Bcl-2 protein in centrocytic lymphoma; a paraffin section study.

Bcl-2 is an inner mitochondrial membrane protein which blocks apoptosis. Although present in many B cells, the vast majority of follicular center cells do not have detectable bcl-2 protein. The bcl-2 gene is translocated in most conventional small cleaved follicular center cell (SCFCC) lymphomas (centroblastic/centrocytic) but not in centrocytic lymphomas (CC). The translocated gene in the SCFCC lymphomas leads to 'aberrant' bcl-2 expression by the neoplastic follicular center cells. The frequency with which the normal non-translocated gene is expressed in CC lymphomas is, however, not well documented. Paraffin sections from 22 cases of centrocytic lymphoma were therefore stained with an anti-bcl-2 antibody. Genotypic studies in 14 cases demonstrated bcl-1/PRAD1 (cyclin D1; CCND1) rearrangements in ten and bcl-2 rearrangements in none. All centrocytic lymphomas demonstrated bcl-2 protein expression in the majority of neoplastic cells. Negative staining residual follicular centers were identified in four cases emphasizing the mantle zone growth pattern of a subset of CC lymphomas. Expression of bcl-2 protein in the absence of bcl-2 gene rearrangement is a feature shared by centrocytic lymphomas and mantle zone cells. However, because this type of bcl-2 expression is not specific for B-cells of the mantle zone, it does not further elucidate the true cell of origin for the centrocytic lymphomas.

The plasma membrane electrical gradient (membrane potential) in Leishmania donovani promastigotes and amastigotes.

The equilibrium distribution of tetraphenylphosphonium bromide was used to measure the membrane potential in Leishmania donovani amastigotes and promastigotes and to investigate mechanisms underlying the maintenance of membrane potential. At pH 7.0, membrane potential ranges between -90 and -113 mV. Increasing the external concentrations of hydrogen or potassium ions decreased membrane potential as did treatments with carbonylcyanide chlorophenylhydrazone or valinomycin. These observations are consistent with a membrane potential set by hydrogen and potassium ion diffusion gradients. Anaerobiosis lowered membrane potential, suggesting the involvement of ATPase(s) in maintaining membrane potential. Membrane potential was insensitive to treatment with ouabain, demonstrating the absence of a Na+/K(+)-ATPase. Treatment with dicyclohexylcarbodiimide caused a temporary hyperpolarization of the membrane suggesting the participation of a proton ATPase in the maintenance of membrane potential. Determination of the membrane potential makes it possible to quantitate the total proton motive force which is the force for active transport across the parasite membrane.

Immune activation and virologic response to immunization in recent HIV type 1 seroconverters.

Antigenic stimulation from invasive bacterial infections, and the vaccines designed to prevent them, may promote T cell activation and enhancement of HIV-1 replication. Changes in viral load have been correlated with antigen-specific responses. We prospectively determined the impact of immunization with 23-valent pneumococcal vaccine (PVAX) and Haemophilus influenzae type b (Hib)-modified diphtheria toxoid CRM197 (DT) vaccine on HIV-1 replication in recent HIV-1 seroconverters (n = 14; median, 5.5 months from infection; median CD4+ T cells, 535 microl), and correlated results with vaccine-related immune activation. Specific antibody responses, markers of CD4+ T cell activation (transferrin and interleukin 2 receptors), and viral burden were measured at weeks -2 (pre), 0, 1, 2, 6, and 12 after immunization. By week 2, levels of IgG had increased significantly over baseline in both HIV-1-infected patients and HIV-1-seronegative control subjects (n = 9) for each antigen (geometric mean fold rise: PVAX, 10.1 versus 5.3; Hib, 16.0 versus 11.7; and DT, 26.2 versus 24.5, respectively). Despite these vigorous responses to both polysaccharide and protein antigens, HIV-1-infected patients showed limited evidence of CD4+ T cell activation at 1 week, no consistent rise in HIV-1 burden at any point, and no decline in CD4+ T cell number over time. We conclude that recent HIV-1 seroconverters show vigorous humoral responses to vaccine antigens and limited early evidence of T cell activation, but no substantial or sustained increase in viral replication or decline in CD4+ T cell number. Thus, respiratory bacterial vaccines appear immunogenic and safe early in HIV-1 infection.

