cells to which they have been successfully delivered. To cure cancer these genes would have to be delivered to all the patient’s cancer cells but the heterogeneity and inaccessibility of the target cells make this an elusive goal. 100% efficient delivery is not required for genes encoding secreted proteins that can (directly or indirectly) mediate the destruction of surrounding tumour cells. Bystander effects, apparently mediated through paracrine stimulation of host antitumour effector cells, have been demonstrated after expression of interleukin-2 and interleukin-4 genes in rodent tumour models.2-4 Many other gene products may be capable of stimulating local antitumour immunity or generating locally cytotoxic "crossfire". Examples include other immunostimulatory cytokines, chemotactic peptides, antibodies, and toxins. Also, it may be possible to modify the VDEPT approach by engineering the genes to encode the drug-activating enzyme in a cell surface-associated or secreted form. Extracellular activation of the prodrug by enzyme derived from a small number of genetransduced tumour cells might then lead to wholesale tumour destruction. The major obstacle to tumour-targeted gene therapy is inability to deliver genes efficiently to tumour deposits in vivo.s Until gene transfer technology is up to this task the potential of this form of gene therapy cannot be tested, even in animal models. Virus vectors, the most promising vehicles for in-vivo gene delivery, are too large to cross the vascular endothelial lining of tumour blood vessels in numbers large enough to reach more than a small fraction of target cells. Vectors capable of replicating and spreading through a tumour may provide part of the answer to this problem but there are serious concerns about safety. Even on the most optimistic view, it is was a
1110
difficult, if one takes account of target cell heterogeneity and poor vascular access,6 to envisage a time when it will be possible to deliver a therapeutic gene to every tumour cell. However, by choosing genes that encode locally active secreted proteins, the requirement for 100% efficient delivery is bypassed, making targeted gene therapy for cancer a technically demanding, but feasible
proposition. MRC Centre, Cambridge CB2 5ER, UK
STEPHEN J. RUSSELL
CA, Krenitsky TA. Retroviral-mediated gene therapy for the hepatocellular carcinoma: an innovative approach for cancer therapy.
1. Huber BE, Richards treatment of
Proc Natl Acad Sci USA 1991; 88: 8039-43. 2. Russell SJ, Eccles SA, Flemming C, Johnson CA, Collins MKL. Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA. Int J Cancer 1991; 47: 244-51. 3. Gansbacher B, Zier K, Kaniels B, Cronin K, Bannerji R, Gilboa E. Interleukin 2 gene transfer mto tumour cells abrogates tumorigenicity and induces protective
immunity. J Exp Med 1990; 172: 1217-24. Tepper RI, Pattengale PK, Leder P. Murine interleukin 4 displays potent anti-tumor activity in vivo. Cell 1989; 57: 503-12. 5. Russell SJ. Lymphokine gene therapy for cancer. Immunol Today 1990; 11: 196-200. 6. Jam RK. Delivery of novel therapeutic agents in tumors. physiological barriers and strategies. J Natl Cancer Inst 1989; 81: 570-76. 4.
non-immune binding of more than 3 x 107 S aureus per ml in the IDEIA test is also noted in the manufacturer’s information sheets. But the clinical relevance of this false-positive reaction has not yet been recognised. It is unlikely that the required number of S aureus will be present in urethral swabs, which are usually tested by this assay; however, EIA is done for concentrated early morning urine samples, and absolute concentrations of more than 107 S aureus may therefore be achieved. Thus false-positive results due to S aureus can be obtained in contaminated urine samples, and we think that bacterial contamination should be excluded before testing for chlamydial antigens by EIAs.
