OCEANOGRAPHY. Contrasting futures for ocean and society from different anthropogenic CO2 emissions scenarios.

The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems­and the goods and services they provide­for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario­consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2°C­is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.

Ocular manifestations of leukemia: leukemic infiltration versus infectious process.

OBJECTIVE: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available. INTERVENTION: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs. MAIN OUTCOME MEASURES: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records. RESULTS: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection. CONCLUSIONS: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.

Combined nevi of the conjunctiva.

OBJECTIVE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but rarely has been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas in the files of the University of California at San Francisco Eye Pathology Laboratory from 1984 to 1999 were reviewed for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty combined nevi were discovered between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some may favor a clinical diagnosis of melanoma, no lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus, a combination of a nevocytic and a blue nevus, is common and has been overlooked in the past.

Combined nevi of the conjunctiva.

PURPOSE: To report the clinical and histologic features of combined nevi of the conjunctiva, a type of nevus that is not uncommon in the skin but has rarely been reported in the conjunctiva. METHODS: Conjunctival nevi and melanomas from the files of the University of California, San Francisco, eye pathology laboratory were reviewed from 1984 to 1999 for the presence of features of both standard nevocytic nevi and blue nevi. Clinical histories and, when available, clinical photographs were obtained. RESULTS: Thirty-one combined nevi were discovered during the 15-year period between 1984 and 1999. One case before 1984 had been incorrectly diagnosed as a junctional nevus. The dendritic and spindle-shaped blue nevus cells had been overlooked because they were not recognized as distinct from the standard nevocytic nevus cells. The recognition of a blue as well as a brown color, a deep as well as a superficial component in the lesion, or a history of pigmentation since birth may help to establish the correct clinical diagnosis and prevent an unnecessarily deep surgical resection. Although growth of the lesion or "satellites" in some patients may favor a clinical diagnosis of melanoma, none of the lesions in this series were malignant. CONCLUSION: Despite a paucity of reports of combined nevi of the conjunctiva in the medical literature, this type of nevus--a combination of a nevocytic and a blue nevus--is common and has been overlooked in the past.

Vitreitis and Waldenström's macroglobulinemia.

PURPOSE: To describe vitreitis in a patient with Waldenström's macroglobulinemia. METHODS: Case report and review of pertinent literature. RESULTS: A 90-year-old man developed vitreitis 10 years after a systemic diagnosis of a lymphoproliferative disorder. Numerous small, normal-appearing lymphocytes were seen on pathologic examination of the vitreous. He developed worsening lymphadenopathy and was diagnosed with Waldenström's macroglobulinemia after systemic review. CONCLUSION: Chronic lymphoproliferative diseases such as Waldenstrom's macroglobulinemia may cause vitreitis.

Complex limbal choristomas in linear nevus sebaceous syndrome.

OBJECTIVE: This study aimed to describe the clinical and histopathologic findings in four patients with complex limbal choristomas associated with linear nevus sebaceous syndrome (LNSS), a rare disorder including nevus sebaceous, seizures, and mental retardation, and often accompanied by ocular anomalies. DESIGN: Small observational case series. METHODS: A retrospective review of the clinical and histopathologic records of four patients. RESULTS: Each of four patients had complex limbal choristomas in the setting of clinical and histopathologic LNSS. The limbal choristomas were multiple in three patients and bilateral in two patients. Most choristomas involved the superotemporal limbus (6 of 10), although nasal (3 of 10) and inferior (1 of 10) limbal tumors also were present. Three patients had significant corneal astigmatism or involvement of the central cornea requiring surgical removal of their choristomas, one accompanied by a lamellar keratoplasty and another accompanied by two consecutive penetrating keratoplasties. Each graft eventually vascularized, reducing vision. One patient's vision was limited by amblyopia and another by occipital cortical dysgenesis with visual impairment. Histopathologic examination of the excised choristomas showed foci of lacrimal gland (3 of 4 patients), adipose tissue (3 of 4), neural tissue (1 of 4), cartilage (1 of 4), lymphoid follicles (1 of 4), skin adnexal tissue (1 of 4), and smooth muscle (1 of 4). Other associated ocular findings included an eyelid mass (1 of 4), colobomas of the eyelid (3 of 4), colobomas of the choroid and retina (2 of 4), nonparalytic strabismus (2 of 4), scleral ectasia (1 of 4), partial oculomotor palsy with ptosis and anisocoria (1 of 4), microphthalmia (1 of 4), hypertelorism (1 of 4), and cortical visual impairment (1 of 4). CONCLUSIONS: Complex limbal choristomas, although rare, can occur in the setting of LNSS and can be associated with multiple ocular and systemic abnormalities. Visual prognosis appears poor in most cases despite aggressive management.