Distinction of follicular hyperplasia from follicular lymphoma in B5-fixed tissues: comparison of MT2 and bcl-2 antibodies.

The distinction between follicular hyperplasia (FH) and follicular lymphoma (FL) is one of the classic problems in diagnostic hematopathology. Both MT2 and bcl-2 antibodies have been reported to be useful in making this distinction. To compare the utility of these two commercially obtained antibodies in paraffin-embedded sections, B5-fixed sections from 21 cases of follicular hyperplasia and from 46 follicular lymphomas were immunostained and the follicles evaluated. Neither MT2 nor the bcl-2 antibody showed definite follicular positivity in FH. In contrast, 66% of FLs were MT2 positive and 89% were bcl-2 positive (P < .02). MT2 staining was equivocal in 30% of FHs and 7% of FLs, whereas bcl-2 staining was equivocal in only one FL. In addition, MT2 staining was unsatisfactory in three cases. CD10 was negative (0% to 3%) in the three bcl-2-negative FLs tested and positive (> 10%) in 26 of 38 bcl-2-positive cases. These results demonstrate the utility of the commercially obtained bcl-2 antibody in distinguishing FL from FH in B5-fixed, paraffin-embedded tissue sections. They also illustrate the superiority of the bcl-2 antibody over MT2, which was less sensitive and more problematic to interpret.

Incidence of symptomatic and asymptomatic Plasmodium falciparum infection following curative therapy in adult residents of northern Ghana.

Adult residents of holoendemic malaria regions in Africa have a naturally acquired immunity (NAI) to malaria that renders them more resistant to new infections, limits parasitemia, and reduces the frequency and severity of illness. Given such attributes, it is not clear how one might evaluate drug or vaccine efficacy in adults without serious confounding. To determine symptomatic and asymptomatic malaria attack rates in adults of northern Ghana, 197 men and women underwent curative therapy for any pre-existing malaria infections at the start of the high transmission (wet) season. They were monitored for first parasitemia and first clinical episode of infection by Plasmodium falciparum over a 20-week period (May-October 1996). The cumulative incidence of primary infection by P. falciparum was 0.98 and incidence density of infection was calculated to be 7.0 cases/person-year. Symptoms were reported by 19.5% of the individuals at the time of first recurrent parasitemia. Incidence of infection, parasite density, and the frequency of symptoms were comparable in males and females. The results suggest that NAI did not provide these adults with significant defense against rapid re-infection and suggest that this population-infection design could serve to demonstrate the efficacy of a drug or vaccine in preventing parasitemia.

Severe anemia in young children after high and low malaria transmission seasons in the Kassena-Nankana district of northern Ghana.

Malaria and anemia accounted for 41% and 18% respectively of hospital deaths in the Kassena-Nankana district of northern Ghana during 1996. We measured hemoglobin (Hb), malaria prevalence, and anthropometric indices of 6--24-month-old infants and young children randomly selected from this community at the end of the high (May-October, n = 347) and low (November-April, n = 286) malaria transmission seasons. High transmission season is characterized by rainfall (the equivalent of 800-900 mm/yr.), while the remaining months receive less than 50 mm/yr. Severe anemia, defined as Hb < 6.0 g/dL, was 22.1% at the end of the high transmission season compared to 1.4% at the end of the low transmission season (Odds Ratio [OR] = 20.1; 95% CI: 7.1-55.3). Parasitemia was 71% and 54.3% at these time points (OR = 2.1; 95% CI: 1.5-2.9). Nutritional anemia appeared to have little impact upon this seasonal difference since anthropometric indices were comparable. Although the relative contributions of other causes of severe anemia were not assessed, repeated malaria infections may be a primary determinant of severe anemia among infants and young children during the high transmission season.

Coccidioidomycosis in California: regional outbreak, global diagnostic challenge.

Beginning in 1991, case reports of coccidioidomycosis in California increased dramatically, pursuant to a variety of natural and demographic factors. This highly infectious fungal disease with propensity to disseminate widely, mimic other conditions, and cause pathology at locations distant in place and time is readily treatable if recognized at an early stage. The concentration of military bases in endemic areas and the mobility of military personnel suggest a heightened potential for case presentations elsewhere and a need for elevated diagnostic suspicion on the part of military physicians worldwide. We review three cases of disseminated disease recently referred to our facility.