J. WOLLENHAUPT Departments of Rheumatology and Microbiology, Medical School Hannover, D-3000 Hannover, Germany
EO, Paul ID, Milne JD, Crowley T. Non-invasive sampling method for detecting Chlamydia trachomatis. Lancet 1988; ii. 1246-47. 2. Paul ID, Caul EO. Evaluation of three Chlamydia trachomatis immunoassays with an unbiased, noninvasive clinical sample. Clin Microbiol 1990; 28: 220-22. 3. Chernesky M, Castriciano S, Sellors J, et al Detection of Chlamydia trachomatis antigens in urine as an alternative to swabs and cultures. J Infect Dis 1990; 161: 1. Caul
124-26. 4. Thomas
HTLV-I and uveitis SIR,-Dr Bloch-Michel and colleagues (March 21, p 750) report in uveitis associated with multiple sclerosis a local immune reaction leading to an increased production of specific antibodies to measles virus. We have reportedl evidence that a human retrovirus has an aetiological role in certain types of uveitis. Our study was done in an area endemic for HTLV-I.1 The relative risk (odds ratio) of idiopathic uveitis for HTLV-1 infection in younger patients (20-49 years) was estimated at 11-0; it was only 2-0 in older patients, indicating a role for HTLV-1 in idiopathic uveitis in younger people. Proviral DNA of HTLV-I was detected by polymerase chain reaction in all 12 samples tested from inflammatory cells in aqueous humour. Department of Ophthalmology, Kurume University School of Medicine, Kurume 830, Japan
MANABU MOCHIZUKI
Department of Internal Medicine, Kukmamoto University School of Medicine
KAZUNARI YAMAGUCHI KIYOSHI TAKATSUKI
Department of Pathology, Institute of Medical Science, Tokyo University Division of Epidemiology, Aichi Cancer Centre Research Institute
TOSHIKI WATANABE SHIGEO MORI
BJ, Gilchrist C, Hay PE, Taylor-Robinson D. Simplification of procedures test urine samples for Chlamydia trachomatis. J Clan Pathol 1991; 44:
used to 374-75.
Psoriasis of
regression in terminal AIDS
SIR,-Dr Allen (March 14, p 686) describes the disappearance psoriasis lesions in a severely immunocompromised HIV-
seropositive patient treated with cyclosporin. Allen suggests that cyclosporin had a beneficial effect in this patient. We have lately seen a patient with AID S and a very severe form of psoriasis resistant to standard topical therapy. Lesions persisted for about 2 years but finally regressed progressively when he was in the preterminal phase of his illness (CD4 count 0-01 x 109/1). During this period, the patient was treated only with multivitamins and pentamidine inhalations once every 4 weeks. The interpretation of this observation, as well as the one reported by Allen, is very difficult because spontaneous remissions of psoriasis have been noted in other patients with end-stage AIDS.! In view of the potential toxicity of cyclosporin in HIV infectionwe caution against the use of this drug in patients with psoriasis and HIV infection. Institute of
KAZUO TAJIMA
F. HARTMANN H. ZEIDLER M. FROSCH
Tropical Medicine, Antwerp, Belgium; and University Hospital, Antwerp
R. COLEBUNDERS K. BLOT V. MERTENS P. DOCKX
1. Mochizuki
M, Watanabe T, Yamaguchi K, et al. HTLV-I uveitis: a distinct clinical entity caused by HTLV-I. Jpn J Cancer Res 1992; 83: 236-39.
Staphylococcus aureus in urine and falsepositive immunoassay for chlamydia a
SIR,-Infection with Chlamydia trachomatis is now recognised as major cause of acute and chronic genitourinary diseases, and
infected patients need to be identified. Caul et all reported that examination of urine samples by enzyme immunoassay (EIA) was a non-invasive method to diagnose genitourinary chlamydial infection. Subsequent studies confirmed the value of this technique,2-4 but did not address the difficulty of false-positive results caused by bacterial contamination. We examined by IDEIA immunoassay (Novo BioLabs, Cambridge, UK; Roehm Pharma, Darmstadt, Germany) 55 urine samples from patients with bacterial urinary tract infection, but not containing chlamydia. Samples were prepared and processed by Paul and Caul’s method.2 47 urine samples containing more than 1 ()4 bacteria of various species were negative (8 Pseudomonas spp; 10 Proteus spp; 5 Escherichia coli; 3 Klebsiella spp; 1 Staphylococcus epidermidis; 20 others). By contrast, 5 of 8 urine samples with S aureus yielded positive EIA results. Further analysis by serial dilution of S aureus in otherwise sterile urine showed a dose-dependent reactivity, yielding positive results in concentrations greater than 107 S aureus per sample. A possible
Johnson T, Rapini R, Freese T, Brewton G, Rios A. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol 1987; 123: 1622-32. 2. Walgate R. Politics of premature French claim of cure. Nature 1985; 318: 3 1. Duvic M,
Fibroblast growth factor 6 gene expression in AIDS-associated Kaposi’s sarcoma SIR,-Kaposi’s sarcoma (KS) represents an opportunistic neoplasm of unknown aetiology which is especially prevalent in individuals infected with HIV, most notably in homosexual men. The possibility of a direct role for HIV in the aetiology of KS has been raised by experiments describing the introduction of HIV-tat sequences into transgenic mice,l and has been supported by the fmding that the tat protein stimulates growth of KS-derived cells in cultureCultured KS cells proliferate in response to various autocrine and paracrine growth factors and cytokines.3,4Few studies on intact fresh KS tumour tissue have been done.s To help characterise the pathophysiology of KS cells in vivo, we used the reverse transcriptase-polymerase chain reaction (RT-PCR)6 to detect expression of fibroblast growth factors (FGFs) and their receptors in fresh KS tissue. We were surprised to find FGF6 expressed in two specimens from different individuals with AIDS. To our knowledge, this is the first report of FGF6 in KS or any other human
tumour
tissue.