Intraocular coccidioidomycosis diagnosed by skin biopsy.

OBJECTIVE: To describe ocular findings in 2 patients with disseminated coccidioidomycosis diagnosed by skin biopsy. METHODS: The clinical and histopathologic findings of the 2 patients were reviewed retrospectively. RESULTS: One patient had a unilateral, granulomatous iridocyclitis with multiple iris nodules and a large vascularized anterior chamber mass, in the setting of pulmonary, cutaneous, and skeletal infection by Coccidioides immitis. The second patient developed papilledema and multifocal chorioretinitis accompanied by pulmonary, cutaneous, and meningeal C immitis infection. In each case, examination of the skin biopsy specimen revealed C immitis spherules. Treatments included local and systemic amphotericin B and oral fluconazole. CONCLUSIONS: Although rare, intraocular involvement can occur in the setting of disseminated coccidioidomycosis. A thorough systemic evaluation and biopsy of suspicious skin lesions can aid in the diagnosis.

Distribution of tumor necrosis factor receptor messenger RNA in normal and herpes simplex virus infected trigeminal ganglia in the mouse.

PURPOSE: to investigate the distribution of p55 and p75 tumor necrosis factor (TNF) receptor mRNA in normal murine trigeminal ganglia, and in murine trigeminal ganglia acutely infected with McKrae strain herpes simplex virus (HSV). METHODS: in situ hybridization with antisense 35S-labeled riboprobes for mRNA encoding both the p55 and p75 TNF receptor (TNFR) subtypes was used in normal and HSV-infected murine trigeminal ganglia. Sense riboprobes were used as controls. RESULTS: in situ hybridization with both p55 and p75 riboprobes produced a strong autoradiographic signal over many, but not all, trigeminal sensory neurons. Signal for mRNA encoding both TNFR subtypes was also present over the arachnoid layers surrounding trigeminal ganglia. Acute ocular HSV infection was accompanied by an intense leukocytic infiltrate into the ophthalmic portion of the trigeminal ganglia, and, in this setting, increased p55 and p75 mRNA signal was closely related to the location and number of infiltrating white blood cells. The distribution and number of trigeminal sensory neurons expressing mRNA for the two TNFR subtypes did not appear to change following infection. Signal over control sections hybridized with sense p55 and p75 TNFR cRNA probes was comparable to background. CONCLUSIONS: the observed distribution of p55 and p75 TNFR mRNA over trigeminal sensory neurons and over the arachnoid layers surrounding trigeminal ganglia supports suggestions that TNF has a direct effect on neurons, either as a neuromodulator or neurotrophic factor, and that TNF may play a central role in blood-brain barrier regulation. Increased signal for TNFR mRNA in acutely infected trigeminal ganglia appears to reflect infiltration by receptor-bearing white blood cells.

Hyaluronan in the human trabecular meshwork.

PURPOSE: Hyaluronan (HA) is a high-molecular weight glycosaminoglycan that can affect water and solute fluxes in the extracellular matrix. The distribution of HA in the human trabecular meshwork of nonglaucomatous eyes was examined to help understand the potential role of HA in the regulation of aqueous outflow resistance. METHODS: Histolocalization of HA was established in situ in the trabecular meshwork of human eyes with no known diseases of the anterior segment. A specific biotinylated HA-binding peptide was used as a probe for this study, with enhanced sensitivity of HA detection achieved by modifications of the fixation and staining procedures. RESULTS: Evaluation of HA staining in the aqueous outflow pathway in comparison to that in other ocular structures (e.g., the vitreous) showed pronounced staining in the trabecular meshwork. The staining intensity was similar between various layers of the meshwork. Both the filtering and the anterior nonfiltering portions of the trabecular meshwork showed pronounced HA staining. The staining was localized primarily to the trabecular meshwork endothelial cells. CONCLUSIONS: Pronounced HA staining observed in the various layers of the trabecular meshwork suggests that substantial amount of HA is present in the nonglaucomatous outflow pathway. The staining pattern suggests that HA is associated with the endothelial cells lining the trabecular beams. This finding supports potential roles for this glycosaminoglycan in the regulation of the physiological aqueous outflow resistance or in the maintenance of the outflow channels or both. Histochemical localization of HA in the various layers of the non-glaucomatous meshwork provides a useful basis for future comparative studies of HA distribution and relative amounts in the trabecular meshworks of eyes affected by various types of glaucoma.