[Oral application of calcium and vitamin D2 in allergic bronchial asthma (author's transl)]. / Orale anwendung von Kalzium plus Vitamin D2 bei allergischem Asthma bronchiale

In 12 patients with allergic bronchial asthma and airway obstruction the effect of calcium in combination with vitamin D 2 (calciferol), given orally, was tested in a cross-over double blind study. Within 60 minutes after application, a statistically significant reduction of airway resistance (Rt) and intrathoracic gas volume (IGV), as well as an increase of forced exspiratory one second volume (FEV1) and forced inspiratory one second volume (FIV1) was observed, in comparison with placebo. It is concluded that calcium, given orally in combination with calciferol, causes a decrease of airway obstruction in patients with allergic bronchial asthma.

Alpha1-antitrypsin deficiency with M-like phenotype.

A patient with a low serum concentration of alpha1-antitrypsin (0-1 g/l) but with an M-like phenotype is described. Her parents and 2 sibs have a PIM phenotype, but all except the father have approximately half-normal levels of alpha1-antitrypsin: The M-like variant apparently cannot be distinguished from M-alpha1-antitrypsin, when it occurs with M in heterozygotes. The proposita has severe airways obstruction and emphysema, and her father has moderate chronic obstructive pulmonary disease. The mother and 2 sibs are healthy.

[Neurological manifestations of Whipple's disease]. / Neurologische Manifestationen des Morbus Whipple

Three consecutive cases of Whipple's disease observed by us in recent years have involved neurologic symptoms, i.e. psychoorganic syndromes, gaze palsy, nystagmus, masseteric and pharyngeal myoclonus or papilledema. In one case mononuclear cells in the cerebrospinal fluid, most probably of ependymal origin, were loaded with periodic-acid-Schiff (PAS) positive granules. On treatment with antibiotics the neurologic signs cleared considerably or completely. The findings suggest (a) that neurologic involvement Whipple's disease may not be so uncommon as appears from the literature, (b) that examination of the spinal fluid with PAS staining may be helpful in the diagnosis of such cases, and (c) that neurologic involvement in Whipple's disease may also be amenable to treatment with antibiotics.

[Recurrent retroperitoneal giant lipoma (author's transl)]. / Rezidivierendes retroperitoneales Riesenlipom.

A giant lipoma weighing 9.1 kg situated retroperitoneally which was removed by operation from a 74-year-old woman is reported. The diagnosis of tumors is discussed. The characteristics of this primary benign tumor such as the rapid growth, tendency to malignant degeneration and recurrence make radical surgical removal necessary.

The effect of propranolol and phentolamine on serum gastrin concentration in response to respiratory acidosis in normal man.

Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.

[Giant-cell (Takayasu) arteritis as a cause of renovascular hypertension]. / Riesenzell-(Takayasu-) Arteriitis als Ursache einer renovaskul'aren Hypertonie

In a young female with renovascular hypertension multiple stenoses affecting both renal arteries, abdominal aorta and left axillary artery could be demonstrated. The elevated blood pressure could be normalized by bypass operation of the renal arteries. Histopathologic findings were those of giant cell (Takayasu) arteritis.

Exercise tolerance at 4 and 6 ATA.

Seven normal male subjects performed 5-min bicycle exercise ranging from 50-100% maximum oxygen uptake at 4 ATA and three were also studied at 6 ATA. At all pressures, the subjects breathed 0.2 ATA O2 plus nitrogen. All subjects were able to perform maximum work at all pressures. No pressure-dependent variations in heart rate, O2 uptake, or CO2 output were noted. At both 4 and 6 ATA, ventilation was decreased at exercise levels greater than 80% maximum O2 uptake. The magnitude of the decrease was not great, however, and signified only minor CO2 retention. In some instances exercise ventilation closely approached the 15-S maximum breathing capacity and these subjects noted severe dyspnea, possibly due to dynamic compression of large airways. In three subjects, respiratory frequency was measured as well as minute ventilation; this relationship did not change with depth. Subjects performing heavy exercise at 6 ATA noted disturbances of consciousness, presumably due to N2 narcosis.

[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)]. / Panarteriitis nodosa. Therapie mit Glukokortikoiden und Immunsuppressiva

Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.