history of breast cancer who were premenopausal, so menopausal status is not a confounding variable in our study. An additional factor affecting Kd could be receptor protein structure. Multiple polymorphisms of ER and PR have been identified, and the results presented here suggest that some women with a family history of breast cancer might inherit a variant receptor gene with
an altered Kd. The same inherited structural also induce familial breast cancer susceptibility. abnormality might
Department of Radiation Oncology, Mount Sinai Medical Center, New York, NY 10029, USA
Fig 1-ERKd and PRKd (mean and SE)
in breast tumours.
Numbers of cases indicated above SE bar Values nanomolar Kd values.
as
square-roots of
history. Breast tumour ER, ERKd, PR, and PRKD concentrations were measured with a Rianen Assay Systems kit (DuPont). There was a significant reduction in ERKd and in PRKD in the tumours of women with a family history of breast cancer. The results are expressed as the square-roots of nanomolar values, to normalise variances (fig 1). There was no significant association of ER or PR with family history (fig 2). 15 women had a first-degree family history of breast cancer in mother, daughter, or sister. The other women had affected aunts or cousins. There was no significant difference in the proportion of women with or without a family history who were premenopausal (23% and 19%, respectively). Although Kd values are estimated in several laboratories, little has been published about their character or clinical usefulness.5 In one study, postmenopausal patients with high Kd values tended to have shorter recurrence-free survival.6 Since Kd reflects binding affinity between receptor and ligand, the "true" Kd value should be identical within the same tissue in the same species. But the observed Kd depends on assay method6 and receptor phosphorylation.7 Menopausal status also affects Kd because of high endogenous oestrogen and progesterone levels in premenopausal women.6 However, there was no significant difference in the proportion of women with or without a family
Fig 2-ER and
PR.
STEVEN LEHRER EVA LEVINE PENNY SAVORETTI JOAN CROPLEY SWAN N. THUNG H. K. SONG LYNDA MANDELL BRENDA SHANK
1. McGuire WL, Chamness GC, Fuqua SAW. Estrogen receptor variants in clinical breast cancer. Mol Endocrinol 1991; 5: 1571-77. 2. Fuqua SW, Hill SM, Chamness GC, et al. Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. J Natl Cancer Inst 1991; 83: 1157-60. 3. Lehrer S, Sanchez M, Song HK, et al. Oestrogen receptor B-region polymorphism and spontaneous abortion in women with breast cancer. Lancet 1990; 335: 622-24. 4. Callahan R, Campbel G. Mutations in human breast cancer: an overview. J Natl Cancer Inst 1989; 81: 1780-86. 5. Witliff JL. Steroid receptor analyses, quality control, and clinical significance In: Donegan WL, Spratt JS, eds. Cancer of the breast, 3rd ed. Philadelphia: Saunders, 1988: 303-55. 6 Thorpe SM, Rose C. Biological and clinical relevance of Kd values for estradiol binding in primary breast cancer tumors. Eur J Cancer Clin Oncol 1988; 24: 1163-70. 7. Dayani N, McNaught RW, Smith RG. ATP mediated receptor interconversion as a model of estrogen receptor action: isolation of the factor which converts the non-estrogen binding form of the receptor to the low affinity binding form. J Steroid Biochem 1988; 30: 219-24.