Localization of tumor necrosis factor receptor messenger RNA in normal and herpes simplex virus-infected mouse eyes.

PURPOSE: To investigate the distribution of p75 and p55 tumor necrosis factor receptor (TNFR) mRNA in normal mouse eyes and in mouse eyes acutely infected with McKrae strain herpes simplex virus (HSV). METHODS: In situ hybridization with antisense 35S-labeled riboprobes for p55 and p75 TNFR subtypes was used in uninfected and HSV-infected mouse eyes. Controls included the use of sense riboprobes and corneas inoculated with vehicle alone. RESULTS: In uninfected and infected mouse eyes, in situ hybridization produced an autoradiographic signal for mRNA, encoding both p75 and p55 over the corneal endothelium, iris, ciliary body, choroid, and arachnoid layers of the optic nerve sheath. In addition, the signal was observed over scattered cells at the vitreoretinal interface. Signal for p75, but not p55, was observed over cells in the retinal ganglion cell layer. Acute HSV infection was accompanied by an intense leukocytic infiltrate in the conjunctiva, the corneal subepithelium and stroma, the anterior and posterior chambers, the iris root and ciliary body, and the vitreous cavity. In this setting, increased p75 and p55 mRNA signal was correlated closely with the number and location of receptor-bearing white blood cells. Signal over control sections hybridized with sense p75 and p55 TNFR cRNA probes was comparable to background. Signal over control eyes inoculated with sterile vehicle showed slight increased signal in the immediate vicinity of the traumatic keratitis, but otherwise it was comparable to that observed in uninfected animals. CONCLUSIONS: The observed distribution of p75 and p55 TNFR mRNA in normal and acutely infected mouse eyes, and particularly over the heavily vascularized uveal tract and over cells at the vitreoretinal interface, supports a role for TNF as a mediator of intraocular inflammation, perhaps as a key regulator of the blood-ocular barrier.

Cytokine-mediated survival from lethal herpes simplex virus infection: role of programmed neuronal death.

The mechanisms responsible for cytokine-mediated antiviral effects are not fully understood. We approached this problem by studying the outcome of intraocular herpes simplex (HSV) infection in transgenic mice that express interferon gamma in the photoreceptor cells of the retina. These transgenic mice showed selective survival from lethal HSV-2 infection manifested in both eyes, the optic nerve, and the brain. Although transgenic mice developed greater inflammatory responses to the virus in the eyes, inflammation and viral titers in their brains were equivalent to nontransgenic mice. However, survival of transgenic mice correlated with markedly lower numbers of central neurons undergoing apoptosis. The protooncogene Bcl2 was found to be induced in the HSV-2-infected brains of transgenic mice, allowing us to speculate on its role in fostering neuronal survival in this model. These observations imply a complex interaction between cytokine, virus, and host cellular factors. Our results suggest a cytokine-regulated salvage pathway that allows for survival of infected neurons.

Cellular and vascular responses in acute experimental ocular inflammation.

PURPOSE: To measure simultaneously blood volume, altered vascular permeability, and leukocyte extravasation in ocular inflammation in rabbits at various times and in different anatomic locations after intravitreal endotoxin (lipopolysaccharide [LPS]). METHODS: Nuclides of different emission and decay were used for labeling and then injected intravenously. Ocular blood volumes were measured with technetium 99m, altered vascular permeability with I-125 albumin, and polymorphonuclear leukocyte or mononuclear cell extravasation after labeling with Indium 111. Eyes were divided into anterior eye section, iris-ciliary body, aqueous, and vitreous and posterior eye sections, and measurements were made at 3, 6, 9, 18, and 24 hours after intravitreal LPS injection. Blood volume measurements made it possible to estimate the amount of extravascular protein and the number of extravascular leukocytes. RESULTS: Blood volumes were consistently elevated at all times, usually by approximately 50% and predominantly in the anterior segment. Altered vascular permeability was present at 3 hours, increased at 6 hours, decreased at 9 hours, and was elevated at 18 to 24 hours, predominantly in the anterior eye. Leukocytes in iris-ciliary body appeared in small numbers at 6 hours, increased at 9 hours, and continued to extravasate at 18 and 24 hours. Mononuclear cells were as numerous as polymorphonuclear leukocytes at each time measured. CONCLUSIONS: The quantitation of multiple parameters of ocular inflammation in this experimental model has been helpful in defining when and in what tissue changes occur. Leukocytes are primarily within tissues, particularly in the iris-ciliary body region. Mononuclear leukocytes are a prominent feature at all times and add further support to the concept that the mononuclear phagocyte plays a pivotal role in reactions to LPS.

Ectopic expression of gamma interferon in the eye protects transgenic mice from intraocular herpes simplex virus type 1 infections.

Transgenic (rho gamma) mice provide a model for studying the influence of gamma interferon (IFN-gamma) produced in the eye on ocular and cerebral viral infection. To establish this model, we injected BALB/c- and C57BL/6-derived transgenic and nontransgenic mice of different ages intravitreally with herpes simplex virus type 1 (HSV-1) strain F. Eye and brain tissues of these mice were assessed for pathological and immunocytochemical changes. HSV-1 infection induced severe retinitis of the injected eyes and infection of the brain in all mice. In transgenic mice inoculated with HSV-1, the left, nontreated eyes were protected from retinitis, whereas nontransgenic mice developed bilateral retinitis. Additional intravitreal injection of IFN-gamma with the virus protected the noninoculated eyes of nontransgenic mice. Three-week-old nontransgenic mice died from HSV-1 infection, whereas transgenic mice of the same age and nontransgenic mice intravitreally treated with IFN-gamma survived. Ocular IFN-gamma production increased the extent of inflammation in transgenic mice but did not have a significant influence on the growth of HSV-1 until day 3 after inoculation and did not influence the neuroinvasion of this virus. Thus, the effects of IFN-gamma were not caused by an early block of viral replication. Possible mechanisms of IFN-gamma action include activation of the immune response, alteration of the properties of the virus, and direct protection of neurons.

Resection of intraocular squamous cell carcinoma.

A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva.

Cytomorphometry of uveal melanoma. Comparison of fine needle aspiration biopsy samples with histologic sections.

A number of approaches are being investigated to increase the prognostic accuracy for uveal melanoma patients; the standard deviation of nucleolar area measurements and the DNA content appear to correlate better with survival than do classic histologic parameters. The utility of performing cytomorphometric measurements on fine needle aspiration (FNA) biopsy samples was prospectively analyzed for 24 eyes containing uveal melanomas that were examined with both 25-gauge FNA biopsy and standard histologic techniques. "Masked" analysis of the cellular composition of the 24 cases showed the presence or absence of epithelioid cells to be accurately predicted on the FNA samples in all cases. Image analysis cytomorphometric measurements of nucleolar area showed marked variability (with r less than 0.4) when FNA and histologic samples from the same case were compared. The relationship between these measurements was affected by cell type, sampling, specimen processing and investigator experience.

Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens.

Two prospective studies were undertaken to evaluate a commercial indirect fluorescent-antibody (IFA) stain for the detection of Pneumocystis carinii in respiratory specimens from individuals at risk for or with the acquired immunodeficiency syndrome. The first study compared IFA with Diff-Quik (DQ; a rapid Giemsa-like stain) for detecting P. carinii in 95 induced sputa obtained from 77 asymptomatic patients who had survived one previous episode of P. carinii pneumonia and who were being treated prophylactically with aerosolized pentamidine. Only one induced sputum specimen was found to contain P. carinii; organisms were detected by both stains. The second study compared the performance of the IFA stain versus DQ, modified toluidine blue O, and Gomori methenamine silver stains for detecting P. carinii in symptomatic individuals at risk for or with acquired immunodeficiency syndrome. Of 182 specimens examined, P. carinii was detected in 105 by one or more stains; the DQ stain detected 73 (70%), the modified toluidine blue O stain detected 75 (71%), the Gomori methenamine silver stain detected 76 (72%), and the IFA stain detected 95 (90%). The IFA stain was more sensitive (P less than 0.01) than the other traditional stains for detecting P. carinii; however, a subsequent clinical evaluation revealed that a subset of IFA-positive-only specimens were from patients whose clinical symptoms resolved without specific anti-P. carinii therapy.