Gene therapy for cancer SIR,-Dr Gutierrez and colleagues’ review (March 21,
p
715)
useful introduction to some of the gene therapy ideas circulating in cancer research. However, in the context of tumourcell-targeted gene therapy, insufficient emphasis was given to the important point that the genes must either reach all the target cells or destroy indirectly those tumour cells they cannot reach. Tumour-suppressor genes, MHC genes, and the varicella-zoster virus thymidine kinase gene proposed for virus-directed enzyme prodrug therapy (VDEPT)* have no "bystander effect" and influence only the tumour cells to which they have been successfully delivered. To cure cancer these genes would have to be delivered to all the patient’s cancer cells but the heterogeneity and inaccessibility of the target cells make this an elusive goal. 100% efficient delivery is not required for genes encoding secreted proteins that can (directly or indirectly) mediate the destruction of surrounding tumour cells. Bystander effects, apparently mediated through paracrine stimulation of host antitumour effector cells, have been demonstrated after expression of interleukin-2 and interleukin-4 genes in rodent tumour models.2-4 Many other gene products may be capable of stimulating local antitumour immunity or generating locally cytotoxic "crossfire". Examples include other immunostimulatory cytokines, chemotactic peptides, antibodies, and toxins. Also, it may be possible to modify the VDEPT approach by engineering the genes to encode the drug-activating enzyme in a cell surface-associated or secreted form. Extracellular activation of the prodrug by enzyme derived from a small number of genetransduced tumour cells might then lead to wholesale tumour destruction. The major obstacle to tumour-targeted gene therapy is inability to deliver genes efficiently to tumour deposits in vivo.s Until gene transfer technology is up to this task the potential of this form of gene therapy cannot be tested, even in animal models. Virus vectors, the most promising vehicles for in-vivo gene delivery, are too large to cross the vascular endothelial lining of tumour blood vessels in numbers large enough to reach more than a small fraction of target cells. Vectors capable of replicating and spreading through a tumour may provide part of the answer to this problem but there are serious concerns about safety. Even on the most optimistic view, it is was a
1110
difficult, if one takes account of target cell heterogeneity and poor vascular access,6 to envisage a time when it will be possible to deliver a therapeutic gene to every tumour cell. However, by choosing genes that encode locally active secreted proteins, the requirement for 100% efficient delivery is bypassed, making targeted gene therapy for cancer a technically demanding, but feasible
proposition. MRC Centre, Cambridge CB2 5ER, UK
STEPHEN J. RUSSELL
CA, Krenitsky TA. Retroviral-mediated gene therapy for the hepatocellular carcinoma: an innovative approach for cancer therapy.
1. Huber BE, Richards treatment of
Proc Natl Acad Sci USA 1991; 88: 8039-43. 2. Russell SJ, Eccles SA, Flemming C, Johnson CA, Collins MKL. Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA. Int J Cancer 1991; 47: 244-51. 3. Gansbacher B, Zier K, Kaniels B, Cronin K, Bannerji R, Gilboa E. Interleukin 2 gene transfer mto tumour cells abrogates tumorigenicity and induces protective
immunity. J Exp Med 1990; 172: 1217-24. Tepper RI, Pattengale PK, Leder P. Murine interleukin 4 displays potent anti-tumor activity in vivo. Cell 1989; 57: 503-12. 5. Russell SJ. Lymphokine gene therapy for cancer. Immunol Today 1990; 11: 196-200. 6. Jam RK. Delivery of novel therapeutic agents in tumors. physiological barriers and strategies. J Natl Cancer Inst 1989; 81: 570-76. 4.
non-immune binding of more than 3 x 107 S aureus per ml in the IDEIA test is also noted in the manufacturer’s information sheets. But the clinical relevance of this false-positive reaction has not yet been recognised. It is unlikely that the required number of S aureus will be present in urethral swabs, which are usually tested by this assay; however, EIA is done for concentrated early morning urine samples, and absolute concentrations of more than 107 S aureus may therefore be achieved. Thus false-positive results due to S aureus can be obtained in contaminated urine samples, and we think that bacterial contamination should be excluded before testing for chlamydial antigens by EIAs.
J. WOLLENHAUPT Departments of Rheumatology and Microbiology, Medical School Hannover, D-3000 Hannover, Germany
EO, Paul ID, Milne JD, Crowley T. Non-invasive sampling method for detecting Chlamydia trachomatis. Lancet 1988; ii. 1246-47. 2. Paul ID, Caul EO. Evaluation of three Chlamydia trachomatis immunoassays with an unbiased, noninvasive clinical sample. Clin Microbiol 1990; 28: 220-22. 3. Chernesky M, Castriciano S, Sellors J, et al Detection of Chlamydia trachomatis antigens in urine as an alternative to swabs and cultures. J Infect Dis 1990; 161: 1. Caul
124-26. 4. Thomas
HTLV-I and uveitis SIR,-Dr Bloch-Michel and colleagues (March 21, p 750) report in uveitis associated with multiple sclerosis a local immune reaction leading to an increased production of specific antibodies to measles virus. We have reportedl evidence that a human retrovirus has an aetiological role in certain types of uveitis. Our study was done in an area endemic for HTLV-I.1 The relative risk (odds ratio) of idiopathic uveitis for HTLV-1 infection in younger patients (20-49 years) was estimated at 11-0; it was only 2-0 in older patients, indicating a role for HTLV-1 in idiopathic uveitis in younger people. Proviral DNA of HTLV-I was detected by polymerase chain reaction in all 12 samples tested from inflammatory cells in aqueous humour. Department of Ophthalmology, Kurume University School of Medicine, Kurume 830, Japan
MANABU MOCHIZUKI
Department of Internal Medicine, Kukmamoto University School of Medicine
KAZUNARI YAMAGUCHI KIYOSHI TAKATSUKI
Department of Pathology, Institute of Medical Science, Tokyo University Division of Epidemiology, Aichi Cancer Centre Research Institute
TOSHIKI WATANABE SHIGEO MORI
BJ, Gilchrist C, Hay PE, Taylor-Robinson D. Simplification of procedures test urine samples for Chlamydia trachomatis. J Clan Pathol 1991; 44:
used to 374-75.
Psoriasis of
regression in terminal AIDS
SIR,-Dr Allen (March 14, p 686) describes the disappearance psoriasis lesions in a severely immunocompromised HIV-
seropositive patient treated with cyclosporin. Allen suggests that cyclosporin had a beneficial effect in this patient. We have lately seen a patient with AID S and a very severe form of psoriasis resistant to standard topical therapy. Lesions persisted for about 2 years but finally regressed progressively when he was in the preterminal phase of his illness (CD4 count 0-01 x 109/1). During this period, the patient was treated only with multivitamins and pentamidine inhalations once every 4 weeks. The interpretation of this observation, as well as the one reported by Allen, is very difficult because spontaneous remissions of psoriasis have been noted in other patients with end-stage AIDS.! In view of the potential toxicity of cyclosporin in HIV infectionwe caution against the use of this drug in patients with psoriasis and HIV infection. Institute of
KAZUO TAJIMA
F. HARTMANN H. ZEIDLER M. FROSCH
Tropical Medicine, Antwerp, Belgium; and University Hospital, Antwerp
R. COLEBUNDERS K. BLOT V. MERTENS P. DOCKX
1. Mochizuki
M, Watanabe T, Yamaguchi K, et al. HTLV-I uveitis: a distinct clinical entity caused by HTLV-I. Jpn J Cancer Res 1992; 83: 236-39.
Staphylococcus aureus in urine and falsepositive immunoassay for chlamydia a
SIR,-Infection with Chlamydia trachomatis is now recognised as major cause of acute and chronic genitourinary diseases, and
infected patients need to be identified. Caul et all reported that examination of urine samples by enzyme immunoassay (EIA) was a non-invasive method to diagnose genitourinary chlamydial infection. Subsequent studies confirmed the value of this technique,2-4 but did not address the difficulty of false-positive results caused by bacterial contamination. We examined by IDEIA immunoassay (Novo BioLabs, Cambridge, UK; Roehm Pharma, Darmstadt, Germany) 55 urine samples from patients with bacterial urinary tract infection, but not containing chlamydia. Samples were prepared and processed by Paul and Caul’s method.2 47 urine samples containing more than 1 ()4 bacteria of various species were negative (8 Pseudomonas spp; 10 Proteus spp; 5 Escherichia coli; 3 Klebsiella spp; 1 Staphylococcus epidermidis; 20 others). By contrast, 5 of 8 urine samples with S aureus yielded positive EIA results. Further analysis by serial dilution of S aureus in otherwise sterile urine showed a dose-dependent reactivity, yielding positive results in concentrations greater than 107 S aureus per sample. A possible
Johnson T, Rapini R, Freese T, Brewton G, Rios A. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol 1987; 123: 1622-32. 2. Walgate R. Politics of premature French claim of cure. Nature 1985; 318: 3 1. Duvic M,
Fibroblast growth factor 6 gene expression in AIDS-associated Kaposi’s sarcoma SIR,-Kaposi’s sarcoma (KS) represents an opportunistic neoplasm of unknown aetiology which is especially prevalent in individuals infected with HIV, most notably in homosexual men. The possibility of a direct role for HIV in the aetiology of KS has been raised by experiments describing the introduction of HIV-tat sequences into transgenic mice,l and has been supported by the fmding that the tat protein stimulates growth of KS-derived cells in cultureCultured KS cells proliferate in response to various autocrine and paracrine growth factors and cytokines.3,4Few studies on intact fresh KS tumour tissue have been done.s To help characterise the pathophysiology of KS cells in vivo, we used the reverse transcriptase-polymerase chain reaction (RT-PCR)6 to detect expression of fibroblast growth factors (FGFs) and their receptors in fresh KS tissue. We were surprised to find FGF6 expressed in two specimens from different individuals with AIDS. To our knowledge, this is the first report of FGF6 in KS or any other human
tumour
tissue.
